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Sample records for modification alters serum

  1. Serum Protein Profile Alterations in Hemodialysis Patients

    SciTech Connect

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

    2003-11-18

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

  2. Alterations of histone modifications by cobalt compounds

    PubMed Central

    Li, Qin; Ke, Qingdong; Costa, Max

    2009-01-01

    In the present study, we examined the effects of CoCl2 on multiple histone modifications at the global level. We found that in both human lung carcinoma A549 cells and human bronchial epithelial Beas-2B cells, exposure to CoCl2 (≥200 μM) for 24 h increased H3K4me3, H3K9me2, H3K9me3, H3K27me3, H3K36me3, uH2A and uH2B but decreased acetylation at histone H4 (AcH4). Further investigation demonstrated that in A549 cells, the increase in H3K4me3 and H3K27me3 by cobalt ions exposure was probably through enhancing histone methylation processes, as methionine-deficient medium blocked the induction of H3K4me3 and H3K27me3 by cobalt ions, whereas cobalt ions increased H3K9me3 and H3K36me3 by directly inhibiting JMJD2A demethylase activity in vitro, which was probably due to the competition of cobalt ions with iron for binding to the active site of JMJD2A. Furthermore, in vitro ubiquitination and deubiquitination assays revealed that the cobalt-induced histone H2A and H2B ubiquitination is the result of inhibition of deubiquitinating enzyme activity. Microarray data showed that exposed to 200 μM of CoCl2 for 24 h, A549 cells not only increased but also decreased expression of hundreds of genes involved in different cellular functions, including tumorigenesis. This study is the first to demonstrate that cobalt ions altered epigenetic homeostasis in cells. It also sheds light on the possible mechanisms involved in cobalt-induced alteration of histone modifications, which may lead to altered programs of gene expression and carcinogenesis since cobalt at higher concentrations is a known carcinogen. PMID:19376846

  3. Modifications of human total serum N-glycome during liver fibrosis-cirrhosis, is it all about immunoglobulins?

    PubMed

    Klein, André; Michalski, Jean-Claude; Morelle, Willy

    2010-04-01

    The study of the total serum N-glycome during liver cirrhosis has demonstrated numerous alterations. The identification of the glycoproteins carrying these modifications and their relative contribution to the modification of the total serum N-glycome has shown the important role of IgA and IgG. The possible mechanisms of glycosylation alteration of the Igs and of liver secreted glycoproteins, the consequences in the pathophysiology of cirrhosis and their relation to the biomarkers of liver diseases are also discussed in the present review. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. 49 CFR 180.513 - Repairs, alterations, conversions, and modifications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars § 180.513 Repairs, alterations, conversions, and modifications. (a) To work on tank cars, a tank car facility must comply with... facility must report all work performed to the owner. The tank car facility must also report...

  5. 49 CFR 180.513 - Repairs, alterations, conversions, and modifications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars § 180.513 Repairs, alterations, conversions, and modifications. (a) To work on tank cars, a tank car facility must comply with... facility must report all work performed to the owner. The tank car facility must also report...

  6. 49 CFR 180.513 - Repairs, alterations, conversions, and modifications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars § 180.513 Repairs, alterations, conversions, and modifications. (a) To work on tank cars, a tank car facility must comply with... facility must report all work performed to the owner. The tank car facility must also report...

  7. Effect of Chemical Modifications on Aptamer Stability in Serum.

    PubMed

    Kratschmer, Christina; Levy, Matthew

    2017-09-25

    There is increasing interest in the use of aptamers for the development of therapeutics. However, as oligonucleotides, aptamers are susceptible to nuclease degradation; poor serum stability is likely to negatively affect in vivo function. Modified nucleotides have been used to thwart nuclease degradation. However, few studies report the serum stability of selected aptamers. In this study, we examined the effect of various chemical modifications (2'-deoxy, 2'-hydroxyl, 2'-fluoro, and 2'-O-methyl) on the stability of a control oligonucleotide sequence following incubation in frozen human, fresh mouse, and fresh human serum. We also assessed the effect of the 3' inverted dT cap on stability. Surprisingly, we found that fYrR (2'-fluoro RNA) is only roughly as stable as DNA (2'-deoxy). Interestingly, the inclusion of a 3' inverted dT cap had only a modest effect on serum stability, if any. In one instance, the addition of a 3' inverted dT cap rendered a molecule composed of DNA more stable than its fYrR counterpart. By far, fully modified oligonucleotides (100% 2-O-Methyl or 2'-O-methyl A, C, and U in combination with 2'-fluoro G, termed fGmH) had the longest half-lives. These compositions demonstrated little degradation in human serum even after prolonged incubation. Together these results support the need for using fully modified aptamers for in vivo applications and should encourage those in the field to exploit newer polymerase variants capable of directly generating such polymers.

  8. Altered Human Memory Modification in the Presence of Normal Consolidation.

    PubMed

    Censor, Nitzan; Buch, Ethan R; Nader, Karim; Cohen, Leonardo G

    2016-09-01

    Following initial learning, the memory is stabilized by consolidation mechanisms, and subsequent modification of memory strength occurs via reconsolidation. Yet, it is not clear whether consolidation and memory modification are the same or different systems-level processes. Here, we report disrupted memory modification in the presence of normal consolidation of human motor memories, which relate to differences in lesioned brain structure after stroke. Furthermore, this behavioral dissociation was associated with macrostructural network architecture revealed by a graph-theoretical approach, and with white-matter microstructural integrity measured by diffusion-weighted MRI. Altered macrostructural network architecture and microstructural integrity of white-matter underlying critical nodes of the related network predicted disrupted memory modification. To the best of our knowledge, this provides the first evidence of mechanistic differences between consolidation, and subsequent memory modification through reconsolidation, in human procedural learning. These findings enable better understanding of these memory processes, which may guide interventional strategies to enhance brain function and resulting behavior. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  9. Oxidative modification of serum proteins in multiple sclerosis.

    PubMed

    Sadowska-Bartosz, Izabela; Adamczyk-Sowa, Monika; Galiniak, Sabina; Mucha, Sebastian; Pierzchala, Krystyna; Bartosz, Grzegorz

    2013-11-01

    Multiple sclerosis (MS) has been demonstrated to involve oxidative stress and augmented glycoxidation. In this study, several markers of protein oxidative damage and glycoxidation have been compared in 14 relapsing remittent in MS (RRMS) patients without immunomodifying treatment, 10 patients in clinical relapse, and clinically stable patient groups treated with interferon β 1a (18) , β 1b (19) and glatiramer acetate (GA; 6) in relation to healthy subjects (12). The glycophore content was increased in RRSM patients without treatment and in patients treated with GA. The level of advanced protein oxidation products (AOPP) was increased in RRSM patients without treatment and in patients with clinical relapse. The level of protein carbonyls was elevated in RRSM patients without treatment and in patients treated with interferon β 1b. The levels of dityrosine level and N'-formylkynureine were elevated in RRSM patients without treatment while serum protein thiol groups were decreased in RRSM patients in clinical relapse as well as RRMS patients treated with interferon β 1a. Several markers of protein modification showed correlation with the C-reactive protein level and white blood cell count, suggesting that oxidative protein modifications are linked to the inflammatory processes in MS. Results of this study confirm the occurrence of protein oxidative and glycoxidative damage in MS and show that spectrophotometric and fluorimetric markers of this damage, especially the AOPP level, may be useful in monitoring oxidative stress in the course of therapy of MS.

  10. Comparison of Posttranslational Modification and the Functional Impairment of Human Serum Albumin in Commercial Preparations.

    PubMed

    Miyamura, Shigeyuki; Imafuku, Tadashi; Anraku, Makoto; Taguchi, Kazuaki; Yamasaki, Keishi; Tominaga, Yuna; Maeda, Hitoshi; Ishima, Yu; Watanabe, Hiroshi; Otagiri, Masaki; Maruyama, Toru

    2016-03-01

    On account of its long circulating half-life, human serum albumin (HSA) is susceptible to posttranslational modifications that can alter its functions. Here, we comprehensively compared the degree of posttranslational modifications with the functional impairment of HSA derived from 5 different commercially available albumin preparations and clarified their relationships. We used electrospray ionization-time of flight mass spectrometry to evaluate the degree of posttranslational modification of the entire HSA molecule that was associated with disease development and found that the fraction of Cys34-cysteinylated HSA (Cys-Cys34-HSA), a major form of oxidative modification, varied substantially among the albumin preparations. Meanwhile, no remarkable difference was found in the degree of glycated or N-terminal truncated HSA among the preparations tested. The nonosmotic pressure maintenance functions of HSA, such as its antioxidative and ligand-binding activities significantly differed among the preparations. Interestingly, the alternations of these functions showed a significantly negative correlation only with the Cys-Cys34-HSA fraction. These findings suggest that the Cys-Cys34-HSA fraction, as estimated by electrospray ionization-time of flight mass spectrometry can be used as a predictive marker for the functional impairment of albumin preparations and that it would be preferable to use albumin preparations with higher contents of functionally effective albumin that correspond to a lower degree of cysteinylation of Cys34 in clinical practice.

  11. Modification of Pointing Performance in Altered Gravitational Environments

    NASA Astrophysics Data System (ADS)

    Ciofani, Gianni; Migliore, Antonio; Mazzei, Daniele; Carrozza, Maria Chiara; Dario, Paolo

    2010-04-01

    The Fitts' law describes a correlation between the time needed to complete basic tasks such as pointing movements and the level of knowledge of the specific target to be reached. While it has been largely proved in normal gravity, very few experiments have been carried out in altered gravitational conditions. In our experiment, four subjects were positioned in front of a panel where round targets were placed along a circumference. They carried out pointing movements towards the targets when these were switched on. The task time was acquired and processed off-line. In all the cases, the performance of each subject have been significantly modified in the altered gravitational environment and, in particular, hypergravity seems to affect motor performance more considerably than microgravity. Even if experiments involving several subjects and more complex tasks have to be carried out in order to confirm our findings, these results show that ergonomics could be strongly affected by the modification of gravity, especially during the first phase of exposure to gravity alteration.

  12. Tributyltin exposure alters cytokine levels in mouse serum.

    PubMed

    Lawrence, Shanieek; Pellom, Samuel T; Shanker, Anil; Whalen, Margaret M

    2016-11-01

    Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, keratinocyte chemoattractant (KC), macrophage inflammatory protein 1β (MIP), MIP2 and regulated on activation normal T-cell-expressed and secreted (RANTES) was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40 and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in the serum of mice exposed to TBT for less than 24 h. Levels of IL1β, IL-12 βp40, IL-5 and IL-15 were also modulated in mouse serum, depending on the specific experiment and exposure level. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines.

  13. Serum Levels of Acylcarnitines Are Altered in Prediabetic Conditions

    PubMed Central

    Mai, Manuel; Tönjes, Anke; Kovacs, Peter; Stumvoll, Michael; Fiedler, Georg Martin; Leichtle, Alexander Benedikt

    2013-01-01

    Objective The role of mitochondrial function in the complex pathogenesis of type 2 diabetes is not yet completely understood. Therefore, the aim of this study was to investigate serum concentrations of short-, medium- and long-chain acylcarnitines as markers of mitochondrial function in volunteers with normal, impaired or diabetic glucose control. Methods Based on a 75 g oral glucose tolerance test, 1019 studied subjects were divided into a group with normal glucose tolerance (NGT; n = 636), isolated impaired fasting glycaemia (IFG; n = 184), impaired glucose tolerance (IGT; n = 87) or type 2 diabetes (T2D; n = 112). Serum concentrations of free carnitine and 24 acylcarnitines were measured by mass spectrometry. Results Serum levels of acetylcarnitine (C2), propionylcarnitine (C3), octanoylcarnitine (C8), malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH), hexanoylcarnitine (C6), octenoylcarnitine (C8:1), decanoylcarnitine (C10), decenoylcarnitine (C10:1), dodecanoylcarnitine (C12), tetradecenoylcarnitine (C14:1), tetradecadienylcarnitine (C14:2), hydroxytetradecanoylcarnitine (C14OH), hydroxyhexadecanoylcarnitine (C16OH) and octadecenoylcarnitine (C18:1) were significantly different among the groups (all p<0.05 adjusted for age, gender and BMI). Between the prediabetic states C14:1, C14:2 and C18:1 showed significantly higher serum concentrations in persons with IGT (p<0.05). Compared to T2D the IFG and the IGT subjects showed lower serum concentrations of malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH) (p<0.05). Conclusion Alterations in serum concentrations of several acylcarnitines, in particular tetradecenoylcarnitine (C14:1), tetradecadienylcarnitine (C14:2), octadecenoylcarnitine (C18:1) and malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH) are associated not only with T2D but also with prediabetic states. PMID:24358186

  14. [Oxidative modification of serum proteins in rats exposed to nonsymmetric dimethylhydrazine poisoning].

    PubMed

    Kulmagambetov, I R; Muravleva, L E; Koĭkov, V V

    2009-01-01

    Studies of serum proteins modifications both spontaneous and catalyzed by metals in rats under single exposure to nonsymmetric dimethylhydrazine revealed reliable, significant increase in oxidative destruction of proteins. That proves deep peroxidative syndrome in the experimental animals.

  15. Adductomics Pipeline for Untargeted Analysis of Modifications to Cys34 of Human Serum Albumin.

    PubMed

    Grigoryan, Hasmik; Edmands, William; Lu, Sixin S; Yano, Yukiko; Regazzoni, Luca; Iavarone, Anthony T; Williams, Evan R; Rappaport, Stephen M

    2016-11-01

    An important but understudied class of human exposures is comprised of reactive electrophiles that cannot be measured in vivo because they are short-lived. An avenue for assessing these meaningful exposures focuses on adducts from reactions with nucleophilic loci of blood proteins, particularly Cys34 of human serum albumin, which is the dominant scavenger of reactive electrophiles in serum. We developed an untargeted analytical scheme and bioinformatics pipeline for detecting, quantitating, and annotating Cys34 adducts in tryptic digests of human serum/plasma. The pipeline interrogates tandem mass spectra to find signatures of the Cys34-containing peptide, obtains accurate masses of putative adducts, quantitates adduct levels relative to a "housekeeping peptide", and annotates modifications based on a combination of retention time, accurate mass, elemental composition, and database searches. We used the adductomics pipeline to characterize 43 adduct features in archived plasma from healthy human subjects and found several that were highly associated with smoking status, race, and other covariates. Since smoking is a strong risk factor for cancer and cardiovascular disease, our ability to discover adducts that distinguish smokers from nonsmokers with untargeted adductomics indicates that the pipeline is suitable for use in epidemiologic studies. In fact, adduct features were both positively and negatively associated with smoking, indicating that some adducts arise from reactions between Cys34 and constituents of cigarette smoke (e.g., ethylene oxide and acrylonitrile) while others (Cys34 oxidation products and disulfides) appear to reflect alterations in the serum redox state that resulted in reduced adduct levels in smokers.

  16. Alteration of human serum albumin tertiary structure induced by glycation. Spectroscopic study

    NASA Astrophysics Data System (ADS)

    Szkudlarek, A.; Maciążek-Jurczyk, M.; Chudzik, M.; Równicka-Zubik, J.; Sułkowska, A.

    2016-01-01

    The modification of human serum albumin (HSA) structure by non-enzymatic glycation is one of the underlying factors that contribute to the development of complications of diabetes and neurodegenerative diseases. The aim of the present work was to estimate how glycation of HSA altered its tertiary structure. Changes of albumin conformation were investigated by comparison of glycated (gHSA) and non-glycated human serum albumin (HSA) absorption spectra, red edge excitation shift (REES) and synchronous spectra. Effect of glycation on human serum albumin tertiary structure was also investigated by 1H NMR spectroscopy. Formation of gHSA Advanced Glycation End-products (AGEs) caused absorption of UV-VIS light between 310 nm and 400 nm while for non-glycated HSA in this region no absorbance has been registered. Analysis of red edge excitation shift effect allowed for observation of structural changes of gHSA in the hydrophobic pocket containing the tryptophanyl residue. Moreover changes in the microenvironment of tryptophanyl and tyrosyl residues brought about AGEs on the basis of synchronous fluorescence spectroscopy have been confirmed. The influence of glycation process on serum albumin binding to 5-dimethylaminonaphthalene-1-sulfonamide (DNSA), 2-(p-toluidino) naphthalene-6-sulfonic acid (TNS), has been studied. Fluorescence analysis showed that environment of both binding site I and II is modified by galactose glycation.

  17. Alteration of human serum albumin tertiary structure induced by glycation. Spectroscopic study.

    PubMed

    Szkudlarek, A; Maciążek-Jurczyk, M; Chudzik, M; Równicka-Zubik, J; Sułkowska, A

    2016-01-15

    The modification of human serum albumin (HSA) structure by non-enzymatic glycation is one of the underlying factors that contribute to the development of complications of diabetes and neurodegenerative diseases. The aim of the present work was to estimate how glycation of HSA altered its tertiary structure. Changes of albumin conformation were investigated by comparison of glycated (gHSA) and non-glycated human serum albumin (HSA) absorption spectra, red edge excitation shift (REES) and synchronous spectra. Effect of glycation on human serum albumin tertiary structure was also investigated by (1)H NMR spectroscopy. Formation of gHSA Advanced Glycation End-products (AGEs) caused absorption of UV-VIS light between 310 nm and 400 nm while for non-glycated HSA in this region no absorbance has been registered. Analysis of red edge excitation shift effect allowed for observation of structural changes of gHSA in the hydrophobic pocket containing the tryptophanyl residue. Moreover changes in the microenvironment of tryptophanyl and tyrosyl residues brought about AGEs on the basis of synchronous fluorescence spectroscopy have been confirmed. The influence of glycation process on serum albumin binding to 5-dimethylaminonaphthalene-1-sulfonamide (DNSA), 2-(p-toluidino) naphthalene-6-sulfonic acid (TNS), has been studied. Fluorescence analysis showed that environment of both binding site I and II is modified by galactose glycation.

  18. [Modification of placenta blood serum proteins under low temperature effect].

    PubMed

    Fal'ko, O V; Zemlianskikh, N G; Lipina, O V; Prokopiuk, O S

    2013-01-01

    Changes in environmental physical and chemical factors upon freeze-thawing and low temperature storage of biological samples can result in impairments of protein structures. This work specifies spontaneous and diamide-induced protein aggregations of placenta blood serum stored at -20 degrees and -196 degrees C during 2 years with SDS-PAGE. It was shown that storage of placenta blood serum at low temperatures did not cause any quantitative and qualitative changes in fraction distribution of proteins denatured with SDS in comparison to the native samples which were not frozen. Application of beta-mercaptoethanol revealed that placenta blood serum proteins upon freeze-thawing did not form spontaneous aggregates linked by disulphide bridges. Oxidation of amino acid sulfhydryl groups induced by diamide and accompanied by high molecular aggregate formation proved to be a quite effective way for indirect estimation of structural changes in protein upon low temperature effects. In samples thawed after low temperature storage the protein aggregation with 4 microM diamide was significantly higher than in native serum. These discrepancies between native and frozen-thawed samples are stipulated by impairments of protein structure under low temperature and increased in accessibility of reactive SH-groups of proteins for oxidation with diamide. Structural changes in placenta blood serum proteins, which caused by low temperatures and revealed by elevated sensibility to diamide-induced aggregate formation, did not depend on temperature (-20 degrees and -196 degrees C) and storage terms (2 years and 3 weeks). They reflect protein reaction to freeze-thawing processes and could be sequence of ice crystal formation which takes place in unprotected media.

  19. Altering 5-hydroxymethylcytosine modification impacts ischemic brain injury.

    PubMed

    Miao, Zhigang; He, Yuquan; Xin, Ning; Sun, Miao; Chen, Li; Lin, Li; Li, Jizhen; Kong, Jiming; Jin, Peng; Xu, Xingshun

    2015-10-15

    Epigenetic modifications such as cytosine methylation and histone modification are linked to the pathology of ischemic brain injury. Recent research has implicated 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC) via oxidation by ten-eleven translocation (Tet) enzymes, in DNA methylation-related plasticity. Here we show that 5hmC abundance was increased after ischemic injury, and Tet2 was responsible for this increase; furthermore, inhibiting Tet2 expression abolished the increase of 5hmC caused by ischemic injury. The decrease in 5hmC modifications from inhibiting Tet2 activity was accompanied by increased infarct volume after ischemic injury. Genome-wide profiling of 5hmC revealed differentially hydroxymethylated regions (DhMRs) associated with ischemic injury, and DhMRs were enriched among the genes involved in cell junction, neuronal morphogenesis and neurodevelopment. In particular, we found that 5hmC modifications at the promoter region of brain-derived neurotrophic factor (BDNF) increased, which was accompanied by increased BDNF mRNA, whereas the inhibition of Tet2 reduced BDNF mRNA and protein expression. Finally, we show that the abundance of 5hmC in blood samples from patients with acute ischemic stroke was also significantly increased. Together, these data suggest that 5hmC modification could serve as both a potential biomarker and a therapeutic target for the treatment of ischemic stroke. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Alteration and modulation of protein activity by varying post-translational modification

    DOEpatents

    Thompson, David N; Reed, David W; Thompson, Vicki S; Lacey, Jeffrey A; Apel, William A

    2015-03-03

    Embodiments of the invention include methods of altering the enzymatic activity or solubility of an extremophilic enzyme or post-translationally modifying a protein of interest via using isolated or partially purified glycosyltransferases and/or post-translational modification proteins, extracts of cells comprising glycosyltransferases and/or post-translational modification proteins, and/or in cells comprising one or more glycosyltransferases and/or post-translational modification proteins.

  1. Alteration and modulation of protein activity by varying post-translational modification

    DOEpatents

    Thompson, David N.; Reed, David W.; Thompson, Vicki S.; Lacey, Jeffrey A.; Apel, William A.

    2016-07-12

    Embodiments of the invention include methods of altering the enzymatic activity or solubility of an extremophilic enzyme or post-translationally modifying a protein of interest via using isolated or partially purified glycosyltransferases and/or post-translational modification proteins, extracts of cells comprising glycosyltransferases and/or post-translational modification proteins, and/or in cells comprising one or more glycosyltransferases and/or post-translational modification proteins.

  2. Alteration of the serum N-glycome of mice locally exposed to high doses of ionizing radiation.

    PubMed

    Chaze, Thibault; Slomianny, Marie-Christine; Milliat, Fabien; Tarlet, Georges; Lefebvre-Darroman, Tony; Gourmelon, Patrick; Bey, Eric; Benderitter, Marc; Michalski, Jean-Claude; Guipaud, Olivier

    2013-02-01

    Exposure of the skin to ionizing radiation leads to characteristic reactions that will often turn into a pathophysiological process called the cutaneous radiation syndrome. The study of this disorder is crucial to finding diagnostic and prognostic bioindicators of local radiation exposure or radiation effects. It is known that irradiation alters the serum proteome content and potentially post-translationally modifies serum proteins. In this study, we investigated whether localized irradiation of the skin alters the serum glycome. Two-dimensional differential in-gel electrophoresis of serum proteins from a man and from mice exposed to ionizing radiation showed that potential post-translational modification changes occurred following irradiation. Using a large-scale quantitative mass-spectrometry-based glycomic approach, we performed a global analysis of glycan structures of serum proteins from non-irradiated and locally irradiated mice exposed to high doses of γ-rays (20, 40, and 80 Gy). Non-supervised descriptive statistical analyses (principal component analysis) using quantitative glycan structure data allowed us to discriminate between uninjured/slightly injured animals and animals that developed severe lesions. Decisional statistics showed that several glycan families were down-regulated whereas others increased, and that particular structures were statistically significantly changed in the serum of locally irradiated mice. The observed increases in multiantennary N-glycans and in outer branch fucosylation and sialylation were associated with the up-regulation of genes involved in glycosylation in the liver, which is the main producer of serum proteins, and with an increase in the key proinflammatory serum cytokines IL-1β, IL-6, and TNFα, which can regulate the expression of glycosylation genes. Our results suggest for the first time a role of serum protein glycosylation in response to irradiation. These protein-associated glycan structure changes might

  3. Alteration of the Serum N-glycome of Mice Locally Exposed to High Doses of Ionizing Radiation*

    PubMed Central

    Chaze, Thibault; Slomianny, Marie-Christine; Milliat, Fabien; Tarlet, Georges; Lefebvre-Darroman, Tony; Gourmelon, Patrick; Bey, Eric; Benderitter, Marc; Michalski, Jean-Claude; Guipaud, Olivier

    2013-01-01

    Exposure of the skin to ionizing radiation leads to characteristic reactions that will often turn into a pathophysiological process called the cutaneous radiation syndrome. The study of this disorder is crucial to finding diagnostic and prognostic bioindicators of local radiation exposure or radiation effects. It is known that irradiation alters the serum proteome content and potentially post-translationally modifies serum proteins. In this study, we investigated whether localized irradiation of the skin alters the serum glycome. Two-dimensional differential in-gel electrophoresis of serum proteins from a man and from mice exposed to ionizing radiation showed that potential post-translational modification changes occurred following irradiation. Using a large-scale quantitative mass-spectrometry-based glycomic approach, we performed a global analysis of glycan structures of serum proteins from non-irradiated and locally irradiated mice exposed to high doses of γ-rays (20, 40, and 80 Gy). Non-supervised descriptive statistical analyses (principal component analysis) using quantitative glycan structure data allowed us to discriminate between uninjured/slightly injured animals and animals that developed severe lesions. Decisional statistics showed that several glycan families were down-regulated whereas others increased, and that particular structures were statistically significantly changed in the serum of locally irradiated mice. The observed increases in multiantennary N-glycans and in outer branch fucosylation and sialylation were associated with the up-regulation of genes involved in glycosylation in the liver, which is the main producer of serum proteins, and with an increase in the key proinflammatory serum cytokines IL-1β, IL-6, and TNFα, which can regulate the expression of glycosylation genes. Our results suggest for the first time a role of serum protein glycosylation in response to irradiation. These protein-associated glycan structure changes might

  4. Bias modification training can alter approach bias and chocolate consumption.

    PubMed

    Schumacher, Sophie E; Kemps, Eva; Tiggemann, Marika

    2016-01-01

    Recent evidence has demonstrated that bias modification training has potential to reduce cognitive biases for attractive targets and affect health behaviours. The present study investigated whether cognitive bias modification training could be applied to reduce approach bias for chocolate and affect subsequent chocolate consumption. A sample of 120 women (18-27 years) were randomly assigned to an approach-chocolate condition or avoid-chocolate condition, in which they were trained to approach or avoid pictorial chocolate stimuli, respectively. Training had the predicted effect on approach bias, such that participants trained to approach chocolate demonstrated an increased approach bias to chocolate stimuli whereas participants trained to avoid such stimuli showed a reduced bias. Further, participants trained to avoid chocolate ate significantly less of a chocolate muffin in a subsequent taste test than participants trained to approach chocolate. Theoretically, results provide support for the dual process model's conceptualisation of consumption as being driven by implicit processes such as approach bias. In practice, approach bias modification may be a useful component of interventions designed to curb the consumption of unhealthy foods. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Serum vitamin D levels are not altered after controlled diesel ...

    EPA Pesticide Factsheets

    Past research has suggested that exposure to urban air pollution may be associated with vitamin D deficiency in human populations. Vitamin D is widely known for its importance in bone growth/remodeling, muscle metabolism, and its ability to promote calcium absorption in the gut; deficiency in vitamin D results in the development of rickets in children and osteomalacia in adults. In the current study, we assessed whether vitamin D levels are altered under controlled exposures to a commonly measured urban air pollutant, diesel. For this study, we exposed 12 healthy volunteers to clean air and diesel exhaust (300 μg/m3) for 2 hours while undergoing intermittent exercise. Venous blood was collected before, 0 hrs post-, and 18 hrs post-exposure, and 25-hydroxyvitamin D [25(OH)D] was measured in the serum. The average baseline value of 25(OH)D (mean ± standard error) was 22.9 ± 2.5 ng/mL. Four subject’s baseline values were vitamin D deficient (30 ng/mL). Additionally, there was no significant change in the baseline values between the clean air and diesel exposures (paired t-test, p = 0.54), suggesting minimal variability in 25(OH)D over the experiment's time course. Small inductions in 25(OH)D were found following clean air exposures (12.5 ± 4.9% and a 7.1 ± 5.0% for 0 hrs post- and 18 hrs post-exposure values compared to baseline, respectively). Minimal changes in 25(OH)D were observed following diesel exhaust exposures 0 hrs (3.5 ± 5.2%) and 18 hrs followin

  6. Interaction of human serum albumin and its clinically relevant modification with oligoribonucleotides.

    PubMed

    Gerasimova, Yuliya V; Erchenko, Irina A; Shakirov, Makhmut M; Godovikova, Tatyana S

    2008-08-15

    Human serum albumin (HSA) was shown to mediate oligoribonucleotide cleavage. Nonenzymatic glycation of HSA decreased the ribonuclease-like activity of the protein. According to (31)P NMR data, both native and glycated albumins induced hydrolysis of RNA molecule through 2',3'-cyclophosphate intermediates. A feasible mechanism of RNA hydrolysis by native albumin and its clinically relevant modification was discussed.

  7. COMPARISON OF MODIFICATION SITES FORMED ON HUMAN SERUM ALBUMIN AT VARIOUS STAGES OF GLYCATION

    PubMed Central

    Barnaby, Omar S.; Cerny, Ronald L.; Clarke, William; Hage, David S.

    2010-01-01

    Background Many of the complications encountered during diabetes can be linked to the non-enzymatic glycation of proteins, including human serum albumin (HSA). However, there is little information regarding how the glycation pattern of HSA changes as the total extent of glycation is varied. The goal of this study was to identify and conduct a semi-quantitative comparison of the glycation products on HSA that are produced in the presence of various levels of glycation. Methods Three glycated HSA samples were prepared in vitro by incubating physiological concentrations of HSA with 15 mmol/l glucose for 2 or 5 weeks, or with 30 mmol/l glucose for 4 weeks. These samples were then digested and examined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to identify the glycation products that were formed. Results It was found that the glycation pattern of HSA changed with its overall extent of total glycation. Many modifications including previously-reported primary glycation sites (e.g., K199, K281, and the N-terminus) were consistently found in the tested samples. Lysines 199 and 281, as well as arginine 428, contained the most consistently identified and abundant glycation products. Lysines 93, 276, 286, 414, 439, and 524/525, as well as the N-terminus and arginines 98, 197, and 521, were also found to be modified at various degrees of HSA glycation. Conclusions The glycation pattern of HSA was found to vary with different levels of total glycation and included modifications at the 2 major drug binding sites on this protein. This result suggests that different modified forms of HSA, both in terms of the total extent of glycation and glycation pattern, may be found at various stages of diabetes. The clinical implication of these results is that the binding of HSA to some drug may be altered at various stages of diabetes as the extent of glycation and types of modifications in this protein are varied. PMID:21034726

  8. Altered Serum Uric Acid Level in Lichen Planus Patients

    PubMed Central

    Chakraborti, Goutam; Biswas, Rabindranath; Chakraborti, Sandip; Sen, Pradyot Kumar

    2014-01-01

    Background: Lichen planus (LP) is a common disorder whose etiopathogenesis is not clear. Recently, it has been suggested that increased reactive oxygen species (ROS) play important roles in the underlying mechanism of LP. Objectives: The principal aim of this study was to evaluate serum uric acid (UA) levels as a measure of the antioxidant defense status in LP patients. Methods: Serum UA levels were determined in 58 LP patients and 61 controls. Results: Serum UA levels were significantly decreased in patients with respect to controls. Moreover, serum UA level was decreased according to increasing duration of disease. Conclusions: The results of our study suggest that LP is associated with decrease of UA levels in serum. UA may be a potential, useful biomarker of antioxidant status in LP for elaboration of treatment strategy and monitoring. PMID:25484383

  9. Alteration of maternal serum irisin levels in gestational diabetes mellitus.

    PubMed

    Ural, Ulku Mete; Sahin, Serap Baydur; Tekin, Yesim Bayoglu; Cüre, Medine Cumhur; Sezgin, Hacer

    2016-01-01

    The aim of our study was to compare serum irisin concentrations in pregnant women with and without ges-tational diabetes mellitus (GDM). This study was performed at the Tertiary Care Center, Department of Obstetrics and Gynecol-ogy, between January 2014 and April 2014. A total of 45 pregnant women with GDM (diabetes group) and 41 BMI- and age-matched healthy pregnant women (control group) were recruited. Maternal serum irisin levels were measured by enzyme-linked immunosorbent assay kit at 24-28 weeks of gestation. An association between maternal serum irisin lev-els and metabolic parameters was analyzed. Body mass index, serum levels of glucose, insulin and irisin were tested and analyzed in the study group and controls. Pregnant women with GDM had significantly higher fasting plasma glucose (p = 0.001), first-hour OGTT glucose (p = 0.001), second-hour OGTT glucose (p = 0.001), and fasting insulin (p = 0.045) levels as compared to controls. Serum irisin levels were 1.04 ± 0.3 and 1.3 ± 0.2 in pregnant women with GDM and healthy pregnant controls, respectively (p = 0.001). Correlation analysis between irisin levels and anthropometric and biochemical parameters in patients with gestational diabetes revealed that none of the investigated parameters correlated with serum irisin level. Our results suggest that serum irisin levels might be introduced as a novel marker for GDM, with decreased levels of irisin being indicative of GDM.

  10. [Seasonal alterations in serum iron levels in elite football players].

    PubMed

    Malićević, Sead; Nesić, Dejan; Rosić, Ilija

    2008-01-01

    It is very important to monitor levels of serum iron and other factors of iron metabolism and oxygen transport system as they play a very important role in functional ability of football players. A decrease in serum iron level can be the very first sign of development of iron deficiency anaemia, which seriously influences health and functional ability of an athlete and is a common problem in competitive sports. The aim of this study was to observe and evaluate changes in serum iron values during the competition season in relation to the training process. During four years, serum iron level was measured in 28-34 players of one of the top football clubs in Serbia, four times a year: at the beginning and at peak-point of both half-seasons. Differences between basic and control findings, relative and absolute changes in serum iron levels and statistical significance of the findings were than calculated. There was a significant decrease in mean serum iron levels on each control test, compared to basic values. Mean value of control serum iron levels is significantly lower than mean of preseason values (20.64 +/- 6.58 vs. 16.38 +/- 5.51 micromol/l). A significant decrease in serum iron level among footballers during both half-seasons is most probably due to an increased loss and/or diminished absorption resulting from a high intensity training process. Because the decline in serum iron may be an early sign of iron store depletion and iron deficiency anaemia, it is very important to evaluate it regularly, along with other factors of iron metabolism and oxygen transport system.

  11. Opium and heroin alter biochemical parameters of human's serum.

    PubMed

    Kouros, Divsalar; Tahereh, Haghpanah; Mohammadreza, Afarinesh; Minoo, Mahmoudi Zarandi

    2010-05-01

    Iran is a significant consumer of opium, and, generally, of opioids, in the world. Addiction is one of the important issues of the 21st century and is an imperative issue in Iran. Long-term consumption of opioids affects homeostasis. To determine the effects of opium and heroin consumption on serum biochemical parameters. In a cross-sectional study, subjects who had consumed heroin (n = 35) or opium (n = 42) for more than two years and 35 nonaddict volunteers as the control group were compared in regard to various biochemical parameters such as fasting blood sugar (FBS), Na(+), K(+), Ca(2+), blood urea nitrogen (BUN), uric acid (UA), triglyceride (TG), cholesterol, creatinine, and total protein. Chromatography was used to confirm opioid consumption, and the concentration of biochemical parameters was determined by laboratory diagnostic tests on serum. No significant differences were found in Na(+), Ca(2+), BUN, UA, TG, creatinine, and total protein concentrations among the three groups. FBS, K(+), and UA levels were significantly lower in opium addicts compared to the control group. Serum Ca(2+) concentration of heroin addicts showed a significant decrease compared to that of the control group. Both addict groups showed a significant decrease in serum cholesterol levels. Chronic use of opium and heroin can change serum FBS, K(+), Ca(2+), UA, and cholesterol. This study, one of few on the effects of opium on serum biochemical parameters in human subjects, has the potential to contribute to the investigation of new approaches for further basic studies.

  12. Ocean acidification alters fish populations indirectly through habitat modification

    NASA Astrophysics Data System (ADS)

    Nagelkerken, Ivan; Russell, Bayden D.; Gillanders, Bronwyn M.; Connell, Sean D.

    2016-01-01

    Ocean ecosystems are predicted to lose biodiversity and productivity from increasing ocean acidification. Although laboratory experiments reveal negative effects of acidification on the behaviour and performance of species, more comprehensive predictions have been hampered by a lack of in situ studies that incorporate the complexity of interactions between species and their environment. We studied CO2 vents from both Northern and Southern hemispheres, using such natural laboratories to investigate the effect of ocean acidification on plant-animal associations embedded within all their natural complexity. Although we substantiate simple direct effects of reduced predator-avoidance behaviour by fishes, as observed in laboratory experiments, we here show that this negative effect is naturally dampened when fish reside in shelter-rich habitats. Importantly, elevated CO2 drove strong increases in the abundance of some fish species through major habitat shifts, associated increases in resources such as habitat and prey availability, and reduced predator abundances. The indirect effects of acidification via resource and predator alterations may have far-reaching consequences for population abundances, and its study provides a framework for a more comprehensive understanding of increasing CO2 emissions as a driver of ecological change.

  13. Oxidative stress alters global histone modification and DNA methylation.

    PubMed

    Niu, Yingmei; DesMarais, Thomas L; Tong, Zhaohui; Yao, Yixin; Costa, Max

    2015-05-01

    The JmjC domain-containing histone demethylases can remove histone lysine methylation and thereby regulate gene expression. The JmjC domain uses iron Fe(II) and α-ketoglutarate (αKG) as cofactors in an oxidative demethylation reaction via hydroxymethyl lysine. We hypothesize that reactive oxygen species will oxidize Fe(II) to Fe(III), thereby attenuating the activity of JmjC domain-containing histone demethylases. To minimize secondary responses from cells, extremely short periods of oxidative stress (3h) were used to investigate this question. Cells that were exposed to hydrogen peroxide (H2O2) for 3h exhibited increases in several histone methylation marks including H3K4me3 and decreases of histone acetylation marks including H3K9ac and H4K8ac; preincubation with ascorbate attenuated these changes. The oxidative stress level was measured by generation of 2',7'-dichlorofluorescein, GSH/GSSG ratio, and protein carbonyl content. A cell-free system indicated that H2O2 inhibited histone demethylase activity where increased Fe(II) rescued this inhibition. TET protein showed a decreased activity under oxidative stress. Cells exposed to a low-dose and long-term (3 weeks) oxidative stress also showed increased global levels of H3K4me3 and H3K27me3. However, these global methylation changes did not persist after washout. The cells exposed to short-term oxidative stress also appeared to have higher activity of class I/II histone deacetylase (HDAC) but not class III HDAC. In conclusion, we have found that oxidative stress transiently alters the epigenetic program process through modulating the activity of enzymes responsible for demethylation and deacetylation of histones.

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

    PubMed

    Silva, M Luísa S

    2015-12-01

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

  15. Storage of serum in plastic and glass containers may alter the serum concentration of polychlorinated biphenyls.

    PubMed

    Karmaus, Wilfried; Riebow, John F

    2004-05-01

    Valid exposure assessment and biomonitoring of toxicants rely on standardized specimen collection, handling, storage, and measurement. In a study designed to determine organochlorine concentrations in blood samples, we recruited participants from registered anglers in Michigan. After participants were interviewed, blood was collected from study subjects, either at home by a phlebotomist or in a commercial blood-draw station. The phlebotomists stored their samples in glass containers, but without our knowledge, the commercial laboratory transferred the specimens to plastic containers for freezing in its central facility. Samples were analyzed in the Analytical Chemistry Section Laboratory of the Michigan Department of Community Health. This laboratory also provided information on storage in glass (n = 28) versus plastic containers (n = 113). We conducted linear regression analyses to assess factors that may explain the concentrations of polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and polybrominated biphenyls (PBBs). Our results indicate that storage of serum in plastic containers altered the total concentrations of PCBs, in particular, the higher chlorinated PCBs (PCB-180 and PCB-199), but not DDE or PBBs. No other characteristics of the samples could explain the higher PCB values (0.75 micro g/L vs. 0.45 micro g/L; p = 0.025) of those stored in plastic containers. The proportion of PCB detects in both subsamples did not differ. Some preceding studies have provided information on whether specimens were stored in glass or plastic containers; however, a number of studies have not. We suggest the initiation of a new review process to determine whether these earlier reports were based on unbiased PCB determinations. We recommend standardizing specimen collection, handling, storage, and measurement, which is particularly necessary for newly emerging analytes.

  16. A NASTRAN DMAP alter for determining a local stiffness modification to obtain a specified eigenvalue

    NASA Technical Reports Server (NTRS)

    Case, W. R., Jr.

    1973-01-01

    A technique is described which has been programmed as a DMAP Alter to Rigid Format 3, for determining a stiffness matrix modification to obtain a specified eigenvalue for a structure. The stiffness matrix modifications allowable are those that can be described as the product of a single scalar variable and a matrix of constant coefficients input by the user. The program solves for the scalar variable multiplier which will yield a specified eigenvalue for the complete structure (provided it exists), makes the modification to the stiffness matrix, and proceeds in Rigid Format 3 to obtain the eigenvalues and eigenvectors of the modified structure.

  17. Equine endurance exercise alters serum branched-chain amino acid and alanine concentrations.

    PubMed

    Trottier, N L; Nielsen, B D; Lang, K J; Ku, P K; Schott, H C

    2002-09-01

    Six 2-year-old Arabian horses were used to determine whether 60 km prolonged endurance exercise (approximately 4 h) alters amino acid concentrations in serum and muscle, and the time required for serum amino acid concentrations to return to basal resting values. Blood and muscle samples were collected throughout exercise and during a 3 day recovery period. Isoleucine concentration in muscle tended to increase and leucine and valine did not change due to exercise. Serum alanine concentrations did not increase immediately after exercise, but increased at 24, 48 and 72 h postexercise. Serum isoleucine, leucine, and valine concentrations decreased after exercise and time required to reach pre-exercising concentrations was 48 h. In conclusion, endurance exercise in the horse decreases serum isoleucine, leucine, and valine concentrations, and increases serum alanine concentration. The decrease in serum branched-chain amino acid concentrations did not correspond to a measurable increase in total muscle branched-chain amino acid concentrations.

  18. Iron Deficiency in Infancy Predicts Altered Serum Prolactin Response 10 Years Later

    PubMed Central

    FELT, BARBARA; JIMENEZ, ELIAS; SMITH, JULIA; CALATRONI, AGUSTIN; KACIROTI, NIKO; WHEATCROFT, GLORIA; LOZOFF, BETSY

    2007-01-01

    Serum prolactin may reflect CNS dopaminergic function. Because iron deficiency (ID) alters brain dopamine in rats, serum prolactin levels were previously investigated in infants with varied iron status. High serum prolactin levels correlated with behaviors typical of chronic ID. The objective of this study was to determine the effect of infant iron status on serum prolactin levels after a stressor in early adolescence. One hundred fifty-nine of 191 children enrolled in infancy (chronic ID, n = 46; good iron comparison group, n = 113) had serum prolactin measurements after catheter placement at 11–14 y of age. Serum prolactin levels were compared by sex, pubertal status and infant iron status and the pattern of change over time was compared by infant iron status controlling for pubertal stage and background factors. Males and less mature adolescents had lower serum prolactin concentrations than females and more mature adolescents. Controlling for these factors, the serum prolactin response pattern differed significantly by infant iron status. Serum prolactin declined earlier for the chronic ID group. In conclusion, an altered serum prolactin response pattern was observed 10 y after chronic ID in infancy and may suggest a long-lasting effect of ID on the regulation of prolactin. PMID:16966351

  19. Altered kynurenine pathway metabolites in serum of chronic migraine patients.

    PubMed

    Curto, Martina; Lionetto, Luana; Negro, Andrea; Capi, Matilde; Fazio, Francesco; Giamberardino, Maria Adele; Simmaco, Maurizio; Nicoletti, Ferdinando; Martelletti, Paolo

    2015-01-01

    Activation of glutamate (Glu) receptors plays a key role in the pathophysiology of migraine. Both NMDA and metabotropic Glu receptors are activated or inhibited by metabolites of the kynurenine pathway, such as kynureninic acid (KYNA), quinolinic acid (QUINA), and xanthurenic acid (XA). In spite of the extensive research carried out on KYNA and other kynurenine metabolites in experimental models of migraine, no studies have ever been carried out in humans. Here, we measured all metabolites of the kynurenine pathway in the serum of patients affected by chronic migraine (CM) and age- and gender-matched healthy controls. We assessed serum levels of tryptophan (Trp), L-kynurenine (KYN), KYNA, anthranilic acid (ANA), 3-hydroxyanthranilic acid (3-HANA), 3-hydroxykynirenine (3-HK), XA, QUINA, and 5-hydroxyindolacetic acid (5-HIAA) in 119 patients affected by CM (ICHD-3beta criteria) and 84 age-matched healthy subjects. Patients with psychiatric co-morbidities, systemic inflammatory, endocrine or neurological disorders, and mental retardation were excluded. Serum levels of all metabolites were assayed using liquid chromatography/tandem mass spectrometry (LC-MS/MS). LC-MS/MS analysis of kynurenine metabolites showed significant reductions in the levels of KYN (-32 %), KYNA (-25 %), 3-HK (-49 %), 3-HANA (-63 %), 5-HIAA (-36 %) and QUINA (-80 %) in the serum of the CM patients, as compared to healthy controls. Conversely, levels of Trp, ANA and XA were significantly increased in CM patients (+5 %, +339 % and +28 %, respectively). These findings suggest that in migraine KYN is unidirectionally metabolized into ANA at expenses of KYNA and 3-HK. The reduction in the levels of KYNA, which behaves as a competitive antagonist of the glycine site of NMDA receptors, is consistent with the hypothesis that NMDA receptors are overactive in migraine. The increase in XA, a putative activator of Glu2 receptors, may represent a compensatory event aimed at reinforcing endogenous

  20. Modification of the Kaolin Serum Treatment Used in the Hemagglutination-Inhibition Test for California Arbovirus Encephalitis

    PubMed Central

    Robinson, P. R.; Allen, M. R.; Marcovici, M.

    1970-01-01

    Modification of the pH of kaolin-serum treatment produces hemagglutination-inhibition test results comparable with the plaque neutralization test in duck embryo tissue culture; the standard treatment does not. PMID:5437311

  1. 33 CFR 149.15 - What is the process for submitting alterations and modifications affecting the design and...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... submitting alterations and modifications affecting the design and construction of a deepwater port? 149.15...) DEEPWATER PORTS DEEPWATER PORTS: DESIGN, CONSTRUCTION, AND EQUIPMENT General § 149.15 What is the process for submitting alterations and modifications affecting the design and construction of a deepwater...

  2. Salmonella enterica Serovar Typhi Lipopolysaccharide O-Antigen Modification Impact on Serum Resistance and Antibody Recognition

    PubMed Central

    Heiss, Christian; Black, Ian; Donohue, Nicholas; Brown, Naj; Davies, Mark R.; Azadi, Parastoo; Baker, Stephen; Kaye, Paul M.

    2017-01-01

    ABSTRACT Salmonella enterica serovar Typhi is a human-restricted Gram-negative bacterial pathogen responsible for causing an estimated 27 million cases of typhoid fever annually, leading to 217,000 deaths, and current vaccines do not offer full protection. The O-antigen side chain of the lipopolysaccharide is an immunodominant antigen, can define host-pathogen interactions, and is under consideration as a vaccine target for some Gram-negative species. The composition of the O-antigen can be modified by the activity of glycosyltransferase (gtr) operons acquired by horizontal gene transfer. Here we investigate the role of two gtr operons that we identified in the S. Typhi genome. Strains were engineered to express specific gtr operons. Full chemical analysis of the O-antigens of these strains identified gtr-dependent glucosylation and acetylation. The glucosylated form of the O-antigen mediated enhanced survival in human serum and decreased complement binding. A single nucleotide deviation from an epigenetic phase variation signature sequence rendered the expression of this glucosylating gtr operon uniform in the population. In contrast, the expression of the acetylating gtrC gene is controlled by epigenetic phase variation. Acetylation did not affect serum survival, but phase variation can be an immune evasion mechanism, and thus, this modification may contribute to persistence in a host. In murine immunization studies, both O-antigen modifications were generally immunodominant. Our results emphasize that natural O-antigen modifications should be taken into consideration when assessing responses to vaccines, especially O-antigen-based vaccines, and that the Salmonella gtr repertoire may confound the protective efficacy of broad-ranging Salmonella lipopolysaccharide conjugate vaccines. PMID:28167670

  3. Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel

    PubMed Central

    2013-01-01

    Background Poly lactic-co-glycolic acid (PLGA) based nanoparticles are considered to be a promising drug carrier in tumor targeting but suffer from the high level of opsonization by reticuloendothelial system due to their hydrophobic structure. As a result surface modification of these nanoparticles has been widely studied as an essential step in their development. Among various surface modifications, human serum albumin (HSA) possesses advantages including small size, hydrophilic surface and accumulation in leaky vasculature of tumors through passive targeting and a probable active transport into tumor tissues. Methods PLGA nanoparticles of docetaxel were prepared by emulsification evaporation method and were surface conjugated with human serum albumin. Fourier transform infrared spectrum was used to confirm the conjugation reaction where nuclear magnetic resonance was utilized for conjugation ratio determination. In addition, transmission electron microscopy showed two different contrast media in conjugated nanoparticles. Furthermore, cytotoxicity of free docetaxel, unconjugated and conjugated PLGA nanoparticles was studied in HepG2 cells. Results Size, zeta potential and drug loading of PLGA nanoparticles were about 199 nm, −11.07 mV, and 4%, respectively where size, zeta potential and drug loading of conjugated nanoparticles were found to be 204 nm, −5.6 mV and 3.6% respectively. Conjugated nanoparticles represented a three-phasic release pattern with a 20% burst effect for docetaxel on the first day. Cytotoxicity experiment showed that the IC50 of HSA conjugated PLGA nanoparticles (5.4 μg) was significantly lower than both free docetaxel (20.2 μg) and unconjugated PLGA nanoparticles (6.2 μg). Conclusion In conclusion surface modification of PLGA nanoparticles through HSA conjugation results in more cytotoxicity against tumor cell lines compared with free docetaxel and unconjugated PLGA nanoparticles. Albumin conjugated PLGA nanoparticles may

  4. Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma

    PubMed Central

    Kantola, T; Klintrup, K; Väyrynen, J P; Vornanen, J; Bloigu, R; Karhu, T; Herzig, K-H; Näpänkangas, J; Mäkelä, J; Karttunen, T J; Tuomisto, A; Mäkinen, M J

    2012-01-01

    Background: Inflammation contributes to the pathogenesis of colorectal cancer (CRC), and cytokine levels are altered during colorectal carcinogenesis. Methods: The serum levels of 13 cytokines and their relation to clinical and pathological parameters, and systemic inflammatory response (mGPS, CRP and neutrophil–lymphocyte ratio), were analysed from a prospective series of 148 CRC patients and 86 healthy age- and sex-matched controls. Results: CRC patients had higher serum platelet-derived growth factor, interleukin (IL)-6, IL-7, and IL-8 levels and lower monocyte chemotactic protein-1 (MCP-1) levels than the controls. A logistic regression model for discriminating the patients from the controls – including the five most predictive cytokines (high IL-8, high IL-6, low MCP-1, low IL-1ra, and low IP-10) – yielded an area under curve value of 0.890 in receiver operating characteristics analysis. Serum cytokines showed distinct correlation with other markers of systemic inflammatory response, and advanced CRCs were associated with higher levels of IL-8, IL-1ra, and IL-6. A metastasised disease was accompanied by an orientation towards Th2 cytokine milieu. Conclusion: CRC is associated with extensive alterations in serum cytokine environment, highlighting the importance of studying relative cytokine level alterations. Serum cytokine profile shows promise in separating CRC patients from healthy controls but its clinical value is yet to be confirmed. PMID:23059742

  5. Human Ozone (O3) Exposure Alters Serum Profile of Lipid Metabolites

    EPA Science Inventory

    HUMAN OZONE (O3) EXPOSURE ALTERS SERUM PROFILE OF LIPID METABOLITES Miller, D B.1; Kodavanti, U P.2 Karoly, E D.3; Cascio W.E2, Ghio, A J. 21. UNC-Chapel Hill, Chapel Hill, N.C., United States. 2. NHEERL, U.S. EPA, RTP, N.C., United States. 3. METABOLON INC., Durham, N.C., United...

  6. Human Ozone (O3) Exposure Alters Serum Profile of Lipid Metabolites

    EPA Science Inventory

    HUMAN OZONE (O3) EXPOSURE ALTERS SERUM PROFILE OF LIPID METABOLITES Miller, D B.1; Kodavanti, U P.2 Karoly, E D.3; Cascio W.E2, Ghio, A J. 21. UNC-Chapel Hill, Chapel Hill, N.C., United States. 2. NHEERL, U.S. EPA, RTP, N.C., United States. 3. METABOLON INC., Durham, N.C., United...

  7. MATERNAL ATRAZINE (ATR) ALTERS HYPOTHALAMIC DOPAMINE (HYP-DA) AND SERUM PROLACTIN (SPRL) IN MALE PUPS

    EPA Science Inventory

    Maternal Atrazine (ATR) alters hypothalamic dopamine (HYP-DA) and serum prolactin (sPRL) in male pups. 1Christopher Langdale, 2Tammy Stoker and 2Ralph Cooper. 1 Dept. of Cell Biology, North Carolina State University College of Veterinary Medicine, Raleigh, NC. 2 Endocrinology ...

  8. MATERNAL ATRAZINE (ATR) ALTERS HYPOTHALAMIC DOPAMINE (HYP-DA) AND SERUM PROLACTIN (SPRL) IN MALE PUPS

    EPA Science Inventory

    Maternal Atrazine (ATR) alters hypothalamic dopamine (HYP-DA) and serum prolactin (sPRL) in male pups. 1Christopher Langdale, 2Tammy Stoker and 2Ralph Cooper. 1 Dept. of Cell Biology, North Carolina State University College of Veterinary Medicine, Raleigh, NC. 2 Endocrinology ...

  9. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention.

    PubMed

    Liu, Ruixin; Hong, Jie; Xu, Xiaoqiang; Feng, Qiang; Zhang, Dongya; Gu, Yanyun; Shi, Juan; Zhao, Shaoqian; Liu, Wen; Wang, Xiaokai; Xia, Huihua; Liu, Zhipeng; Cui, Bin; Liang, Peiwen; Xi, Liuqing; Jin, Jiabin; Ying, Xiayang; Wang, Xiaolin; Zhao, Xinjie; Li, Wanyu; Jia, Huijue; Lan, Zhou; Li, Fengyu; Wang, Rui; Sun, Yingkai; Yang, Minglan; Shen, Yuxin; Jie, Zhuye; Li, Junhua; Chen, Xiaomin; Zhong, Huanzi; Xie, Hailiang; Zhang, Yifei; Gu, Weiqiong; Deng, Xiaxing; Shen, Baiyong; Xu, Xun; Yang, Huanming; Xu, Guowang; Bi, Yufang; Lai, Shenghan; Wang, Jian; Qi, Lu; Madsen, Lise; Wang, Jiqiu; Ning, Guang; Kristiansen, Karsten; Wang, Weiqing

    2017-07-01

    Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.

  10. Chemical modification of the bifunctional human serum pseudocholinesterase. Effect on the pseudocholinesterase and aryl acylamidase activities.

    PubMed

    Boopathy, R; Balasubramanian, A S

    1985-09-02

    The effect of chemical modification on the pseudocholinesterase and aryl acylamidase activities of purified human serum pseudocholinesterase was examined in the absence and presence of butyrylcholine iodide, the substrate of pseudocholinesterase. Modification by 2-hydroxy-5-nitrobenzyl bromide, N-bromosuccinimide, diethylpyrocarbonate and trinitrobenzenesulfonic acid caused a parallel inactivation of both pseudocholinesterase and aryl acylamidase activities that could be prevented by butyrylcholine iodide. With phenylglyoxal and 2,4-pentanedione as modifiers there was a selective activation of pseudocholinesterase alone with no effect on aryl acylamidase. This activation could be prevented by butyrylcholine iodide. N-Ethylmaleimide and p-hydroxy-mercuribenzoate when used for modification did not have any effect on the enzyme activities. The results suggested essential tryptophan, lysine and histidine residues at a common catalytic site for pseudocholinesterase and aryl acylamidase and an arginine residue (or residues) exclusively for pseudocholinesterase. The use of N-acetylimidazole, tetranitromethane and acetic anhydride as modifiers indicated a biphasic change in both pseudocholinesterase and aryl acylamidase activities. At low concentrations of the modifiers a stimulation in activities and at high concentrations an inactivation was observed. Butyrylcholine iodide or propionylcholine chloride selectively protected the inactivation phase without affecting the activation phase. Protection by the substrates at the inactivation phase resulted in not only a reversal of the enzyme inactivation but also an activation. Spectral studies and hydroxylamine treatment showed that tyrosine residues were modified during the activation phase. The results suggested that the modified tyrosine residues responsible for the activation were not involved in the active site of pseudocholinesterase or aryl acylamidase and that they were more amenable for modification in comparison to

  11. Serum Proteins Alteration in Association with Body Mass Index in Human Volunteers.

    PubMed

    Madhuvanthi, M; Lathadevi, G V

    2016-06-01

    Serum proteins are an important indicator of the nutritional status in an individual. There is a worldwide prevalence of both undernourishment and obesity. It has been suggested that low Body Mass Index (BMI) is associated with a decrease in serum protein levels predisposing them to other illnesses. Overweight and obese individuals carry risk for various other non-communicable diseases. To compare the serum protein levels in underweight, overweight and obese individuals with that of normal body mass index individuals. This prospective study was conducted in subjects who attended the master health checkup clinic of PSG hospitals. Subjects in the age group of 20-50 years were selected. Their serum proteins and BMI was measured. Twenty subjects each of underweight, normal, overweight and obese individuals were selected, categorized and compared. The serum protein level of normal individuals (Group I) was compared with underweight (Group II), overweight (Group III) and obese subjects (Group IV) by one-way ANOVA analysis. The mean serum total proteins in gm/dl in group I controls was 7.555±0.37 compared to Group II (underweight) which was 7.295±0.419. Low BMI was found to be associated with a decrease in serum protein level which was not statistically significant. Elevated BMI as in overweight and obese subjects showed no significant alterations in serum protein levels with p >0.05 and the changes were found to be independent of the body mass index. Underweight individuals showed a decrease in serum protein levels whereas there were no significant changes in the serum protein levels in overweight and obese individuals.

  12. [Alteration of intestinal permeability: the missing link between gut microbiota modifications and inflammation in obesity?].

    PubMed

    Genser, Laurent; Poitou, Christine; Brot-Laroche, Édith; Rousset, Monique; Vaillant, Jean-Christophe; Clément, Karine; Thenet, Sophie; Leturque, Armelle

    2016-05-01

    The increasing incidence of obesity and associated metabolic complications is a worldwide public health issue. The role of the gut in the pathophysiology of obesity, with an important part for microbiota, is becoming obvious. In rodent models of diet-induced obesity, the modifications of gut microbiota are associated with an alteration of the intestinal permeability increasing the passage of food or bacterial antigens, which contribute to low-grade inflammation and insulin resistance. In human obesity, intestinal permeability modification, and its role in the crosstalk between gut microbiota changes and inflammation at systemic and tissular levels, are still poorly documented. Hence, further characterization of the triggering mechanisms of such inflammatory responses in obese subjects could enable the development of personalized intervention strategies that will help to reduce the risk of obesity-associated diseases.

  13. Acute ethanol alters multiple histone modifications at model gene promoters in the cerebral cortex.

    PubMed

    Finegersh, Andrey; Homanics, Gregg E

    2014-07-01

    Ethanol (EtOH) exposure alters gene expression in the cerebral cortex (CCx); however, mechanisms of EtOH-induced gene regulation are not well understood. We hypothesized that EtOH regulates gene expression by differentially altering histone modifications at gene promoters that are up- and down-regulated by EtOH. Such epigenetic mechanisms may ultimately contribute to EtOH-induced neuro-adaptations that underlie tolerance, dependence, and EtOH-use disorders. Eight-week-old, male C57BL/6J mice were treated with 3 g/kg EtOH (intraperitoneally) or saline and sacrificed 6 hours after injection; the CCx and hippocampus (HC) were immediately removed and flash frozen. Chromatin immunoprecipitation was used to study the association of model gene promoters with histone modifications. Western blot was used to detect global changes in the histone modifications studied. We also used a polymerase chain reaction (PCR) array to identify changes in expression of chromatin-modifying enzymes. In CCx, acute EtOH decreased expression of Gad1, Hdac2, and Hdac11, which was associated with decreased histone acetylation at the Gad1 and Hdac2 promoters; we also identified increased expression of Mt1, Mt2, Egr1, which was associated with increased H3K4me3 levels at the Mt2 promoter and decreased H3K27me3 levels at the Mt1 promoter. We identified an increase in global levels of H3K4me3 in CCx as well as a global increase in H3K9ac and H3K14ac in HC. The PCR array identified decreased expression of Csrp2 bp, Hdac2, and Hdac11 as well as increased expression of Kat2b in CCx. Acute EtOH induces chromatin remodeling at model up- and down-regulated genes in CCx. Different patterns of histone modifications at these gene promoters indicate that EtOH may be acting through multiple histone-modifying enzymes to alter gene expression; in particular, differential expression of Kat2b, Hdac2, Hdac11, and Csrp2 bp in CCx may mediate EtOH-induced chromatin remodeling. Additional studies are necessary to

  14. Flower color alteration in Lotus japonicus by modification of the carotenoid biosynthetic pathway.

    PubMed

    Suzuki, Sakae; Nishihara, Masahiro; Nakatsuka, Takashi; Misawa, Norihiko; Ogiwara, Isao; Yamamura, Saburo

    2007-07-01

    To establish a model system for alteration of flower color by carotenoid pigments, we modified the carotenoid biosynthesis pathway of Lotus japonicus using overexpression of the crtW gene isolated from marine bacteria Agrobacterium aurantiacum and encoding beta-carotene ketolase (4,4'-beta-oxygenase) for the production of pink to red color ketocarotenoids. The crtW gene with the transit peptide sequence of the pea Rubisco small subunit under the regulation of the CaMV35S promoter was introduced to L. japonicus. In most of the resulting transgenic plants, the color of flower petals changed from original light yellow to deep yellow or orange while otherwise exhibiting normal phenotype. HPLC and TLC analyses revealed that leaves and flower petals of these plants accumulated novel carotenoids, believed to be ketocarotenoids consisting of including astaxanthin, adonixanthin, canthaxanthin and echinenone. Results indicated that modification of the carotenoid biosynthesis pathway is a means of altering flower color in ornamental crops.

  15. Brain Injury Alters Ectonucleotidase Activities and Adenine Nucleotide Levels in Rat Serum

    PubMed Central

    Laketa, Danijela; Savić, Jasmina; Bjelobaba, Ivana; Lavrnja, Irena; Vasić, Vesna; Stojiljković, Mirjana; Nedeljković, Nadežda

    2015-01-01

    Summary Background Cortical stab injury (CSI) induces changes in the activity, expression and cellular distribution of specific ectonucleotidases at the injury site. Also, several experimentally induced neuropathologies are associated with changes in soluble ectonucleotidase activities in the plasma and serum, whilst various insults to the brain alter purine compounds levels in cerebrospinal fluid, but also in serum, indicating that insults to the brain may induce alterations in nucleotides release and rate of their hydrolysis in the vascular system. Since adenine nucleotides and adenosine regulate diverse cellular functions in the vascular system, including vascular tone, platelet aggregation and inflammatory responses of lymphocytes and macrophages, alterations of ectonucleotidase activities in the vascular system may be relevant for the clinical outcome of the primary insult. Methods We explored ectonucleotidase activities using specific enzyme assays and determined adenine nucleotides concentrations by the UPLC method in the rat serum after cortical stab injury. Results At 4-h post-injury, ATP and AMP hydrolysis increased by about 60% and 40%, respectively, while phosphodiesterase activity remained unchanged. Also, at 4-h post-injury a marked decrease in ATP concentration and more than 2-fold increase in AMP concentration were recorded. Conclusions CSI induces rapid up-regulation of nucleotide catabolizing soluble ectonucleotidases in rat serum, which leads to the observed shift in serum nucleotide levels. The results obtained imply that ectonucleotidases and adenine nucleotides participate in the communication between the brain and the vascular system in physiological and pathological conditions and thereby may be involved in the development of various human neuropathologies.

  16. Altering the interfacial activation mechanism of a lipase by solid-phase selective chemical modification.

    PubMed

    López-Gallego, Fernando; Abian, Olga; Guisán, Jose Manuel

    2012-09-04

    This study presents a combined protein immobilization, directed mutagenesis, and site-selective chemical modification approach, which was used to create a hyperactivated semisynthetic variant of BTL2. Various alkane chains were tethered at three different positions in order to mimic the lipase interfacial activation exogenously triggered by detergents. Optimum results were obtained when a dodecane chain was introduced at position 320 by solid-phase site-selective chemical modification. The resulting semisynthetic variant showed a 2.5-fold higher activity than the wild-type nonmodified variant in aqueous conditions. Remarkably, this is the maximum hyperactivation ever observed for BTL2 in the presence of detergents such as Triton X-100. We present evidence to suggest that the endogenous dodecane chain hyperactivates the enzyme in a similar fashion as an exogenous detergent molecule. In this way, we also observe a faster irreversible enzyme inhibition and an altered detergent sensitivity profile promoted by the site-selective chemical modification. These findings are also supported by fluorescence studies, which reveal that the structural conformation changes of the semisynthetic variant are different to those of the wild type, an effect that is more pronounced in the presence of detergent. Finally, the optimal immobilized semisynthetic variant was successfully applied to the selective synthesis of oxiran-2-yl butyrate. Significantly, this biocatalyst is 12-fold more efficient than the immobilized wild-type enzyme, producing the S-enantiomer with higher enantiospecificity (ee = 92%).

  17. Altering protein surface charge with chemical modification modulates protein-gold nanoparticle aggregation

    NASA Astrophysics Data System (ADS)

    Jamison, Jennifer A.; Bryant, Erika L.; Kadali, Shyam B.; Wong, Michael S.; Colvin, Vicki L.; Matthews, Kathleen S.; Calabretta, Michelle K.

    2011-02-01

    Gold nanoparticles (AuNP) can interact with a wide range of molecules including proteins. Whereas significant attention has focused on modifying the nanoparticle surface to regulate protein-AuNP assembly or influence the formation of the protein "corona," modification of the protein surface as a mechanism to modulate protein-AuNP interaction has been less explored. Here, we examine this possibility utilizing three small globular proteins—lysozyme with high isoelectric point (pI) and established interactions with AuNP; α-lactalbumin with similar tertiary fold to lysozyme but low pI; and myoglobin with a different globular fold and an intermediate pI. We first chemically modified these proteins to alter their charged surface functionalities, and thereby shift protein pI, and then applied multiple methods to assess protein-AuNP assembly. At pH values lower than the anticipated pI of the modified protein, AuNP exposure elicits changes in the optical absorbance of the protein-NP solutions and other properties due to aggregate formation. Above the expected pI, however, protein-AuNP interaction is minimal, and both components remain isolated, presumably because both species are negatively charged. These data demonstrate that protein modification provides a powerful tool for modulating whether nanoparticle-protein interactions result in material aggregation. The results also underscore that naturally occurring protein modifications found in vivo may be critical in defining nanoparticle-protein corona compositions.

  18. Fluorescent derivative of cysteine-10 reveals thyroxine-dependent conformational modifications in human serum prealbumin.

    PubMed

    González, G

    1989-05-15

    Fluorescence studies on the N-(iodoacetyl)-N'-(5-sulfo-1-naphthyl)ethylenediamine-labeled cysteine-10 residue of human prealbumin were carried out to detect conformational changes induced by the binding of the ligand thyroxine to the two structurally identical binding sites. A red shift of the spectrum was observed and the total change was confined to the first ligand. This was interpreted as resulting from a conformational change which increases the exposure of the fluorescent probe moiety. Thyroxine also alters the effect of the collisional quencher, acrylamide, confirming the greater exposure of the probe. This modification in structure is associated with changes in relaxation time which indicate that when thyroxine is bound there is an increase in the rotational freedom of the segment or domain of prealbumin which contains the fluorescent probe.

  19. No alterations of serum levels of adrenal and gonadal hormones in patients with ankylosing spondylitis.

    PubMed

    Straub, R H; Struhárová, S; Schölmerich, J; Härle, P

    2002-01-01

    Ankylosing spondylitis (AS) is a chronic inflammatory disease with a marked preponderance of affected males compared to females of approximately 6 to 1. During the last two decades, this circumstance stimulated several research groups to investigate serum levels of gonadal and adrenal sex hormones. From available results of cross-sectional studies, there seems to be no particular defect in secretion or production of adrenal, gonadal, and pituitary hormones. This is in striking contrast to diseases such as rheumatoid arthritis and other chronic inflammatory diseases. In the latter diseases, low serum levels of dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), and testosterone have been described in an advanced chronic disease stage, whereas estrogen serum levels remain normal. Although AS is an inflammatory disease with signs of systemic inflammation such as elevated erythrocyte sedimentation rate or increased circulating proinflammatory cytokines, serum levels of adrenal and gonadal androgens are normal. It is unclear whether this can be considered as unexpected. It may be that inflammation does not reach the pituitary, adrenal, and gonadal glands or does not alter the aromatase complex in peripheral tissue. Furthermore, the inflammation-induced changes may be subtle so that only specific endocrine examination of these axes may reveal signs of alterations. In conclusion, current data on sex steroid hormones provide no straightforward explanation for the male predominance in AS. At the moment, there is no rationale to treat AS patients with sex steroid hormones.

  20. Modifications and oxidation of lipids and proteins in human serum detected by thermochemiluminescence.

    PubMed

    Shnizer, Sergei; Kagan, Tamara; Lanir, Amos; Maor, Irit; Reznick, Abraham Z

    2003-01-01

    Detection of electronically excited species (EES) in body fluids may constitute an important diagnostic tool in various pathologies. Examples of such products are triplet excited carbonyls (TEC), which can be a source for photon emission in the 400-550 nm range. The aim of the present study was to determine the actual contribution of lipid and protein components (protein carbonyls) to photon emission generated by thermochemiluminescence (TCL) during the heating of biological fluids. In this study, a new TCL Photometer device, designed by Lumitest Ltd, Israel, was used. Samples were heated to a constant temperature of 80 +/- 0.5 degrees C for 280 s and photon emission was measured at several time points. In order to compare the results of TCL measurements to conventional methods of detecting lipid and protein oxidation, each examined sample was also heated in a waterbath at 80 degrees C for 10-280 s. Lipid and protein oxidation were subsequently measured using conventional methods. The TCL of four polyunsaturated fatty acids (PUFA) with three to six double bonds was measured. The elevation of the PUFA TCL amplitude correlated with the increase in the number of double bonds of PUFA. A correlation between the increase in TCL intensity and protein carbonyl generation in bovine serum albumin (BSA) was also observed. In the venous blood serum, our study showed that an increase of TCL intensity during heating reflected the cleavage of TEC of lipid origin. Our study suggests that biological molecules such as proteins, lipids and other molecules, which may become unstable during heating, are capable of generating EES. We demonstrated that a TCL curve can be used as a kinetic model for measuring oxidative processes, which reflects modifications of different molecules involved in the oxidative stress phenomena.

  1. Modifications in rat testicular morphology and increases in IFN-gamma serum levels by the oral administration of subtoxic doses of mercuric chloride.

    PubMed

    Penna, Salvador; Pocino, Marisol; Marval, Maria Josefina; Lloreta, José; Gallardo, Luis; Vila, Joan

    2009-01-01

    Mercury induces structural and functional damage in several organs, however the effects of subtoxic doses of the metal on the male reproductive system are not well defined. In order to analyze testicular and epididymal morphological alterations and changes in IL-4 or IFN-gamma serum levels, adult male Sprague-Dawley rats received 0.01, 0.05 or 0.1 microg/ml of mercuric chloride (HgCl(2)) in deionized water for 1 to 7 months by oral route. Controls received deionized water alone. Twenty rats, separated in four groups of five animals each, were used per time of exposure. Progressive degenerative lesions consisting of lack of germ cell cohesion and desquamation, arrest at spermatocyte stage and hypospermatogenesis were observed in seminiferous epithelium by light and electron microscopy. Leydig cells showed cytoplasmic vacuolation and nuclear signs of cell death. Loss of peritubular cell aggregation was evidenced in the epididymis. Mercury accumulation was detected in both organs by mass spectroscopy. Rats showed enhanced IFN-gamma serum levels as compared to controls but only reached significance after 7 months of mercury administration. Subtoxic doses of inorganic mercury could lead to reproductive and immunological alterations. The results demonstrate that sublethal concentrations of mercuric chloride are enough to induce morphological and ultrastructural modifications in male reproductive organs. These contribute to functional alterations of spermatogenesis with arrest at spermatocyte stage, hypospermatogenesis and possibly impaired steroidogenesis which together could affect male fertility.

  2. Iron overload alters glucose homeostasis, causes liver steatosis, and increases serum triacylglycerols in rats.

    PubMed

    Silva, Maísa; Silva, Marcelo E; de Paula, Heberth; Carneiro, Cláudia Martins; Pedrosa, Maria Lucia

    2008-06-01

    The objective of this study was to investigate the effect of iron overload with a hyperlipidemic diet on the histologic feature of hepatic tissue, the lipid and glycemic serum profiles, and the markers of oxidative damage and stress in a rat model. Twenty-four male Fischer rats, purchased from Experimental Nutrition Laboratory, Federal University of Ouro Preto, were assigned to 4 equal groups, 2 were fed a standard cholesterol-free diet (group C or control and CI or control with iron) containing 8.0% soybean oil and 2 were fed a hyperlipidemic diet (group H or hyperlipidemic and HI or hyperlipidemic with iron) containing 1.0% cholesterol and 25.0% soybean oil. A total of 50 mg of iron was administered to rats in groups CI and HI in 5 equal doses (1 every 3 weeks for a 16-week period) by intraperitoneal injections of 0.1 mL of iron dextran solution (100 g Fe(2+)/L; Sigma, St Louis, Mo). The other rats in groups C and H were treated in a similar manner but with sterile saline (0.1 mL). Irrespective of the diet, iron excess enhanced serum triacylglycerols (P < .05) and reduced serum glucose and glycated hemoglobin levels (P < .05) but did not affect serum cholesterol concentration. Histologic analysis showed steatosis in groups H and to a lesser extent in HI. No significant differences (P > .05) were observed in paraoxonase activities or in serum levels of free or total sulfhydryl radicals, malondialdehyde, or total antioxidants. The findings suggest that iron excess in the rat probably modifies lipid metabolism and, as a consequence, alters glucose homeostasis and increases the level of serum triacylglycerols but not of cholesterol.

  3. Altered Serum Levels of Matrix Metalloproteinase-2, -9 in Response to Electroconvulsive Therapy for Mood Disorders.

    PubMed

    Shibasaki, Chiyo; Takebayashi, Minoru; Itagaki, Kei; Abe, Hiromi; Kajitani, Naoto; Okada-Tsuchioka, Mami; Yamawaki, Shigeto

    2016-09-01

    Inflammatory processes could underlie mood disorders. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMP) are inflammation-related molecules. The current study sought an association between mood disorders and systemic levels of MMPs and TIMPs. Serum was obtained from patients with mood disorders (n=21) and patients with schizophrenia (n=13) scheduled to undergo electroconvulsive therapy. Serum was also obtained from healthy controls (n=40). Clinical symptoms were assessed by the Hamilton Rating Score for Depression and the Brief Psychiatric Rating Scale. Serum levels of MMPs and TIMPs were quantified by ELISA. The serum levels of MMP-2 in mood disorder patients, but not in schizophrenia patients, prior to the first electroconvulsive therapy session (baseline) was significantly lower than that of healthy controls. At baseline, levels of MMP-9 and TIMP-2, -1 were not different between patients with mood disorder and schizophrenia and healthy controls. After a course of electroconvulsive therapy, MMP-2 levels were significantly increased in mood disorder patients, but MMP-9 levels were significantly decreased in both mood disorder and schizophrenia patients. In mood disorder patients, there was a significant negative correlation between depressive symptoms and serum levels of MMP-2 and a positive correlation between depressive symptoms and MMP-9. In addition, alterations of serum levels of MMP-2 and MMP-9 were significantly correlated each other and were associated with certain depressive symptoms. A change in inflammatory homeostasis, as indicated by MMP-2 and MMP-9, could be related to mood disorders, and these markers appear to be sensitive to electroconvulsive therapy. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  4. Cartap and carbofuran induced alterations in serum lipid profile of Wistar rats.

    PubMed

    Rai, Devendra K; Rai, Prashant Kumar; Gupta, Aradhna; Watal, Geeta; Sharma, Bechan

    2009-04-01

    Wistar rats of 6-8 weeks in age weighing between 120-150 g were exposed to the fixed doses of each of the carbamate pesticides such as cartap (50% LD(50)) and carbofuran (50% LD(50)) as well as a combination of these two with 25% LD(50) of each for one week. The effect of treatments was studied in terms of serum lipid parameters such as high-density lipoprotein, total cholesterol, triglyceride, low-density lipoprotein and very low-density lipoprotein. Treatment with individual doses of carbofuran (50% LD(50)) and cartap (50 % LD(50)) caused significant alterations in the levels of serum lipid parameters. The pesticides treatment resulted in marked decrease in the level of serum high-density lipoprotein where as that of other lipids got significantly elevated. Further, the rats exhibited relatively higher impact of pesticides when treated with the compounds in combination (25 % LD(50) of each). The results indicated that these compounds when used together may exert enhanced effect on the levels of serum lipids in rat.

  5. Alteration of prolactin serum levels during alcohol withdrawal correlates with craving in female patients.

    PubMed

    Hillemacher, Thomas; Bayerlein, Kristina; Wilhelm, Julia; Reulbach, Udo; Frieling, Helge; Bönsch, Dominikus; Kornhuber, Johannes; Bleich, Stefan

    2005-12-01

    Dopaminergic transmission has been suggested to be a main mechanism mediating reinforcement, withdrawal and craving in alcohol dependency. Dopamine is associated with prolactin secretion, acting as a prolactin inhibitor. The aim of the present study was to investigate whether there is an association between altered prolactin levels and craving during early and late alcohol withdrawal. Therefore, we examined 145 patients suffering from alcohol dependency after admission to the detoxification unit, assessing craving with the Obsessive Compulsive Drinking Scale (OCDS) and measuring prolactin serum levels during early withdrawal (-EW: day 0 or day 1) and late withdrawal (-LW: day 7-day 10). We observed a significant influence of the alteration of prolactin during withdrawal on craving in female patients (Spearman's rho, OCDS-EW: r=-0.607, p=0.001; OCDS-LW: r=-0.730, p<0.001; n=26). The association between prolactin alteration in percentage and craving in females was confirmed with general linear models (OCDS-EW: F=15.819, p=0.001, r(2)=0.530; OCDS-LW: F=17.091, p<0.001, r(2)=0.535). In male patients we did not find any significant results. Our findings support the previously described role of the hypothalamic-pituitary-adrenal (HPA) axis in the neurobiology of alcohol craving and show evidence of an association between increased prolactin serum levels and lower craving during alcohol withdrawal in female patients.

  6. Neutral buoyancy and sleep-deprived serum factors alter expression of cytokines regulating osteogenesis

    NASA Astrophysics Data System (ADS)

    Gorczynski, Reginald M.; Gorczynski, Christopher P.; Gorczynski, Laura Y.; Hu, Jiang; Lu, Jin; Manuel, Justin; Lee, Lydia

    2005-05-01

    We examined expression of genes associated with cytokine production, and genes implicated in regulating bone metabolism, in bone stromal and osteoblast cells incubated under standard ground conditions and under conditions of neutral buoyancy, and in the presence/absence of serum from normal or sleep-deprived mice. We observed a clear interaction between these two conditions (exposure to neutral buoyancy and serum stimulation) in promoting enhanced osteoclastogenesis. Both conditions independently altered expression of a number of cytokines implicated in the regulation of bone metabolism. However, using stromal cells from IL-1 and TNF α cytokine r KO mice, we concluded that the increased bone loss under microgravity conditions was not primarily cytokine mediated.

  7. Sugar alters the level of serum insulin and plasma glucose and the serum cortisol:DHEAS ratio in female migraine sufferers.

    PubMed

    Kokavec, Anna; Crebbin, Susan J

    2010-12-01

    Early work has highlighted that a large percentage of migraineurs may have an altered glucidic methabolis due to carbohydrate-induced hyperinsulinism. The aim of this study was to assess the effect of sucrose on biomarkers of energy metabolism and utilization in migraineous females. A total of 16 participants (8 = Migraine, 8 = Non-migraine) at the mid-point of their menstrual cycle underwent a 15-h fast prior to ingesting 75 g sucrose dissolved in 175 g water. Blood sampling for the assessment of serum insulin, serum cortisol and serum dehydroepiandrosterone sulfate (DHEAS) and plasma glucose was conducted upon arrival at 09:00 h and then at regular 15-min intervals across a 150-min experimental period. The results showed a significant alteration in serum insulin and plasma glucose following sucrose ingestion in the migraine and non-migraine groups. In addition, significant group differences were observed in the level of serum insulin, serum DHEAS, and the cortisol:DHEAS ratio with migraine participants on average recording a higher sucrose-induced serum insulin level and lower DHEAS level and cortisol:DHEAS ratio when group data was compared. It was concluded that while sucrose consumption may potentiate serum insulin in migraineurs this does not result in the development of sucrose-induced hypoglycemia in migraine or non-migraine participants.

  8. Alterations in serum immunoglobulin levels in workers occupationally exposed to trichloroethylene

    PubMed Central

    Zhang, Luoping; Bassig, Bryan A.; Huang, Hanlin; Tang, Xiaojiang; Rothman, Nathaniel; Lan, Qing

    2013-01-01

    Trichloroethylene (TCE) has been associated with a variety of immunotoxic effects and may be associated with an increased risk of non-Hodgkin lymphoma (NHL). Altered serum immunoglobulin (Ig) levels have been reported in NHL patients and in animals exposed to TCE. Recently, we reported that occupational exposure to TCE is associated with immunosuppressive effects and immune dysfunction, including suppression of B-cell counts and activation, even at relatively low levels. We hypothesized that TCE exposure would also affect Ig levels in humans. We measured serum levels of IgG, IgM and IgE, by enzyme-linked immunosorbent assay, in TCE-exposed workers (n = 80) and unexposed controls (n = 45), matched by age and gender, in a cross-sectional, molecular epidemiology study of occupational exposure to TCE in Guangdong, China. Exposed workers had about a 17.5% decline in serum levels of IgG compared with unexposed controls (P = 0.0002). Similarly, serum levels of IgM were reduced by about 38% in workers exposed to TCE compared with unexposed controls (P < 0.0001). Serum levels of both IgG and IgM were significantly decreased in workers exposed to TCE levels below 12 p.p.m., the median exposure level. Adjustment for B-cell counts had minimal impact on our findings. IgE levels were not significantly different between exposed and control subjects. These results provide further evidence that TCE is immunotoxic at relatively low exposure levels and provide additional biologic plausibility for the reported association of TCE with NHL. PMID:23276795

  9. Porphyrin mediated photo-modification of the structure and function of human serum albumin

    NASA Astrophysics Data System (ADS)

    Rozinek, Sarah C.

    Photosensitization reactions involve irradiating (with visible light) molecules with a high efficiency for either electron transfer or entering an excited triplet state (photosensitizer). Such reactions are applied to photodynamic cancer therapy, many medical laser-treatments, and a potential array of disinfection and pest elimination techniques. To understand the biophysical mechanisms of how these applications are effective at the protein level, the group of Dr. Brancaleon (UTSA) has investigated the irradiation of several dye-protein combinations, and discovered effects on protein structure and function. To further that work, we have investigated irradiation of the protein, human serum albumin (HSA), photosensitized by either protoporphyrin IX (PPIX) or meso-tetrakis(4-sulfonatophenyl)porphyrin (TSPP). HSA is the most abundant plasma protein, making it a likely substrate in PDT, and it possesses a specific binding pocket for iron-PPIX (heme) and possibly other porphyrin derivatives. The results of our research are summarized as follows. First, a thorough characterization of the binding of each photosensitizer to albumin was completed, elucidating a probable binding location for TSPP. Next, fluorescence lifetime emission of the single tryptophan residue, alongside circular dichroism, found tertiary structural changes around tryptophan and an overall 20% decrease in protein secondary structure after irradiation with TSPP bound. Finally, to determine if protein function was lost after photosensitization, size exclusion chromatography found modified albumin still recognizable by its receptor-protein, and comparative ex vivo up-take studies revealed that modified albumin is not processed the same way as native albumin in live tapeworm larva (Mesocestoides corti). Thus we found that visible light can induce partial unfolding of a protein by using a photo-activated ligand. These small structural modifications were sufficient to affect the protein's biological function.

  10. Short-term lifestyle modification alters circulating biomarkers of endothelial health in sedentary, overweight adults.

    PubMed

    Rector, R Scott; Turk, James R; Sun, Grace Y; Guilford, Brianne L; Toedebusch, Brian W; McClanahan, Matt W; Thomas, Tom R

    2006-10-01

    Obesity and inactivity are associated with endothelial dysfunction that may contribute to the development of atherosclerosis. We examined the effects of a short-term lifestyle intervention on circulating biomarkers of endothelial health. Nineteen overweight or obese (mean body mass index (BMI): 28.9 +/- 0.7 kg/m2) men and women underwent 6 weeks of body mass reduction induced by moderate energy restriction (approximately 750 kcal/d; 1 kcal = 4.184 kJ) and aerobic training (approximately 400 kcal/d). Fasting serum samples were collected at baseline and after reduction in body mass (week 6) to assess concentrations of nitrotyrosine (NT), secretory phospholipase A2 (sPLA2), and soluble intracellular adhesion molecule-1 (sICAM-1). Body mass was significantly reduced from 81.3 +/- 2.8 to 77.3 +/- 2.6 kg (p < 0.05). Circulating concentrations of NT and sICAM-1 were significantly reduced with treatment (approximately 25% and approximately 10%, respectively), whereas sPLA2 levels were significantly elevated (approximately 45%). Elevations in sPLA2 were negatively correlated with changes in NT (r = -0.58, p = 0.047); reductions in NT did not correlate significantly with reductions in sICAM-1. It appears that circulating markers of endothelial health are susceptible to short-term exercise interventions with modest reduction in body mass, and such a lifestyle modification may improve endothelial health by reducing protein nitration products and cellular adhesion.

  11. Arsenic alters global histone modifications in lymphocytes in vitro and in vivo.

    PubMed

    Pournara, Angeliki; Kippler, Maria; Holmlund, Teresa; Ceder, Rebecca; Grafström, Roland; Vahter, Marie; Broberg, Karin; Wallberg, Annika E

    2016-08-01

    Arsenic, an established carcinogen and toxicant, occurs in drinking water and food and affects millions of people worldwide. Arsenic appears to interfere with gene expression through epigenetic processes, such as DNA methylation and post-translational histone modifications. We investigated the effects of arsenic on histone residues in vivo as well as in vitro. Analysis of H3K9Ac and H3K9me3 in CD4+ and CD8+ sorted blood cells from individuals exposed to arsenic through drinking water in the Argentinean Andes showed a significant decrease in global H3K9me3 in CD4+ cells, but not CD8+ cells, with increasing arsenic exposure. In vitro studies of inorganic arsenic-treated T lymphocytes (Jurkat and CCRF-CEM, 0.1, 1, and 100 μg/L) showed arsenic-related modifications of H3K9Ac and changes in the levels of the histone deacetylating enzyme HDAC2 at very low arsenic concentrations. Further, in vitro exposure of kidney HEK293 cells to arsenic (1 and 5 μM) altered the protein levels of PCNA and DNMT1, parts of a gene expression repressor complex, as well as MAML1. MAML1 co-localized and interacted with components of this complex in HEK293 cells, and in silico studies indicated that MAML1 expression correlate with HDAC2 and DNMT1 expression in kidney cells. In conclusion, our data suggest that arsenic exposure may lead to changes in the global levels of H3K9me3 and H3K9Ac in lymphocytes. Also, we show that arsenic exposure affects the expression of PCNA and DNMT1-proteins that are part of a gene expression silencing complex.

  12. Serum sodium based modification of the MELD does not improve prediction of outcome in acute liver failure

    PubMed Central

    2013-01-01

    Background Acute liver failure (ALF) is a devastating clinical syndrome with a high mortality rate. The MELD score has been implied as a prognostic tool in ALF. Hyponatremia is associated with lethal outcome in ALF. Inclusion of serum sodium (Na) into the MELD score was found to improve its predictive value in cirrhotic patients. Therefore the aim of this study was to determine whether inclusion of serum Na improves the predictive value of MELD in ALF compared to established criteria. Methods In a prospective single center study (11/2006–12/2010), we recruited 108 consecutive ALF patients (64% females / 36% males), who met the criteria defined by the “Acute Liver Failure Study Group Germany”. Upon admission, clinical and laboratory data were collected, King’s College Criteria (KCC), Model of End Stage Liver Disease score (MELD), and serum sodium based modifications like the MELD-Na score and the United Kingdom Model of End Stage Liver Disease score (UKELD) were calculated and area under the receiver operating characteristic curve analyses were performed regarding the prediction of spontaneous recovery (SR) or non-spontaneous recovery (NSR; death or transplantation). Results Serum bilirubin was of no prognostic value in ALF, and Na also failed to predict NSR in ALF. The classical MELD score was superior to sodium-based modifications and KCC. Conclusions We validated the prognostic value of MELD-Na and UKELD in ALF. Classic MELD score calculations performed superior to KCC in the prediction of NSR. Serum Na and Na-based modifications of MELD did not further improve its prognostic value. PMID:23551795

  13. Curcumin Supplementation Decreases Intestinal Adiposity Accumulation, Serum Cholesterol Alterations, and Oxidative Stress in Ovariectomized Rats

    PubMed Central

    Morrone, Maurilio da Silva; Schnorr, Carlos Eduardo; Behr, Guilherme Antônio; Gasparotto, Juciano; Bortolin, Rafael Calixto; da Boit Martinello, Katia; Saldanha Henkin, Bernardo; Rabello, Thallita Kelly; Zanotto-Filho, Alfeu; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2016-01-01

    The aim of this study was to investigate the potential of curcumin oral supplementation (50 and 100 mg/Kg/day, for 30 days) in circumventing menopause-associated oxidative stress and lipid profile dysfunctions in a rat ovariectomy (OVX) model. Female Wistar rats were operated and randomly divided into either sham-operated or OVX groups. Sham-operated group (n = 8) and one OVX group (n = 11) were treated with vehicle (refined olive oil), and the other two OVX groups received curcumin at 50 or 100 mg/Kg/day doses (n = 8/group). OVX vehicle-treated animals presented a higher deposition of intestinal adipose tissue as well as increased serum levels of IL-6, LDL, and total cholesterol when compared to sham-operated rats. In addition, several oxidative stress markers in serum, blood, and liver (such as TBARS, carbonyl, reduced-sulphydryl, and nonenzymatic antioxidant defenses) were altered toward a prooxidant status by OVX. Interestingly, curcumin supplementation attenuated most of these parameters to sham comparable values. Thus, the herein presented results show that curcumin may be useful to ameliorate lipid metabolism alterations and oxidative damage associated with hormone deprivation in menopause. PMID:26640615

  14. The role of developing breast cancer in alteration of serum lipid profile

    PubMed Central

    Abdelsalam, Kamal Eldin A.; Hassan, Ikhlas K.; Sadig, Isam A.

    2012-01-01

    Aims: The major aim of this study is to examine the role of alterations in lipid profile in women developing breast cancer. This study was carried out between May 2009 and December 2010. Background: The relationship between lipids and breast cancer is undistinguished. Until now, conflicting results have been reported on the association between lipids and risk of breast cancer development in women. Materials and Methods: Plasma lipids (i.e., total cholesterol [TC], high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides [TG] were analyzed from 60 controls and 120 untreated breast cancer patients with clinical and histopathological evidence, under aseptic conditions. Venous blood was drawn from the cases and controls and estimations of lipid profile were done utilizing the standard procedures. Statistical Analysis Used: Independent sample t-test to compare the mean serum levels of lipid profile and TC/HDL ratio between patients and controls. Results: A significant rise in serum total cholesterol, low-density lipoprotein cholesterol, and ratio of total cholesterol: high density lipoprotein cholesterol values, whereas high density lipoprotein cholesterol and very low density lipoprotein cholesterol were not affected significantly by the breast cancer. Conclusions: The developing breast cancer might be considered as one of the factors in alterations in lipid profile levels. PMID:23626635

  15. Di-(2-Ethylhexyl)-Phthalate (DEHP) Causes Impaired Adipocyte Function and Alters Serum Metabolites

    PubMed Central

    Klöting, Nora; Hesselbarth, Nico; Gericke, Martin; Kunath, Anne; Biemann, Ronald; Chakaroun, Rima; Kosacka, Joanna; Kovacs, Peter; Kern, Matthias; Stumvoll, Michael; Fischer, Bernd; Rolle-Kampczyk, Ulrike; Feltens, Ralph; Otto, Wolfgang; Wissenbach, Dirk K.; von Bergen, Martin; Blüher, Matthias

    2015-01-01

    Di-(2-ethylhexyl)-phthalate (DEHP), an ubiquitous environmental contaminant, has been shown to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies, but the underlying mechanisms are still unknown. We therefore tested the hypothesis that chronic DEHP exposure causes impaired insulin sensitivity, affects body weight, adipose tissue (AT) function and circulating metabolic parameters of obesity resistant 129S6 mice in vivo. An obesity-resistant mouse model was chosen to reduce a potential obesity bias of DEHP effects on metabolic parameters and AT function. The metabolic effects of 10-weeks exposure to DEHP were tested by insulin tolerance tests and quantitative assessment of 183 metabolites in mice. Furthermore, 3T3-L1 cells were cultured with DEHP for two days, differentiated into mature adipocytes in which the effects on insulin stimulated glucose and palmitate uptake, lipid content as well as on mRNA/protein expression of key adipocyte genes were investigated. We observed in female mice that DEHP treatment causes enhanced weight gain, fat mass, impaired insulin tolerance, changes in circulating adiponectin and adipose tissue Pparg, adiponectin and estrogen expression. Serum metabolomics indicated a general increase in phospholipid and carnitine concentrations. In vitro, DEHP treatment increases the proliferation rate and alters glucose uptake in adipocytes. Taken together, DEHP has significant effects on adipose tissue (AT) function and alters specific serum metabolites. Although, DEHP treatment led to significantly impaired insulin tolerance, it did not affect glucose tolerance, HOMA-IR, fasting glucose, insulin or triglyceride serum concentrations. This may suggest that DEHP treatment does not cause impaired glucose metabolism at the whole body level. PMID:26630026

  16. TALEN-mediated modification of the bovine genome for large-scale production of human serum albumin.

    PubMed

    Moghaddassi, Shaida; Eyestone, Will; Bishop, Colin E

    2014-01-01

    As an initial step towards creating genetically modified cattle as a biopharming source of recombinant human serum albumin (rHSA), we report modification of the bovine albumin (bA) locus by transcription activator-like effector nuclease (TALEN)-stimulated homology-directed repair (HDR). Pedigreed bovine fibroblasts were co-transfected with TALENs and an 11.5-kb human serum albumin (HSA) minigene donor construct, designed to simultaneously disrupt and replace bovine serum albumin (BSA) expression with controlled rHSA expression in both the liver and the milk. Targeted integration of the HSA minigene was confirmed in transfected fibroblasts at a frequency of approximately 11% and transgenic bovine embryos were produced from targeted fibroblasts using somatic cell nuclear transfer (SCNT). The research delineated here lays the foundation for the future generation of transgenic rHSA cattle with the potential to provide a large-scale, reliable, and quality-controlled source of rHSA.

  17. Postranslational modifications significantly alter the binding-folding pathways of proteins associating with DNA

    NASA Astrophysics Data System (ADS)

    Papoian, Garegin

    2012-02-01

    Many important regulators of gene activity are natively disordered, but fully or partially order when they bind to their targets on DNA. Interestingly, the ensembles of disordered states for such free proteins are not structurally featureless, but can qualitatively differ from protein to protein. In particular, in random coil like states the chains are swollen, making relatively few contacts, while in molten globule like states a significant collapse occurs, with ensuing high density of intra-protein interactions. Furthermore, since many DNA binding proteins are positively charged polyelectrolytes, the electrostatic self-repulsion also influences the degree of collapse of the chain and its conformational preferences in the free state and upon binding to DNA. In our work, we have found that the nature of the natively disordered ensemble significantly affects the way the protein folds upon binding to DNA. In particular, we showed that posttranslational modifications of amino acid residues, such as lysine acetylation, can alter the degree of collapse and conformational preferences for a free protein, and also profoundly impact the binding affinity and pathways for the protein DNA association. These trends will be discussed in the context of DNA interacting with various histone tails and the p53 protein.

  18. Alterations in the Rat Serum Proteome Induced by Prepubertal Exposure to Bisphenol A and Genistein

    PubMed Central

    2015-01-01

    Humans are exposed to an array of chemicals via the food, drink and air, including a significant number that can mimic endogenous hormones. One such chemical is Bisphenol A (BPA), a synthetic chemical that has been shown to cause developmental alterations and to predispose for mammary cancer in rodent models. In contrast, the phytochemical genistein has been reported to suppress chemically induced mammary cancer in rodents, and Asians ingesting a diet high in soy containing genistein have lower incidence of breast and prostate cancers. In this study, we sought to: (1) identify protein biomarkers of susceptibility from blood sera of rats exposed prepubertally to BPA or genistein using Isobaric Tandem Mass Tags quantitative mass spectrometry (TMT-MS) combined with MudPIT technology and, (2) explore the relevance of these proteins to carcinogenesis. Prepubertal exposures to BPA and genistein resulted in altered expression of 63 and 28 proteins in rat sera at postnatal day (PND) 21, and of 9 and 18 proteins in sera at PND35, respectively. This study demonstrates the value of using quantitative proteomic techniques to explore the effect of chemical exposure on the rat serum proteome and its potential for unraveling cellular targets altered by BPA and genistein involved in carcinogenesis. PMID:24552547

  19. Multipronged quantitative proteomics reveals serum proteome alterations in breast cancer intrinsic subtypes.

    PubMed

    Gajbhiye, Akshada; Dabhi, Raju; Taunk, Khushman; Jagadeeshaprasad, Mashanipalya G; RoyChoudhury, Sourav; Mane, Anupama; Bayatigeri, Santhakumari; Chaudhury, Koel; Santra, Manas K; Rapole, Srikanth

    2017-06-23

    Being molecularly heterogeneous, breast cancer tends to be a complicated oncological disease with high incidence rates throughout the world. The primary aim of this study was to identify the set of serum proteins with discriminatory capabilities towards the four major subtypes of breast cancer. We employed multipronged quantitative proteomic approaches like 2D-DIGE, iTRAQ and SWATH-MS and identified 307 differentially regulated proteins. Luminal A subtype consisted of 24, Luminal B subtype 38, HER2 Enriched subtype 17 and Triple negative breast cancer subtype 10 differentially regulated subtype specific proteins. These specific proteins were further subjected to bioinformatic tools which revealed the involvement in platelet degranulation, fibrinolysis, lipid metabolism, immune response, complement activation, blood coagulation, glycolysis and cancer signaling pathways in the subtypes of the breast cancer. The significant discrimination efficiency of the models generated through multivariate statistical analysis was decent to distinguish each of the four subtypes from controls. Further, some of the statistically significant differentially regulated proteins were verified and validated by immunoblotting and mass spectrometry based selected reaction monitoring (SRM) approach. Our Multipronged proteomics approaches revealed panel of serum proteins specifically altered for individual subtypes of breast cancer. The mass spectrometry data are available via ProteomeXchange with identifier PXD006441. Worldwide, breast cancer continues to be one of the leading causes of cancer related deaths in women and it encompasses four major molecular subtypes. As breast cancer treatment majorly depends on identification of specific subtype, it is important to diagnosis the disease at subtype level. Our results using multipronged quantitative proteomics identified 307 differentially regulated proteins in which 24 were specific for Luminal A, 38 for Luminal B, 17 for HER2 enriched and 10

  20. Serum lipids in rats as related to modifications in dietary fat, fiber, and sodium with magnesium deficiency

    SciTech Connect

    Howe, C.A.; Kubena, K.S. )

    1991-03-11

    Recommendations to modify dietary intake to attenuate risk of cardiovascular disease have been released by numerous governmental and health organizations. Since magnesium is associated with lipid metabolism and normal cardiovascular function, this study was designed to determine the effect of modifications in dietary fat, fiber, and sodium with magnesium deficiency on serum lipids and tissue minerals. The control (C) diet was based upon the AIN-76 diet formulation; the American (A) diet included average fat, fiber, and sodium levels in the US; and the recommended (R) diet was lower in fat and sodium and higher in fiber. Diets contained either 1,000 or 150 (L) mg Mg/kg diet. Male weanling Sprague-Dawley rats were fed one of the diets (C, CL, A, Al, R, RL) for six weeks. Levels of tissue Mg, Ca, Zn, and P were determined. Neither initial nor final body weights varied between groups. Serum levels of triglyceride were higher in the C and Cl groups than in the others. Serum cholesterol was lower in the R and Rl groups than in the Cl and A groups. Animals which were fed the diet modified with regard to fat, fiber, and sodium had lower serum cholesterol levels than did those fed the American diet. Magnesium deficiency was not consistently related to serum lipid levels.

  1. Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease

    PubMed Central

    Minamoto, Yasushi; Otoni, Cristiane C; Steelman, Samantha M; Büyükleblebici, Olga; Steiner, Jörg M; Jergens, Albert E; Suchodolski, Jan S

    2015-01-01

    Idiopathic inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal (GI) disease in dogs. The combination of an underlying host genetic susceptibility, an intestinal dysbiosis, and dietary/environmental factors are suspected as main contributing factors in the pathogenesis of canine IBD. However, actual mechanisms of the host-microbe interactions remain elusive. The aim of this study was to compare the fecal microbiota and serum metabolite profiles between healthy dogs (n = 10) and dogs with IBD before and after 3 weeks of medical therapy (n = 12). Fecal microbiota and metabolite profiles were characterized by 454-pyrosequencing of 16 S rRNA genes and by an untargeted metabolomics approach, respectively. Significantly lower bacterial diversity and distinct microbial communities were observed in dogs with IBD compared to the healthy control dogs. While Gammaproteobacteria were overrepresented, Erysipelotrichia, Clostridia, and Bacteroidia were underrepresented in dogs with IBD. The functional gene content was predicted from the 16 S rRNA gene data using PICRUSt, and revealed overrepresented bacterial secretion system and transcription factors, and underrepresented amino acid metabolism in dogs with IBD. The serum metabolites 3-hydroxybutyrate, hexuronic acid, ribose, and gluconic acid lactone were significantly more abundant in dogs with IBD. Although a clinical improvement was observed after medical therapy in all dogs with IBD, this was not accompanied by significant changes in the fecal microbiota or in serum metabolite profiles. These results suggest the presence of oxidative stress and a functional alteration of the GI microbiota in dogs with IBD, which persisted even in the face of a clinical response to medical therapy. PMID:25531678

  2. Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease.

    PubMed

    Minamoto, Yasushi; Otoni, Cristiane C; Steelman, Samantha M; Büyükleblebici, Olga; Steiner, Jörg M; Jergens, Albert E; Suchodolski, Jan S

    2015-01-01

    Idiopathic inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal (GI) disease in dogs. The combination of an underlying host genetic susceptibility, an intestinal dysbiosis, and dietary/environmental factors are suspected as main contributing factors in the pathogenesis of canine IBD. However, actual mechanisms of the host-microbe interactions remain elusive. The aim of this study was to compare the fecal microbiota and serum metabolite profiles between healthy dogs (n = 10) and dogs with IBD before and after 3 weeks of medical therapy (n = 12). Fecal microbiota and metabolite profiles were characterized by 454-pyrosequencing of 16 S rRNA genes and by an untargeted metabolomics approach, respectively. Significantly lower bacterial diversity and distinct microbial communities were observed in dogs with IBD compared to the healthy control dogs. While Gammaproteobacteria were overrepresented, Erysipelotrichia, Clostridia, and Bacteroidia were underrepresented in dogs with IBD. The functional gene content was predicted from the 16 S rRNA gene data using PICRUSt, and revealed overrepresented bacterial secretion system and transcription factors, and underrepresented amino acid metabolism in dogs with IBD. The serum metabolites 3-hydroxybutyrate, hexuronic acid, ribose, and gluconic acid lactone were significantly more abundant in dogs with IBD. Although a clinical improvement was observed after medical therapy in all dogs with IBD, this was not accompanied by significant changes in the fecal microbiota or in serum metabolite profiles. These results suggest the presence of oxidative stress and a functional alteration of the GI microbiota in dogs with IBD, which persisted even in the face of a clinical response to medical therapy.

  3. Serum metabolomics indicate altered cellular energy metabolism in children with cystic fibrosis.

    PubMed

    Joseloff, Elizabeth; Sha, Wei; Bell, Sara C; Wetmore, Diana R; Lawton, Kay A; Milburn, Michael V; Ryals, John A; Guo, Lining; Muhlebach, Marianne S

    2014-05-01

    Cystic fibrosis (CF) is a multi-system disease affecting multiple organs and cells besides the respiratory system. Metabolomic profiling allows simultaneous detection of biochemicals originating from cells, organs, or exogenous origin that may be valuable for monitoring of disease severity or in diagnosis. We hypothesized that metabolomics using serum from children would differentiate CF from non-CF lung disease subjects and would provide insight into metabolism in CF. Serum collected from children with CF (n = 31) and 31 age and gender matched children with other lung diseases was used for metabolomic profiling by gas- and liquid-chromatography. Relative concentration of metabolites was compared between the groups using partial least square discriminant analyses (PLS-DA) and linear modeling. A clear separation of the two groups was seen in PLS-DA. Linear model found that among the 459 detected metabolites 92 differed between CF and non-CF. These included known biochemicals in lipid metabolism, oxidants, and markers consistent with abnormalities in bile acid processing. Bacterial metabolites were identified and differed between the groups indicating intestinal dysbiosis in CF. As a novel finding several pathways were markedly different in CF, which jointly point towards decreased activity in the β-oxidation of fatty acids. These pathways include low ketone bodies, low medium chain carnitines, elevated di-carboxylic acids and decreased 2-hydroxybutyrate from amino acid metabolism in CF compared to non-CF. Serum metabolomics discriminated CF from non-CF and show altered cellular energy metabolism in CF potentially reflecting mitochondrial dysfunction. Future studies are indicated to examine their relation to the underlying CF defect and their use as biomarkers for disease severity or for cystic fibrosis transmembrane regulator (CFTR) function in an era of CFTR modifying drugs. © 2013 Wiley Periodicals, Inc.

  4. Serum Metabolic Profiling Reveals Altered Metabolic Pathways in Patients with Post-traumatic Cognitive Impairments

    PubMed Central

    Yi, Lunzhao; Shi, Shuting; Wang, Yang; Huang, Wei; Xia, Zi-an; Xing, Zhihua; Peng, Weijun; Wang, Zhe

    2016-01-01

    Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4-trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment. PMID:26883691

  5. Alteration of the serum biomarker profiles of visceral leishmaniasis during treatment

    PubMed Central

    Duthie, Malcolm S.; Guderian, Jeffrey; Vallur, Aarthy; Bhatia, Ajay; dos Santos, Priscila Lima; de Melo, Enaldo Vieira; de Jesus, Amelia Ribeiro; Todt, Matheus; Mondal, Dinesh; Almeida, Roque; Reed, Steven G.

    2013-01-01

    Until recently, chemotherapy for visceral leishmaniasis (VL; also known as kala-azar) was severely limited by factors such as high cost, route of administration, generation of side effects and potential for resistance. Although largely effective chemotherapies have become available with the introduction of new drugs and multi-drug regimens for VL, these could be further improved by the identification of biomarkers that are altered during effective treatment. The identification of such biomarkers in the circulation would also simplify efficacy trials. In this study we determined immunological signatures within the serum of ethnically and geographically-distinct VL patients (from Bangladesh and Brazil). Our results indicate that inflammatory and regulatory cytokines (IFNγ, TNFα, IL-10, IL-17), as well as levels of growth factors (FGF, VEGF), are elevated within the serum of VL patients from these sites. Examination of samples from Brazilian VL patients during and beyond standard treatment with meglumine antimoniate identified multiple parameters that revert to levels comparable to those of healthy endemic control individuals. The consolidation of these results provides a `response to treatment' signature that could be used within efficacy trials to rapidly and simply determine successful interruption of VL. PMID:24173820

  6. Serum Metabolic Profiling Reveals Altered Metabolic Pathways in Patients with Post-traumatic Cognitive Impairments.

    PubMed

    Yi, Lunzhao; Shi, Shuting; Wang, Yang; Huang, Wei; Xia, Zi-an; Xing, Zhihua; Peng, Weijun; Wang, Zhe

    2016-02-17

    Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4-trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment.

  7. Alteration of methotrexate binding to human serum albumin induced by oxidative stress. Spectroscopic comparative study

    NASA Astrophysics Data System (ADS)

    Maciążek-Jurczyk, M.; Sułkowska, A.; Równicka-Zubik, J.

    2016-01-01

    Changes of oxidative modified albumin conformation by comparison of non-modified (HSA) and modified (oHSA) human serum albumin absorption spectra, Red Edge Excitation Shift (REES) effect and fluorescence synchronous spectra were investigated. Studies of absorption spectra indicated that changes in the value of absorbance associated with spectral changes in the region from 200 to 250 nm involve structural alterations related to variations in peptide backbone conformation. Analysis of the REES effect allowed for the observation of changes caused by oxidation in the region of the hydrophobic pocket containing the tryptophanyl residue. Synchronous fluorescence spectroscopy confirmed changes of the position of the tryptophanyl and tyrosil residues fluorescent band. Effect of oxidative stress on binding of methotrexate (MTX) was investigated by spectrofluorescence, UV-VIS and 1HNMR spectroscopy. MTX caused the fluorescence quenching of non-modified (HSA) and modified (oHSA) human serum albumin molecule. The values of binding constants, Hill's coefficients and a number of binding sites in the protein molecule in the high affinity binding site were calculated for the binary MTX-HSA and MTX-oHSA systems. For these systems, qualitative analysis in the low affinity binding sites was performed with the use of the 1HNMR technique.

  8. Serum chemistry alterations, including creatine kinase isoenzymes, in furazolidone toxicosis of ducklings: preliminary findings.

    PubMed

    Webb, D M; DeNicola, D B; Van Vleet, J F

    1991-01-01

    Furazolidone induces a cardiotoxicosis when fed in toxic concentrations to newly hatched ducklings. This preliminary experiment was designed to determine if creatine kinase (CK) isoenzymic activities or other serum analytes would be useful as indicators of these cardiac alterations. Sera from 12 ducklings (six fed a control ration and six fed the control ration with 700 mg furazolidone added per kg of feed [700 ppm] for 28 days) were analyzed for CK isoenzymic activities, electrolytes, nitrogenous metabolites, hepatic enzymic activities, bilirubin, and glucose. Statistically significant differences between control and treated groups were detected for creatine kinase MB (CK-MB, cardiac muscle origin) isoenzymic activity and bilirubin, potassium, calcium, and total carbon dioxide concentrations. Differences other than CK-MB isoenzymic activity were generally explained by factors related to the toxicosis or sample handling. These findings suggest that CK-MB isoenzymic activity may be useful to detect and monitor the progress of cardiac injury in furazolidone toxicosis, thereby increasing the usefulness of this model of dilated cardiomyopathy. Our findings, analyzed on the Kodak Ektachem 700 Dry Chemistry Analyzer, are compared with serum chemistry values reported in the literature.

  9. Effect of quercetin against lindane induced alterations in the serum and hepatic tissue lipids in wistar rats

    PubMed Central

    Padma, Viswanadha Vijaya; Lalitha, Gurusamy; Shirony, Nicholson Puthanveedu; Baskaran, Rathinasamy

    2012-01-01

    Objective To assess the effect of quercetin (flavonoid) against lindane induced alterations in lipid profile of wistar rats. Methods Rats were administered orally with lindane (100 mg/kg body weight) and quercetin (10 mg/kg body weight) for 30 days. After the end of treatment period lipid profile was estimated in serum and tissue. Results Elevated levels of serum cholesterol, triglycerides, low density lipoprotein (LDL), very Low Density Lipoprotein (VLDL) and tissue triglycerides, cholesterol with concomitant decrease in serum HDL and tissue phospholipids were decreased in lindane treated rats were found to be significantly decreased in the quercetin and lindane co-treated rats. Conclusions Our study suggests that quercetin has hypolipidemic effect and offers protection against lindane induced toxicity in liver by restoring the altered levels of lipids. The quercetin cotreatment along with lindane for 30 days reversed these biochemical alterations in lipids induced by lindane. PMID:23569870

  10. Surface modification of zinc oxide nanoparticles with amorphous silica alters their fate in the circulation

    PubMed Central

    Konduru, Nagarjun V.; Murdaugh, Kimberly M.; Swami, Archana; Jimenez, Renato; Donaghey, Thomas C.; Demokritou, Philip; Brain, Joseph D.; Molina, Ramon M.

    2016-01-01

    Nanoparticle (NP) pharmacokinetics and biological effects are influenced by many factors, especially surface physicochemical properties. We assessed the effects of an amorphous silica coating on the fate of zinc after intravenous (IV) injection of neutron activated uncoated 65ZnO or silica-coated 65ZnO NPs in male Wistar Han rats. Groups of IV-injected rats were sequentially euthanized, and 18 tissues were collected and analyzed for 65Zn radioactivity. The protein coronas on each ZnO NP after incubation in rat plasma were analyzed by SDS-PAGE gel electrophoresis and mass spectrometry of selected gel bands. Plasma clearance for both NPs was biphasic with rapid initial and slower terminal clearance rates. Half-lives of plasma clearance of silica-coated 65ZnO were shorter (initial - <1 minute; terminal - 2.5 minutes) than uncoated 65ZnO (initial - 1.9 minutes; terminal - 38 minutes). Interestingly, the silica-coated 65ZnO group had higher 65Zn associated with red blood cells and higher initial uptake in the liver. The 65Zn concentrations in all the other tissues were significantly lower in the silica-coated than uncoated groups. We also found that the protein corona formed on silica-coated ZnO NPs had higher amounts of plasma proteins, particularly albumin, transferrin, A1 inhibitor 3, α-2-hs-glycoprotein, apoprotein E, and α-1 antitrypsin. Surface modification with amorphous silica alters the protein corona, agglomerate size, and zeta potential of ZnO NPs, which in turn influences ZnO biokinetic behavior in the circulation. This emphasizes the critical role of the protein corona in the biokinetics, toxicology, and nanomedical applications of nanoparticles. PMID:26581431

  11. Radiation-induced alterations in histone modification patterns and their potential impact on short-term radiation effects

    PubMed Central

    Friedl, Anna A.; Mazurek, Belinda; Seiler, Doris M.

    2012-01-01

    Detection and repair of radiation-induced DNA damage occur in the context of chromatin. An intricate network of mechanisms defines chromatin structure, including DNA methylation, incorporation of histone variants, histone modifications, and chromatin remodeling. In the last years it became clear that the cellular response to radiation-induced DNA damage involves all of these mechanisms. Here we focus on the current knowledge on radiation-induced alterations in post-translational histone modification patterns and their effect on the chromatin accessibility, transcriptional regulation and chromosomal stability. PMID:23050241

  12. Altered serum levels of kynurenine metabolites in patients affected by cluster headache.

    PubMed

    Curto, Martina; Lionetto, Luana; Negro, Andrea; Capi, Matilde; Perugino, Francesca; Fazio, Francesco; Giamberardino, Maria Adele; Simmaco, Maurizio; Nicoletti, Ferdinando; Martelletti, Paolo

    2015-01-01

    The reported efficacy of memantine in the treatment of patients with cluster headache (CH) suggests that NMDA receptors are involved in mechanisms of nociceptive sensitization within the trigeminal system associated with CH. NMDA receptors are activated or inhibited by neuroactive compounds generated by tryptophan metabolism through the kynurenine pathway. In the accompanying manuscript, we have found that serum levels of all kynurenine metabolites are altered in patients with chronic migraine. Here, we have extended the study to patients affected by episodic or chronic CH as compared to healthy controls. We assessed serum levels of kynurenine (KYN), kynurenic Acid (KYNA), anthranilic acid (ANA), 3-hydroxy-anthranilic acid (3-HANA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), quinolinic acid (QUINA), tryptophan (Trp) and 5-hydroxyindolacetic acid (5-HIAA) by means of a liquid chromatography/tandem mass spectrometry (LC/MS-MS) method in 21 patients affected by CH (15 with episodic and 6 with chronic CH), and 35 age-matched healthy subjects. Patients with psychiatric co-morbidities, systemic inflammatory, endocrine or neurological disorders, and mental retardation were excluded. LC/MS-MS analysis of kynurenine metabolites showed significant reductions in the levels of KYN (-36 %), KYNA (-34 %), 3-HK (-51 %), 3-HANA (-54 %), XA (-25 %), 5-HIAA (-39 %) and QUINA (-43 %) in the serum of the overall population of patients affected by CH, as compared to healthy controls. Serum levels of Trp and ANA were instead significantly increased in CH patients (+18 % and +54 %, respectively). There was no difference in levels of any metabolite between patients affected by episodic and chronic CH, with the exception of KYN levels, which were higher in patients with chronic CH. The reduced levels of KYNA (an NMDA receptor antagonist) support the hypothesis that NMDA receptors are overactive in CH. A similar reduction in KYNA levels was shown in the accompanying

  13. Serum S100 protein could predict altered consciousness in glyphosate or glufosinate poisoning patients.

    PubMed

    Lee, Jung-Won; Choi, Young-Jin; Park, Samel; Gil, Hyo-Wook; Song, Ho-Yeon; Hong, Sae-Yong

    2017-06-01

    Central nervous system (CNS) complications such as seizures and reduced consciousness are important in glufosinate and may occur in severe glyphosate poisoning. The aim of this study was to assess the possible role of serum S100B protein as a biochemical marker of CNS complications associated with glyphosate or glufosinate poisoning. The study enrolled 40 patients (23 glyphosate poisoning and 17 glufosinate poisoning). Altered consciousness and seizure were observed during hospitalization. S100B level was measured with fully automated modular analytic E170 system using electrochemoluminometric immunoassay. Among 40 patients, neurologic features were observed in 12 patients with a median time to onset of 21.5 (IQR 8.25-24.75) h. Serum S100B concentrations measured on admission were higher in the group with neurologic features than in the group without neurologic features [0.148 μg/L (IQR 0.128-0.248) vs. 0.072 μg/L (IQR 0.047-0.084), p < .001]. Univariate analysis of measured patient raw parameters using a ROC curve showed that S100B was a significant predictor of neurologic features in glyphosate and glufosinate poisoning. The area under the ROC curve was 0.894 (95% confidential interval 0.791-0.998). When S100B was set at 0.0965, its sensitivity and specificity for predicting neurologic features in glyphosate and glufosinate poisoning were 92% and 82%, respectively. In our pilot study, S100B was a significant predictor of neurologic complications in patients with glyphosate and glufosinate poisoning. Large prospective cohorts are needed to confirm this finding.

  14. Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder.

    PubMed

    Bumb, J M; Enning, F; Mueller, J K; van der List, Till; Rohleder, C; Findeisen, P; Noelte, I; Schwarz, E; Leweke, F M

    2016-07-01

    Melatonin, which plays an important role for regulation of circadian rhythms and the sleep/wake cycle has been linked to the pathophysiology of major depressive and bipolar disorder. Here we investigated melatonin levels in cerebrospinal fluid (CSF) and serum of depression and bipolar patients to elucidate potential differences and commonalities in melatonin alterations across the two disorders. Using enzyme-linked immunosorbent assays, CSF and serum melatonin levels were measured in 108 subjects (27 healthy volunteers, 44 depressed and 37 bipolar patients). Covariate adjusted multiple regression analysis was used to investigate group differences in melatonin levels. In CSF, melatonin levels were significantly decreased in bipolar (P<0.001), but not major depressive disorder. In serum, we observed a significant melatonin decrease in major depressive (P=0.003), but not bipolar disorder. No associations were found between serum and CSF melatonin levels or between melatonin and measures of symptom severity or sleep disruptions in either condition. This study suggests the presence of differential, body fluid specific alterations of melatonin levels in bipolar and major depressive disorder. Further, longitudinal studies are required to explore the disease phase dependency of melatonin alterations and to mechanistically explore the causes and consequences of site-specific alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Correlation of serum cytokine and acute phase reactant levels with alterations in weight and serum albumin in patients receiving immunotherapy with recombinant IL-2.

    PubMed Central

    Deehan, D J; Heys, S D; Simpson, W; Herriot, R; Broom, J; Eremin, O

    1994-01-01

    Recombinant IL-2 (rIL-2) has been used alone or in combination with other chemotherapeutic agents to enhance host defences against cancer. Prolonged administration of high doses, required for clinical efficacy, may precipitate serious dose-limiting toxicity. rIL-2-induced 'vascular leak syndrome' leads to hypotension, renal insufficiency, respiratory disturbances and other organ dysfunctions. Serial measurements of serum cytokines and the acute phase protein C-reactive protein (CRP) were performed on nine patients who received high-dose i.v. continuous therapy with rIL-2. The influence of these immunological parameters upon alterations in patients' weight and serum albumin, as indicators of toxicity, was assessed. All patients experienced weight increases during the cycle (3-11% of total body weight). The serum levels of tumour necrosis factor (TNF-alpha) and CRP were highly predictive of alterations in patients' weight (both P < 0.001), while no correlation was found with IL-6 and weight change. Serum albumin fell linearly throughout the infusion cycle, but this showed no correlation with variations in serum levels of IL-6, TNF-alpha, or CRP. The complement components C3 and C4 were significantly reduced at the end of the infusion, suggesting a possible role for this cascade system in mediating these clinical changes. The strong association between serum TNF-alpha and weight change, not previously documented, further supports the hypothesis that TNF-alpha is a key mediator in the pathogenesis of the 'vascular leak syndrome'. PMID:7511074

  16. Alterations of serum biomarkers associated with lung ventilation function impairment in coal Workers: A cross-sectional study

    PubMed Central

    2011-01-01

    Background Previous studies have demonstrated that alterations in certain circulating biomarkers may be correlated with Coal workers' pneumoconiosis (CWP). This study investigated the relationship between changes of serum biomarkers and pulmonary function during the development of CWP. Methods Lung function parameters and specific serum indices were measured in 69 non-smoking coal workers, including 34 miners with CWP, 24 asymptomatic miners and 11 miners with minimal symptoms. The associations between changes in pulmonary function and serum indices were tested with Pearson's correlation coefficients. Multivariable analysis was used to estimate the predictive power of potential determinant variables for lung function. Results Compared to healthy miners, lung function (FVC, FEV1, FEF50, FEF75, FEF25-75 % of predicted values) was decreased in miners with CWP (p < 0.05). Increased serum matrix metalloproteinase-9 (MMP-9) was associated with decreased FVC% of predicted values in the asymptomatic miners (r = -0.503, p = 0.014). Conclusions In coal mine workers, alterations of lung function parameters are associated with the development of CWP and with changes in circulating MMP-9, TIMP-9, IL-13 and IL-18R. These serum biomarkers may likely reflect the pathogenesis and progression of CWP in coal workers, and may provide for the importance of serum indicators in the early diagnosis of lung function injury in coal miners. PMID:21943057

  17. Increased Serum Uric Acid Levels Blunt the Antihypertensive Efficacy of Lifestyle Modifications in Children at Cardiovascular Risk.

    PubMed

    Viazzi, Francesca; Rebora, Paola; Giussani, Marco; Orlando, Antonina; Stella, Andrea; Antolini, Laura; Valsecchi, Maria Grazia; Pontremoli, Roberto; Genovesi, Simonetta

    2016-05-01

    Primary hypertension is a growing concern in children because of the obesity epidemic largely attributable to western lifestyles. Serum uric acid is known to be influenced by dietary habits, correlates with obesity, and could represent a risk factor for hypertension. Preliminary studies in children highlighted uric acid as a potentially modifiable risk factor for the prevention and treatment of hypertension. The effect of lifestyle changes (increase of physical activity and dietary modifications) on blood pressure values, weight status, and serum uric acid levels in a cohort of 248 children referred for cardiovascular risk assessment were evaluated over a mean 1.5-year follow-up. At baseline, 48% of children were obese and 50% showed blood pressure values >90th percentile. At follow-up, a significant improvement in weight class (24% obese;P<0.0001) and blood pressure category (22% >90th percentile;P<0.0001) was found. Systolic blood pressure z-score (P<0.0001), uric acid value (P=0.0056), and puberty at baseline (P=0.0048) were independently associated with higher systolic blood pressure z-score at follow-up, whereas a negative association was observed with body mass index z-score decrease during follow-up (P=0.0033). The risk of hypertension at follow-up was associated with body mass index (P=0.0025) and systolic blood pressure (P<0.0001) z-score at baseline and inversely related to delta body mass index (P=0.0002), whereas the risk of showing hypertension ≥99th percentile was more than doubled for each baseline 1 mg/dL increase of serum uric acid (P=0.0130). Uric acid is a powerful determinant of blood pressure over time, independent of lifestyle modifications. © 2016 American Heart Association, Inc.

  18. Surface-modification-directed controlled adsorption of serum albumin onto magnetite nanocuboids synthesized in a gel-diffusion technique.

    PubMed

    Borah, Ballav Moni; Saha, Bedabrata; Dey, Sandeep Kumar; Das, Gopal

    2010-09-01

    Magnetite nanocuboids have been synthesized via gel-diffusion technique in agarose gel. Here, the agarose gel matrix has been used as an organic template for formation and growth modification of magnetite. Gel mineralization mimics the membrane-based biomineralization, controls the diffusion process and gives the micro/nano environment for the crystal growth. We also attempt to understand the influence of different surface modifications of synthesized magnetite nanocuboids on protein interaction. For this purpose, magnetite particles were coated with trimesic acid (benzene-1,3,5-tricarboxylic acid) and stearic acid, which generates a hydrophilic and a hydrophobic modified surface, respectively. We report controlled adsorption behavior of bovine serum albumin (BSA) by surface modification of magnetite nanocuboids with different functional groups. The adsorption capacity of BSA increases on trimesic acid-coated surfaces compared to bare magnetite surfaces, while it decreases on stearic acid-coated surfaces. In situ fluorescence spectroscopy has been used to analyze the tertiary protein structure in the adsorbed state on these three surfaces. Partial unfolding in the tertiary structure of BSA was observed upon adsorption onto bare magnetite surfaces. On trimesic acid-coated surfaces, tertiary unfolding of BSA was greater than on bare magnetite surfaces, while BSA undergoes minor tertiary structural change on stearic acid-coated surfaces. Copyright 2010 Elsevier Inc. All rights reserved.

  19. Pregnancy amelioration of arthritis in SKG mice corresponds with alterations in serum amyloid A3 levels.

    PubMed

    Shaw, Laura A; Stefanski, Adrianne L; Peterson, Lisa K; Rumer, Kristen K; Vondracek, Andrea; Phang, Tzu L; Sakaguchi, Shimon; Winn, Virginia D; Dragone, Leonard L

    2012-06-30

    OBJECTIVES: Pregnancy leads to rheumatoid arthritis remission in humans. The objective of this study was to determine if the SKG mouse could serve as a model for pregnancy-associated inflammatory arthritis amelioration. In addition, the maternal peripheral blood mononuclear cell (PBMC) transcriptome was assessed to define a biomarker associated with remission. METHODS: Cohorts of zymosan-treated pregnant SKG mice and controls were monitored for arthritis progression. Microarray analysis evaluated alterations in gene expression in maternal PBMCs at embryonic day 14.5 (E14.5) between arthritic and pregnancy-remitted mice. A selected target, serum amyloid A3 (SAA3), was further investigated using quantitative reverse transcriptase PCR (qRT-PCR) and an enzyme-linked immunosorbent assay (ELISA). RESULTS: Pregnancy resulted in complete or partial remission in the majority of the zymosan-treated SKG mice. Twenty-seven transcripts were differentially expressed in the PBMCs between arthritic and pregnancy-remitted mice. Expression and plasma SAA3 levels decreased with pregnancy-induced arthritis amelioration and plasma SAA3 levels correlated with arthritis severity. CONCLUSIONS: These results establish the SKG mouse as a model system to study pregnancy-induced amelioration of arthritis. These studies also establish SAA3 as a biomarker of arthritis amelioration in SKG mice. This model can be used to elucidate the molecular and cellular mechanisms underlying the impact of pregnancy on the maternal immune system that results in arthritis amelioration.

  20. Surface hydrophilic modification with a sugar moiety for a uniform-sized polymer molecularly imprinted for phenobarbital in serum.

    PubMed

    Hua, Kuichang; Zhang, Lei; Zhang, Zhenhui; Guo, Yong; Guo, Tianying

    2011-08-01

    A uniform-sized polymer molecularly imprinted for phenobarbital, which is surface modified by a sugar moiety, has been prepared through a two-step swelling polymerization method using polystyrene beads as seeds, phenobarbital as the template, 4-vinylpyridine as a functional monomer, ethylene glycol dimethacrylate as a cross-linker and 2-O-meth-acryloyloxyethoxyl-(2,3,4,6- tetra-O-acetyl-β-d-galactopyranosyl)-(1-4)-2,3,6-tri-O-acetyl-β-d-glucopyranoside as a surface-modifying glycomonomer, respectively. After deprotecting the glycopolymer, a surface sugar moiety-modified, hydrophilic, molecularly imprinted polymer for phenobarbital (glyco-MIP) was obtained. The resulting polymer beads were packed into a stainless steel column to evaluate their chromatographic characteristics by high-performance liquid chromatography (HPLC). Good selectivity for phenobarbital was obtained with the glyco-MIP compared to the unmodified molecularly imprinted polymer, which revealed that the recognition sites of phenobarbital were unchanged with sugar moiety surface modification. Furthermore, bovine serum albumin was almost completely recovered from the glyco-MIP column, which indicates that the glyco-MIP materials can be used to separate and analyze drugs in complex samples, such as biological samples. The results of pretreatment with and analysis of phenobarbital in serum suggest that this material can be used to analyze phenobarbital in serum through a pretreatment and reverse-phase HPLC analysis process. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  1. Expression of Serum microRNAs is Altered During Acute Graft-versus-Host Disease

    PubMed Central

    Crossland, Rachel E.; Norden, Jean; Juric, Mateja Kralj; Green, Kile; Pearce, Kim F.; Lendrem, Clare; Greinix, Hildegard T.; Dickinson, Anne M.

    2017-01-01

    Acute graft-versus-host disease (aGvHD) is the most frequent and serious complication following hematopoietic stem cell transplantation (HSCT), with a high mortality rate. A clearer understanding of the molecular pathogenesis may allow for improved therapeutic options or guide personalized prophylactic protocols. Circulating microRNAs are expressed in body fluids and have recently been associated with the etiology of aGvHD, but global expression profiling in a HSCT setting is lacking. This study profiled expression of n = 799 mature microRNAs in patient serum, using the NanoString platform, to identify microRNAs that showed altered expression at aGvHD diagnosis. Selected microRNAs (n = 10) were replicated in independent cohorts of serum samples taken at aGvHD diagnosis (n = 42) and prior to disease onset (day 14 post-HSCT, n = 47) to assess their prognostic potential. Sera from patients without aGvHD were used as controls. Differential microRNAs were investigated in silico for predicted networks and mRNA targets. Expression analysis identified 61 microRNAs that were differentially expressed at aGvHD diagnosis. miR-146a (p = 0.03), miR-30b-5p (p = 0.007), miR-374-5p (p = 0.02), miR-181a (p = 0.03), miR-20a (p = 0.03), and miR-15a (p = 0.03) were significantly verified in an independent cohort (n = 42). miR-146a (p = 0.01), miR-20a (p = 0.03), miR-18 (p = 0.03), miR-19a (p = 0.03), miR-19b (p = 0.01), and miR-451 (p = 0.01) were differentially expressed 14 days post-HSCT in patients who later developed aGvHD (n = 47). High miR-19b expression was associated with improved overall survival (OS) (p = 0.008), whereas high miR-20a and miR-30b-5p were associated with lower rates of non-relapse mortality (p = 0.05 and p = 0.008) and improved OS (p = 0.016 and p = 0.021). Pathway analysis associated the candidate microRNAs with hematological and inflammatory disease. Circulating

  2. Alteration of Serum Concentrations of Manganese, Iron, Ferritin, and Transferrin Receptor Following Exposure to Welding Fumes Among Career Welders

    PubMed Central

    Lu, Ling; Zhang, Long-lian; Li, G. Jane; Guo, Wenrui; Liang, Wannian; Zheng, Wei

    2014-01-01

    This study was performed to determine airborne manganese levels during welding practice and to establish the relationship between long-term, low-level exposure to manganese and altered serum concentrations of manganese, iron, and proteins associated with iron metabolism in career welders. Ninety-seven welders (average age of 36 years) who have engaged in electric arc weld in a vehicle manufacturer were recruited as the exposed group. Welders worked 7–8 h per day with employment duration of 1–33 years. Control subjects consisted of 91 employees (average age of 35 years) in the same factory but not in the welding profession. Ambient manganese levels in welders’ breathing zone were the highest inside the vehicle (1.5 ± 0.7 mg/m3), and the lowest in the center of the workshop (0.2 ± 0.05 mg/m3). Since the filter size was 0.8 μm, it is possible that these values may be likely an underestimation of the true manganese levels. Serum levels of manganese and iron in welders were about three-fold (p < 0.01) and 1.2-fold (p < 0.01), respectively, higher than those of controls. Serum concentrations of ferritin and transferrin were increased among welders, while serum transferrin receptor levels were significantly decreased in comparison to controls. Linear regression analyses revealed a lack of association between serum levels of manganese and iron. However, serum concentrations of iron and ferritin were positively associated with years of welder experience (p < 0.05). Moreover, serum transferrin receptor levels were inversely associated with serum manganese concentrations (p < 0.05). These findings suggest that exposure to welding fume among welders disturbs serum homeostasis of manganese, iron, and the proteins associated with iron metabolism. Serum manganese may serve as a reasonable biomarker for assessment of recent exposure to airborne manganese. PMID:15713346

  3. Human serum albumin Cys34 oxidative modifications following infiltration in the carotid atherosclerotic plaque.

    PubMed

    Lepedda, Antonio Junior; Zinellu, Angelo; Nieddu, Gabriele; De Muro, Pierina; Carru, Ciriaco; Spirito, Rita; Guarino, Anna; Piredda, Franco; Formato, Marilena

    2014-01-01

    To evaluate if the prooxidant environment present in atherosclerotic plaque may oxidatively modify filtered albumin. Fluorescein-5-maleimide labelled plasma samples and plaque extracts from 27 patients who had undergone carotid endarterectomy were analysed through nonreducing SDS-PAGE for albumin-Cys(34) oxidation. Furthermore, degree and pattern of S-thiolation in both circulating and plaque-filtered albumin were assayed. Albumin filtered in the atherosclerotic plaque showed higher levels of Cys(34) oxidative modifications than the corresponding circulating form as well as different patterns of S-thiolation. Data indicate that the circulating albumin, once filtered in plaque, undergoes Cys(34) oxidative modifications and demonstrate for the first time that albumin is a homocysteine and cysteinylglycine vehicle inside the plaque environment.

  4. Human Serum Albumin Cys34 Oxidative Modifications following Infiltration in the Carotid Atherosclerotic Plaque

    PubMed Central

    Zinellu, Angelo; De Muro, Pierina; Carru, Ciriaco; Spirito, Rita; Guarino, Anna

    2014-01-01

    Objectives. To evaluate if the prooxidant environment present in atherosclerotic plaque may oxidatively modify filtered albumin. Methods. Fluorescein-5-maleimide labelled plasma samples and plaque extracts from 27 patients who had undergone carotid endarterectomy were analysed through nonreducing SDS-PAGE for albumin-Cys34 oxidation. Furthermore, degree and pattern of S-thiolation in both circulating and plaque-filtered albumin were assayed. Results. Albumin filtered in the atherosclerotic plaque showed higher levels of Cys34 oxidative modifications than the corresponding circulating form as well as different patterns of S-thiolation. Conclusions. Data indicate that the circulating albumin, once filtered in plaque, undergoes Cys34 oxidative modifications and demonstrate for the first time that albumin is a homocysteine and cysteinylglycine vehicle inside the plaque environment. PMID:24738021

  5. Metabolomics reveals trichloroacetate as a major contributor to trichloroethylene-induced metabolic alterations in mouse urine and serum.

    PubMed

    Fang, Zhong-Ze; Krausz, Kristopher W; Tanaka, Naoki; Li, Fei; Qu, Aijuan; Idle, Jeffrey R; Gonzalez, Frank J

    2013-11-01

    Trichloroethylene (TCE)-induced liver toxicity and carcinogenesis is believed to be mediated in part by activation of the peroxisome proliferator-activated receptor α (PPARα). However, the contribution of the two TCE metabolites, dichloroacetate (DCA) and trichloroacetate (TCA) to the toxicity of TCE, remains unclear. The aim of the present study was to determine the metabolite profiles in serum and urine upon exposure of mice to TCE, to aid in determining the metabolic response to TCE exposure and the contribution of DCA and TCA to TCE toxicity. C57BL/6 mice were administered TCE, TCA, or DCA, and urine and serum subjected to ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS)-based global metabolomics analysis. The ions were identified through searching metabolomics databases and by comparison with authentic standards, and quantitated using multiple reactions monitoring. Quantitative polymerase chain reaction of mRNA, biochemical analysis, and liver histology were also performed. TCE exposure resulted in a decrease in urine of metabolites involved in fatty acid metabolism, resulting from altered expression of PPARα target genes. TCE treatment also induced altered phospholipid homeostasis in serum, as revealed by increased serum lysophosphatidylcholine 18:0 and 18:1, and phosphatidylcholine metabolites. TCA administration revealed similar metabolite profiles in urine and serum upon TCE exposure, which correlated with a more robust induction of PPARα target gene expression associated with TCA than DCA treatment. These data show the metabolic response to TCE exposure and demonstrate that TCA is the major contributor to TCE-induced metabolite alterations observed in urine and serum.

  6. Medical image integrity control and forensics based on watermarking--approximating local modifications and identifying global image alterations.

    PubMed

    Huang, H; Coatrieux, G; Shu, H Z; Luo, L M; Roux, Ch

    2011-01-01

    In this paper we present a medical image integrity verification system that not only allows detecting and approximating malevolent local image alterations (e.g. removal or addition of findings) but is also capable to identify the nature of global image processing applied to the image (e.g. lossy compression, filtering …). For that purpose, we propose an image signature derived from the geometric moments of pixel blocks. Such a signature is computed over regions of interest of the image and then watermarked in regions of non interest. Image integrity analysis is conducted by comparing embedded and recomputed signatures. If any, local modifications are approximated through the determination of the parameters of the nearest generalized 2D Gaussian. Image moments are taken as image features and serve as inputs to one classifier we learned to discriminate the type of global image processing. Experimental results with both local and global modifications illustrate the overall performances of our approach.

  7. Alteration of histone acetylation pattern during long-term serum-free culture conditions of human fetal placental mesenchymal stem cells.

    PubMed

    Zhu, Yongzhao; Song, Xumei; Han, Fei; Li, Yukui; Wei, Jun; Liu, Xiaoming

    2015-01-01

    Increasing evidence suggests that the mesenchymal stem cells (MSCs) derived from placenta of fetal origin (fPMSCs) are superior to MSCs of other sources for cell therapy. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications, during which MSCs may undergo genetic and/or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic and epigenetic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical settings. To date, the genetic and epigenetic stability of fPMSCs after long-term in vitro expansion has not been fully investigated. In this report, alterations to histone acetylation and consequence on the expression pattern of fPMSCs following in vitro propagation under serum-free conditions were explored. The results show that fPMSCs maintain their MSC characteristics before they reached a senescent state. Furthermore, acetylation modification patterns were changed in fPMSCs along with gradually increased global histone deacetylase (HDAC) activity and expression of HDAC subtypes HDAC4, HDAC5 and HDAC6, as well as a down-regulated global histone H3/H4 acetylation during in vitro culturing. In line with the acetylation alterations, the expression of oncogenes Oct4, Sox2 and TERT were significantly decreased over the propagation period. Of note, the down-regulation of Oct4 was strongly associated with changes in acetylation. Intriguingly, telomere length in fPMSCs did not significantly change during the propagating process. These findings suggest that human fPMSCs may be a safe and reliable resource of MSCs and can be propagated under serum-free conditions with less risk of spontaneous malignancy, and warrants further validation in clinical settings.

  8. DETECTING STREAM INVERTEBRATE COMMUNITY ALTERATION DUE TO MID TO LOW LEVELS OF WATERSHED LANDSCAPE MODIFICATION

    EPA Science Inventory

    As part of an investigation into the effects of watershed landscape alteration on stream ecosystems, quantitative invertebrate samples were collected from riffles in 26 second and third order south shore Lake Superior streams. Nonmetric multidimensional scaling (NMDS) ordination ...

  9. Posttranslational Modifications of Transthyretin Are Serum Markers in Patients with Mycosis Fungoides1

    PubMed Central

    Escher, Niko; Kaatz, Martin; Melle, Christian; Hipler, Christina; Ziemer, Mirjana; Driesch, Dominik; Wollina, Uwe; von Eggeling, Ferdinand

    2007-01-01

    Cutaneous T-cell lymphomas (CTCLs) are characterized by the recruitment of malignant T-cell clones, predominantly of the CD4+ T-helper subpopulation, into the skin. Mycosis fungoides (MF) is the most common type of CTCL and accounts for almost 50% of all primary cutaneous lymphomas. The ProteinChip technology surface-enhanced laser desorption/ionization time of flight/mass spectrometry (SELDI-TOF-MS) was used to detect biomarkers in sera from MF patients (n = 25) and healthy controls (n = 26). Therefore, diluted sera were applied to IMAC30 ProteinChip arrays, and the resulting protein profiles were bioinformatically analyzed. A protein set that distinguishes MF patients from healthy controls with a sensitivity of 82.6% and a specificity of 100% was identified. Four significant peaks were identified by two-dimensional gel electrophoresis, immunodepletion, and SELDI-TOF-MS as transthyretin (TTR) and three TTR modifications. A subsequent enzyme-linked immunosorbent assay confirmed these findings. The ability to detect and identify proteins and protein modifications using SELDI-TOF-MS might reveal a better insight on this kind of disease and may lead to a better understanding and earlier detection of MF patients. PMID:17401465

  10. Alteration of saliva and serum concentrations of manganese, copper, zinc, cadmium and lead among career welders

    PubMed Central

    Wang, Dixin; Du, Xuqin; Zheng, Wei

    2014-01-01

    Human saliva offers a unique noninvasive approach for populational study. Purposes of this study were to investigate the feasibility of using saliva manganese (Mn) concentration as a biomarker of Mn exposure among career welders and to study the variations of Mn, copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) in saliva as affected by the welding profession. Forty-nine male welders, of whom 28 were in the low exposed group and 21 in the high exposed group, were recruited. Control subjects were 33 military soldiers without metal exposure. Ambient Mn levels in breathing zones were 0.01, 0.24 and 2.21 mg/m3for control, low, and high exposed groups, respectively. Saliva samples were collected to quantify metals by inductive coupled plasma mass spectrometer (ICP-MS). Saliva concentrations of Mn and Cu were significantly higher in welders than in controls (p < 0.01); the variation in saliva levels appeared likely to be associated with airborne Mn levels among study populations. Saliva levels of Zn were significantly lower in welders than in controls (p < 0.05), while Cd and Pb levels in saliva were unchanged. Significant associations were observed between saliva and serum for Mn (r = 0.575, p < 0.05) and Cu (r = 0.50, p < 0.05). Moreover, saliva Mn concentrations were higher among welders with 5–10 years of employment than those with less than 5 years of employment. Linear regression analysis revealed a significant correlation between saliva Mn and Cu and between saliva Mn and Zn. Taken together, these data suggest that Mn concentrations in saliva appear reflective of welders’ exposure to airborne Mn and their years of welding experience. respectively. Elevated Mn levels among welders may alter the homeostasis of Cu and Zn. PMID:18054180

  11. Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain.

    PubMed

    Nayak, Prasunpriya; Chatterjee, Ajay K

    2003-02-25

    Alteration of glutamate and gamma-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and gamma-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and gamma-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity. Protein restriction does not have any significant impact on regional aluminum and gamma-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate alpha-decarboxylase and gamma-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area. The alterations of regional brain glutamate and gamma-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders.

  12. Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

    PubMed Central

    Nayak, Prasunpriya; Chatterjee, Ajay K

    2003-01-01

    Background Alteration of glutamate and γ-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and γ-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and γ-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity. Results Protein restriction does not have any significant impact on regional aluminum and γ-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate α-decarboxylase and γ-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area. Conclusion The alterations of regional brain glutamate and γ-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders. PMID:12657166

  13. Alterations in serum lipids in lepromatous leprosy patients with and without ENL reactions and their relationship to acute phase proteins.

    PubMed

    Memon, R A; Hussain, R; Raynes, J G; Lateff, A; Chiang, T J

    1996-06-01

    The concentrations of serum lipids were measured in patients with lepromatous (LL/BL) leprosy and erythema nodosum leprosum (ENL). The relationships between serum lipid levels and serum amyloid A (SAA) and C-reactive protein (CRP) were also examined in these patients. LL/BL patients had significantly higher serum triglyceride and lower HDL-cholesterol concentrations compared to the endemic controls. ENL patients had significantly lower total, HDL- and LDL-cholesterol levels compared to the endemic controls. The levels of all lipid metabolites also were significantly lower in ENL patients compared to LL/BL patients. The concentrations of SAA and CRP were markedly elevated in ENL patients but were not statistically different in LL/BL patients compared to control subjects. There was a significant negative correlation between SAA and HDL-cholesterol levels in both stable lepromatous and reactional (ENL) patients; there was no statistically significant correlation between CRP and HDL-cholesterol levels. SAA levels also had a significant negative correlation with total and LDL-cholesterol levels. Our results indicate that serum lipids are significantly altered in patients with lepromatous disease and ENL reaction. Our results also suggest that an increase in SAA levels may divert the metabolism of lipoproteins from hepatocytes toward macrophages, resulting in a decrease in serum lipoprotein levels.

  14. Serum albumin alters the expression of iron-controlled genes in Pseudomonas aeruginosa

    PubMed Central

    Kruczek, Cassandra; Wachtel, Mitchell; Alabady, Magdy S.; Payton, Paxton R.; Colmer-Hamood, Jane A.

    2012-01-01

    Pseudomonas aeruginosa, which causes serious infections in immunocompromised patients, produces numerous virulence factors, including exotoxin A and the siderophore pyoverdine. As production of these virulence factors is influenced by the host environment, we examined the effect serum has on global transcription within P. aeruginosa strain PAO1 at different phases of growth in an iron-deficient medium. At early exponential phase, serum significantly enhanced expression of 138 genes, most of which are repressed by iron, including pvdS, regA and the pyoverdine synthesis genes. However, serum did not interfere with the repression of these genes by iron. Serum enhanced regA expression in a fur mutant of PAO1 but not in a pvdS mutant. The serum iron-binding protein apotransferrin, but not ferritin, enhanced regA and pvdS expression. However, in PAO1 grown in a chemically defined medium that contains no iron, serum but not apotransferrin enhanced pvdS and regA expression. While complement inactivation failed to eliminate this effect, albumin absorption reduced the effect of serum on pvdS and regA expression in the iron-deficient medium chelexed tryptic soy broth dialysate. Additionally, albumin absorption eliminated the effect of serum on pvdS and regA expression in the chemically defined medium. These results suggest that serum enhances the expression of P. aeruginosa iron-controlled genes by two mechanisms: one through apotransferrin and another one through albumin. PMID:22053004

  15. Peptide modifications differentially alter G protein-coupled receptor internalization and signaling bias.

    PubMed

    Mäde, Veronika; Babilon, Stefanie; Jolly, Navjeet; Wanka, Lizzy; Bellmann-Sickert, Kathrin; Diaz Gimenez, Luis E; Mörl, Karin; Cox, Helen M; Gurevich, Vsevolod V; Beck-Sickinger, Annette G

    2014-09-15

    Although G protein-coupled receptors (GPCRs) are targeted by more clinically used drugs than any other type of protein, their ligand development is particularly challenging. Humans have four neuropeptide Y receptors: hY1R and hY5R are orexigenic, while hY2R and hY4R are anorexigenic, and represent important anti-obesity drug targets. We show for the first time that PEGylation and lipidation, chemical modifications that prolong the plasma half-lives of peptides, confer additional benefits. Both modifications enhance pancreatic polypeptide preference for hY2R/hY4R over hY1R/hY5R. Lipidation biases the ligand towards arrestin recruitment and internalization, whereas PEGylation confers the opposite bias. These effects were independent of the cell system and modified residue. We thus provide novel insights into the mode of action of peptide modifications and open innovative venues for generating peptide agonists with extended therapeutic potential.

  16. Peptide Modifications Differentially Alter G Protein-Coupled Receptor Internalization and Signaling Bias**

    PubMed Central

    Mäde, Veronika; Babilon, Stefanie; Jolly, Navjeet; Wanka, Lizzy; Bellmann-Sickert, Kathrin; Diaz Gimenez, Luis E.; Mörl, Karin; Cox, Helen M.; Gurevich, Vsevolod V.; Beck-Sickinger, Annette G.

    2016-01-01

    Although G protein-coupled receptors (GPCRs) are targeted by more clinically used drugs than any other type of protein, their ligand development is particularly challenging. Humans have four neuropeptide Y receptors: hY1R and hY5R are orexigenic, while hY2R and hY4R are anorexigenic, and represent important anti-obesity drug targets. We show for the first time that PEGylation and lipidation, chemical modifications that prolong the plasma half-lives of peptides, confer additional benefits. Both modifications enhance pancreatic polypeptide preference for hY2R/hY4R over hY1R/hY5R. Lipidation biases the ligand towards arrestin recruitment and internalization, whereas PEGylation confers the opposite bias. These effects were independent of the cell system and modified residue. We thus provide novel insights into the mode of action of peptide modifications and open innovative venues for generating peptide agonists with extended therapeutic potential. PMID:25065900

  17. Histone modifications and alcohol-induced liver disease: are altered nutrients the missing link?

    PubMed

    Moghe, Akshata; Joshi-Barve, Swati; Ghare, Smita; Gobejishvili, Leila; Kirpich, Irina; McClain, Craig J; Barve, Shirish

    2011-05-28

    Alcoholism is a major health problem in the United States and worldwide, and alcohol remains the single most significant cause of liver-related diseases and deaths. Alcohol is known to influence nutritional status at many levels including nutrient intake, absorption, utilization, and excretion, and can lead to many nutritional disturbances and deficiencies. Nutrients can dramatically affect gene expression and alcohol-induced nutrient imbalance may be a major contributor to pathogenic gene expression in alcohol-induced liver disease (ALD). There is growing interest regarding epigenetic changes, including histone modifications that regulate gene expression during disease pathogenesis. Notably, modifications of core histones in the nucleosome regulate chromatin structure and DNA methylation, and control gene transcription. This review highlights the role of nutrient disturbances brought about during alcohol metabolism and their impact on epigenetic histone modifications that may contribute to ALD. The review is focused on four critical metabolites, namely, acetate, S-adenosylmethionine, nicotinamide adenine dinucleotide and zinc that are particularly relevant to alcohol metabolism and ALD.

  18. Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells

    PubMed Central

    Streng-Ouwehand, Ingeborg; Ho, Nataschja I; Litjens, Manja; Kalay, Hakan; Boks, Martine Annemarie; Cornelissen, Lenneke AM; Kaur Singh, Satwinder; Saeland, Eirikur; Garcia-Vallejo, Juan J; Ossendorp, Ferry A; Unger, Wendy WJ; van Kooyk, Yvette

    2016-01-01

    Antigen uptake by dendritic cells and intracellular routing of antigens to specific compartments is regulated by C-type lectin receptors that recognize glycan structures. We show that the modification of Ovalbumin (OVA) with the glycan-structure LewisX (LeX) re-directs OVA to the C-type lectin receptor MGL1. LeX-modification of OVA favored Th1 skewing of CD4+ T cells and enhanced cross-priming of CD8+ T cells. While cross-presentation of native OVA requires high antigen dose and TLR stimuli, LeX modification reduces the required amount 100-fold and obviates its dependence on TLR signaling. The OVA-LeX-induced enhancement of T cell cross-priming is MGL1-dependent as shown by reduced CD8+ effector T cell frequencies in MGL1-deficient mice. Moreover, MGL1-mediated cross-presentation of OVA-LeX neither required TAP-transporters nor Cathepsin-S and was still observed after prolonged intracellular storage of antigen in Rab11+LAMP1+ compartments. We conclude that controlled neo-glycosylation of antigens can crucially influence intracellular routing of antigens, the nature and strength of immune responses and should be considered for optimizing current vaccination strategies. DOI: http://dx.doi.org/10.7554/eLife.11765.001 PMID:26999763

  19. Serum Albumin Alters the Expression of Pseudomonas Aeruginosa Iron Controlled Genes

    USDA-ARS?s Scientific Manuscript database

    The objectives of this study were to examine the effect serum on global transcription within P. aeruginosa at different phases of growth and the role of iron in this regulation. Results presented in this study suggest a novel mechanism through which serum regulates the expression of different P. ae...

  20. Serum proteases alter the antigenicity of peptides presented by class I major histocompatibility complex molecules.

    PubMed Central

    Falo, L D; Colarusso, L J; Benacerraf, B; Rock, K L

    1992-01-01

    Any effect of serum on the antigenicity of peptides is potentially relevant to their use as immunogens in vivo. Here we demonstrate that serum contains distinct proteases that can increase or decrease the antigenicity of peptides. By using a functional assay, we show that a serum component other than beta 2-microglobulin enhances the presentation of ovalbumin peptides produced by cyanogen bromide cleavage. Three features of this serum activity implicate proteolysis: it is temperature dependent, it results in increased antigenicity in a low molecular weight peptide fraction, and it is inhibited by the protease inhibitor leupeptin. Conversely, presentation of the synthetic peptide OVA-(257-264) is inhibited by serum. This inhibition is unaffected by leupeptin but is blocked by bestatin, a protease inhibitor with distinct substrate specificities. Implications for peptide-based vaccine design and immunotherapy are discussed. PMID:1518868

  1. c-Myc Alters Substrate Utilization and O-GlcNAc Protein Posttranslational Modifications without Altering Cardiac Function during Early Aortic Constriction

    PubMed Central

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.

    2015-01-01

    Hypertrophic stimuli cause transcription of the proto-oncogene c-Myc (Myc). Prior work showed that myocardial knockout of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we assessed the interplay between Myc, substrate oxidation and cardiac function during early pressure overload hypertrophy. Mice with cardiac specific, inducible Myc knockout (MycKO-TAC) and non-transgenic littermates (Cont-TAC) were subjected to transverse aortic constriction (TAC; n = 7/group). Additional groups underwent sham surgery (Cont-Sham and MycKO-Sham, n = 5 per group). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. In sham hearts, Myc knockout did not affect cardiac function or substrate preferences for the citric acid cycle. However, Myc knockout altered fractional contributions during TAC. The unlabeled fractional contribution increased in MycKO-TAC versus Cont-TAC, whereas ketone and free fatty acid fractional contributions decreased. Additionally, protein posttranslational modifications by O-GlcNAc were significantly greater in Cont-TAC versus both Cont-Sham and MycKO-TAC. In conclusion, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy, which may regulate Myc-induced metabolic changes. PMID:26266538

  2. c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

    DOE PAGES

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; ...

    2015-08-12

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated workingmore » hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.« less

  3. c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

    SciTech Connect

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.; Bertrand, Luc

    2015-08-12

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.

  4. Evidence of bovine serum albumin-viologen herbicide binding interaction and associated structural modifications

    NASA Astrophysics Data System (ADS)

    Roy, Swarup; Saxena, Shailendra K.; Mishra, Suryakant; Yogi, Priyanka; Sagdeo, P. R.; Kumar, Rajesh

    2017-07-01

    The binding ability of viologen herbicide with bovine serum albumin (BSA) has been investigated to understand viologen associated hazards by investigating ethyl viologen's (EV) binding using various spectroscopies and in-silico molecular docking approaches. Apparent association constant (1.3 × 104 L/mol), calculated using UV-Vis spectra indicating a moderate complex formation between BSA and EV. A static mode of fluorescence quenching has been observed as evident from inverse temperature dependence of Stern-Volmer quenching constant which also confirms an EV-BSA complex formation. Emission and time resolved fluorescence studies reveal that the emission quenching of BSA with EV is initiated by static quenching mechanism. A moderately strong binding affinity between EV and BSA has been observed (binding constant value of 7.58 × 104 L/Mol) using fluorescence quenching titration, obtained at 298 K. Quantitative measurements of thermodynamic parameters like enthalpy and entropy changes clearly indicates hydrophobic force responsible for EV-BSA complex formation. The binding distance between EV and BSA was found to be 4.48 nm are involved in non-radiative energy transfer process. Furthermore, from the circular dichroism spectra it was observed that addition of EV is also found to change the secondary structure of BSA which leads to decrease in α-helix. Above mentioned results are found to be in consonance with molecular docking simulations and supports the EV-BSA binding.

  5. Structural modification of serum vitamin D3-binding protein and immunosuppression in AIDS patients.

    PubMed

    Yamamoto, N; Naraparaju, V R; Srinivasula, S M

    1995-11-01

    A serum glycoprotein, vitamin D3-binding protein (Gc protein), can be converted by beta-galactosidase of stimulated B lymphocytes and sialidase of T lymphocytes to a potent macrophage-activating factor (MAF), a protein with N-acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is a precursor for MAF. Treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generates an extremely high-titered MAF (GcMAF). When peripheral blood monocytes/macrophages of 46 HIV-infected patients were treated with GcMAF (100 pg/ml), the monocytes/macrophages of all patients were efficiently activated. However, the MAF precursor activity of plasma Gc protein was low in 16 (35%) of of these patients. Loss of the MAF precursor activity appeared to be due to deglycosylation of plasma Gc protein by alpha-N-acetylgalactosaminidase found in the patient blood stream. Levels of plasma alpha-N-acetylgalactosaminidase activity in individual patients had an inverse correlation with the MAF precursor activity of their plasma Gc protein. Thus, precursor activity of Gc protein and alpha-N-acetylgalactosaminidase activity in patient blood can serve as diagnostic and prognostic indices.

  6. Oxidative modification of blood serum proteins in multiple sclerosis after interferon or mitoxantrone treatment.

    PubMed

    Sadowska-Bartosz, Izabela; Adamczyk-Sowa, Monika; Gajewska, Agnieszka; Bartosz, Grzegorz

    2014-01-15

    This study was aimed at (i) comparison of the usefulness of serum protein oxidation parameters for assessment of oxidative stress (OS) in multiple sclerosis (MS), and (ii) comparison of OS in MS patients subject to various therapies. Elevated glycophore level was noted in relapsing-remitting (RRMS) patients without treatment and patients treated with interferons β1a and β1b (10.33±3.27, 8.02±2.22 and 8.56±2.45 vs control 5.27±0.73 fluorescence units (FU)/mg protein). Advanced oxidation protein products (295±135 vs 83±65nmol/mg protein), carbonyl groups (3.68±1.44nmol/mg protein vs 2.03±0.23nmol/mg protein), kynurenine (7.71±0.1.67 vs 5.5±0.63 FU/mg protein) and N'-formylkynurenine (7.69±0.7 vs 4.97±0.59 FU/mg protein) levels were increased, while thioredoxin level was decreased in RRMS patients without treatment (5.03±2.18 vs 10.83±2.75ng/ml) with respect to control. The level of OS was higher in untreated RRMS patients and in SPMS patients treated with mitoxantrone than in patients treated with interferon.

  7. Serum lipids and arterial plaque load are altered independently with high-dose progesterone in hypercholesterolemic male rabbits.

    PubMed

    Houser, S L; Aretz, H T; Quist, W C; Chang, Y; Schreiber, A D

    2000-01-01

    Antiatherogenic effects of sex steroids in premenopausal women are not well defined. Therefore, we employed an established rabbit model for atherosclerosis to study the effects of exogenous estrogen and a progesterone analogue (P) on serum lipids and aortic plaque load. Serum cholesterol (C) and triglyceride (T) levels and atherosclerotic plaque loads were compared in 5 groups of male New Zealand White rabbits fed a 12-week, C-rich diet: 1 control group (CG) and 4 groups treated with estriol (E), haloperidol (H), low-dose 17-hydroxyprogesterone (LDP), or high-dose 17-hydroxyprogesterone (HDP). Serum P was measured in the LDP and HDP groups. Serial histologic sections (15 each of 27 ascending aortas) were studied by light microscopy and computerized morphometric analysis. Plaque load is defined as the ratio of intimal area to medial area (I/M). Exogenous E (p<0.001), H (P = 0. 02), LDP and HDP (P<0.001, each) were found to be significantly associated with less aortic plaque load than controls. In a multivariate analysis, after controlling for the differences in serum C and T levels, HDP (p = 0.014) was found to be associated with less aortic plaque load than controls, and this association approached statistical significance in the E (p = 0.052) and H (p = 0.069) groups. These data suggest that the mechanism(s) involved with the antiatherogenic effect of HDP in this animal model is, or are, independent of an alteration in serum lipids.

  8. Alteration of serum and cardiac tissue adropin, copeptin, irisin and TRPM2 expressions in DOX treated male rats.

    PubMed

    Aydin, S; Eren, M N; Kuloglu, T; Aydin, S; Yilmaz, M; Gul, E; Kalayci, M; Yel, Y; Cakmak, T; Bico, S

    2015-04-01

    Doxorubicin (DOX) cardiotoxicity is a significant side effect in cancer survivors. DOX and its metabolites alter cardiac gene expression and affect metabolic energy-related peptides. Adropin, copeptin, irisin and TRPM2 are produced locally in the heart and play a role in energy homeostasis. We investigated the fates of adropin, copeptin, irisin and TRPM2 in serum and cardiac tissues of DOX treated rats. Animals were divided into three groups of six: 1) untreated controls, 2) DOX treated and 3) saline treated. The rats were fed a standard diet ad libitum for 14 days then were sacrificed and heart and serum samples were taken. Adropin, copeptin, irisin levels in tissue homogenates and serum were measured using ELISA. Immunoreactivity of heart tissue adropin, copeptin, irisin and TRPM2 also were investigated. The peptides increased in both serum and cardiac tissue homogenates in animals treated with DOX compared to the other groups. DOX increased adropin in endocardial and myocardial cells, but it decreased expression of copeptin. DOX did not affect endocardial irisin and TRPM2 expressions, but myocardial irisin and TRPM2 expressions were increased. Serum adropin, irisin and copeptin were increased in DOX treated rats. Cardiac adropin, copeptin, irisin and TRPM2 are affected by DOX and may play a role in DOX cardiotoxicity.

  9. Cell wall modifications in Arabidopsis plants with altered alpha-L-arabinofuranosidase activity.

    PubMed

    Chávez Montes, Ricardo A; Ranocha, Philippe; Martinez, Yves; Minic, Zoran; Jouanin, Lise; Marquis, Mélanie; Saulnier, Luc; Fulton, Lynette M; Cobbett, Christopher S; Bitton, Frédérique; Renou, Jean-Pierre; Jauneau, Alain; Goffner, Deborah

    2008-05-01

    Although cell wall remodeling is an essential feature of plant growth and development, the underlying molecular mechanisms are poorly understood. This work describes the characterization of Arabidopsis (Arabidopsis thaliana) plants with altered expression of ARAF1, a bifunctional alpha-L-arabinofuranosidase/beta-D-xylosidase (At3g10740) belonging to family 51 glycosyl-hydrolases. ARAF1 was localized in several cell types in the vascular system of roots and stems, including xylem vessels and parenchyma cells surrounding the vessels, the cambium, and the phloem. araf1 T-DNA insertional mutants showed no visible phenotype, whereas transgenic plants that overexpressed ARAF1 exhibited a delay in inflorescence emergence and altered stem architecture. Although global monosaccharide analysis indicated only slight differences in cell wall composition in both mutant and overexpressing lines, immunolocalization experiments using anti-arabinan (LM6) and anti-xylan (LM10) antibodies indicated cell type-specific alterations in cell wall structure. In araf1 mutants, an increase in LM6 signal intensity was observed in the phloem, cambium, and xylem parenchyma in stems and roots, largely coinciding with ARAF1 expression sites. The ectopic overexpression of ARAF1 resulted in an increase in LM10 labeling in the secondary walls of interfascicular fibers and xylem vessels. The combined ARAF1 gene expression and immunolocalization studies suggest that arabinan-containing pectins are potential in vivo substrates of ARAF1 in Arabidopsis.

  10. Cell Wall Modifications in Arabidopsis Plants with Altered α-l-Arabinofuranosidase Activity[C][W

    PubMed Central

    Chávez Montes, Ricardo A.; Ranocha, Philippe; Martinez, Yves; Minic, Zoran; Jouanin, Lise; Marquis, Mélanie; Saulnier, Luc; Fulton, Lynette M.; Cobbett, Christopher S.; Bitton, Frédérique; Renou, Jean-Pierre; Jauneau, Alain; Goffner, Deborah

    2008-01-01

    Although cell wall remodeling is an essential feature of plant growth and development, the underlying molecular mechanisms are poorly understood. This work describes the characterization of Arabidopsis (Arabidopsis thaliana) plants with altered expression of ARAF1, a bifunctional α-l-arabinofuranosidase/β-d-xylosidase (At3g10740) belonging to family 51 glycosyl-hydrolases. ARAF1 was localized in several cell types in the vascular system of roots and stems, including xylem vessels and parenchyma cells surrounding the vessels, the cambium, and the phloem. araf1 T-DNA insertional mutants showed no visible phenotype, whereas transgenic plants that overexpressed ARAF1 exhibited a delay in inflorescence emergence and altered stem architecture. Although global monosaccharide analysis indicated only slight differences in cell wall composition in both mutant and overexpressing lines, immunolocalization experiments using anti-arabinan (LM6) and anti-xylan (LM10) antibodies indicated cell type-specific alterations in cell wall structure. In araf1 mutants, an increase in LM6 signal intensity was observed in the phloem, cambium, and xylem parenchyma in stems and roots, largely coinciding with ARAF1 expression sites. The ectopic overexpression of ARAF1 resulted in an increase in LM10 labeling in the secondary walls of interfascicular fibers and xylem vessels. The combined ARAF1 gene expression and immunolocalization studies suggest that arabinan-containing pectins are potential in vivo substrates of ARAF1 in Arabidopsis. PMID:18344421

  11. Association of Type 2 Diabetes Mellitus related SNP genotypes with altered serum adipokine levels and metabolic syndrome phenotypes

    PubMed Central

    Al-Daghri, Nasser M; Al-Attas, Omar S; Krishnaswamy, Soundararajan; Mohammed, Abdul Khader; Alenad, Amal M; Chrousos, George P; Alokail, Majed S

    2015-01-01

    The pathogenesis of T2DM involves secretion of several pro-inflammatory molecules by the dramatically increased adipocytes, both by number and size, and associated macrophages of adipose tissue. Since T2DM is usually preceded by obesity and chronic systemic inflammation, the objective of this study was to explore for any association between genetic variants of previously established 36 T2DM-associated SNPs and altered serum adipocytokine levels and metabolic syndrome phenotypes. Study consisted of 566 subjects (284 males and 282 females) of whom 147 were T2DM patients and 419 healthy controls. Study subjects were genotyped for 36 T2DM-linked single nucleotide polymorphisms (SNPs) using the KASPar SNP Genotyping System and grouped into different genotypes for each SNP. Various anthropometric and biochemical parameters were measured following standard procedures. The mean values of serum levels of individual adipocytokines and the presence/absence of metabolic syndrome phenotypes corresponding to various genotypes were compared by determining the odds ratios. Genotypic variants of five and seven of the 36 T2DM-related SNPs were significantly associated with altered serum levels of adiponectin and aPAI, respectively. Six variants of the 36 SNPs were associated with metabolic syndrome manifestations. This study identified positive associations between genotypic variants of five and seven of the 36 T2DM related SNPs and altered serum levels of adiponectin and aPAI, respectively. Six of 36 SNPs were also associated with metabolic syndrome in the studied population. The relation between specific SNPs and individual phenotypic traits may be useful in explaining the causal mechanisms of hereditary component of T2DM. PMID:26064370

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

    ERIC Educational Resources Information Center

    Cohen, Jonathan C.; And Others

    1986-01-01

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

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

    ERIC Educational Resources Information Center

    Cohen, Jonathan C.; And Others

    1986-01-01

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

  14. Effectiveness of a low-fat vegetarian diet in altering serum lipids in healthy premenopausal women.

    PubMed

    Barnard, N D; Scialli, A R; Bertron, P; Hurlock, D; Edmonds, K; Talev, L

    2000-04-15

    Few controlled trials have studied cholesterol-lowering diets in premenopausal women. None has examined the cholesterol-lowering effect of a low-fat vegetarian diet, which, in other population groups, leads to marked reductions in serum cholesterol concentrations and, in combination with other life-style changes, a regression of atherosclerosis. We tested the hypothesis that a low-fat, vegetarian diet significantly reduces serum total and low-density lipoprotein (LDL) cholesterol concentrations in premenopausal women. In a crossover design, 35 women, aged 22 to 48, followed a low-fat vegetarian diet deriving approximately 10% of energy from fat for 2 menstrual cycles. For 2 additional cycles, they followed their customary diet while also taking a "supplement" (placebo) pill. Serum lipid concentrations were assessed at baseline and during each intervention phase. Mean serum LDL, high-density lipoprotein (HDL), and total cholesterol concentrations decreased 16. 9%, 16.5%, and 13.2%, respectively, from baseline to the intervention diet phase (p<0.001), whereas mean serum triacylglycerol concentration increased 18.7% (p<0.01). LDL/HDL ratio remained unchanged. Thus, in healthy premenopausal women, a low-fat vegetarian diet led to rapid and sizable reductions in serum total, LDL, and HDL cholesterol concentrations.

  15. The posttranslational modification cascade to the thiopeptide berninamycin generates linear forms and altered macrocyclic scaffolds.

    PubMed

    Malcolmson, Steven J; Young, Travis S; Ruby, J Graham; Skewes-Cox, Peter; Walsh, Christopher T

    2013-05-21

    Berninamycin is a member of the pyridine-containing thiopeptide class of antibiotics that undergoes massive posttranslational modifications from ribosomally generated preproteins. Berninamycin has a 2-oxazolyl-3-thiazolyl-pyridine core embedded in a 35-atom macrocycle rather than typical trithiazolylpyridine cores embedded in 26-atom and 29-atom peptide macrocycles. We describe the cloning of an 11-gene berninamycin cluster from Streptomyces bernensis UC 5144, its heterologous expression in Streptomyces lividans TK24 and Streptomyces venezuelae ATCC 10712, and detection of variant and incompletely processed scaffolds. Posttranslational maturation in S. lividans of both the wild-type berninamycin prepeptide (BerA) and also a T3A mutant generates macrocyclic compounds as well as linear variants, which have failed to form the pyridine and the macrocycle. Expression of the gene cluster in S. venezuelae generates a variant of the 35-atom skeleton of berninamycin, containing a methyloxazoline in the place of a methyloxazole within the macrocyclic framework.

  16. The posttranslational modification cascade to the thiopeptide berninamycin generates linear forms and altered macrocyclic scaffolds

    PubMed Central

    Malcolmson, Steven J.; Young, Travis S.; Ruby, J. Graham; Skewes-Cox, Peter; Walsh, Christopher T.

    2013-01-01

    Berninamycin is a member of the pyridine-containing thiopeptide class of antibiotics that undergoes massive posttranslational modifications from ribosomally generated preproteins. Berninamycin has a 2-oxazolyl-3-thiazolyl-pyridine core embedded in a 35-atom macrocycle rather than typical trithiazolylpyridine cores embedded in 26-atom and 29-atom peptide macrocycles. We describe the cloning of an 11-gene berninamycin cluster from Streptomyces bernensis UC 5144, its heterologous expression in Streptomyces lividans TK24 and Streptomyces venezuelae ATCC 10712, and detection of variant and incompletely processed scaffolds. Posttranslational maturation in S. lividans of both the wild-type berninamycin prepeptide (BerA) and also a T3A mutant generates macrocyclic compounds as well as linear variants, which have failed to form the pyridine and the macrocycle. Expression of the gene cluster in S. venezuelae generates a variant of the 35-atom skeleton of berninamycin, containing a methyloxazoline in the place of a methyloxazole within the macrocyclic framework. PMID:23650400

  17. Modifications to the NIST reference measurement procedure (RMP) for the determination of serum glucose by isotope dilution gas chromatography/mass spectrometry.

    PubMed

    Prendergast, Jocelyn L; Sniegoski, Lorna T; Welch, Michael J; Phinney, Karen W

    2010-07-01

    The definitive method (DM), now known as the reference measurement procedure (RMP), for the analysis of glucose in serum was originally published in 1982 by the National Institute of Standards and Technology (NIST). Over the years the method has been subject to a number of modifications to adapt to newer technologies and simplify sample preparation. We discuss here an adaptation of the method associated with serum glucose measurements using a modified isotope dilution gas chromatography/mass spectrometry (ID-GC/MS) method. NIST has used this modified method to certify the concentrations of glucose in SRM 965b, Glucose in Frozen Human Serum, and SRM 1950, Metabolites in Human Plasma. Comparison of results from the revised method with certified values for existing Standard Reference Materials (SRMs) demonstrated that these modifications have not affected the quality of the measurements, giving both good precision and accuracy, while reducing the sample preparation time by a day and a half.

  18. Physical and chemical modifications of surface properties lead to alterations in osteoblast behavior

    NASA Astrophysics Data System (ADS)

    Dorst, Kathryn Elizabeth

    Proper formation of the bone extracellular matrix (ECM), or osteoid, depends on the surface properties of pre-existing tissue and the aqueous chemical environment. Both of these factors greatly influence osteoblast migration, cytoskeletal organization, and calcium nodule production, important aspects when considering the biocompatibility of bone implants. By perturbing the physical and/or chemical micro-environment, it may be possible to elucidate effects on cellular function. To examine these factors, murine pre-osteoblasts (MC3T3-E1 subclones 4 and 24) were seeded on polydimethylsiloxane (PDMS) substrates containing "wide" micro-patterned ridges (20 mum width, 30 mum pitch, & 2 mum height), "narrow" micro-patterned ridges (2 mum width, 10 mum pitch, 2 mum height), no patterns (flat PDMS), and standard tissue culture (TC) polystyrene as a control. Zinc concentration was adjusted to mimic deficient (0.23 muM), serum-level (3.6 muM), and zinc-rich (50 muM) conditions. It was found that cells exhibited distinct anisotropic migration in serum-level zinc and zinc-deficient media on the wide PDMS patterns, however this was disrupted under zinc-rich conditions. Production of differentiation effectors, activated metalloproteinase-2 (MMP-2) and transforming growth factor - beta 1 (TGF-beta1), was increased with the addition of exogenous zinc. Early stage differentiation, via alkaline phosphatase, was modified by zinc levels on patterned polydimethylsiloxane (PDMS) surfaces, but not on flat PDMS or tissue culture polystyrene (TC). Late stage differentiation, visualized through calcium phosphate nodules, was markedly different at various zinc levels when the cells were cultured on TC substrates. This susceptibility to zinc content can lead to differences in bone mineral production on certain substrates if osteoblasts are not able to maintain and remodel bone effectively, a process vital to successful biomaterial integration.

  19. Serum alters the uptake and relative potencies of halogenated aromatic hydrocarbons in cell culture bioassays.

    PubMed

    Hestermann, E V; Stegeman, J J; Hahn, M E

    2000-02-01

    The effects of many chemicals on cellular processes are governed by their ability to enter the cell, which is in turn a function of the composition of the cell's external environment. To examine this relationship, the effect of serum in cell culture medium on the bioavailability of cytochrome P450 1A (CYP1A)-inducing compounds was determined in PLHC-1 (Poeciliopsis lucida hepatocellular carcinoma) cells. The presence of 10% calf serum in the medium increased the EC50 (effective concentration to achieve 50% maximal response) for induction of ethoxyresorufin O-deethylase (EROD) activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 20-fold as compared to treatment in serum-free medium. Measurement of [3H]TCDD uptake and Ah receptor binding indicated that the apparent difference in potencies was a result of decreased bioavailability in the presence of serum, effectively reducing the concentration of TCDD within the cells. Induction of EROD and CYP1A protein in response to treatment with each of three coplanar polychlorinated biphenyls (PCB congeners 77, 126, and 169) was similarly affected by serum, although the magnitude varied among inducers and assays. Relative potencies (calculated as EC50TCDD / EC50PCB) for EROD induction by the three PCBs were significantly higher in the absence of serum. However, serum showed no significant effect on the relative potencies for CYP1A protein induction. These results demonstrate that measured inducing potencies, and relative potencies for EROD induction, by halogenated aromatic hydrocarbons are strongly dependent on the composition of culture medium, which can lead to artificial differences in comparisons among cell types.

  20. Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels.

    PubMed

    Peng, Xian-E; Wu, Yun-Li; Zhu, Yi-Bing; Huang, Rong-Dong; Lu, Qing-Qing; Lin, Xu

    2015-01-01

    Liver fatty acid-binding protein (L-FABP), also known as fatty acid-binding protein 1 (FABP1), is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD) and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs) of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182) from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032).Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05). The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01). In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (β = -0.320, P = 0.003), while serum TG levels were positively associated with serum FABP1 levels (β = 0.487, P = 0.014). Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans.

  1. Regulation of heat shock protein message in Jurkat cells cultured under serum-starved and gravity-altered conditions

    NASA Technical Reports Server (NTRS)

    Lewis, M. L.; Hughes-Fulford, M.

    2000-01-01

    Although our understanding of effects of space flight on human physiology has advanced significantly over the past four decades, the potential contribution of stress at the cellular and gene regulation level is not characterized. The objective of this ground-based study was to evaluate stress gene regulation in cells exposed to altered gravity and environmentally suboptimal conditions. We designed primers to detect message for both the constitutive and inducible forms of the heat shock protein, HSP-70. Applying the reverse transcriptase-polymerase chain reaction (RT-PCR), we probed for HSP-70 message in human acute T-cell leukemia cells, Jurkat, subjected to three types of environmental stressors: (1) altered gravity achieved by centrifugation (hypergravity) and randomization of the gravity vector in rotating bioreactors, (2) serum starvation by culture in medium containing 0.05% serum, and (3) temperature elevation (42 degrees C). Temperature elevation, as the positive control, significantly increased HSP-70 message, while centrifugation and culture in rotating bioreactors did not upregulate heat shock gene expression. We found a fourfold increase in heat shock message in serum-starved cells. Message for the housekeeping genes, actin and cyclophilin, were constant and comparable to unstressed controls for all treatments. We conclude that gravitational perturbations incurred by centrifugal forces, exceeding those characteristic of a Space Shuttle launch (3g), and culture in rotating bioreactors do not upregulate HSP-70 gene expression. In addition, we found RT-PCR useful for evaluating stress in cultured cells. Copyright 2000 Wiley-Liss, Inc.

  2. Altered characteristics of silica nanoparticles in bovine and human serum: the importance of nanomaterial characterization prior to its toxicological evaluation

    PubMed Central

    2013-01-01

    Background Many toxicological studies on silica nanoparticles (NPs) have been reported, however, the literature often shows various conclusions concerning the same material. This is mainly due to a lack of sufficient NPs characterization as synthesized as well as in operando. Many characteristics of NPs may be affected by the chemistry of their surroundings and the presence of inorganic and biological moieties. Consequently, understanding the behavior of NPs at the time of toxicological assay may play a crucial role in the interpretation of its results. The present study examines changes in properties of differently functionalized fluorescent 50 nm silica NPs in a variety of environments and assesses their ability to absorb proteins from cell culture medium containing either bovine or human serum. Methods The colloidal stability depending on surface functionalization of NPs, their concentration and time of exposure was investigated in water, standard biological buffers, and cell culture media by dynamic light scattering (DLS), zeta potential measurements and transmission electron microscopy (TEM). Interactions of the particles with biological media were investigated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in bovine and human serum, and extracted proteins were assessed using matrix-assisted laser desorption/ionization-time of flight technique (MALDI-TOF). Results It was recognized that all of the studied silica NPs tended to agglomerate after relatively short time in buffers and biological media. The agglomeration depended not only on the NPs functionalization but also on their concentration and the incubation time. Agglomeration was much diminished in a medium containing serum. The protein corona formation depended on time and functionalization of NP, and varied significantly in different types of serum. Conclusions Surface charge, ionic strength and biological molecules alter the properties of silica NPs and potentially affect

  3. Lifestyle modification and behavior therapy effectively reduce body weight and increase serum level of brain-derived neurotrophic factor in obese non-diabetic patients with schizophrenia.

    PubMed

    Kuo, Feng-Chih; Lee, Chien-Hsing; Hsieh, Chang-Hsun; Kuo, Philip; Chen, Yi-Chyan; Hung, Yi-Jen

    2013-09-30

    The goal of the study was to elucidate the relationship between serum circulating brain-derived neurotrophic factor (BDNF) and body weight reduction via lifestyle modification and behavior therapy in obese non-diabetic patients with chronic schizophrenia. Thirty-three obese non-diabetic subjects with schizophrenia treated with stable antipsychotic medication in a day-care unit for at least 3 months were recruited. Thirty age-, body weight-matched subjects without psychiatric disorders were enrolled as controls. All participants underwent a 10-week weight reduction program, including lifestyle modification, psychosocial treatment, behavior therapy and exercise in the day-care unit. Blood biochemistry, serum BDNF, adipokine (adiponectin), inflammatory markers (C-reactive protein, tumor necrosis factor-alpha and interleukin-6) and oral glucose tolerance test were evaluated before and after the program. Serum BDNF concentrations were significantly lower among patients with schizophrenia compared to control subjects. Serum BDNF levels were significantly increased following the weight reduction program. Elevations in serum BDNF levels were positively correlated with body weight and body mass index reduction. Altogether, our results demonstrate that a non-pharmacological weight reduction program effectively reduces body weight with significant elevation of serum BDNF levels in obese non-diabetic patients with schizophrenia.

  4. Insulin induced alteration in post-translational modifications of histone H3 under a hyperglycemic condition in L6 skeletal muscle myoblasts.

    PubMed

    Kabra, Dhiraj G; Gupta, Jeena; Tikoo, Kulbhushan

    2009-06-01

    Chromatin remodelling events, especially histone modifications are proposed to form the mainstay for most of the biological processes. However, the role of these histone modifications in the progression of diabetes is still unknown. Hyperglycemia plays a major role in diabetes and its complications. The present study was undertaken to check the effect of insulin on alterations in post-translational modifications of histone H3 in L6 myoblasts under a hyperglycemic condition. We provide first evidence that insulin under hyperglycemic condition alters multiple histone modifications by enhanced production of reactive oxygen species. Insulin induces dose dependent changes in Lysine 4 and 9 methylation, Ser 10 phosphorylation and acetylation of histone H3. Interestingly, insulin induced generation of reactive oxygen species induces dephosphorylation and deacetylation of histone H3. Preincubation with catalase and DPI prevents these changes in post-translational modifications of histone H3. Furthermore, changes in histone H3 phosphorylation was found to be independent of ERK, p38, RSK2 and MSK1. Moreover, serine/threonine phosphatase inhibitor, okadaic acid attenuates insulin induced dephosphorylation and deacetylation of histone H3, suggesting a role of serine/threonine phosphatases in altering modifications of histone H3. These changes in epigenetic modifications can provide new insights into pathogenesis of diabetes.

  5. Reactive oxygen species production, induced by atmospheric modification, alter conidial quality of Beauveria bassiana.

    PubMed

    Pérez-Guzmán, D; Montesinos-Matías, R; Arce-Cervantes, O; Gómez-Quiroz, L E; Loera, O; Garza-López, P M

    2016-08-01

    The aim of this study was to determine the relationship between reactive oxygen species (ROS) production and conidial infectivity in Beauveria bassiana. Beauveria bassiana Bb 882.5 was cultured in solid-state culture (SSC) using rice under three oxygen conditions (21%, or pulses at 16 and 26%). Hydrophobicity was determined using exclusion phase assay. Bioassays with larvae or adults of Tenebrio molitor allowed the measurements of infectivity parameters. A fluorometric method was used for ROS quantification (superoxide and total peroxides). NADPH oxidase (NOX) activity was determined by specific inhibition. Conidial hydrophobicity decreased by O2 pulses. Mortality of larvae was only achieved with conidia harvested from cultures under 21% O2 ; whereas for adult insects, the infectivity parameters deteriorated in conidia obtained after pulses at 16 and 26% O2 . At day 7, ROS production increased after 16 and 26% O2 treatments. NOX activity induced ROS production at early stages of the culture. Modification of atmospheric oxygen increases ROS production, reducing conidial quality and infectivity. This is the first study in which conidial infectivity and ROS production in B. bassiana has been related, enhancing the knowledge of the effect of O2 pulses in B. bassiana. © 2016 The Society for Applied Microbiology.

  6. Structural modifications of mitochondria-targeted chlorambucil alter cell death mechanism but preserve MDR evasion.

    PubMed

    Jean, Sae Rin; Pereira, Mark P; Kelley, Shana O

    2014-08-04

    Multidrug resistance (MDR) remains one of the major obstacles in chemotherapy, potentially rendering a multitude of drugs ineffective. Previously, we have demonstrated that mitochondrial targeting of DNA damaging agents is a promising tool for evading a number of common resistance factors that are present in the nucleus or cytosol. In particular, mitochondria-targeted chlorambucil (mt-Cbl) has increased potency and activity against resistant cancer cells compared to the parent compound chlorambucil (Cbl). However, it was found that, due to its high reactivity, mt-Cbl induces a necrotic type of cell death via rapid nonspecific alkylation of mitochondrial proteins. Here, we demonstrate that by tuning the alkylating activity of mt-Cbl via chemical modification, the rate of generation of protein adducts can be reduced, resulting in a shift of the cell death mechanism from necrosis to a more controlled apoptotic pathway. Moreover, we demonstrate that all of the modified mt-Cbl compounds effectively evade MDR resulting from cytosolic GST-μ upregulation by rapidly accumulating in mitochondria, inducing cell death directly from within. In this study, we systematically elucidated the advantages and limitations of targeting alkylating agents with varying reactivity to mitochondria.

  7. Angiopoietin-1 alters microvascular permeability coefficients in vivo via modification of endothelial glycocalyx.

    PubMed

    Salmon, Andrew H J; Neal, Christopher R; Sage, Leslie M; Glass, Catherine A; Harper, Steven J; Bates, David O

    2009-07-01

    In this study, we wished to determine whether angiopoietin-1 (Ang1) modified the permeability coefficients of non-inflamed, intact continuous, and fenestrated microvessels in vivo and to elucidate the underlying cellular mechanisms. Permeability coefficients were measured using the Landis-Michel technique (in frog and rat mesenteric microvessels) and an oncopressive permeability technique (in glomeruli). Ang1 decreased water permeability (L(P): hydraulic conductivity) in continuous and fenestrated microvessels and increased the retention of albumin (sigma: reflection coefficient) in continuous microvessels. Endothelial glycocalyx is common to these anatomically distinct microvascular beds, and contributes to the magnitude of both L(P) and sigma. Ang1 treatment increased the depth of endothelial glycocalyx in intact microvessels and increased the content of glycosaminoglycan of cultured microvascular endothelial cell supernatant. Ang1 also prevented the pronase-induced increase in L(P) (attributable to selective removal of endothelial glycocalyx by pronase) by restoration of glycocalyx at the endothelial cell surface. The reduction in permeability was inhibited by a cell transport inhibitor, Brefeldin. Ang1 modifies basal microvessel permeability coefficients, in keeping with previous reports demonstrating reduced solute flux in inflamed vessels. Anatomical, biochemical, and physiological evidence indicates that modification of endothelial glycocalyx is a novel mechanism of action of Ang1 that contributes to these effects.

  8. 3D geometry and hydrodynamic modifications in fractured and porous rock samples through chemical alterations.

    NASA Astrophysics Data System (ADS)

    Noiriel, C. N.

    2011-12-01

    Fractured and porous rocks are the principal path for water flow and potential contamination. Modification of fracture topology and transmissivity by reactive fluids is an important and complex geological process. In carbonate rocks, fractures and porous media properties may change quickly and strongly due to natural processes (e.g. karstification, salt intrusion) or anthropogenic practice (e.g. CO2 geological sequestration). Recent application of X-ray micro-tomography to the Earth Sciences, which allows the visualization of 3D objects with a micrometre resolution, has considerably increased experimental capability by giving access to a 4D spatio-temporal vision (3D geometry + time) of the physical-chemical processes within the rocks. New information is now accessible, which provides a better understanding of the processes and allows the numerical models to be better constrained. I will present the application of X-ray micro-tomography to study changes of petrophysical properties (e.g. porosity, permeability, mineral surface area, etc.) of fractured and porous rocks in response to fluid-rock interactions (dissolution and precipitation). Experimental results will be discussed in regard to numerical modelling of flow and transport. Keywords: X-ray micro-tomography, fracture, porous media, dissolution, precipitation, carbon dioxide sequestration, limestone, reactive surface, geochemical modelling,

  9. Biomimeticity in tissue engineering scaffolds through synthetic peptide modifications-altering chemistry for enhanced biological response.

    PubMed

    Sreejalekshmi, Kumaran G; Nair, Prabha D

    2011-02-01

    Biomimetic and bioactive biomaterials are desirable as tissue engineering scaffolds by virtue of their capability to mimic natural environments of the extracellular matrix. Biomimeticity has been achieved by the incorporation of synthetic short peptide sequences into suitable materials either by surface modification or by bulk incorporation. Research in this area has identified several novel synthetic peptide segments, some of them with cell-specific interactions, which may serve as potential candidates for use in explicit tissue applications. This review focuses on the developments and prospective directions of incorporating short synthetic peptide sequences onto scaffolds for tissue engineering, with emphasis on the chemistry of peptide immobilization and subsequent cell responses toward modified scaffolds. The article provides a decision-tree-type flow chart indicating the most probable cellular events on a given peptide-modified scaffold along with the consolidated list of synthetic peptide sequences, supports as well as cell types used in various tissue engineering studies, and aims to serve as a quick reference guide to peptide chemists and material scientists interested in the field.

  10. The presence of serum alters the properties of iron oxide nanoparticles and lowers their accumulation by cultured brain astrocytes

    NASA Astrophysics Data System (ADS)

    Geppert, Mark; Petters, Charlotte; Thiel, Karsten; Dringen, Ralf

    2013-01-01

    Iron oxide nanoparticles (IONPs) are considered for various diagnostic and therapeutic applications. Such particles are able to cross the blood-brain barrier and are taken up into brain cells. To test whether serum components affect the properties of IONPs and/or their uptake into brain cells, we have incubated dimercaptosuccinate-coated magnetic IONPs without and with fetal calf serum (FCS) and have exposed cultured brain astrocytes with IONPs in the absence or presence of FCS. Incubation with FCS caused a concentration-dependent increase in the average hydrodynamic diameter of the particles and of their zeta-potential. In the presence of 10 % FCS, the diameter of the IONPs increased from 57 ± 2 to 107 ± 6 nm and the zeta-potential of the particles from -22 ± 5 to -9 ± 1 mV. FCS affected also strongly the uptake of IONPs by cultured astrocytes. The efficient time- and temperature-dependent cellular accumulation of IONPs was lowered with increasing concentration of FCS by up to 90 %. In addition, in the absence of serum, endocytosis inhibitors did not alter the IONP accumulation by astrocytes, while chlorpromazine or wortmannin lowered significantly the accumulation of IONPs in the presence of FCS, suggesting that clathrin-mediated endocytosis and macropinocytosis are involved in astrocytic IONP uptake from serum-containing medium. These data demonstrate that the presence of FCS strongly affects the properties of IONPs as well as their accumulation by cultured brain cells.

  11. Preclinical Alterations in the Serum of COL(IV)A3(-)/(-) Mice as Early Biomarkers of Alport Syndrome.

    PubMed

    Muckova, Petra; Wendler, Sindy; Rubel, Diana; Büchler, Rita; Alert, Mandy; Gross, Oliver; Rhode, Heidrun

    2015-12-04

    The efficiency of the inhibition of the angiotensin converting enzyme, the most widely used therapy for the Alport syndrome, depends on the onset of the therapy-the earlier the better. Hence, early progressive biomarkers are urgently required to allow for preclinical diagnosis, an early start of possible therapy as well as the monitoring of this therapy. In the present study, an improved comprehensive and precise proteomic approach has been applied to the serum of juvenile Alport-mice, nontreated and treated, and wild-type controls of various ages to search for biomarkers. With a total of 2542 stringently altered proteins, the serum composition clearly shows a dependency on age, that is, stage, and therapy. Initially, the serum constituents indicate an enhanced extracellular matrix remodeling, cell damage, and the production of particular acute phase proteins. A panel of 15 potential biomarker candidates has been identified. In later stages, renal filtration failure and systemic acute phase reaction determine the composition of the serum; an effect that is well-known for manifested human Alport syndrome. With a small number of mouse urine samples, for example, the proteomic results for gelsolin could be verified using ELISA. Once verified in man, these early biomarkers would allow for a sensitive and specific diagnosis of the Alport syndrome in children as well as facilitate the monitoring of a possible therapy.

  12. Galectin-7 serum levels are altered prior to the onset of pre-eclampsia.

    PubMed

    Menkhorst, E; Koga, K; Van Sinderen, M; Dimitriadis, E

    2014-04-01

    Galectins regulate many cell functions important for placental development, however, the localization and role of galectin-7 is unknown. We hypothesized galectin-7 would be expressed by the placenta and detected in serum. Galectin-7 immunolocalized to syncytiotrophoblast, extravillous trophoblast and glandular epithelium in 1st trimester placenta/decidua and to syncytiotrophoblast and endothelial cells in term placenta, but in pre-eclamptic placentas endothelial staining was absent. Galectin-7 serum concentration was significantly elevated in women (weeks 10-12 and 17-20) who subsequently developed pre-eclampsia compared to women with healthy pregnancies. Galectin-7 is a promising prospective serum biomarker for pre-eclampsia and likely has important functions in placentation.

  13. Alteration of serum lipid profile and its prognostic value in head and neck squamous cell carcinoma.

    PubMed

    Li, Gang; Da, Mingjie; Zhang, Wei; Wu, Heming; Ye, Jinhai; Chen, Jie; Ma, Lu; Gu, Ning; Wu, Yunong; Song, Xiaomeng

    2016-03-01

    Several serum lipid components have been implicated in the development of cancer. However, the prognostic significance of serum lipid components in head and neck squamous cell carcinoma is unknown. Here, we investigated the predictive value of serum lipid profile at diagnosis and in the overall survival of the patients. The study population consists of 136 pathologically confirmed head and neck squamous cell carcinoma cases diagnosed between years 2009 and 2014 at a tertiary medical center. Levels of preoperative serum lipid component's total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, apolipoprotein A, apolipoprotein B, and lipoprotein (a) were compared between patients and normal controls matched for age and gender. Serum lipid profiles and their association with clinical parameters were analyzed. The effects of the serum lipid components on survival were examined using the proportional hazards regression model to estimate hazard ratio. Significant lower levels of cholesterol, low-density lipoprotein, apolipoprotein A, and apolipoprotein B were found in patients with oral cancer (P < 0.0001). However, a significantly higher level of lipoprotein (a) was found in the cancer group (P < 0.0001). Patients with higher lipoprotein (a) had significantly shorter overall survival than those with lower lipoprotein (a) (P = 0.0042). Multivariate analysis showed that both higher lipoprotein (a) and lymph node metastasis are independent prognostic factors in the patient population (P < 0.01). A higher lipoprotein (a) was associated with poorer prognosis and might be a novel marker in patients with head and neck squamous cell carcinoma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Alteration of serum inflammatory cytokines in active pulmonary tuberculosis following anti-tuberculosis drug therapy.

    PubMed

    Chowdhury, Imran Hussain; Ahmed, Albin Mostaque; Choudhuri, Subhadip; Sen, Aditi; Hazra, Avijit; Pal, Nishith Kumar; Bhattacharya, Basudev; Bahar, Bojlul

    2014-11-01

    Active pulmonary tuberculosis (APTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis (Mtb). The objective of this study was to quantify and assess the role of serum inflammatory cytokines in active pulmonary tuberculosis patients following anti-tuberculosis drug (ATD) therapy. Blood samples were collected from APTB patients and normal healthy subjects (NHS) (total n=204) at baseline and 2, 4 and 6 months post-therapy and the abundance of serum inflammatory cytokines were measured by cytokine specific ELISA. Compared to NHS, APTB patients at baseline had higher levels of serum pro-inflammatory cytokines IL-12p40 (P<0.001), IFN-γ (P<0.001), TNF-α (P<0.01), IL-1β (P<0.001) and IL-6 (P<0.001) and anti-inflammatory cytokines IL-10 (P<0.001) and TGF-β1 (P<0.001) while there was no change in the level of IL-4. In APTB patients, the serum levels of IFN-γ, TNF-α, IL-6 and TGF-β1 directly relate to the bacterial load while the TNF-α, IL-1β, IL-6 and TGF-β1 relate to radiological severity. At baseline, the IL-6 level in NHS and APTB patients differed most and following ATD therapy, this level rapidly decreased and stabilized by 4-month in APTB patients. It is concluded that a subtle reduction in the serum level of IL-6 of the APTB patients following ATD therapy might play a vital role in immune-protection of the host against Mtb infection and hence the serum IL-6 level can be a useful marker to diagnose the effectiveness of therapy in the patients.

  15. Alteration in inflammatory/apoptotic pathway and histone modifications by nordihydroguaiaretic acid prevents acute pancreatitis in swiss albino mice.

    PubMed

    Mahajan, Ujwal Mukund; Gupta, Chanchal; Wagh, Preshit Ravindra; Karpe, Pinakin Arun; Tikoo, Kulbhushan

    2011-11-01

    Reactive oxygen radicals, pro-inflammatory mediators and cytokines have been implicated in caerulein induced acute pancreatitis. Nordihydroguaiaretic acid (NDGA), a plant lignin, has marked anti-inflammatory properties. The present study aimed to investigate the possible protective effect of NDGA against caerulein induced pancreatitis. Acute pancreatitis was induced by intraperitoneal administration of eight doses of caerulein in male swiss albino mice. NDGA was administered after 9 h of acute pancreatitis induction. Pancreatic damage and the protective effect of NDGA were assessed by oxidative stress parameters and histopathology of pancreas. The mRNA expression of heat shock proteins (DNAJ C15 and HSPD1) was examined by real-time RT-PCR analysis. Expression of HSP 27, NF-κB, TNF-α, p-p38, Bcl-2, p-PP2A, procaspase-3, caspase-3 and histone modifications were examined by western blotting. NDGA attenuated the oxidative stress, led to increased plasma α-amylase and decreased IGF-1 in AP mice. It modulated the mRNA and protein levels of heat shock proteins and reduced the expression of NF-κB, TNF-α and p-p38. It increased the number of TUNEL positive apoptotic cells in the pancreas of AP mice. In addition, NDGA prevented the changes in modifications of histone H3 in acute pancreatitis. To best of our knowledge, this is the first report which suggests that NDGA prevents the progression of acute pancreatitis by involving alteration of histone H3 modifications and modulating the expression of genes involved in inflammatory/apoptotic cascade, which may be responsible for decreased necrosis and increased apoptosis in this model of acute pancreatitis.

  16. Early social deprivation impairs pair bonding and alters serum corticosterone and the NAcc dopamine system in mandarin voles.

    PubMed

    Yu, Peng; An, Shucheng; Tai, Fadao; Wang, Jianli; Wu, Ruiyong; Wang, Bo

    2013-12-01

    Early life stress has a long-term negative impact on emotion, learning, memory and adult sexual behavior, and these deficits most likely impair pair bonding. Here, we investigated whether early social deprivation (ED) affects the formation of pair bonds in socially monogamous mandarin voles (Microtus mandarinus). In a partner preference test (PPT), ED-reared adult females and males did not show a preference for their partner, spent more time exploring the cage of an unfamiliar animal and directed high levels of aggression toward unfamiliar animals. In social interaction test, ED increased exploring behavior only in females, but increased movement around the partner and reduced inactivity in both males and females. Three days of cohabitation did not alter serum corticosterone levels in ED-reared males, but increased corticosterone levels in males that received bi-parental care (PC). Interestingly, serum corticosterone levels in ED- and PC-reared females declined after cohabitation. ED significantly increased basal serum corticosterone levels in males, but had no effect on females. ED significantly up-regulated the levels of dopamine and the mRNA expression of dopamine 1-type receptor (D1R) in the nucleus accumbens (NAcc) in females and males. ED suppressed dopamine 2-type receptor mRNA (D2R) expression in females, but increased this in males. After three days of cohabitation, levels of D1R mRNA and D2R mRNA expression changed in opposite directions in PC-reared voles, but in the same direction in ED-reared males, and only the expression of D2R mRNA increased in ED-reared females. Our results indicate that early social deprivation inhibits pair bonding at adulthood. This inhibition is possibly associated with sex-specific alterations in serum corticosterone, levels of dopamine and mRNA expression of two types of dopamine receptors in the NAcc. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. The Serotonin Transporter Gene Alters Sensitivity to Attention Bias Modification: Evidence for a Plasticity Gene

    PubMed Central

    Fox, Elaine; Zougkou, Konstantina; Ridgewell, Anna; Garner, Kelly

    2011-01-01

    Background Attention bias modification (ABM) procedures have been shown to modify biased attention with important implications for emotional vulnerability and resilience. The use of ABM to reduce potentially toxic biases, for instance, is a newly emerging therapy for anxiety disorders. A separate line of gene-by-environment interaction research proposes that many so-called vulnerability genes or risk alleles are better seen as plasticity genes, as they seem to make individuals more susceptible to environmental influences for better and for worse. Methods A standard ABM procedure was used with a sample of 116 healthy adults. Participants were randomly assigned to one of two training groups. One received an ABM procedure designed to induce a bias in attention toward negative material, while the other was trained toward positive pictures. Individuals with low- and high-expressing forms of the serotonin transporter gene (5-HTTLPR) were compared. Results Those with a low-expression form (S/S, S/Lg, or Lg/Lg) of the 5-HTTLPR gene developed stronger biases for both negative and positive affective pictures relative to those with the high-expression (La/La) form of the gene. Conclusions Here, we report the first evidence that allelic variation in the promotor region of the 5-HTTLPR gene predicts different degrees of sensitivity to ABM. These results suggest a potential cognitive mechanism for the gene-by-environment interactions that have been found in relation to the serotonin transporter gene. Variation on this genotype may therefore determine who will benefit most (and least) from therapeutic interventions, adversity, and supportive environments. PMID:21840502

  18. The serotonin transporter gene alters sensitivity to attention bias modification: evidence for a plasticity gene.

    PubMed

    Fox, Elaine; Zougkou, Konstantina; Ridgewell, Anna; Garner, Kelly

    2011-12-01

    Attention bias modification (ABM) procedures have been shown to modify biased attention with important implications for emotional vulnerability and resilience. The use of ABM to reduce potentially toxic biases, for instance, is a newly emerging therapy for anxiety disorders. A separate line of gene-by-environment interaction research proposes that many so-called vulnerability genes or risk alleles are better seen as plasticity genes, as they seem to make individuals more susceptible to environmental influences for better and for worse. A standard ABM procedure was used with a sample of 116 healthy adults. Participants were randomly assigned to one of two training groups. One received an ABM procedure designed to induce a bias in attention toward negative material, while the other was trained toward positive pictures. Individuals with low- and high-expressing forms of the serotonin transporter gene (5-HTTLPR) were compared. Those with a low-expression form (S/S, S/Lg, or Lg/Lg) of the 5-HTTLPR gene developed stronger biases for both negative and positive affective pictures relative to those with the high-expression (La/La) form of the gene. Here, we report the first evidence that allelic variation in the promotor region of the 5-HTTLPR gene predicts different degrees of sensitivity to ABM. These results suggest a potential cognitive mechanism for the gene-by-environment interactions that have been found in relation to the serotonin transporter gene. Variation on this genotype may therefore determine who will benefit most (and least) from therapeutic interventions, adversity, and supportive environments. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Dietary quercetin supplementation increases serum antioxidant capacity and alters hepatic gene expression profile in rats.

    PubMed

    Zhao, Liting; Wu, Jianquan; Yang, Jijun; Wei, Jingyu; Gao, Weina; Guo, Changjiang

    2011-06-01

    The aim of this study was to determine the effect of quercetin on hepatic gene expression profile in rats. Twenty male Wistar rats were divided into the control group and the quercetin-treated group, in which a diet containing 0.5% quercetin was provided. After two weeks of feeding, serum and liver samples were collected. Biomarkers of oxidative stress, including serum ferric reducing antioxidant power (FRAP) values and levels of ascorbic acid, vitamin E (VE), glutathione (GSH) and malondialdehyde (MDA) were measured. The hepatic gene expression profile was examined using a microarray technique. The results showed that serum FRAP value, levels of ascorbic acid and VE were increased significantly, whereas serum levels of GSH and MDA were not changed significantly after quercetin supplementation. The microarray analysis revealed that some hepatic genes involved in phase 2 reaction, metabolism of cholesterol and homocysteine, and energy production were expressed differentially in response to quercetin administration. These findings provide a molecular basis for the elucidation of the actions played by quercetin in vivo.

  20. Lost at sea: ocean acidification undermines larval fish orientation via altered hearing and marine soundscape modification.

    PubMed

    Rossi, Tullio; Nagelkerken, Ivan; Pistevos, Jennifer C A; Connell, Sean D

    2016-01-01

    The dispersal of larvae and their settlement to suitable habitat is fundamental to the replenishment of marine populations and the communities in which they live. Sound plays an important role in this process because for larvae of various species, it acts as an orientational cue towards suitable settlement habitat. Because marine sounds are largely of biological origin, they not only carry information about the location of potential habitat, but also information about the quality of habitat. While ocean acidification is known to affect a wide range of marine organisms and processes, its effect on marine soundscapes and its reception by navigating oceanic larvae remains unknown. Here, we show that ocean acidification causes a switch in role of present-day soundscapes from attractor to repellent in the auditory preferences in a temperate larval fish. Using natural CO2 vents as analogues of future ocean conditions, we further reveal that ocean acidification can impact marine soundscapes by profoundly diminishing their biological sound production. An altered soundscape poorer in biological cues indirectly penalizes oceanic larvae at settlement stage because both control and CO2-treated fish larvae showed lack of any response to such future soundscapes. These indirect and direct effects of ocean acidification put at risk the complex processes of larval dispersal and settlement. © 2016 The Author(s).

  1. Probiotic Bifidobacterium longum alters gut luminal metabolism through modification of the gut microbial community

    PubMed Central

    Sugahara, Hirosuke; Odamaki, Toshitaka; Fukuda, Shinji; Kato, Tamotsu; Xiao, Jin-zhong; Abe, Fumiaki; Kikuchi, Jun; Ohno, Hiroshi

    2015-01-01

    Probiotics are well known as health-promoting agents that modulate intestinal microbiota. However, the molecular mechanisms underlying this effect remain unclear. Using gnotobiotic mice harboring 15 strains of predominant human gut-derived microbiota (HGM), we investigated the effects of Bifidobacterium longum BB536 (BB536-HGM) supplementation on the gut luminal metabolism. Nuclear magnetic resonance (NMR)-based metabolomics showed significantly increased fecal levels of pimelate, a precursor of biotin, and butyrate in the BB536-HGM group. In addition, the bioassay revealed significantly elevated fecal levels of biotin in the BB536-HGM group. Metatranscriptomic analysis of fecal microbiota followed by an in vitro bioassay indicated that the elevated biotin level was due to an alteration in metabolism related to biotin synthesis by Bacteroides caccae in this mouse model. Furthermore, the proportion of Eubacterium rectale, a butyrate producer, was significantly higher in the BB536-HGM group than in the group without B. longum BB536 supplementation. Our findings help to elucidate the molecular basis underlying the effect of B. longum BB536 on the gut luminal metabolism through its interactions with the microbial community. PMID:26315217

  2. Probiotic Bifidobacterium longum alters gut luminal metabolism through modification of the gut microbial community.

    PubMed

    Sugahara, Hirosuke; Odamaki, Toshitaka; Fukuda, Shinji; Kato, Tamotsu; Xiao, Jin-zhong; Abe, Fumiaki; Kikuchi, Jun; Ohno, Hiroshi

    2015-08-28

    Probiotics are well known as health-promoting agents that modulate intestinal microbiota. However, the molecular mechanisms underlying this effect remain unclear. Using gnotobiotic mice harboring 15 strains of predominant human gut-derived microbiota (HGM), we investigated the effects of Bifidobacterium longum BB536 (BB536-HGM) supplementation on the gut luminal metabolism. Nuclear magnetic resonance (NMR)-based metabolomics showed significantly increased fecal levels of pimelate, a precursor of biotin, and butyrate in the BB536-HGM group. In addition, the bioassay revealed significantly elevated fecal levels of biotin in the BB536-HGM group. Metatranscriptomic analysis of fecal microbiota followed by an in vitro bioassay indicated that the elevated biotin level was due to an alteration in metabolism related to biotin synthesis by Bacteroides caccae in this mouse model. Furthermore, the proportion of Eubacterium rectale, a butyrate producer, was significantly higher in the BB536-HGM group than in the group without B. longum BB536 supplementation. Our findings help to elucidate the molecular basis underlying the effect of B. longum BB536 on the gut luminal metabolism through its interactions with the microbial community.

  3. Lost at sea: ocean acidification undermines larval fish orientation via altered hearing and marine soundscape modification

    PubMed Central

    Rossi, Tullio; Nagelkerken, Ivan; Connell, Sean D.

    2016-01-01

    The dispersal of larvae and their settlement to suitable habitat is fundamental to the replenishment of marine populations and the communities in which they live. Sound plays an important role in this process because for larvae of various species, it acts as an orientational cue towards suitable settlement habitat. Because marine sounds are largely of biological origin, they not only carry information about the location of potential habitat, but also information about the quality of habitat. While ocean acidification is known to affect a wide range of marine organisms and processes, its effect on marine soundscapes and its reception by navigating oceanic larvae remains unknown. Here, we show that ocean acidification causes a switch in role of present-day soundscapes from attractor to repellent in the auditory preferences in a temperate larval fish. Using natural CO2 vents as analogues of future ocean conditions, we further reveal that ocean acidification can impact marine soundscapes by profoundly diminishing their biological sound production. An altered soundscape poorer in biological cues indirectly penalizes oceanic larvae at settlement stage because both control and CO2-treated fish larvae showed lack of any response to such future soundscapes. These indirect and direct effects of ocean acidification put at risk the complex processes of larval dispersal and settlement. PMID:26763221

  4. Moderate dietary salt restriction does not alter insulin resistance or serum lipids in normal men.

    PubMed

    Grey, A; Braatvedt, G; Holdaway, I

    1996-04-01

    Dietary salt restriction lowers blood pressure and has been advocated as a population-based strategy to reduce the cardiovascular morbidity associated with hypertension. However, the effect of lowering salt intake on metabolic vascular risk factors such as insulin resistance and levels of atherogenic lipids and fasting insulin is uncertain. We have studied the short-term effect of moderate dietary salt restriction on insulin resistance and serum lipids in 34 nonobese (body mass index [mean +/- SD] 23.4 +/- 1.8 kg/m2), normotensive young white men. Subjects were maintained on a low salt diet ( < 80 mmol/day) for the 2-week study period. In a randomized, cross-over, double-blind fashion, each subject also received 120 mmol of sodium chloride per day during one of the study weeks, and a matching placebo during the other. Insulin resistance, serum insulin, lipids, and blood pressure were measured in the fasting state at the end of each study week. Urinary sodium excretion (185 +/- 46 v 52 +/- 25 mmol/day, P < .001), serum sodium (141.2 +/- 1.2 v 140.1 +/- 1.3 mmol/L, P < .001) and body weight (75.4 +/- 9.1 v 75.0 +/- 9.3 kg, P < .05) were higher during the high salt than the low salt period. Serum creatinine was higher during the low salt period (100 +/- 8 v 90 +/- 9 mumols/L, P < .01). There was no difference in blood pressure, insulin resistance, serum insulin, C-peptide, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol or its subfractions, triglycerides, apolipoprotein A1, or apolipoprotein B between the high salt and low salt periods. We conclude that short-term, moderate dietary salt restriction does not adversely affect insulin sensitivity or levels of atherogenic lipids in normotensive nonobese men.

  5. Liver transplantation normalizes serum hepcidin level and cures iron metabolism alterations in HFE hemochromatosis.

    PubMed

    Bardou-Jacquet, Edouard; Philip, Julie; Lorho, Richard; Ropert, Martine; Latournerie, Marianne; Houssel-Debry, Pauline; Guyader, Dominique; Loréal, Olivier; Boudjema, Karim; Brissot, Pierre

    2014-03-01

    Defects in human hemochromatosis protein (HFE) cause iron overload due to reduced hepatic hepcidin secretion. Liver transplantation (LT) is a key treatment for potential complications from HFE-related hereditary hemochromatosis (HH). This study evaluated hepcidin secretion and iron burden after LT to elucidate HH pathophysiology. Patients (n=18) homozygous for the p.Cys282Tyr mutation in the HFE gene underwent LT between 1999 and 2008. Serum iron, serum hepcidin, and hepatic iron concentrations were determined before LT and at the end of follow-up (median 57 months). Mortality and causes of death were determined. Survival was compared to that of the overall patient population that received LT. Before LT, serum hepcidin levels were low (0.54 ± 2.5 nmol/L; normal range: 4-30 nmol/L). After LT, 11 patients had iron evaluations; none received iron depletion therapy; all had normal transferrin saturation. The mean serum ferritin was 185 (± 99) μg/L. Magnetic resonance imaging showed that iron overload was absent in nine patients, mild in one patient with metabolic syndrome, and high (180 μmol/g) in one patient with hereditary spherocytosis discovered after LT. At the end of follow-up, serum hepcidin was normal in 10 patients (11.12 ± 7.6 nmol/L; P<0.05) and low in one patient with iron deficiency anemia. Survival was 83% and 67% at 1 and 5 years, respectively. Survival was similar for patients with HH and patients that received LT for other causes. In HH, LT normalized hepcidin secretion and prevented recurrence of hepatic iron overload. Survival was similar to that of patients who received LTs for other liver diseases. © 2014 by the American Association for the Study of Liver Diseases.

  6. Phosphorylation-related modification at the dimer interface of 14-3-3ω dramatically alters monomer interaction dynamics.

    PubMed

    Denison, Fiona C; Gökirmak, Tufan; Ferl, Robert J

    2014-01-01

    14-3-3 proteins are generally believed to function as dimers in a broad range of eukaryotic signaling pathways. The consequences of altering dimer stability are not fully understood. Phosphorylation at Ser58 in the dimer interface of mammalian 14-3-3 isoforms has been reported to destabilise dimers. An equivalent residue, Ser62, is present across most Arabidopsis isoforms but the effects of phosphorylation have not been studied in plants. Here, we assessed the effects of phosphorylation at the dimer interface of Arabidopsis 14-3-3ω. Protein kinase A phosphorylated 14-3-3ω at Ser62 and also at a previously unreported residue, Ser67, resulting in a monomer-sized band on native-PAGE. Phosphorylation at Ser62 alone, or with additional Ser67 phosphorylation, was investigated using phosphomimetic versions of 14-3-3ω. In electrophoretic and chromatographic analyses, these mutants showed mobilities intermediate between dimers and monomers. Mobility was increased by detergents, by reducing protein concentration, or by increasing pH or temperature. Urea gradient gels showed complex structural transitions associated with alterations of dimer stability, including a previously unreported 14-3-3 aggregation phenomenon. Overall, our analyses showed that dimer interface modifications such as phosphorylation reduce dimer stability, dramatically affecting the monomer-dimer equilibrium and denaturation trajectory. These findings may have dramatic implications for 14-3-3 structure and function in vivo.

  7. Chromatin Modifications during Repair of Environmental Exposure-Induced DNA Damage: A Potential Mechanism for Stable Epigenetic Alterations

    PubMed Central

    O’Hagan, Heather M.

    2014-01-01

    Exposures to environmental toxicants and toxins cause epigenetic changes that likely play a role in the development of diseases associated with exposure. The mechanism behind these exposure-induced epigenetic changes is currently unknown. One commonality between most environmental exposures is that they cause DNA damage either directly or through causing an increase in reactive oxygen species, which can damage DNA. Like transcription, DNA damage repair must occur in the context of chromatin requiring both histone modifications and ATP-dependent chromatin remodeling. These chromatin changes aid in DNA damage accessibility and signaling. Several proteins and complexes involved in epigenetic silencing during both development and cancer have been found to be localized to sites of DNA damage. The chromatin-based response to DNA damage is considered a transient event, with chromatin being restored to normal as DNA damage repair is completed. However, in individuals chronically exposed to environmental toxicants or with chronic inflammatory disease, repeated DNA damage-induced chromatin rearrangement may ultimately lead to permanent epigenetic alterations. Understanding the mechanism behind exposure-induced epigenetic changes will allow us to develop strategies to prevent or reverse these changes. This review focuses on epigenetic changes and DNA damage induced by environmental exposures, the chromatin changes that occur around sites of DNA damage, and how these transient chromatin changes may lead to heritable epigenetic alterations at sites of chronic exposure. PMID:24259318

  8. Exercise-Induced Alterations in Skeletal Muscle, Heart, Liver, and Serum Metabolome Identified by Non-Targeted Metabolomics Analysis.

    PubMed

    Starnes, Joseph W; Parry, Traci L; O'Neal, Sara K; Bain, James R; Muehlbauer, Michael J; Honcoop, Aubree; Ilaiwy, Amro; Christopher, Peter M; Patterson, Cam; Willis, Monte S

    2017-08-08

    The metabolic and physiologic responses to exercise are increasingly interesting, given that regular physical activity enhances antioxidant capacity, improves cardiac function, and protects against type 2 diabetes. The metabolic interactions between tissues and the heart illustrate a critical cross-talk we know little about. To better understand the metabolic changes induced by exercise, we investigated skeletal muscle (plantaris, soleus), liver, serum, and heart from exercise trained (or sedentary control) animals in an established rat model of exercise-induced aerobic training via non-targeted GC-MS metabolomics. Exercise-induced alterations in metabolites varied across tissues, with the soleus and serum affected the least. The alterations in the plantaris muscle and liver were most alike, with two metabolites increased in each (citric acid/isocitric acid and linoleic acid). Exercise training additionally altered nine other metabolites in the plantaris (C13 hydrocarbon, inosine/adenosine, fructose-6-phosphate, glucose-6-phosphate, 2-aminoadipic acid, heptadecanoic acid, stearic acid, alpha-tocopherol, and oleic acid). In the serum, we identified significantly decreased alpha-tocopherol levels, paralleling the increases identified in plantaris muscle. Eleven unique metabolites were increased in the heart, which were not affected in the other compartments (malic acid, serine, aspartic acid, myoinositol, glutamine, gluconic acid-6-phosphate, glutamic acid, pyrophosphate, campesterol, phosphoric acid, creatinine). These findings complement prior studies using targeted metabolomics approaches to determine the metabolic changes in exercise-trained human skeletal muscle. Specifically, exercise trained vastus lateralus biopsies had significantly increased linoleic acid, oleic acid, and stearic acid compared to the inactive groups, which were significantly increased in plantaris muscle in the present study. While increases in alpha-tocopherol have not been identified in

  9. Modification of the Mycobacterium bovis extracellular protein MPB70 with fluorescein for rapid detection of specific serum antibodies by fluorescence polarization.

    PubMed

    Lin, M; Sugden, E A; Jolley, M E; Stilwell, K

    1996-07-01

    The principle of fluorescence polarization described by Perrin (F. Perrin, J. Phys. Radium 7:390-401, 1926) was applied to the development of a novel assay that used fluorescein-labeled Mycobacterium bovis secretory protein MPB70 for rapid detection of anti-MPB70 antibodies in selected sera from three M. bovis-infected species (elk, Ilama, and bison). Labeling of purified MPB70 with fluorescein isothiocyanate resulted in the incorporation of 0.96 +/- 0.08 (mean +/- standard deviation; n = 3) fluorescein group per MPB70 molecule. The labeled protein fluoresced strongly with an emission maximum at 518 nm when excited with light of a wavelength near 493 nm, and its immunoreactivity with anti-MPB70 monoclonal antibody 4C3/17 was not altered by modification with fluorescein. The fluorescence polarization assay protocol was optimized for analysis of serum samples by incorporating into the assay buffer 0.05% lithium dodecyl sulfate, which prevents the occurrence of some nonspecific interactions. Sera from M. bovis-infected animals, selected on the basis of exhibiting the presence of anti-MPB70 antibodies, as detected by enzyme-linked immunosorbent assay (ELISA), reacted with fluorescein-labeled MPB70, resulting in an increase in polarization of up to 330 milli-polarization units, in contrast to the values for noninfected sera (167 to 178 mP), which were close to that obtained in the absence of specific antibodies (164.7 +/- 3.3 mP; n = 6). These results demonstrated the feasibility of using fluorescein-labeled MPB70 to detect anti-MPB70 antibodies by fluorescence polarization and suggested that the assay described here can be an alternative to ELISA or other antibody assay systems. The advantages of this original methodology and its general applicability to the diagnosis of infectious diseases are discussed.

  10. Serum level of scorpion toxins, electrolytes and electrocardiogram alterations in Mexican children envenomed by scorpion sting.

    PubMed

    Osnaya-Romero, N; Acosta-Saavedra, L C; Goytia-Acevedo, R; Lares-Asseff, I; Basurto-Celaya, G; Perez-Guille, G; Possani, L D; Calderón-Aranda, E S

    2016-11-01

    The scorpion Centruroides limpidus limpidus (C.l.l.) is endemic in México, producing hundreds of accidents in humans; children being one of the most susceptible targets. Few studies reported that severe envenoming by scorpion venom induces cardiac damage and electrolytes abnormalities in children, but the relationship of envenoming severity and toxic blood levels is unknown. The aim of this study was to determine the relationship among clinical status of envenoming, serum electrolyte, electrocardiographic abnormalities, and serum toxin levels in 44 children stung by scorpion over a period of 6 months in the State of Morelos, Mexico. The patients were said to be asymptomatic, when they presented just local symptoms, and were said to be symptomatic when showing local symptoms and at least one systemic symptom. The clinical status was evaluated at the admission at the emergency room of the Hospital, and 30 min after the administration of polyspecific F(ab')2 anti-scorpion therapy to symptomatic children. Forty-one percent of the children were asymptomatic and 59% symptomatic. Potassium and sodium imbalance and an elongation of the QT interval were detected; the rate of hypokalemia was higher in symptomatic than on asymptomatic children (50% and 6%, respectively). Hypokalemia persisted in 19% in symptomatic patients, whereas sodium reached normal levels 30 min after anti-venom therapy. The hypokalemia statistically correlated with elongation of the QT interval. The concentration of the toxic components of C.l.l in serum was significantly higher in symptomatic than asymptomatic children, and the serum levels of the toxic component significantly decreased to undetectable levels after the application of anti-venom therapy. Despite the small size of the sample, this study establishes that severity of envenoming was statistically related to potassium imbalance in serum, QT interval and the concentration of toxic components in serum, which decreased at undetectable levels

  11. Treatment with the iron chelator, deferoxamine mesylate, alters serum markers of oxidative stress in stroke patients.

    PubMed

    Selim, Magdy

    2010-03-01

    The iron chelator, deferoxamine mesylate (DFO), has shown neuroprotective effects, mediated via suppression of iron-induced hydroxyl radical formation, in various animal models of ischemic and hemorrhagic stroke. Therefore, the objective of this study was to investigate whether DFO can exert similar actions in stroke patients, by examining the effects of treatment with DFO on biological markers of oxidative stress, namely serum total hydroperoxides and lipoperoxides and total radical trapping antioxidant capacity (TRAP), in stroke patients. We found that serum levels of peroxides were reduced, and TRAP levels increased after a 3-day treatment with DFO (500 mg). These findings provide a preliminary proof of concept that DFO can exert potential antioxidant neuroprotective effects in stroke patients. Future, larger-scale, randomized, and controlled studies to further evaluate the safety and efficacy of DFO in patients with stroke are warranted.

  12. The effect of structural alterations of three mammalian serum albumins on their binding properties

    NASA Astrophysics Data System (ADS)

    Równicka-Zubik, J.; Sułkowski, L.; Maciążek-Jurczyk, M.; Sułkowska, A.

    2013-07-01

    The binding of piroxicam (PIR) to human (HSA), bovine (BSA) and sheep (SSA) serum albumin in native and destabilized/denaturated state was studied by the fluorescence quenching technique. Quenching of the intrinsic fluorescence of three analyzed serum albumins was observed due to selective exciting of tryptophanyl and tyrosil residues at 295 nm and 280 nm. Based on fluorescence emission spectra the quenching (KQ) and binding constants (Ka) were determined. The results showed that PIR is bound mainly in IIA subdomain of HSA and is additionally able to interact with tyrosil groups located in subdomains IB, IIB or IIIA. PIR interacts only with tryptophanyl residues of BSA and SSA [Trp-214, Trp-237 (IIA) and Trp-135, Trp-158 (IB)]. The presence of denaturating factors modified the mechanism of fluorescence quenching of SSA by PIR. Linear Scatchard plots suggest that HSA, BSA and SSA bind PIR in one class of binding sites.

  13. Human cobalamin deficiency: alterations in serum tumour necrosis factor-alpha and epidermal growth factor.

    PubMed

    Peracchi, M; Bamonti Catena, F; Pomati, M; De Franceschi, M; Scalabrino, G

    2001-08-01

    We have previously demonstrated that vitamin B12 (cobalamin)-deficient central neuropathy in the rat is associated with local overexpression of neurotoxic tumour necrosis factor (TNF)-alpha combined with locally decreased synthesis of neurotrophic epidermal growth factor (EGF). The aims of this study were to investigate whether a similar imbalance also occurs in the serum of adult patients with clinically confirmed cobalamin deficiency and whether it can be corrected by vitamin B12 replacement therapy. We studied 34 adult patients with severe cobalamin deficiency, 12 patients with pure iron deficiency anaemia and 34 control subjects. Haematological markers of cobalamin deficiency and serum TNF-alpha and EGF levels were measured using commercial kits. Thirteen cobalamin-deficient patients were re-evaluated after 3 and 6 months of parenteral vitamin B12 treatment. TNF-alpha was significantly higher (p < 0.01) and EGF significantly lower (p < 0.01) in the patients with cobalamin deficiency, but both were unchanged in patients with pure iron deficiency anaemia. In cobalamin-deficient patients the serum TNF-alpha levels correlated significantly with plasma total homocysteine levels (r = 0.425; p < 0.02). In the treated patients TNF-alpha and EGF levels normalised concomitantly with clinical and haematological disease remission. In humans, as in rats, cobalamin concentration appears to be correlated with the synthesis and release of TNF-alpha and EGF in a reciprocal manner, because cobalamin deficiency is accompanied by overproduction of TNF-alpha and underproduction of EGF.

  14. Alterations of erythrocyte antioxidant mechanisms: antioxidant enzymes, lipid peroxidation and serum trace elements associated with anemia in bovine tropical theileriosis.

    PubMed

    Razavi, S M; Nazifi, S; Bateni, M; Rakhshandehroo, E

    2011-08-25

    In order to investigate the alterations of erythrocyte protective antioxidant mechanisms, lipid peroxidation and trace elements associated with anemia in bovine tropical theileriosis, an infected group comprised of 50 crossbred Holstein cattle, about 1-2 years old, naturally infected with Theileria annulata, were divided into 4 subgroups according to their parasitemia rates (<1%, 1-3%, 3-5%, >5%) and also 10 healthy cattle as control were selected. Blood samples were taken and hematological parameters, the activities of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase and serum concentrations of some antioxidant trace elements (copper, iron, zinc, manganese and selenium) were measured. As an index of lipid peroxidation, the level of Malondialdehyde (MDA) was also determined. The results showed a conspicuous decrease in the activities of SOD, GPX and catalase (P<0.01), and a significant decrease in the serum concentrations of Cu, Zn, Mn and Se in cattle with higher than 1% parasitemia (P<0.05) compared to the control. In addition, remarkable elevations in the MDA level (P<0.01) and serum concentration of iron (P<0.05) were observed in the infected animals. These findings pointed to the occurrence of exacerbating oxidative injuries to erythrocytes during parasitemia. Furthermore, it can be concluded that infection with T. annulata can interfere with protective antioxidant mechanisms of RBCs against oxidative damages, which promote the development of anemia.

  15. Alterations in Serum Polyunsaturated Fatty Acids and Eicosanoids in Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD)

    PubMed Central

    Titz, Bjoern; Luettich, Karsta; Leroy, Patrice; Boue, Stephanie; Vuillaume, Gregory; Vihervaara, Terhi; Ekroos, Kim; Martin, Florian; Peitsch, Manuel C.; Hoeng, Julia

    2016-01-01

    Smoking is a major risk factor for several diseases including chronic obstructive pulmonary disease (COPD). To better understand the systemic effects of cigarette smoke exposure and mild to moderate COPD—and to support future biomarker development—we profiled the serum lipidomes of healthy smokers, smokers with mild to moderate COPD (GOLD stages 1 and 2), former smokers, and never-smokers (n = 40 per group) (ClinicalTrials.gov registration: NCT01780298). Serum lipidome profiling was conducted with untargeted and targeted mass spectrometry-based lipidomics. Guided by weighted lipid co-expression network analysis, we identified three main trends comparing smokers, especially those with COPD, with non-smokers: a general increase in glycero(phospho)lipids, including triglycerols; changes in fatty acid desaturation (decrease in ω-3 polyunsaturated fatty acids, and an increase in monounsaturated fatty acids); and an imbalance in eicosanoids (increase in 11,12- and 14,15-DHETs (dihydroxyeicosatrienoic acids), and a decrease in 9- and 13-HODEs (hydroxyoctadecadienoic acids)). The lipidome profiles supported classification of study subjects as smokers or non-smokers, but were not sufficient to distinguish between smokers with and without COPD. Overall, our study yielded further insights into the complex interplay between smoke exposure, lung disease, and systemic alterations in serum lipid profiles. PMID:27657052

  16. Hemodynamic and serum biochemical alterations associated with intravenous administration of three types of contrast media in anesthetized dogs.

    PubMed

    Pollard, Rachel E; Puchalski, Sarah M; Pascoe, Peter J

    2008-10-01

    To determine the incidence and type of alterations in heart rate (HR), peak systolic blood pressure (PSBP), and serum biochemical variables (total bilirubin, BUN, and creatinine concentrations) associated with IV administration of ionic-iodinated contrast (IIC), nonionic-iodinated contrast (NIC), and gadolinium dimeglumine (GD) contrast media in anesthetized dogs. 280 anesthetized dogs undergoing cross-sectional imaging. HR and PSBP were recorded at 5-minute intervals for 20 minutes for untreated control dogs and dogs that received IIC, NIC, or GD contrast medium. The development of an HR of < 60 beats/min or > 130 beats/min that included a > or = 20% change from baseline was considered a response. The development of PSBP of < 90 mm Hg or > 160 mm Hg that included a > or = 20% change from baseline was considered a response. Pre- and postcontrast serum biochemical values were recorded. Results-Of dogs receiving IIC medium, 3% (3/91) had a response in HR and 4% (4/91) had a response in PSBP at > or = 1 time points. None of the dogs receiving NIC medium had a response in HR; 1 of 16 had a response in PSBP. Of dogs receiving GD contrast medium, 1% (1/92) had a response in HR and 4% (4/92) had a response in PSBP. Of control dogs, 2% (2/81) had a response in HR and 4% (3/81) had a response in PSBP. No serum biochemical alterations were observed. IV administration of contrast media in anesthetized dogs caused moderate bradycardia, tachycardia, hypotension, or hypertension.

  17. Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium

    PubMed Central

    Ryan, Zachary C.; Ketha, Hemamalini; McNulty, Melissa S.; McGee-Lawrence, Meghan; Craig, Theodore A.; Grande, Joseph P.; Westendorf, Jennifer J.; Singh, Ravinder J.; Kumar, Rajiv

    2013-01-01

    Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin (sost) gene was replaced by the β-D-galactosidase (lacZ) gene in the germ line. Knockout (KO) (sost−/−) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of sost KO mice but was undetectable in WT mice. Eight-week-old, male sost KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 (cyp27B1) mRNA was increased in kidneys of sost KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased cyp27B1 mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in sost KO mice compared with WT mice. Sost KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion. PMID:23530237

  18. Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium.

    PubMed

    Ryan, Zachary C; Ketha, Hemamalini; McNulty, Melissa S; McGee-Lawrence, Meghan; Craig, Theodore A; Grande, Joseph P; Westendorf, Jennifer J; Singh, Ravinder J; Kumar, Rajiv

    2013-04-09

    Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin (sost) gene was replaced by the β-D-galactosidase (lacZ) gene in the germ line. Knockout (KO) (sost(-/-)) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of sost KO mice but was undetectable in WT mice. Eight-week-old, male sost KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 (cyp27B1) mRNA was increased in kidneys of sost KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased cyp27B1 mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in sost KO mice compared with WT mice. Sost KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion.

  19. Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter α-synuclein conformation and aggregation kinetics

    NASA Astrophysics Data System (ADS)

    Mohammad-Beigi, Hossein; Shojaosadati, Seyed Abbas; Marvian, Amir Tayaranian; Pedersen, Jannik Nedergaard; Klausen, Lasse Hyldgaard; Christiansen, Gunna; Pedersen, Jan Skov; Dong, Mingdong; Morshedi, Dina; Otzen, Daniel E.

    2015-11-01

    The interaction between nanoparticles (NPs) and the small intrinsically disordered protein α-synuclein (αSN), whose aggregation is central in the development of Parkinson's disease, is of great relevance in biomedical applications of NPs as drug carriers. Here we showed using a combination of different techniques that αSN interacts strongly with positively charged polyethylenimine-coated human serum albumin (PEI-HSA) NPs, leading to a significant alteration in the αSN secondary structure. In contrast, the weak interactions of αSN with HSA NPs allowed αSN to remain unfolded. These different levels of interactions had different effects on αSN aggregation. While the weakly interacting HSA NPs did not alter the aggregation kinetic parameters of αSN, the rate of primary nucleation increased in the presence of PEI-HSA NPs. The aggregation rate changed in a PEI-HSA NP-concentration dependent and size independent manner and led to fibrils which were covered with small aggregates. Furthermore, PEI-HSA NPs reduced the level of membrane-perturbing oligomers and reduced oligomer toxicity in cell assays, highlighting a potential role for NPs in reducing αSN pathogenicity in vivo. Collectively, our results highlight the fact that a simple modification of NPs can strongly modulate interactions with target proteins, which may have important and positive implications in NP safety.The interaction between nanoparticles (NPs) and the small intrinsically disordered protein α-synuclein (αSN), whose aggregation is central in the development of Parkinson's disease, is of great relevance in biomedical applications of NPs as drug carriers. Here we showed using a combination of different techniques that αSN interacts strongly with positively charged polyethylenimine-coated human serum albumin (PEI-HSA) NPs, leading to a significant alteration in the αSN secondary structure. In contrast, the weak interactions of αSN with HSA NPs allowed αSN to remain unfolded. These different

  20. Inflammatory Serum Proteins Are Severely Altered in Metastatic Gastric Adenocarcinoma Patients from the Chinese Population

    PubMed Central

    Sharma, Ashok; He, Mingfang; Xue, Jing; Wu, Jianzhong; Dun, Boying; Li, Gang; Wang, Xiaoxiao; Ji, Minghua; She, Jin-Xiong; Tang, Jinhai

    2015-01-01

    Background Inflammation is one of the major hallmarks of cancer. This study was designed to profile a panel of inflammatory mediators in gastric adenocarcinoma (GA) and to identify their potential differences separately in metastatic and non-metastatic patient subgroups. Methods Serum samples from 216 GA patients and 333 healthy controls from China were analyzed for six proteins using the Luminex multiplex assay. Results The serum levels for all the six proteins were significantly elevated in metastatic GA compared to non-metastatic GA. Two acute phase proteins (SAA and CRP) and a CXC chemokine (GRO) were significantly elevated in metastatic GA (p <0.01) but smaller changes were observed in non-metastatic GA compared to healthy controls. OPN is moderately increased in non-metastatic GA (2.05-fold) and more severely elevated in metastatic GA (3.34-fold). Surprisingly, soluble VCAM1 and AGP were significantly lower in both non-metastatic and metastatic GA patients compared to controls. Several individual proteins were shown to possess moderate diagnostic value for non-metastatic GA (AUC = 0.786, 0.833, 0.823 for OPN, sVCAM1 and AGP, respectively) and metastatic GA (AUC = 0.931, 0.720, 0.834 and 0.737 for OPN, sVCAM1, SAA and CRP, respectively). However, protein combinations further improve the diagnostic potential for both non-metastatic GA (best AUC = 0.946) and metastatic GA (best AUC = 0.963). The protein combination with best AUC value for both comparisons is OPN+sVCAM1+AGP+SAA. Conclusions These results suggest that several serum proteins are directly related to the severity of gastric cancer. Overall, stronger associations are observed with metastatic than non-metastatic GA as the protein changes are greater with the metastatic status. A combination of these serum proteins may serve as non-invasive markers to assess the severity status and stage of gastric cancer. PMID:25884401

  1. Decrease in serum levels of advanced glycation end-products by short-term lifestyle modification in non-diabetic middle-aged females.

    PubMed

    Yoshikawa, Takahiro; Miyazaki, Aiko; Fujimoto, Shigeo

    2009-06-01

    Advanced glycation end products (AGEs) play an important role in development of atherosclerosis in diabetes and uremic diseases. However, there is currently little information available on the effects of lifestyle modification on circulating AGEs in subjects without these diseases. Serum levels of Nepsilon-(carboxymethyl) lysine (CML), pentosidine, derivatives of reactive oxygen metabolites (d-ROMs), adipokines, and renal function were determined in forty-seven middle-aged females. Among them, seventeen participated in a 12-week lifestyle modification (LM) program and twelve age-matched subjects were assigned to a control group. The LM program consisted of an initial educational session and encouragement. At baseline, serum HDL-cholesterol was correlated with CML level (P=0.003), whereas body fat mass (P=0.012) and fat consumption (P=0.007) were correlated with pentosidine levels. After intervention, significant reductions were observed in the LM group in body fat, serum HDL-cholesterol, CML, and pentosidine. Of note, in the LM group, average number of steps in daily walking was significantly correlated with decrease in CML level (P=0.044). Decrease in pentosidine level exhibited significant positive correlations with reduction in body weight (P=0.007) and body fat mass (P=0.038). The present findings suggest lifestyle modification as a promising approach to reducing circulating AGE levels even in healthy middle-aged females with neither overt diabetes nor renal dysfunction.

  2. Pain-mediated altered absorption and metabolism of ibuprofen: an explanation for decreased serum enantiomer concentration after dental surgery

    PubMed Central

    Jamali, Fakhreddin; Kunz-Dober, Cornelia M

    1999-01-01

    Aims Rapid onset of analgesia is essential in the treatment of acute pain. There is evidence that conditions of stress cause delayed and decreased pain relief from oral analgesic products through impaired absorption. The aim was to determine the effect of surgery for removal of wisdom teeth on the plasma concentration-time profile of ibuprofen enantiomers. Methods Racemic ibuprofen, 200 mg in one group (n=7) and 600 mg in another group (n=7) was administered 1 week before (control) and again after (test) surgical removal of wisdom teeth. Serum concentrations of ibuprofen enantiomers were measured for 6 h. Results During the control phase, S- and R-ibuprofen concentrations were within the suggested therapeutic range. Surgery resulted in a 2 h delay in the mean time to peak concentration, significant decreases in serum ibuprofen concentration following both doses, and a fall to sub-optimal serum concentrations following the 200 mg dose. During the first 2 h after the 200 mg dose, dental extraction resulted in a significant reduction of the area under serum drug concentration (AUC (0, 2 h) mg l−1 h) from 5.6±2.9 to 1.6±1.8 (P<0.01) and from 5.5±3.0 to 2.1±2.0 (P<0.05) for S and R-ibuprofen, respectively. Similar observations were made following the 600 mg dose for AUC (0, 2 h) of S-ibuprofen (from 14.2±6.1 to 7.2±5.5 mg l−1 h, P<0.05) with no significant difference for R-ibuprofen (from 14.4±9.5 to 5.8±7.1). AUC (0, 6 h) was also significantly reduced by surgery. The pattern of stereoselectivity in serum ibuprofen concentration was reversed by surgery such that the S enantiomer was predominant in the control phase but not in the post-surgery phase, which is suggestive of reduced metabolic chiral inversion. Conclusions Surgery for wisdom tooth removal resulted in substantial decreases in the serum concentration of ibuprofen enantiomers and a prolongation in the time to peak concentration. Reduced absorption and altered metabolism are the likely cause of

  3. Consumption of pasteurized human lysozyme transgenic goats’ milk alters serum metabolite profile in young pigs

    PubMed Central

    Brundige, Dottie R.; Maga, Elizabeth A.; Klasing, Kirk C.

    2009-01-01

    Nutrition, bacterial composition of the gastrointestinal tract, and general health status can all influence the metabolic profile of an organism. We previously demonstrated that feeding pasteurized transgenic goats’ milk expressing human lysozyme (hLZ) can positively impact intestinal morphology and modulate intestinal microbiota composition in young pigs. The objective of this study was to further examine the effect of consuming hLZ-containing milk on young pigs by profiling serum metabolites. Pigs were placed into two groups and fed a diet of solid food and either control (non-transgenic) goats’ milk or milk from hLZ-transgenic goats for 6 weeks. Serum samples were collected at the end of the feeding period and global metabolite profiling was performed. For a total of 225 metabolites (160 known, 65 unknown) semi-quantitative data was obtained. Levels of 18 known and 4 unknown metabolites differed significantly between the two groups with the direction of change in 13 of the 18 known metabolites being almost entirely congruent with improved health status, particularly in terms of the gastrointestinal tract health and immune response, with the effects of the other five being neutral or unknown. These results further support our hypothesis that consumption of hLZ-containing milk is beneficial to health. PMID:19847666

  4. ALTERATIONS IN SERUM GLOBULINS DURING THE FORMATION AND RESORPTION OF AMYLOID IN RABBITS

    PubMed Central

    Richter, Goetz W.

    1956-01-01

    A marked increase of the serum beta globulins was found in rabbits developing amyloidosis as a result of prolonged treatment with ribonucleate administered by subcutaneous injections. Following cessation of treatment the beta globulin levels gradually returned to normal while the gamma globulin levels rose strikingly, the changes being accompanied by a resorption of amyloid from the spleen, and probably also from the kidneys. Electrophoretic studies provided some evidence that the increase in beta globulins which accompanied the development of amyloidosis resulted from the production of a globulin not normally present in rabbit serum. A protein or protein derivative that moved as a beta globulin when subjected to filter paper electrophoresis was excreted in substantial quantities in the urine of several amyloidotic rabbits, along with much smaller quantities of substances moving as albumin, alpha and gamma globulins. Considered as a whole, the findings indicate a causal relationship between the abnormal production of circulating beta globulins and the deposition of amyloid in rabbits treated with ribonucleate. Hence it appears that a beta globulin may be directly involved in the formation of amyloid under the conditions of the experiments here reported. PMID:13376808

  5. Serum-free culture alters the quantity and protein composition of neuroblastoma-derived extracellular vesicles

    PubMed Central

    Li, Jinghuan; Lee, Yi; Johansson, Henrik J.; Mäger, Imre; Vader, Pieter; Nordin, Joel Z.; Wiklander, Oscar P. B.; Lehtiö, Janne; Wood, Matthew J. A.; Andaloussi, Samir EL

    2015-01-01

    Extracellular vesicles (EVs) play a significant role in cell–cell communication in numerous physiological processes and pathological conditions, and offer promise as novel biomarkers and therapeutic agents for genetic diseases. Many recent studies have described different molecular mechanisms that contribute to EV biogenesis and release from cells. However, little is known about how external stimuli such as cell culture conditions can affect the quantity and content of EVs. While N2a neuroblastoma cells cultured in serum-free (OptiMEM) conditions did not result in EVs with significant biophysical or size differences compared with cells cultured in serum-containing (pre-spun) conditions, the quantity of isolated EVs was greatly increased. Moreover, the expression levels of certain vesicular proteins (e.g. small GTPases, G-protein complexes, mRNA processing proteins and splicing factors), some of which were previously reported to be involved in EV biogenesis, were found to be differentially expressed in EVs under different culture conditions. These data, therefore, contribute to the understanding of how extracellular factors and intracellular molecular pathways affect the composition and release of EVs. PMID:26022510

  6. Altered antibacterial activity of Curcumin in the presence of serum albumin, plasma and whole blood.

    PubMed

    Teow, Sin Yeang; Ali, Syed A

    2017-03-01

    Antibacterial effect is one of the major therapeutic activities of plant-derived Curcumin. This work evaluated the effect of serum albumin, human plasma, and whole blood on the in vitro activity of Curcumin against eight clinical bacterial isolates by standard broth microdilution and plate-counting methods. Toxicological effects of Curcumin towards human red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) were also investigated. Curcumin exhibited weak activity against gram-negative bacteria, except Escherichia coli and Shigella flexneri were susceptible and was most active against gram-positive bacteria: Staphylococcus aureus, Streptococcus pyogenes and Enterococcus faecalis. The antibacterial activity was impaired in the presence of bovine serum albumin (BSA), human plasma and whole blood. Curcumin was not toxic to PBMCs and RBCs at 200μg/mL. Furthermore, Curcumin showed synergistic activity in combination with antibiotics: Ciprofloxacin, Gentamicin, Vancomycin and Amikacin against Staphylococcus aureus. This study demonstrated that the interaction of Curcumin with plasma proteins diminishes its in vitro antibacterial activity. Curcumin derivatives with reduced affinity for plasma protein may improve the bioavailability and antibacterial activities.

  7. Serum-free culture alters the quantity and protein composition of neuroblastoma-derived extracellular vesicles.

    PubMed

    Li, Jinghuan; Lee, Yi; Johansson, Henrik J; Mäger, Imre; Vader, Pieter; Nordin, Joel Z; Wiklander, Oscar P B; Lehtiö, Janne; Wood, Matthew J A; Andaloussi, Samir El

    2015-01-01

    Extracellular vesicles (EVs) play a significant role in cell-cell communication in numerous physiological processes and pathological conditions, and offer promise as novel biomarkers and therapeutic agents for genetic diseases. Many recent studies have described different molecular mechanisms that contribute to EV biogenesis and release from cells. However, little is known about how external stimuli such as cell culture conditions can affect the quantity and content of EVs. While N2a neuroblastoma cells cultured in serum-free (OptiMEM) conditions did not result in EVs with significant biophysical or size differences compared with cells cultured in serum-containing (pre-spun) conditions, the quantity of isolated EVs was greatly increased. Moreover, the expression levels of certain vesicular proteins (e.g. small GTPases, G-protein complexes, mRNA processing proteins and splicing factors), some of which were previously reported to be involved in EV biogenesis, were found to be differentially expressed in EVs under different culture conditions. These data, therefore, contribute to the understanding of how extracellular factors and intracellular molecular pathways affect the composition and release of EVs.

  8. Comparison of measured glomerular filtration rates with isotope infusion and with the modification of diet in renal disease equation in cancer patients with raised serum creatinine.

    PubMed

    Javaid, Amrah; Jaffri, Saghir Ahmed; Munir, Iqbal; Qazi, Muhammad H; Nawaz, Muhammad Khalid

    2015-03-01

    To compare the measured glomerular filtration rate (rGFR) using [99mTc] diethylene triamine pentacetic acid (DTPA) clearance or estimated GFR (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation in cancer patients with raised serum creatinine level, we studied 100 cancer patients; 50 patients with normal serum creatinine (control group) and 50 patients with abnormal serum creatinine (study group). History of patients, including site of cancer, chemotherapy regime and dose of chemotherapy, was recorded. The rGFR and eGFR were increased in the study group as compared with the control group, but the GFR recorded by the MDRD formula or DTPA revealed similar values. It is therefore concluded that the MDRD equation may be recommended for eGFR estimation even with abnormal creatinine, without the need for exposure to radiation.

  9. Restricted nutrient intake does not alter serum-mediated measures of implant response in cell culture

    PubMed Central

    2013-01-01

    Background During nutritional stress, reduced intake may reduce the efficacy of anabolic implants. This study was conducted to evaluate basic cellular responses to a growth promotant implant at two intake levels. Methods Sixteen crossbred steers (293 ± 19.3 kg) were used to evaluate the impact of anabolic implants in either an adequate or a restricted nutritional state. Steers were trained to individual Calan gates, and then randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement. Treatments consisted of: presence or absence of an anabolic growth implant (Revalor-XS, 200 mg TBA and 40 mg estradiol; IMPLANT or CONTROL) and a moderate energy, pelleted, starting cattle diet fed at either 2.0 × or 1.0 × maintenance energy (NEM) requirements (HIGH or LOW). Serum (d 0, 14, and 28) was used for application to bovine muscle satellite cells. After treatment with the serum (20% of total media) from the trial cattle, the satellite cells were incubated for 72 h. Protein abundance of myosin heavy chain (MHC), phosphorylated extracellular signal-related kinase (phospho-ERK), and phosphorylated mammalian target of rapamycin (phospho-mTOR) were analyzed to determine the effects of implant, intake, and their interaction (applied via the serum). Results Intake had no effect on MHC (P = 0.85) but IMPLANT increased (P < 0.01) MHC abundance vs. CONTROL. Implant status, intake status, and the interaction had no effect on the abundance of phospho-ERK (P ≥ 0.23). Implanting increased phospho-mTOR (P < 0.01) but there was no effect (P ≥ 0.51) of intake or intake × implant. Conclusions The nearly complete lack of interaction between implant and nutritional status indicates that the signaling molecules measured herein respond to implants and nutritional status independently. Furthermore, results suggest that the muscle hypertrophic effects of anabolic implants may not be mediated by circulating IGF-1. PMID:24245980

  10. Beta-Actin Deficiency with Oxidative Posttranslational Modifications in Rett Syndrome Erythrocytes: Insights into an Altered Cytoskeletal Organization

    PubMed Central

    Pecorelli, Alessandra; Belmonte, Giuseppe; Signorini, Cinzia; Leoncini, Silvia; Zollo, Gloria; Capone, Antonietta; Giovampaola, Cinzia Della; Sticozzi, Claudia; Valacchi, Giuseppe; Ciccoli, Lucia; Guerranti, Roberto; Hayek, Joussef

    2014-01-01

    Beta-actin, a critical player in cellular functions ranging from cell motility and the maintenance of cell shape to transcription regulation, was evaluated in the erythrocyte membranes from patients with typical Rett syndrome (RTT) and methyl CpG binding protein 2 (MECP2) gene mutations. RTT, affecting almost exclusively females with an average frequency of 1∶10,000 female live births, is considered the second commonest cause of severe cognitive impairment in the female gender. Evaluation of beta-actin was carried out in a comparative cohort study on red blood cells (RBCs), drawn from healthy control subjects and RTT patients using mass spectrometry-based quantitative analysis. We observed a decreased expression of the beta-actin isoforms (relative fold changes for spots 1, 2 and 3: −1.82±0.15, −2.15±0.06, and −2.59±0.48, respectively) in pathological RBCs. The results were validated by western blotting and immunofluorescence microscopy. In addition, beta-actin from RTT patients also showed a dramatic increase in oxidative posttranslational modifications (PTMs) as the result of its binding with the lipid peroxidation product 4-hydroxy-2-nonenal (4-HNE). Our findings demonstrate, for the first time, a beta-actin down-regulation and oxidative PTMs for RBCs of RTT patients, thus indicating an altered cytoskeletal organization. PMID:24671107

  11. Alterations in Aspergillus brasiliensis (niger) ATCC 9642 membranes associated to metabolism modifications during application of low-intensity electric current.

    PubMed

    Velasco-Alvarez, Nancy; Gutiérrez-Rojas, Mariano; González, Ignacio

    2017-12-01

    The effects of electric current on membranes associated with metabolism modifications in Aspergillus brasiliensis (niger) ATCC 9642 were studied. A 450-mL electrochemical cell with titanium ruthenium-oxide coated electrodes and packed with 15g of perlite, as inert support, was inoculated with A. brasiliensis spores and incubated in a solid inert-substrate culture (12 d; 30°C). Then, 4.5days after starting the culture, a current of 0.42mAcm(-2) was applied for 24h. The application of low-intensity electric current increased the molecular oxygen consumption rate in the mitochondrial respiratory chain, resulting in high concentrations of reactive oxygen species, promoting high lipoperoxidation levels, according to measured malondialdehyde, and consequent alterations in membrane permeability explained the high n-hexadecane (HXD) degradation rates observed here (4.7-fold higher than cultures without current). Finally, cell differentiation and spore production were strongly stimulated. The study contributes to the understanding of the effect of current on the cell membrane and its association with HXD metabolism. Copyright © 2017. Published by Elsevier B.V.

  12. Levels of serum immunomodulators and alterations with electroconvulsive therapy in treatment-resistant major depression

    PubMed Central

    Zincir, Serkan; Öztürk, Pelin; Bilgen, Ali Emrah; İzci, Filiz; Yükselir, Cihad

    2016-01-01

    Studies in recent years have indicated that neuroimmunological events and immune activation may have a place in the etiology of depression. It has been suggested from data that there is a causal relationship between activation of the immune system and excessive release of proinflammatory cytokines, such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha), and the etiology of depression. Although the mechanism of action of electroconvulsive therapy (ECT) is unclear, there is evidence that it can reduce cytokines and immune system changes. In our study, we aimed to determine how levels of serum immunomodulators were affected by ECT in major depression patients. This study was conducted on 50 patients with treatment-resistant major depression. The data of the patients were compared with 30 healthy individuals with similar demographic characteristics. A clinical response occurred in the patients and at the end of therapy, IL-1, IL-6, TNF-alpha, IL-10, IL-4, and interferon-gamma levels were measured. The disease severity was assessed with the 17-item Hamilton Depression Rating Scale. Data analysis was performed using SPSS Version 15. Significant differences were determined between the patients with major depression and control group with respect to basal serum IL-1, IL-6, TNF-alpha, IL-10, IL-4, and interferon-gamma levels. ECT treatment was shown to reduce these differences. ECT may cause significant changes in the activity of the immune system. The consideration of the relationship between the immune endocrine neurotransmitter systems could contribute to new theories regarding the mechanism of antidepressant treatment and biology of depression. PMID:27366071

  13. Choline or CDP-choline alters serum lipid responses to endotoxin in dogs and rats: involvement of the peripheral nicotinic acetylcholine receptors.

    PubMed

    Ilcol, Yesim Ozarda; Yilmaz, Zeki; Cansev, Mehmet; Ulus, Ismail H

    2009-09-01

    We showed previously that choline administration protects dogs from endotoxin-induced multiple organ injury and platelet dysfunctions. Because sepsis/endotoxemia is associated with alterations in lipid metabolism, we have investigated whether choline or cytidine-5'-diphosphate choline, a choline donor, alters serum lipid responses to endotoxin in dogs and rats. In response to endotoxin, serum concentrations of triglycerides, choline-containing phospholipids, total cholesterol, and high-density lipoprotein cholesterol increased in a dose- and time-related manner. Administration of choline (20 mg/kg i.v. in dogs or 90 mg/kg i.p. in rats) or cytidine-5'-diphosphate choline (70 mg/kg i.v. in dogs) 5 min before and 4 and 8 h after endotoxin blocked or attenuated the increases in serum triglycerides, total cholesterol, and nonesterified fatty acids. Endotoxin-induced elevations in serum phospholipid levels did not change in rats and were enhanced in dogs by choline. In rats, serum lipid response to endotoxin was accompanied by severalfold elevations in serum levels of hepatorenal injury markers; their elevations were also blocked by choline. Pretreatment with hexamethonium blocked choline's effects on serum lipids and hepatorenal injury markers. Pretreatment with atropine blocked endotoxin-induced elevations in serum lipid and hepatorenal injury markers, but failed to alter choline's actions on these parameters. Choline treatment improved survival rate of rats in lethal endotoxin shock. In conclusion, these data show that choline treatment alters serum lipid responses to endotoxin and prevents hepatorenal injury during endotoxemia through a nicotinic acetylcholine receptor-mediated mechanism. Hence, choline and choline-containing compounds may have a therapeutic potential in the treatment of endotoxemia/sepsis.

  14. Rice Bran and Probiotics Alter the Porcine Large Intestine and Serum Metabolomes for Protection against Human Rotavirus Diarrhea

    PubMed Central

    Nealon, Nora Jean; Yuan, Lijuan; Yang, Xingdong; Ryan, Elizabeth P.

    2017-01-01

    Human rotavirus (HRV) is a leading cause of severe childhood diarrhea, and there is limited vaccine efficacy in the developing world. Neonatal gnotobiotic pigs consuming a prophylactic synbiotic combination of probiotics and rice bran (Pro+RB) did not exhibit HRV diarrhea after challenge. Multiple immune, gut barrier protective, and anti-diarrheal mechanisms contributed to the prophylactic efficacy of Pro+RB when compared to probiotics (Pro) alone. In order to understand the molecular signature associated with diarrheal protection by Pro+RB, a global non-targeted metabolomics approach was applied to investigate the large intestinal contents and serum of neonatal gnotobiotic pigs. The ultra-high performance liquid chromatography-tandem mass spectrometry platform revealed significantly different metabolites (293 in LIC and 84 in serum) in the pigs fed Pro+RB compared to Pro, and many of these metabolites were lipids and amino acid/peptides. Lipid metabolites included 2-oleoylglycerol (increased 293.40-fold in LIC of Pro+RB, p = 3.04E-10), which can modulate gastric emptying, andhyodeoxycholate (decreased 0.054-fold in the LIC of Pro+RB, p = 0.0040) that can increase colonic mucus production to improve intestinal barrier function. Amino acid metabolites included cysteine (decreased 0.40-fold in LIC, p = 0.033, and 0.62-fold in serum, p = 0.014 of Pro+RB), which has been found to reduce inflammation, lower oxidative stress and modulate mucosal immunity, and histamine (decreased 0.18-fold in LIC, p = 0.00030, of Pro+RB and 1.57-fold in serum, p = 0.043), which modulates local and systemic inflammatory responses as well as influences the enteric nervous system. Alterations to entire LIC and serum metabolic pathways further contributed to the anti-diarrheal and anti-viral activities of Pro+RB such as sphingolipid, mono/diacylglycerol, fatty acid, secondary bile acid, and polyamine metabolism. Sphingolipid and long chain fatty acid profiles influenced the ability of HRV to

  15. Uremic Serum and Solutes Increase Post–Vascular Interventional Thrombotic Risk Through Altered Stability of Smooth Muscle Cell Tissue Factor

    PubMed Central

    Chitalia, Vipul C.; Shivanna, Sowmya; Martorell, Jordi; Balcells, Mercedes; Bosch, Irene; Kolandaivelu, Kumaran; Edelman, Elazer R.

    2013-01-01

    Background Stent thrombosis (ST), a postinterventional complication with a mortality rate of 50%, has an incidence that rises precipitously in patients at risk. Chronic renal failure and end-stage renal disease have emerged as particularly strong ST risk factors, yet the mechanism remains elusive. Tissue factor (TF) is a crucial mediator of injury-related thrombosis and has been implicated for ST. We posit that uremia modulates TF in the local vessel wall to induce postinterventional thrombosis in patients with end-stage renal disease. Methods and Results As a model of the de-endothelialized, postinterventional state, we exposed primary human vascular smooth muscle cells (vSMCs) pretreated with uremic serum (obtained from ESRD patients on hemodialysis) to coronary-like blood flow. vSMC TF expression, activity, stability, and posttranslational modification were examined after vSMCs were treated with uremic serum or solutes. We found significantly greater clot formation after uremic serum exposure, which was substantially reduced with the prior treatment with anti-TF neutralizing antibody. Uremic sera induced 2- to 3-fold higher TF expression and activity in vSMCs independent of diabetes mellitus. Relevant concentrations of isolated uremic solutes such as indole-3-acetic acid (3.5 μg/mL), indoxyl sulfate (25 μg/mL), and uric acid (80 μg/mL) recapitulated these effects in cell culture and the flow loop model. We show further that TF undergoes ubiquitination at baseline and that uremic serum, indole-3-acetic acid, and indoxyl sulfate significantly prolong TF half-life by inhibiting its ubiquitination. Conclusions The uremic milieu is profoundly thrombogenic and upregulates vSMC TF levels by increasing TF stability and decreasing its ubiquitination. Together, these data demonstrate for the first time that the posttranslational regulation of TF in uremia may have a causative role in the increased ST risk observed in uremic patients. These data suggest that

  16. Prenatal transportation stress alters temperament and serum cortisol concentrations in suckling Brahman calves.

    PubMed

    Littlejohn, B P; Price, D M; Banta, J P; Lewis, A W; Neuendorff, D A; Carroll, J A; Vann, R C; Welsh, T H; Randel, R D

    2016-02-01

    This experiment examined the relationship between prenatal stress and subsequent calf temperament through weaning. The prenatal stressor used was repeated transportation of pregnant Brahman cows for 2 h at 60 ± 5, 80 ± 5, 100 ± 5, 120 ± 5, and 140 ± 5 d of gestation. Prenatally stressed calves ( = 41) were compared with controls ( = 44; dams did not undergo transportation during pregnancy) from 2 wk of age until weaning (average age at weaning = 174.8 ± 1.3 d). Temperament was defined by pen score (PS; 1 = calm and 5 = excitable), exit velocity (EV; m/sec), and temperament score (TS; (PS + EV)/2) and was recorded for each calf on d -168, -140, -112, -84, -56, -28, and 0 relative to weaning (d 0 = weaning). Cortisol concentrations were determined in serum samples obtained on d -168, -140, -28, and 0 relative to weaning. Birth weight and weaning weight were not different between treatment groups ( > 0.1). Pen score was greater ( = 0.03) in prenatally stressed calves (2.84 ± 0.21) relative to controls (2.31 ± 0.21). Exit velocity was greater ( < 0.01) in prenatally stressed calves (2.1 ± 0.14 m/sec) than in controls (1.61 ± 0.14 m/sec). Exit velocity was affected by a treatment × calf sex interaction ( = 0.04) and was greater in prenatally stressed females. Exit velocity was also affected by day ( < 0.0001). Temperament score was greater ( = 0.01) in prenatally stressed calves (2.45 ± 0.16) than in controls (1.95 ± 0.16). Temperament score was affected by day ( < 0.01). Basal cortisol concentrations were greater ( = 0.04) in prenatally stressed calves (15.87 ± 1.04 ng/mL) than in controls (13.42 ± 1.03 ng/mL). Basal cortisol concentrations were greater ( < 0.01) in females (16.61 ± 1.06 ng/mL) than in males (12.68 ± 1.02 ng/mL). Cortisol concentrations were positively correlated ( < 0.01) with PS ( = 0.55, < 0.01), EV ( = 0.4, < 0.01), and TS ( = 0.55, < 0.01). Overall, suckling Brahman calves that were prenatally stressed were more temperamental and

  17. Thirty Minutes of Hypobaric Hypoxia Provokes Alterations of Immune Response, Haemostasis, and Metabolism Proteins in Human Serum

    PubMed Central

    Hinkelbein, Jochen; Jansen, Stefanie; Iovino, Ivan; Kruse, Sylvia; Meyer, Moritz; Cirillo, Fabrizio; Drinhaus, Hendrik; Hohn, Andreas; Klein, Corinna; Robertis, Edoardo De; Beutner, Dirk

    2017-01-01

    Hypobaric hypoxia (HH) during airline travel induces several (patho-) physiological reactions in the human body. Whereas severe hypoxia is investigated thoroughly, very little is known about effects of moderate or short-term hypoxia, e.g. during airline flights. The aim of the present study was to analyse changes in serum protein expression and activation of signalling cascades in human volunteers staying for 30 min in a simulated altitude equivalent to airline travel. After approval of the local ethics committee, 10 participants were exposed to moderate hypoxia (simulation of 2400 m or 8000 ft for 30 min) in a hypobaric pressure chamber. Before and after hypobaric hypoxia, serum was drawn, centrifuged, and analysed by two-dimensional gel electrophoresis (2-DIGE) and matrix-assisted laser desorption/ionization followed by time-of-flight mass spectrometry (MALDI-TOF). Biological functions of regulated proteins were identified using functional network analysis (GeneMania®, STRING®, and Perseus® software). In participants, oxygen saturation decreased from 98.1 ± 1.3% to 89.2 ± 1.8% during HH. Expression of 14 spots (i.e., 10 proteins: ALB, PGK1, APOE, GAPDH, C1QA, C1QB, CAT, CA1, F2, and CLU) was significantly altered. Bioinformatic analysis revealed an association of the altered proteins with the signalling cascades “regulation of haemostasis” (four proteins), “metabolism” (five proteins), and “leukocyte mediated immune response” (five proteins). Even though hypobaric hypoxia was short and moderate (comparable to an airliner flight), analysis of protein expression in human subjects revealed an association to immune response, protein metabolism, and haemostasis PMID:28858246

  18. Early Stress History Alters Serum Insulin-Like Growth Factor-1 and Impairs Muscle Mitochondrial Function in Adult Male Rats.

    PubMed

    Ghosh, S; Banerjee, K K; Vaidya, V A; Kolthur-Seetharam, U

    2016-09-01

    Early-life adversity is associated with an enhanced risk for adult psychopathology. Psychiatric disorders such as depression exhibit comorbidity for metabolic dysfunction, including obesity and diabetes. However, it is poorly understood whether, besides altering anxiety and depression-like behaviour, early stress also evokes dysregulation of metabolic pathways and enhances vulnerability for metabolic disorders. We used the rodent model of the early stress of maternal separation (ES) to examine the effects of early stress on serum metabolites, insulin-like growth factor (IGF)-1 signalling, and muscle mitochondrial content. Adult ES animals exhibited dyslipidaemia, decreased serum IGF1 levels, increased expression of liver IGF binding proteins, and a decline in the expression of specific metabolic genes in the liver and muscle, including Pck1, Lpl, Pdk4 and Hmox1. These changes occurred in the absence of alterations in body weight, food intake, glucose tolerance, insulin tolerance or insulin levels. ES animals also exhibited a decline in markers of muscle mitochondrial content, such as mitochondrial DNA levels and expression of TFAM (transcription factor A, mitochondrial). Furthermore, the expression of several genes involved in mitochondrial function, such as Ppargc1a, Nrf1, Tfam, Cat, Sesn3 and Ucp3, was reduced in skeletal muscle. Adult-onset chronic unpredictable stress resulted in overlapping and distinct consequences from ES, including increased circulating triglyceride levels, and a decline in the expression of specific metabolic genes in the liver and muscle, with no change in the expression of genes involved in muscle mitochondrial function. Taken together, our results indicate that a history of early adversity can evoke persistent changes in circulating IGF-1 and muscle mitochondrial function and content, which could serve to enhance predisposition for metabolic dysfunction in adulthood. © 2016 British Society for Neuroendocrinology.

  19. Periodontitis increases rheumatic factor serum levels and citrullinated proteins in gingival tissues and alter cytokine balance in arthritic rats

    PubMed Central

    Corrêa, Mônica G.; Sacchetti, Silvana B.; Ribeiro, Fernanda Vieira; Pimentel, Suzana Peres; Casarin, Renato Corrêa Viana; Cirano, Fabiano Ribeiro; Casati, Marcio Z.

    2017-01-01

    This study investigated some immunological features by experimental periodontitis (EP) and rheumatoid arthritis (RA) disease interact in destructive processes in arthritic rats. Rats were assigned to the following groups: EP +RA; RA; EP; and Negative Control. RA was induced by immunizations with type-II collagen and a local immunization with Complete Freund’s adjuvant in the paw. Periodontitis was induced by ligating the right first molars. The serum level of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACCPA) were measured before the induction of EP (T1) and at 28 days after (T2) by ELISA assay. ACCPA levels were also measured in the gingival tissue at T2. The specimens were processed for morphometric analysis of bone loss, and the gingival tissue surrounding the first molar was collected for the quantification of interleukin IL-1β, IL-4, IL-6, IL-17 and TNF-α using a Luminex/MAGpix assay. Paw edema was analyzed using a plethysmometer. Periodontitis increased the RF and ACCPA levels in the serum and in the gingival tissue, respectively. Besides, the level of paw swelling was increased by EP and remained in progress until the end of the experiment, when EP was associated with RA. Greater values of IL-17 were observed only when RA was present, in spite of PE. It can be concluded that periodontitis increases rheumatic factor serum levels and citrullinated proteins level in gingival tissues and alter cytokine balance in arthritic rats; at the same time, arthritis increases periodontal destruction, confirming the bidirectional interaction between diseases. PMID:28358812

  20. Brain, Liver, and Serum Salusin-alpha and -beta Alterations in Sprague-Dawley Rats with or without Metabolic Syndrome

    PubMed Central

    Citil, Cihan; Konar, Vahit; Aydin, Suleyman; Yilmaz, Musa; Albayrak, Serdal; Ozercan, Ibrahim Hanifi; Ozkan, Yusuf

    2014-01-01

    Background This metabolic syndrome (MetS) study was designed to investigate changes in expression of the neuropeptides salusin-α (Sal-α) and salusin-β (Sal-β) in brain and liver tissue in response to obesity and related changes induced by high-fructose diet and explored how these changes were reflected in the circulating levels of Sal-α and Sal-β, as well as revealing how the lipid profile and concentrations of glucose and uric acid were altered. Material/Methods The study included 14 Sprague-Dawley rats. The control group was fed ad libitum on standard rat pellets, while the intervention group was given water with 10% fructose in addition to the standard rat pellet for 3 months. Sal-α and Sal-β concentrations in the serum and tissue supernatants were measured by ELISA, and immunohistochemical staining was used to demonstrate expression of the hormones in brain and liver. Results Sal-α and Sal-β levels in both the serum and the brain and liver tissue supernatants were lower in the MetS group than the control group. Sal-α and Sal-β were shown by immunohistochemistry to be produced in the brain epithelium, the supraoptic nucleus of the hypothalamus, and the liver hepatocytes. Conclusions The decrease in Sal-α and Sal-β might be involved in the etiopathology of the metabolic syndrome induced by fructose. PMID:25070707

  1. {sup 1}H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis

    SciTech Connect

    Zhang, Ying; Lin, Lianjie; Xu, Yanbin; Lin, Yan; Jin, Yu; Zheng, Changqing

    2013-04-19

    Highlights: •Twenty ulcerative colitis patients and nineteen healthy controls were enrolled. •Increased 3-hydroxybutyrate, glucose, phenylalanine, and decreased lipid were found. •We report early stage diagnosis of ulcerative colitis using NMR-based metabolomics. -- Abstract: Ulcerative colitis (UC) has seriously impaired the health of citizens. Accurate diagnosis of UC at an early stage is crucial to improve the efficiency of treatment and prognosis. In this study, proton nuclear magnetic resonance ({sup 1}H NMR)-based metabolomic analysis was performed on serum samples collected from active UC patients (n = 20) and healthy controls (n = 19), respectively. The obtained spectral profiles were subjected to multivariate data analysis. Our results showed that consistent metabolic alterations were present between the two groups. Compared to healthy controls, UC patients displayed increased 3-hydroxybutyrate, β-glucose, α-glucose, and phenylalanine, but decreased lipid in serum. These findings highlight the possibilities of NMR-based metabolomics as a non-invasive diagnostic tool for UC.

  2. Serum insulin-like system alterations in patients with spinocerebellar ataxia type 3.

    PubMed

    Saute, Jonas Alex Morales; da Silva, Andrew Chaves Feitosa; Muller, Alexandre Pastoris; Hansel, Gisele; de Mello, Alexandre Silva; Maeda, Fábio; Vedolin, Leonardo; Saraiva-Pereira, Maria Luiza; Souza, Diogo Onofre; Arpa, Javier; Torres-Aleman, Ignacio; Portela, Luis Valmor Cruz; Jardim, Laura Bannach

    2011-03-01

    Spinocerebellar ataxias (SCAs) constitute a group of autosomal dominant neurodegenerative disorders with no current treatment. The insulin/insulin-like growth factor 1 (IGF-1) system (IIS) has been shown to play a role in the neurological dysfunction of SCAs and other polyglutamine disorders. We aimed to study the biomarker profile of serum IIS components in SCA3. We performed a case-control study with 46 SCA3 patients and 42 healthy individuals evaluating the peripheral IIS profile (insulin, IGF-1, IGFBP1 and 3) and the correlation with clinical, molecular, and neuroimaging findings. SCA3 patients presented lower insulin and IGFBP3 levels and higher insulin sensitivity (HOMA2), free IGF-I, and IGFBP1 levels when compared with controls. IGFBP-1 levels were directly associated with CAG expanded repeat length; IGF-1 was associated with the volumetries of specific brainstem regions on magnetic resonance imaging (MRI). Insulin levels and sensitivity were related to age at onset of symptoms. Our findings indicate an involvement of IIS components in SCA3 neurobiology and IGFBP-1 as a potential biomarker of the disease. Copyright © 2010 Movement Disorder Society.

  3. [Alteration of serum lipid profile in young men with different somatotypes after food load].

    PubMed

    Fefelova, V V; Koloskova, T P; Kazakova, T V; Fefelova, Yu A

    2015-01-01

    Serum lipid profiles of 76 men of young age (17-21years) were investigated using thin layer chromatography and determination of somatotypes was realized using the scheme of V.P. Chtetsov et al. (1978). The investigation was conducted on an empty stomach and after one hour after food loads (test meal with energy value of 419 kcal, content of proteins - 17,9 g, fats - 11,9 g, carbohydrates - 60,1 g). Regularities inherent to certain somatotypes were revealed. In young men with the abdominal somatotype (with the most pronounced fat component), changes evidencing membranes rigidity growth were revealed: cholesterol esterification processes inhibition and increase of sphingomyelin after meal (p = 0.001). In young men with muscular somatotype the highest level of phosphatidylcholine and the lowest level of easily-oxidized phospholipid fractions in comparison to other somatotypes [thoracic (p = 0.044), abdominal (p = 0.037) and undetermined (p = 0.021)] were registered. General rule is lowering of the free fatty acids levels after meal in comparison with the indices on the empty stomach for all somatotypes: thoracic (p = 0.0001), muscular (p = 0.012), abdominal (p = 0.041) and undetermined (p = 000018). Definiteness of the effect of lowering of free fatty acids levels after meal for all somatotypes could evidence the importance Of this process for maintaining the homeostatic body constants.

  4. Alterations of primary fatty acid amides in serum of patients with severe mental illness.

    PubMed

    Schwarz, Emanuel; Whitfield, Phil; Nahnsen, Sven; Wang, Lan; Major, Hilary; Leweke, F Markus; Koethe, Dagmar; Lio, Pietro; Bahn, Sabine

    2011-01-01

    Cannabis consumption is a well known risk factor for the onset of schizophrenia and evidence accumulates that the endocannabinoid system may play a central role in the disease etiology. Using a clinical bioinformatics approach, we have previously found primary fatty acid amides, which are linked to the endocannabinoid system, to be elevated in drug naive schizophrenia and affective disorder. Here, we provide a detailed description of these findings and expand the investigation by analyzing serum from 74 patients after short term treatment with antipsychotic medication using a liquid chromatography-mass spectrometry (LC-MS) metabolomics approach. We show that primary fatty acid amide (pFAA) levels normalize after treatment with typical but not after treatment with atypical antipsychotic medication. Also, the comparison of pFAA levels in schizophrenia patients to those of sleep deprived healthy volunteers suggests that pFAA abnormalities were not related to changes in the sleep architecture of patients with mental illness. Our findings support the involvement of the endocannabinoid system in the pathology of schizophrenia.

  5. Quantification of serum C-peptide by isotope-dilution liquid chromatography-tandem mass spectrometry: enhanced detection using chemical modification and immunoaffinity purification.

    PubMed

    Kinumi, Tomoya; Mizuno, Ryoko; Takatsu, Akiko

    2014-03-15

    A method was developed to quantify human serum C-peptide by isotope-dilution mass spectrometry (ID MS). This new approach used immunoaffinity purification and chemical modification to improve the sensitivity which covered the wide range of reference interval of serum C-peptide. The immunoaffinity purification was performed using monoclonal antibody against human C-peptide that was immobilized on magnetic beads, and the purified C-peptide was chemically modified using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) prior to liquid chromatography-tandem mass spectrometry (LC-MS/MS). With this method, the LC-MS/MS peak area increased 23-fold compared with the conventional purification by solid-phase extraction and without chemical modification. The limit of quantification was estimated to be 0.003ng on column, which was lower than previously reported. The validation study showed that (1) the response in the 0.003-2.9ng range on column was linear (regression coefficient, r(2)=0.9994), (2) the relative standard deviation (RSD) within and between days was inferior to 4.0%, and (3) the spike and recovery test showed the mean recoveries ranging between 99% and 108%. Comparison with an established commercial immunoassay showed high correlation (r(2)=0.9994) at serum concentration of 0.19-8.49ng/mL. These assessments suggest that this ID MS-based approach can quantify human serum C-peptide with high sensitivity and precision in the reference interval and find a potential use in the reference measurement procedure of serum C-peptide, allowing traceable measurement. This method may also generally be applied to peptide quantification in biological fluids with high sensitivity. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Endocrine Response Phenotypes Are Altered by Charcoal-Stripped Serum Variability.

    PubMed

    Sikora, Matthew J; Johnson, Michael D; Lee, Adrian V; Oesterreich, Steffi

    2016-10-01

    Charcoal-stripped bovine serum (CSS) is a critical reagent in the study of steroid hormones. However, CSS has high lot-to-lot variability, including residual growth factor and steroid hormone content. Assessing and reporting this variability is challenging but may affect experimental outcomes and data reproducibility. We hypothesized that CSS lot variability would affect endocrine response phenotypes in breast cancer cells, and we tested the effects of five individual CSS lots on endocrine response in MCF-7 and MDA MB 134VI (MM134) cells. Based on the effects of antiestrogens on MCF-7 cell proliferation, we defined CSS lots as having complete vs partial hormone deprivation. In partial deprivation CSS, the absolute effects of residual estrogens on cell proliferation were modest, but these effects masked the partial agonist activity of 4-hydroxytamoxifen in MM134 cells. Importantly, this effectively reversed the interpretation of tamoxifen-resistance in MM134 cells. Variable effects of CSS lots on endocrine resistance phenotypes were also observed in MCF-7 cells. In this context, we observed that partial vs complete deprivation CSS allowed for the development of unique early endocrine resistance phenotypes that correlated with the presence or absence of residual estrogenic hormones. We evaluated the methods of CSS preparation and identified factors contributing to the extent of hormone deprivation. Our observations suggest that CSS lot-to-lot variability has substantial effects on endocrine response phenotypes and that this ubiquitous factor in study methodology may confound reproducibility. Renewed vigilance in testing and reporting CSS phenotypes will greatly aid in interpreting and reproducing endocrine response and resistance data by the community.

  7. Is higher serum cholesterol associated with altered tendon structure or tendon pain? A systematic review.

    PubMed

    Tilley, Benjamin J; Cook, Jill L; Docking, Sean I; Gaida, James E

    2015-12-01

    Tendon pain occurs in individuals with extreme cholesterol levels (familial hypercholesterolaemia). It is unclear whether the association with tendon pain is strong with less extreme elevations of cholesterol. To determine whether lipid levels are associated with abnormal tendon structure or the presence of tendon pain. We conducted a systematic review and meta-analysis. Relevant articles were found through an electronic search of 6 medical databases-MEDLINE, Cochrane, AMED, EMBASE, Web of Science and Scopus. We included all case-control or cross-sectional studies with data describing (1) lipid levels or use of lipid-lowering drugs and (2) tendon structure or tendon pain. 17 studies (2612 participants) were eligible for inclusion in the review. People with altered tendon structure or tendon pain had significantly higher total cholesterol, low-density lipoprotein cholesterol and triglycerides, as well as lower high-density lipoprotein cholesterol; with mean difference values of 0.66, 1.00, 0.33, and -0.19 mmol/L, respectively. The results of this review indicate that a relationship exists between an individual's lipid profile and tendon health. However, further longitudinal studies are required to determine whether a cause and effect relationship exists between tendon structure and lipid levels. This could lead to advancement in the understanding of the pathoaetiology and thus treatment of tendinopathy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. Is higher serum cholesterol associated with altered tendon structure or tendon pain? A systematic review

    PubMed Central

    Tilley, Benjamin J; Cook, Jill L; Docking, Sean I; Gaida, James E

    2015-01-01

    Background Tendon pain occurs in individuals with extreme cholesterol levels (familial hypercholesterolaemia). It is unclear whether the association with tendon pain is strong with less extreme elevations of cholesterol. Objective To determine whether lipid levels are associated with abnormal tendon structure or the presence of tendon pain. Methods We conducted a systematic review and meta-analysis. Relevant articles were found through an electronic search of 6 medical databases—MEDLINE, Cochrane, AMED, EMBASE, Web of Science and Scopus. We included all case–control or cross-sectional studies with data describing (1) lipid levels or use of lipid-lowering drugs and (2) tendon structure or tendon pain. Results 17 studies (2612 participants) were eligible for inclusion in the review. People with altered tendon structure or tendon pain had significantly higher total cholesterol, low-density lipoprotein cholesterol and triglycerides, as well as lower high-density lipoprotein cholesterol; with mean difference values of 0.66, 1.00, 0.33, and −0.19 mmol/L, respectively. Conclusions The results of this review indicate that a relationship exists between an individual’s lipid profile and tendon health. However, further longitudinal studies are required to determine whether a cause and effect relationship exists between tendon structure and lipid levels. This could lead to advancement in the understanding of the pathoaetiology and thus treatment of tendinopathy. PMID:26474596

  9. Global alterations of the transcriptional landscape during yeast growth and development in the absence of Ume6-dependent chromatin modification

    PubMed Central

    Lardenois, Aurélie; Becker, Emmanuelle; Walther, Thomas; Law, Michael J.; Xie, Bingning; Demougin, Philippe; Strich, Randy

    2017-01-01

    Chromatin modification enzymes are important regulators of gene expression and some are evolutionarily conserved from yeast to human. Saccharomyces cerevisiae is a major model organism for genome-wide studies that aim at the identification of target genes under the control of conserved epigenetic regulators. Ume6 interacts with the upstream repressor site 1 (URS1) and represses transcription by recruiting both the conserved histone deacetylase Rpd3 (through the co-repressor Sin3) and the chromatin-remodeling factor Isw2. Cells lacking Ume6 are defective in growth, stress response, and meiotic development. RNA profiling studies and in vivo protein-DNA binding assays identified mRNAs or transcript isoforms that are directly repressed by Ume6 in mitosis. However, a comprehensive understanding of the transcriptional alterations, which underlie the complex ume6Δ mutant phenotype during fermentation, respiration, or sporulation, is lacking. We report the protein-coding transcriptome of a diploid MATa/α wild-type and ume6/ume6 mutant strains cultured in rich media with glucose or acetate as a carbon source, or sporulation-inducing medium. We distinguished direct from indirect effects on mRNA levels by combining GeneChip data with URS1 motif predictions and published high-throughput in vivo Ume6-DNA binding data. To gain insight into the molecular interactions between successive waves of Ume6-dependent meiotic genes, we integrated expression data with information on protein networks. Our work identifies novel Ume6 repressed genes during growth and development and reveals a strong effect of the carbon source on the derepression pattern of transcripts in growing and developmentally arrested ume6/ume6 mutant cells. Since yeast is a useful model organism for chromatin-mediated effects on gene expression, our results provide a rich source for further genetic and molecular biological work on the regulation of cell growth and cell differentiation in eukaryotes. PMID:25957495

  10. Global alterations of the transcriptional landscape during yeast growth and development in the absence of Ume6-dependent chromatin modification.

    PubMed

    Lardenois, Aurélie; Becker, Emmanuelle; Walther, Thomas; Law, Michael J; Xie, Bingning; Demougin, Philippe; Strich, Randy; Primig, Michael

    2015-10-01

    Chromatin modification enzymes are important regulators of gene expression and some are evolutionarily conserved from yeast to human. Saccharomyces cerevisiae is a major model organism for genome-wide studies that aim at the identification of target genes under the control of conserved epigenetic regulators. Ume6 interacts with the upstream repressor site 1 (URS1) and represses transcription by recruiting both the conserved histone deacetylase Rpd3 (through the co-repressor Sin3) and the chromatin-remodeling factor Isw2. Cells lacking Ume6 are defective in growth, stress response, and meiotic development. RNA profiling studies and in vivo protein-DNA binding assays identified mRNAs or transcript isoforms that are directly repressed by Ume6 in mitosis. However, a comprehensive understanding of the transcriptional alterations, which underlie the complex ume6Δ mutant phenotype during fermentation, respiration, or sporulation, is lacking. We report the protein-coding transcriptome of a diploid MAT a/α wild-type and ume6/ume6 mutant strains cultured in rich media with glucose or acetate as a carbon source, or sporulation-inducing medium. We distinguished direct from indirect effects on mRNA levels by combining GeneChip data with URS1 motif predictions and published high-throughput in vivo Ume6-DNA binding data. To gain insight into the molecular interactions between successive waves of Ume6-dependent meiotic genes, we integrated expression data with information on protein networks. Our work identifies novel Ume6 repressed genes during growth and development and reveals a strong effect of the carbon source on the derepression pattern of transcripts in growing and developmentally arrested ume6/ume6 mutant cells. Since yeast is a useful model organism for chromatin-mediated effects on gene expression, our results provide a rich source for further genetic and molecular biological work on the regulation of cell growth and cell differentiation in eukaryotes.

  11. Motor restlessness, sleep disturbances, thermal sensory alterations and elevated serum iron levels in Btbd9 mutant mice

    PubMed Central

    DeAndrade, Mark P.; Johnson, Russell L.; Unger, Erica L.; Zhang, Li; van Groen, Thomas; Gamble, Karen L.; Li, Yuqing

    2012-01-01

    Restless legs syndrome (RLS), also known as Willis–Ekbom disease, is a sensory–motor neurological disorder with a circadian component. RLS is characterized by uncomfortable sensations in the extremities, generally at night or during sleep, which often leads to an uncontrollable urge to move them for relief. Recently, genomic studies identified single-nucleotide polymorphisms in BTBD9, along with three other genes, as being associated with a higher risk of RLS. Little is known about the function of BTBD9 or its potential role in the pathophysiology of RLS. We therefore examined a line of Btbd9 mutant mice we recently generated for phenotypes similar to symptoms found in RLS patients. We observed that the Btbd9 mutant mice had motor restlessness, sensory alterations likely limited to the rest phase, and decreased sleep and increased wake times during the rest phase. Additionally, the Btbd9 mutant mice had altered serum iron levels and monoamine neurotransmitter systems. Furthermore, the sensory alterations in the Btbd9 mutant mice were relieved using ropinirole, a dopaminergic agonist widely used for RLS treatment. These results, taken together, suggest that the Btbd9 mutant mice model several characteristics similar to RLS and would therefore be the first genotypic mouse model of RLS. Furthermore, our data provide further evidence that BTBD9 is involved in RLS, and future studies of the Btbd9 mutant mice will help shine light on its role in the pathophysiology of RLS. Finally, our data argue for the utility of Btbd9 mutant mice to discover and screen novel therapeutics for RLS. PMID:22678064

  12. Serum Phosphorus and Mortality in the Third National Health and Nutrition Examination Survey (NHANES III): Effect Modification by Fasting

    PubMed Central

    Chang, Alex R.; Grams, Morgan

    2014-01-01

    Background Serum phosphorus levels have been associated with mortality in some but not all studies. Since dietary intake prior to measurement can affect serum phosphorus levels, we hypothesized that the association between serum phosphorus and mortality is strongest in those who have fasted for longer duration. Study Design Prospective cohort study. Setting & Participants Nationally representative sample of 12,984 participants aged 20 years or older in the Third National Health and Nutrition Examination Survey (1988–1994). Factors Serum phosphorus, fasting duration (dichotomized as ≥12 or <12 hours) Outcomes All-cause and cardiovascular mortality determined by death certificate data from the National Death Index. Measurements Serum phosphorus measured in a central laboratory and fasting duration recorded as amount of time since food or drink other than water was consumed. Results Individuals fasting ≥12 hours had lower serum phosphorus levels than those fasting < 12 hours (3.34 vs. 3.55 mg/dL; p<0.001) and higher correlation with repeated measurement (0.66 vs. 0.53; p=0.002). In multivariable-adjusted Cox regression models, the highest quartile of serum phosphorus was associated with increased mortality in participants fasting ≥12 hours (adjusted HR, 1.74; 95% CI, 1.38–2.20; reference, lowest quartile) but not in participants fasting <12 hours (adjusted HR, 1.08; 95% CI, 0.89–1.32; p for interaction=0.002). Relationships were consistent using 8 hours as the fasting cutpoint or cardiovascular mortality as the outcome. Limitations Observational study, lack of fibroblast growth factor 23 or intact parathyroid hormone measurements. Conclusions Fasting but not non-fasting serum phosphorus levels were associated with increased mortality. Risk prognostication based on serum phosphorus may be improved using fasting levels. PMID:24935232

  13. Identification of Novel Site-Specific Alterations in the Modification Level of Myelin Basic Protein Isolated from Mouse Brain at Different Ages Using Capillary Electrophoresis-Mass Spectrometry.

    PubMed

    Sarg, Bettina; Faserl, Klaus; Lindner, Herbert H

    2017-10-01

    Myelin basic protein (MBP) is a multifunctional protein involved in maintaining the stability and integrity of the myelin sheath by a variety of interactions with membranes and other proteins. MBP is subjected to extensive posttranslational modifications (PTMs) that are known to be crucial for the regulation of these interactions. Here, we report capillary electrophoresis-mass spectrometric (CE-MS) analysis for the separation and identification of MBP peptides that incorporate the same PTM at different sites, creating multiple localization variants, and the ability to analyze challenging modifications such as asparagine and glutamine deamidation, isomerization, and arginine citrullination. Moreover, we observed site-specific alterations in the modification level of MBP purified from brain of mice of different age. In total, we identified 40 modifications at 33 different sites, which include both previously reported and seven novel modifications. The identified modifications include Nα-terminal acetylation, mono- and dimethylation, phosphorylation, oxidation, deamidation, and citrullination. Notably, some new sites of arginine methylation overlap with the sites of citrullination. Our results highlight the need for sensitive and efficient techniques for a comprehensive analysis of PTMs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Elevated Serum Polybrominated Diphenyl Ethers and Alteration of Thyroid Hormones in Children from Guiyu, China

    PubMed Central

    Xu, Xijin; Liu, Junxiao; Zeng, Xiang; Lu, Fangfang; Chen, Aimin; Huo, Xia

    2014-01-01

    Informal electronic waste (e-waste) recycling results in serious environmental pollution of polybrominated diphenyl ethers (PBDEs) and heavy metals. This study explored whether there is an association between PBDEs, heavy metal and key growth- and development-related hormones in children from Guiyu, an e-waste area in southern China. We quantified eight PBDE congeners using gas chromatographic mass spectrometry, lead and cadmium utilizing graphite furnace atomic absorption spectrometry, three thyroids with radioimmunoassay and two types of growth hormones by an enzyme-linked immune-sorbent assay (ELISA) in 162 children, 4 to 6 years old, from Guiyu. In blood, median total PBDE was 189.99 ng/g lipid. Lead and cadmium concentrations in blood averaged 14.53±4.85 µg dL−1 and 0.77±0.35 µg L−1, respectively. Spearman partial correlation analysis illustrated that lead was positively correlated with BDE153 and BDE183. Thyroid-stimulating hormone (TSH) was positively correlated with almost all PBDE congeners and negatively correlated with insulin-like growth factor binding protein-3 (IGFBP-3), whereas free triiodothyronine (FT3) and free thyroxine (FT4) were negatively correlated with BDE154. However, no correlation between the hormones and blood lead or cadmium levels was found in this study. Adjusted multiple linear regression analysis showed that total PBDEs was negatively associated with FT3 and positively associated with TSH. Notably, FT4 was positively correlated with FT3, house functions as a workshop, and father's work involved in e-waste recycling and negatively correlated with vitamin consumptions. TSH was negatively related with FT4, paternal residence time in Guiyu, working hours of mother, and child bean products intake. IGFBP-3 was positively correlated with IGF-1 and house close to an e-waste dump. These results suggest that elevated PBDEs and heavy metals related to e-waste in Guiyu may be important risk factors for hormone alterations in children

  15. A combined chemometric and quantitative NMR analysis of HIV/AIDS serum discloses metabolic alterations associated with disease status.

    PubMed

    McKnight, Tracy R; Yoshihara, Hikari A I; Sitole, Lungile J; Martin, Jeffery N; Steffens, Francois; Meyer, Debra

    2014-11-01

    Individuals infected with the human immunodeficiency virus (HIV) often suffer from concomitant metabolic complications. Treatment with antiretroviral therapy has also been shown to alter the metabolism of patients. Although chemometric analysis of nuclear magnetic resonance (NMR) spectra of human sera can distinguish normal sera (HIVneg) from HIV-infected sera (HIVpos) and sera from HIV-infected patients on antiretroviral therapy (ART), quantitative analysis of the discriminating metabolites and their relationship to disease status has yet to be determined. The objectives of the study were to analyze NMR spectra of HIVneg, HIVpos, and ART serum samples with a combination of chemometric and quantitative methods and to compare the NMR data with disease status as measured by viral load and CD4 count. High-resolution magic angle spinning (HRMAS) NMR spectroscopy was performed on HIVneg (N = 10), HIVpos (N = 10), and ART (N = 10) serum samples. Chemometric linear discriminant analysis classified the three groups of spectra with 100% accuracy. Concentrations of 12 metabolites were determined with a semi-parametric metabolite quantification method named high-resolution quantum estimation (HR-QUEST). CD4 count was directly associated with alanine (p = 0.008), and inversely correlated with both glutamine (p = 0.017) and glucose (p = 0.022) concentrations. A multivariate linear model using alanine, glutamine and glucose as covariates demonstrated an association with CD4 count (p = 0.038). The combined chemometric and quantitative analysis of the data disclosed previously unknown associations between specific metabolites and disease status. The observed associations with CD4 count are consistent with metabolic disorders that are commonly seen in HIV-infected patients.

  16. Phase variation of a Type IIG restriction-modification enzyme alters site-specific methylation patterns and gene expression in Campylobacter jejuni strain NCTC11168

    PubMed Central

    Anjum, Awais; Brathwaite, Kelly J.; Aidley, Jack; Connerton, Phillippa L.; Cummings, Nicola J.; Parkhill, Julian; Connerton, Ian; Bayliss, Christopher D.

    2016-01-01

    Phase-variable restriction-modification systems are a feature of a diverse range of bacterial species. Stochastic, reversible switches in expression of the methyltransferase produces variation in methylation of specific sequences. Phase-variable methylation by both Type I and Type III methyltransferases is associated with altered gene expression and phenotypic variation. One phase-variable gene of Campylobacter jejuni encodes a homologue of an unusual Type IIG restriction-modification system in which the endonuclease and methyltransferase are encoded by a single gene. Using both inhibition of restriction and PacBio-derived methylome analyses of mutants and phase-variants, the cj0031c allele in C. jejuni strain NCTC11168 was demonstrated to specifically methylate adenine in 5′CCCGA and 5′CCTGA sequences. Alterations in the levels of specific transcripts were detected using RNA-Seq in phase-variants and mutants of cj0031c but these changes did not correlate with observed differences in phenotypic behaviour. Alterations in restriction of phage growth were also associated with phase variation (PV) of cj0031c and correlated with presence of sites in the genomes of these phages. We conclude that PV of a Type IIG restriction-modification system causes changes in site-specific methylation patterns and gene expression patterns that may indirectly change adaptive traits. PMID:26786317

  17. The effects of hydroxyapatite/calcium phosphate glass scaffold and its surface modification with bovine serum albumin on 1-wall intrabony defects of beagle dogs: a preliminary study.

    PubMed

    Um, Yoo-Jung; Jung, Ui-Won; Chae, Gyung-Joon; Kim, Chang-Sung; Lee, Yong-Keun; Cho, Kyoo-Sung; Kim, Chong-Kwan; Choi, Seong-Ho

    2008-12-01

    The purpose of this study was to evaluate the effects of biphasic hydroxyapatite/calcium phosphate glass (HA/CPG) scaffold and its surface modification with bovine serum albumin (BSA) on periodontal regeneration. 1-wall intrabony defects were surgically created on five beagle dogs. HA/CPG scaffolds, with a hydroxyapatite (HA)/calcium phosphate glass (CPG) ratio of 95:5 by weight (%) and surface modification done by 2% bovine serum albumin, were used. The control group received surgical flap operation, and the experimental groups were filled with HA/CPG scaffolds and HA/CPG(BSA) scaffolds. The animals were sacrificed eight weeks after surgery. Histological findings revealed better space maintenance in the experimental groups than the control group, and showed new bone formation intermittently in between the residual material particles. The newly formed bone was mostly woven bone and the residual particles were undergoing resorption. Cementum regeneration was observed with limited root resorption in all the groups. Histometric analysis also revealed greater mean values in new bone formation, cementum regeneration and bone area than the control group in both experimental groups. However, similar findings were presented between HA/CPG and HA/CPG(BSA). The result of the present study revealed the newly fabricated HA/CPG scaffold to have a potential use as a bone substitute material.

  18. Modification of the selected method for the determination of serum iron. Substitution of bathophenanthroline by ferene S.

    PubMed

    Charlier, C; Plomteux, G; Vernet, M; Gendre, P; Revenant, M C; Guillemin, C

    1992-01-01

    The previously selected method (1977) for the measurement of iron in human serum has been modified by the working group on Iron and Iron-Transport Proteins (Sociéte Française de Biologie Clinique). Ferene S is used as the chromogen, it is more sensitive and cheaper than bathophenanthroline. The sample size has been reduced from 2 to 0.5 ml. No interference could be shown with high concentrations of bilirubin, copper or hemoglobin.

  19. Tissue and serum samples of patients with papillary thyroid cancer with and without benign background demonstrate different altered expression of proteins

    PubMed Central

    Abdullah, Mardiaty Iryani; Lee, Ching Chin; Mat Junit, Sarni; Ng, Khoon Leong

    2016-01-01

    Background Papillary thyroid cancer (PTC) is mainly diagnosed using fine-needle aspiration biopsy. This most common form of well-differentiated thyroid cancer occurs with or without a background of benign thyroid goiter (BTG). Methods In the present study, a gel-based proteomics analysis was performed to analyse the expression of proteins in tissue and serum samples of PTC patients with (PTCb; n = 6) and without a history of BTG (PTCa; n = 8) relative to patients with BTG (n = 20). This was followed by confirmation of the levels of proteins which showed significant altered abundances of more than two-fold difference (p < 0.01) in the tissue and serum samples of the same subjects using ELISA. Results The data of our study showed that PTCa and PTCb distinguish themselves from BTG in the types of tissue and serum proteins of altered abundance. While higher levels of alpha-1 antitrypsin (A1AT) and heat shock 70 kDa protein were associated with PTCa, lower levels of A1AT, protein disulfide isomerase and ubiquitin-conjugating enzyme E2 N seemed apparent in the PTCb. In case of the serum proteins, higher abundances of A1AT and alpha 1-beta glycoprotein were detected in PTCa, while PTCb was associated with enhanced apolipoprotein A-IV and alpha 2-HS glycoprotein (AHSG). The different altered expression of tissue and serum A1AT as well as serum AHSG between PTCa and PTCb patients were also validated by ELISA. Discussion The distinctive altered abundances of the tissue and serum proteins form preliminary indications that PTCa and PTCb are two distinct cancers of the thyroid that are etiologically and mechanistically different although it is currently not possible to rule out that they may also be due other reasons such as the different stages of the malignant disease. These proteins stand to have a potential use as tissue or serum biomarkers to discriminate the three different thyroid neoplasms although this requires further validation in clinically representative

  20. Effect of Drug Alprazolam on Restrained Stress Induced Alteration of Serum Cortisol and Antioxidant Vitamins (Vitamin C and E) in Male Albino Rats

    PubMed Central

    Kori, Rohini Sharanappa; Aladakatti, Ravindranath H.; Desai, S.D.

    2016-01-01

    Introduction Stress can cause harmful effects in the body that induce a wide range of biochemical and behavioural changes. As anti-stress drugs are routinely used to combat stress hence study is needed to assess the contraindication of these drugs in the physiological systems. Aim To investigate the effect of alprazolam on restrained stress induced alteration of serum cortisol, and antioxidant vitamin levels in male albino rats. Materials and Methods Adult male albino rats (body weight 175-225g) were divided into four groups of six animals in each. Group I (control), kept undisturbed in the metabolic cage throughout the 42 days experimental period. Group II (stress) rats were kept in a wire mesh restrainer for 6 hr/day for 42 days. Group III (stress+ withdrawal) rats were stressed for 21 days and withdrawal of stress for remaining 21 days (total 42 days). Group IV (stress + alprazolam) rats were only stressed for 21 days and treated with drug alprazolam (5mg/kg body weight, intraperitoneal) in continuation with stress for remaining 21 days (total period is 42 days). At the end of 42 days all the rats were sacrificed and serum cortisol, vitamin C and E levels were estimated. Results Group II (stressed) showed a significant increase in serum cortisol level with concomitant decrease of serum vitamin C and E levels. Group III (withdrawal) and Group IV (+alprazolam) rats showed significant reduction of serum cortisol along with subsequent increase of serum vitamin C and E concentrations. Conclusion Results indicate a possible antioxidant effect of alprazolam on restrained stress induced alteration of serum cortisol and antioxidant vitamin levels. PMID:27656428

  1. Effect of Drug Alprazolam on Restrained Stress Induced Alteration of Serum Cortisol and Antioxidant Vitamins (Vitamin C and E) in Male Albino Rats.

    PubMed

    Kori, Rohini Sharanappa; Aladakatti, Ravindranath H; Desai, S D; Das, Kusal Kanti

    2016-08-01

    Stress can cause harmful effects in the body that induce a wide range of biochemical and behavioural changes. As anti-stress drugs are routinely used to combat stress hence study is needed to assess the contraindication of these drugs in the physiological systems. To investigate the effect of alprazolam on restrained stress induced alteration of serum cortisol, and antioxidant vitamin levels in male albino rats. Adult male albino rats (body weight 175-225g) were divided into four groups of six animals in each. Group I (control), kept undisturbed in the metabolic cage throughout the 42 days experimental period. Group II (stress) rats were kept in a wire mesh restrainer for 6 hr/day for 42 days. Group III (stress+ withdrawal) rats were stressed for 21 days and withdrawal of stress for remaining 21 days (total 42 days). Group IV (stress + alprazolam) rats were only stressed for 21 days and treated with drug alprazolam (5mg/kg body weight, intraperitoneal) in continuation with stress for remaining 21 days (total period is 42 days). At the end of 42 days all the rats were sacrificed and serum cortisol, vitamin C and E levels were estimated. Group II (stressed) showed a significant increase in serum cortisol level with concomitant decrease of serum vitamin C and E levels. Group III (withdrawal) and Group IV (+alprazolam) rats showed significant reduction of serum cortisol along with subsequent increase of serum vitamin C and E concentrations. Results indicate a possible antioxidant effect of alprazolam on restrained stress induced alteration of serum cortisol and antioxidant vitamin levels.

  2. Modification of MCF-10A cells with pioglitazone and serum-rich growth medium increases soluble factors in the conditioned medium, likely reducing BT-474 cell growth.

    PubMed

    Khoo, Boon Yin; Miswan, Noorizan; Balaram, Prabha; Nadarajan, Kalpanah; Elstner, Elena

    2012-01-01

    In the present study, we aimed to preincubate MCF-10A cells with pioglitazone and/or serum-rich growth media and to determine adhesive and non-adhesive interactions of the preincubated MCF-10A cells with BT-474 cells. For this purpose, the MCF-10A cells were preincubated with pioglitazone and/or serum-rich growth media, at appropriate concentrations, for 1 week. The MCF-10A cells preincubated with pioglitazone and/or serum-rich growth media were then co-cultured adhesively and non-adhesively with BT-474 cells for another week. Co-culture of BT-474 cells with the preincubated MCF-10A cells, both adhesively and non-adhesively, reduced the growth of the cancer cells. The inhibitory effect of the preincubated MCF-10A cells against the growth of BT-474 cells was likely produced by increasing levels of soluble factors secreted by the preincubated MCF-10A cells into the conditioned medium, as immunoassayed by ELISA. However, only an elevated level of a soluble factor distinguished the conditioned medium collected from the MCF-10A cells preincubated with pioglitazone and serum-rich growth medium than that with pioglitazone alone. This finding was further confirmed by the induction of the soluble factor transcript expression in the preincubated MCF-10A cells, as determined using real-time PCR, for the above phenomenon. Furthermore, modification of the MCF-10A cells through preincubation did not change the morphology of the cells, indicating that the preincubated cells may potentially be injected into mammary fat pads to reduce cancer growth in patients or to be used for others cell-mediated therapy.

  3. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria.

    PubMed

    Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

    2014-10-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UE(UA)) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UE(UA), suggesting that SUA decreased as a result of the increase in the UE(UA). The increase in UE(UA) was correlated with an increase in urinary D-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UE(UA) is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and D-glucose. It was observed that the efflux of [(14) C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm D-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [(14) C]UA by oocytes was cis-inhibited by 100 mm D-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UE(UA) could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose.

  4. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria

    PubMed Central

    Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

    2014-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the UEUA. The increase in UEUA was correlated with an increase in urinary d-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d-glucose. It was observed that the efflux of [14C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm d-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [14C]UA by oocytes was cis-inhibited by 100 mm d-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose. PMID:25044127

  5. Profound Changes in Sex Hormone Levels during Cross-Sex Hormone Therapy of Transsexuals do not Alter Serum Cholesterol Acceptor Capacity.

    PubMed

    Wultsch, Anna; Kaufmann, Ulrike; Ott, Johannes; Stojakovic, Tatjana; Scharnagl, Hubert; Stangl, Herbert; Strobl, Witta Monika

    2015-06-01

    Men and postmenopausal women exhibit a higher risk for atherosclerosis than premenopausal women. These differences were often attributed to sex steroids, but the role of estrogen and testosterone in atherosclerosis are more complex than anticipated. Cross-sex hormone therapy of transsexuals is an interesting model, which has been used to study hormonal effects on serum lipid profile, insulin resistance, and body composition. However, studies on macrophage cholesterol efflux, the first step in reverse cholesterol transport, are not available. The aim of this study was to evaluate the effect of cross-sex hormone therapy in transsexuals on the capacity of serum to accept cholesterol from macrophages. Cholesterol acceptor capacity (CAC) of serum from transsexuals before and after at least 6 months of hormone treatment was measured using macrophage tissue culture models. CAC of serum using the human acute monocytic leukemia cell line (THP-1 cells). Unexpectedly, the CAC of serum from male to female (MtF) transsexuals was not increased, but decreased after hormone therapy. Serum from female to male (FtM) transsexuals showed no changes in CAC. Despite drastic changes in hormone status, no increase in CAC was detected in MtF patients, and no alteration in CAC was seen in FtM patients. These data further challenge the traditional view that estrogen and testosterone exert beneficial and detrimental effects, respectively, on lipoprotein metabolism and ultimately atherosclerosis. © 2015 International Society for Sexual Medicine.

  6. Butyrate, an HDAC inhibitor, stimulates interplay between different posttranslational modifications of histone H3 and differently alters G1-specific cell cycle proteins in vascular smooth muscle cells.

    PubMed

    Mathew, Omana P; Ranganna, Kasturi; Yatsu, Frank M

    2010-12-01

    HDACs and HATs regulate histone acetylation, an epigenetic modification that controls chromatin structure and through it, gene expression. Butyrate, a dietary HDAC inhibitor, inhibits VSMC proliferation, a crucial factor in atherogenesis, and the principle mechanism in arterial and in-stent restenosis. Here, the link between antiproliferation action of butyrate and the portraits of global covalent modifications of histone H3 that it induces are characterized to understand the mechanics of butyrate-arrested VSMC proliferation. Analysis of histone H3 modifications specific to butyrate arrested VSMC proliferation display induction of histone H3-Lysine9 acetylation, inhibition of histone H3-Serine10 phosphorylation, reduction of histone H3-Lysine9 dimethylation and stimulation of histone H3-Lysine4 di-methylation, which is linked to transcriptional activation, cell cycle/mitosis, transcriptional suppression and activation, respectively. Conversely, untreated VSMCs exhibit inhibition of H3-Lysine9 acetylation, induction of H3-Serine10 phosphorylation, stimulation of H3-Lysine9 di-methylation and reduction in H3-Lysine4 di-methylation. Butyrate's cooperative effects on H3-Lysine9 acetylation and H3-Serine10 phosphorylation, and contrasting effects on di-methylation of H3-Lysine9 and H3-Lysine4 suggests that the interplay between these site-specific modifications cause distinct chromatin alterations that allow cyclin D1 and D3 induction, G1-specific cdk4, cdk6 and cdk2 downregulation, and upregulation of cdk inhibitors, p15INK4b and p21Cip1. Regardless of butyrate's effect on D-type cyclins, downregulation of G1-specific cdks and upregulation of cdk inhibitors by butyrate prevents cell cycle progression by failing to inactivate Rb. Overall, through chromatin remodeling, butyrate appears to differentially alter G1-specific cell cycle proteins to ensure proliferation arrest of VSMCs, a crucial cellular component of blood vessel wall.

  7. Methylphenidate Ameliorates Depressive Comorbidity in ADHD Children without any Modification on Differences in Serum Melatonin Concentration between ADHD Subtypes

    PubMed Central

    Cubero-Millán, Isabel; Molina-Carballo, Antonio; Machado-Casas, Irene; Fernández-López, Luisa; Martínez-Serrano, Sylvia; Tortosa-Pinto, Pilar; Ruiz-López, Aida; Luna-del-Castillo, Juan-de-Dios; Uberos, José; Muñoz-Hoyos, Antonio

    2014-01-01

    The vast majority of Attention-deficit/hyperactivity disorder (ADHD) patients have other associated pathologies, with depressive symptoms as one of the most prevalent. Among the mediators that may participate in ADHD, melatonin is thought to regulate circadian rhythms, neurological function and stress response. To determine (1) the serum baseline daily variations and nocturnal excretion of melatonin in ADHD subtypes and (2) the effect of chronic administration of methylphenidate, as well as the effects on symptomatology, 136 children with ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision: DSM-IV-TR criteria) were divided into subgroups using the “Children’s Depression Inventory” (CDI). Blood samples were drawn at 20:00 and 09:00 h, and urine was collected between 21:00 and 09:00 h, at inclusion and after 4.61 ± 2.29 months of treatment. Melatonin and its urine metabolite were measured by radioimmunoassay RIA. Factorial analysis was performed using STATA 12.0. Melatonin was higher predominantly in hyperactive-impulsive/conduct disordered children (PHI/CD) of the ADHD subtype, without the influence of comorbid depressive symptoms. Methylphenidate ameliorated this comorbidity without induction of any changes in the serum melatonin profile, but treatment with it was associated with a decrease in 6-s-melatonin excretion in both ADHD subtypes. Conclusions: In untreated children, partial homeostatic restoration of disrupted neuroendocrine equilibrium most likely led to an increased serum melatonin in PHI/CD children. A differential cerebral melatonin metabolization after methylphenidate may underlie some of the clinical benefit. PMID:25257531

  8. [Serum enzyme alterations during diabetic ketoacidosis. Prospective study of the behaviour of AP, AsAT, AIAT, and GGPT in 24 cases (author's transl)].

    PubMed

    Pérez-Jiménez, F; Muñoz, R; Jiménez Perepérez, J; Jiménez Alonso, J; Grilo, A; Benito, P

    1981-09-25

    Because of the scarcity of data on the changes of serum enzymes during diabetic ketoacidosis, the authors have prospectively studied the alterations of gamma-glutamyl transpeptidase (GGTP), alkaline phosphatase (AP), aspartate aminotransferase (AsAT), and alanine aminotransferase (AIAT) in this metabolic disturbance. The most significant finding was the frequent increase of AP activity on admission, with a systematic fall of the serum levels within the first 24 hours (p less than 0.001). This phenomenon was negatively correlated with patients' age (p less than 0.05), and the same occurred with the bone isoenzyme of AP (p less than 0.01). The remaining enzymes studies were always normal, thus suggesting that any increase of the serum levels of GGTP, AsAT, and AIAT found in a patient with diabetic ketoacidosis must arise the suspicion of an associated disturbance.

  9. Precipitation and selective extraction of human serum endogenous peptides with analysis by quadrupole time-of-flight mass spectrometry reveals posttranslational modifications and low-abundance peptides.

    PubMed

    Williams, Declan; Ackloo, Suzanne; Zhu, Peihong; Bowden, Peter; Evans, Kenneth R; Addison, Christina L; Lock, Chris; Marshall, John G

    2010-02-01

    The endogenous peptides of human serum may have regulatory functions, have been associated with physiological states, and their modifications may reveal some mechanisms of disease. In order to correlate levels of specific peptides with disease alongside internal standards, the polypeptides must first be reliably extracted and identified. Endogenous blood peptides can be effectively enriched by precipitation of the serum with organic solvents followed by selective extraction of peptides using aqueous solutions modified with organic solvents. Polypeptides on filter paper were assayed with Coomasie brilliant blue binding. The polypeptides were resolved by detergent tricine polyacrylamide electrophoresis and visualized by diamine silver staining. Peptides in the extracts were collected by C18 and analyzed by matrix-assisted laser desorption/ionization and liquid chromatography-electrospray ionization-tandem mass spectrometry (MS/MS) quadrupole time-of-flight MS/MS. Peptides were resolved as multiple isotopic peaks in MS mode with mass deviation of 0.1 Da or less and similar accuracy for fragments. The sensitivity of MS and MS/MS analysis was estimated to be in the picomolar range or less. The peptide composition of the extracts was dependent on solvent formulation. Multiple peptides from apolipoproteins, complement proteins, coagulation factors, and many others were identified by X!Tandem with high mass accuracy of peptide ions and fragments from collision-induced dissociation. Many previously unreported posttranslational modifications of peptides including phosphorylations, oxidations, glycosylations, and others were detected with high mass accuracy and may be of clinical importance. About 4,630 redundant peptides were identified with 99% confidence separately, and together some 1,251 distinct proteins were identified with 99% confidence or greater using the Paragon algorithm.

  10. Intestinal Dysbiosis Is Associated with Altered Short-Chain Fatty Acids and Serum-Free Fatty Acids in Systemic Lupus Erythematosus

    PubMed Central

    Rodríguez-Carrio, Javier; López, Patricia; Sánchez, Borja; González, Sonia; Gueimonde, Miguel; Margolles, Abelardo; de los Reyes-Gavilán, Clara G.; Suárez, Ana

    2017-01-01

    Metabolic impairments are a frequent hallmark of systemic lupus erythematosus (SLE). Increased serum levels of free fatty acids (FFA) are commonly found in these patients, although the underlying causes remain elusive. Recently, it has been suggested that factors other than inflammation or clinical features may be involved. The gut microbiota is known to influence the host metabolism, the production of short-chain fatty acids (SCFA) playing a potential role. Taking into account that lupus patients exhibit an intestinal dysbiosis, we wondered whether altered FFA levels may be associated with the intestinal microbial composition in lupus patients. To this aim, total and specific serum FFA levels, fecal SCFA levels, and gut microbiota composition were determined in 21 SLE patients and 25 healthy individuals. The Firmicutes to Bacteroidetes (F/B) ratio was strongly associated with serum FFA levels in healthy controls (HC), even after controlling for confounders. However, this association was not found in lupus patients, where a decreased F/B ratio and increased FFA serum levels were noted. An altered production of SCFA was related to the intestinal dysbiosis in lupus, while SCFA levels paralleled those of serum FFA in HC. Although a different serum FFA profile was not found in SLE, specific FFA showed distinct patterns on a principal component analysis. Immunomodulatory omega-3 FFA were positively correlated to the F/B ratio in HC, but not in SLE. Furthermore, divergent associations were observed for pro- and anti-inflammatory FFA with endothelial activation biomarkers in lupus patients. Overall, these findings support a link between the gut microbial ecology and the host metabolism in the pathological framework of SLE. A potential link between intestinal dysbiosis and surrogate markers of endothelial activation in lupus patients is supported, FFA species having a pivotal role. PMID:28167944

  11. Intestinal Dysbiosis Is Associated with Altered Short-Chain Fatty Acids and Serum-Free Fatty Acids in Systemic Lupus Erythematosus.

    PubMed

    Rodríguez-Carrio, Javier; López, Patricia; Sánchez, Borja; González, Sonia; Gueimonde, Miguel; Margolles, Abelardo; de Los Reyes-Gavilán, Clara G; Suárez, Ana

    2017-01-01

    Metabolic impairments are a frequent hallmark of systemic lupus erythematosus (SLE). Increased serum levels of free fatty acids (FFA) are commonly found in these patients, although the underlying causes remain elusive. Recently, it has been suggested that factors other than inflammation or clinical features may be involved. The gut microbiota is known to influence the host metabolism, the production of short-chain fatty acids (SCFA) playing a potential role. Taking into account that lupus patients exhibit an intestinal dysbiosis, we wondered whether altered FFA levels may be associated with the intestinal microbial composition in lupus patients. To this aim, total and specific serum FFA levels, fecal SCFA levels, and gut microbiota composition were determined in 21 SLE patients and 25 healthy individuals. The Firmicutes to Bacteroidetes (F/B) ratio was strongly associated with serum FFA levels in healthy controls (HC), even after controlling for confounders. However, this association was not found in lupus patients, where a decreased F/B ratio and increased FFA serum levels were noted. An altered production of SCFA was related to the intestinal dysbiosis in lupus, while SCFA levels paralleled those of serum FFA in HC. Although a different serum FFA profile was not found in SLE, specific FFA showed distinct patterns on a principal component analysis. Immunomodulatory omega-3 FFA were positively correlated to the F/B ratio in HC, but not in SLE. Furthermore, divergent associations were observed for pro- and anti-inflammatory FFA with endothelial activation biomarkers in lupus patients. Overall, these findings support a link between the gut microbial ecology and the host metabolism in the pathological framework of SLE. A potential link between intestinal dysbiosis and surrogate markers of endothelial activation in lupus patients is supported, FFA species having a pivotal role.

  12. Reconstituted voltage-sensitive sodium channel from Electrophorus electricus: chemical modifications that alter regulation of ion permeability.

    PubMed Central

    Cooper, E C; Tomiko, S A; Agnew, W S

    1987-01-01

    At equilibrium, voltage-sensitive sodium channels normally are closed at all potentials. They open transiently in response to changes in membrane voltage or chronically under the influence of certain neurotoxins. Covalent modifications that result in chronic opening may help identify molecular domains involved in conductance regulation. Here, the purified sodium channel from electric eel electroplax, reconstituted in artificial liposomes, has been used to screen for such modifications. When the liposomes were treated with the alkaloid neurotoxin batrachotoxin, sodium-selective ion fluxes were produced, with permeability ratios PNa greater than PTl greater than PK greater than PRb greater than PCs. When the liposomes were treated with either of two oxidizing reagents (N-bromoacetamide or N-bromosuccinimide), or with Pronase or trypsin, ion-selective fluxes also were stimulated. These were blocked by tetrodotoxin and the anesthetic QX-314 in a manner suggesting that only modification of the cytoplasmic protein surface resulted in stimulation. Limited exposure to trypsin resulted in strong flux activation, with the concomitant appearance of peptide fragments with masses of approximately equal to 130, 70, and 38 kDa and fragments with masses of 45 and 24 kDa appearing later. We propose that characterization of these fragments may allow identification of channel domains important for inactivation gating. Images PMID:2442755

  13. S-guanylation of human serum albumin is a unique posttranslational modification and results in a novel class of antibacterial agents.

    PubMed

    Ishima, Yu; Hoshino, Hitomi; Shinagawa, Takuya; Watanabe, Kaori; Akaike, Takaaki; Sawa, Tomohiro; Kragh-Hansen, Ulrich; Kai, Toshiya; Watanabe, Hiroshi; Maruyama, Toru; Otagiri, Masaki

    2012-09-01

    8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is a nitric oxide metabolite and an important second messenger. 8-Nitro-cGMP reacts with sulfhydryl groups forming a novel posttranslational modification, namely, S-guanylation. In this work, we found, by using a quantitative competition enzyme-linked immunosorbent assay procedure, that S-guanylated human serum albumin (S-cGMP-HSA) is a component of normal plasma, and that hemodialysis patients decrease its concentration, on an average, from 68 to 34 nM. End-stage renal disease is often accompanied by septicemia, and we found that S-cGMP-HSA possesses an in vitro antibacterial effect with half maximal inhibitory concentration of approximately 2 μM against Escherichia coli American Type Culture Collection. Our findings indicate that S-cGMP-HSA can be regarded as an endogenous antibacterial agent in healthy conditions and as a useful new class of antibacterial agents with a circulation time sufficient for in vivo biological activity. The clinical development of S-cGMP-HSA as a safe and strong antibacterial agent arisen from endogenous posttranslational modification would be expected.

  14. Conformational alteration in serum albumin as a carrier for pyridoxal phosphate: a distinction from pyridoxal phosphate-dependent glutamate decarboxylase.

    PubMed

    Zhang, F; Thottananiyil, M; Martin, D L; Chen, C H

    1999-04-15

    The conformation of bovine serum albumin (BSA), a pyridoxal phosphate (pyridoxal-P) carrier, was investigated by using uv/visible spectrophotometry, fluorescence spectroscopy, circular dichroism, and differential scanning microcalorimetry. Upon interacting with pyridoxal-P, the uv/visible absorption spectrum of BSA exhibits peaks at 330 and 392 nm due to the formation of a Schiff base. Pyridoxal-P quenches the fluorescence emission intensity (excited at 295 or 280 nm) by 24% and enhances fluorescence steady-state polarization of BSA by 20%. These observations suggest a conformational change in BSA when it interacts with pyridoxal-P. However, this conformational change appears to be small since circular dichroism showed only a 2-4% decrease in the alpha-helical content of BSA and no change in the beta-sheet content, and differential scanning microcalorimetry yielded only a 10% change in the enthalpy of thermal unfolding of BSA. 2-Aminoethylisothiouronium bromide, an antioxidant, causes no effect on either uv/visible absorption spectrum or fluorescence emission intensity of BSA, suggesting that BSA lacks sensitive sulfhydryl groups. To help in understanding BSA as a carrier for pyridoxal-P, the results were compared with those for glutamate decarboxylase (GAD), a pyridoxal-P-dependent protein, which requires pyridoxal-P as the cofactor for activity. Although BSA and GAD exhibit comparable molecular weights (66430 versus 65300), numbers of amino acid residues (582 versus 585), and binding affinity (>10(6) M-1), distinct conformational alterations occur between the two proteins upon interacting with pyridoxal-P: a small conformational change for BSA versus a large conformational change for GAD. In contrast to the case of BSA, AET causes significant effects on both the uv/visible spectrum and fluorescence emission intensity of GAD, because GAD contains sensitive sulfhydryl groups. Factors such as disulfide bond and active site sequence were discussed to understand BAS

  15. Alterations in Hemoglobin and Serum 25-hydroxyvitamin D are Related Before and After Weight Loss Independent of African Admixture.

    PubMed

    Carter, Stephen J; Plaisance, Eric P; Fisher, Gordon; Fernandez, Jose R; Gower, Barbara A; Hunter, Gary R

    2017-02-01

    African American (AA) and European American (EA) women often exhibit differences in hemoglobin (Hb) and 25-hydroxyvitamin D [25(OH)D], both of which can be altered by calorie restriction leading to weight loss. Given these known differences, it is of clinical interest to examine the potential for race-specific, adverse responses to weight loss. Sixty-four overweight (BMI 27-29.9 kg/m(2)), premenopausal women consumed a standardized, very-low calorie diet to reduce BMI < 25 kg/m2. Ancestry informative markers provided estimates of African admixture, an objective mean of expressing race. Blood sampling and anthropometric measures were performed at baseline and upon meeting target BMI. At baseline, in the overweight state, Hb (g/dL) (AA, 11.7 ± 0.9 vs. EA, 12.5 ± 0.8; p < .01) and 25(OH)D (nmol/L) (AA, 35.7 ± 12.9 vs. EA, 57.0 ± 20.0; p < .01) were lower in AAs. After weight loss, Hb decreased (AA, -0.5 ± 0.7 vs. EA, -0.4 ± 0.6; p = .48) to a similar extent among races. Conversely, 25(OH)D increased (AA, 43.4 ± 14.0 vs. EA 68.2 ± 24.3; p < .01) though the magnitude of change (Δ) was not different (AA, +7.8 ± 13.5 vs. EA, +11.2 ± 16.7; p = .37) between races. Multiple linear regression revealed a positive association between ΔHb and Δ25(OH)D (r = .386; p < .01) adjusted for African admixture, Δtestosterone, and Δbody fat%. Path analyses revealed a significant indirect effect of Δbody fat% on ΔHb through Δ25(OH)D, β =-0.023, CI [-0.06, -0.004]. Following 15% weight loss, participants with the largest increase in serum 25(OH)D exhibited the smallest decrease in Hb. Future research should clarify the optimal degree of calorie restriction to stimulate weight loss while mitigating the potential risk of anemia associated with dieting efforts.

  16. 33 CFR 149.15 - What is the process for submitting alterations and modifications affecting the design and...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... submitted to the Commandant (CG-5) for review and approval if: (1) A license has not yet been issued; or, (2... alterations prior to approval from the Commandant (CG-5) for the conditions outlined in paragraph (a) and approval by the cognizant OCMI as required in paragraph (b) of this section. (e) The Commandant...

  17. Altered lipid, apolipoprotein, and lipoprotein profiles in inflammatory bowel disease: consequences on the cholesterol efflux capacity of serum using Fu5AH cell system.

    PubMed

    Ripollés Piquer, Blanca; Nazih, Hassan; Bourreille, Arnaud; Segain, Jean Pierre; Huvelin, Jean Michel; Galmiche, Jean-Paul; Bard, Jean-Marie

    2006-07-01

    Epidemiological data suggest a link between chronic inflammation condition and atherosclerosis. Infection and inflammation can also impair lipoprotein metabolism and produce a wide variety of changes in plasma concentrations of lipids and lipoproteins. Twenty-one patients with inflammatory bowel diseases (IBDs) and 28 healthy subjects were recruited. Serum concentrations of lipids, lipoproteins, apolipoproteins, leptin, ghrelin, and inflammation markers (C-reactive protein and serum amyloid A) were measured, and subjects' lipoproteins were characterized. The ability of patients with serum IBD to efflux free cell cholesterol was measured. Serum cholesterol, high-density lipoprotein cholesterol, apolipoprotein (apo) A-I, apoC-II, apoC-III bound to apoB, phospholipid, and phospholipids not bound to apoB levels were significantly lower, whereas serum triglyceride, serum amyloid A, and C-reactive protein levels were significantly higher in patients with active IBD. Apolipoprotein A-I immunoreactivity (pre-beta small particles and small alpha-high-density lipoprotein particles) is decreased in patients with IBD. In contrast, apoE immunoreactivity (slow/small apoE containing lipoprotein particles [LpE particle]) increased in these patients. The efflux capacity of serum from patients with IBD using [(3)H]-cholesterol-labeled Fu5AH cells was reduced (P < .005). Our results demonstrate that, in subjects with active IBD, inflammation leads to alterations in lipid, apolipoprotein, and lipoprotein profiles and reduced cholesterol efflux. These changes are similar to those proposed to promote atherogenesis and may contribute to the development of cardiovascular events.

  18. Modification of Lys-237 on actin by 2,4-pentanedione. Alteration of the interaction of actin with tropomyosin.

    PubMed

    El-Saleh, S C; Thieret, R; Johnson, P; Potter, J D

    1984-09-10

    It has been possible to specifically label rabbit skeletal muscle actin at Lys-237 with 2,4-pentanedione, producing an enamine. This reaction can be reversed with hydroxylamine. The modification can be carried out with actin in either the G- or F-forms and does not affect polymerization-depolymerization. The modification does affect, however, the interaction of tropomyosin (Tm) with the modified F-actin. In the absence of Ca2+ and Mg2+ (mu = 0.12), Tm failed to bind to the modified F-actin whereas it did bind to unmodified F-actin (1 Tm:7 actins). Tm binding could be restored under these conditions by the addition of either troponin (Tn), Mg2+, or Mg2+ and Ca2+. Under certain conditions, Tm alone has been shown to inhibit actin-activated heavy meromyosin (HMM)-Mg2+-ATPase. This inhibition did not occur with the modified F-actin even though Tm was bound (approximately 1 Tm:7 actins). Even when Tn was added to this system (in the absence of Ca2+), no inhibition of ATPase could be observed. Thus, this modification appears to prevent F-actin X Tm from assuming the "blocking" inhibitory position (conformation). In addition, Tn appears to enhance the activation of heavy meromyosin-Mg2+-ATPase by the modified F-actin X Tm complex whether Ca2+ is present or not. This state may be analogous to the potentiated state (Murray, J. M., Knox, M. K., Trueblood, C. E., and Weber, A. (1982) Biochemistry 27, 906-915) seen with myosin subfragment 1-saturated actin at low ATP levels. Thus, using modified and unmodified F-actin, it is possible to produce three Tm X actin states: off (F-actin X Tm), on (modified F-actin X Tm), and "potentiated" (modified F-actin X Tm X Tn).

  19. Modification of continuous venovenous hemodiafiltration with single-pass albumin dialysate allows for removal of serum bilirubin.

    PubMed

    Chawla, Lakhmir S; Georgescu, Florin; Abell, Bruce; Seneff, Michael G; Kimmel, Paul L

    2005-03-01

    A 53-year-old woman was admitted to the hospital with ischemic colitis and underwent a subtotal colectomy. She developed acute renal failure, severe hyperbilirubinemia, and intense pruritus resistant to medical treatment. Extracorporeal albumin dialysis using a Molecular Adsorbent Recirculating System (MARS; Gambro Co, Lund, Sweden) has been used to treat liver failure and reduce total serum bilirubin (SB) levels. A trial of extracorporeal albumin dialysis with continuous renal replacement therapy (RRT) was instituted to achieve net removal of SB. A 25% albumin solution was mixed with conventional dialysate to yield a dialysate concentration of 1.85% or 5.0% albumin. The patient underwent 2 continuous RRT sessions using extracorporeal albumin dialysis (1.85% and 5.0% albumin dialysate). Pretreatment and posttreatment SB levels were determined, and total bilirubin concentration (TB) also was measured in each of the collection bags during conventional and albumin dialysis. Pretreatment and posttreatment SB levels were 50.4 mg/dL (862 micromol/L) and 39.0 mg/dL (667 micromol/L) with 1.85% albumin dialysate and 47.1 mg/dL (805 micromol/L) and 39.7 mg/dL (679 micromol/L) with 5.0% albumin dialysate, respectively. The collected dialysate TB level was 0.3 mg/dL (5 micromol/L) during nonalbumin RRT and increased to 1.37 +/- 0.06 mg/dL (23 +/- 1 micromol/L) with 1.85% albumin dialysis. The collected dialysate fluid TB level was 0.3 mg/dL (5 micromol/L) during the nonalbumin RRT and increased to 1.38 +/- 0.15 mg/dL (24 +/- 3 micromol/L) during 5.0% albumin RRT. Single-pass albumin dialysis with continuous RRT cleared SB better than standard continuous RRT. Single-pass albumin dialysis with continuous RRT is feasible and may be a viable alternative in centers that do not have access to MARS therapy. This modality merits additional evaluation for its efficacy in clearing albumin-bound serum toxins.

  20. ALTERED SERUM SEX STEROIDS AND VITELLOGENIN INDUCTION IN WALLEYE (STIZOSTEDION VITREUM) COLLECTED NEAR A METROPOLITAN SEWAGE TREATMENT PLANT

    EPA Science Inventory

    Feral, male walleye collected from the Mississippi River below the St. Paul metropolitan sewage treatment plant (STP) contained measurable levels of the estrogen-inducible, female egg protein, vitellogenin. These same fish showed significantly decreased serum androgen and signifi...

  1. ALTERED SERUM SEX STEROIDS AND VITELLOGENIN INDUCTION IN WALLEYE (STIZOSTEDION VITREUM) COLLECTED NEAR A METROPOLITAN SEWAGE TREATMENT PLANT

    EPA Science Inventory

    Feral, male walleye collected from the Mississippi River below the St. Paul metropolitan sewage treatment plant (STP) contained measurable levels of the estrogen-inducible, female egg protein, vitellogenin. These same fish showed significantly decreased serum androgen and signifi...

  2. Comparison of the effects of ozone on the modification of amino acid residues in glutamine synthetase and bovine serum albumin.

    PubMed

    Berlett, B S; Levine, R L; Stadtman, E R

    1996-02-23

    During exposure to ozone, the methionine and aromatic amino acid residues of Escherichia coli glutamine synthetase (GS) and bovine serum albumin (BSA) are oxidized rapidly in the order Met > Trp > Tyr approximately His > Phe. The loss of His is matched by a nearly equivalent formation of aspartate or of a derivative that is converted to aspartic acid upon acid hydrolysis. Conversion of His to aspartate was confirmed by showing that the oxidation of E. coli protein in which all His residues were uniformly labeled with 14C gave rise to 14C-labeled aspartic acid in 80% yield and also by the demonstration that His residues in the tripeptides Ala-His-Ala or Ala-Ala-His gave rise to nearly stoichiometric amounts of aspartic acid whereas oxidation of His-Ala-Ala yielded only 36% aspartate. The oxidation of BSA and GS led to formation, respectively, of 11 and 3.3 eq of carbonyl groups and 0.5 and 0.3 eq of quinoprotein per subunit. Although BSA and GS contain nearly identical amounts of each kind of aromatic amino acid residues, oxidation of these residues in BSA was about 1.5-2.0 times faster than in GS indicating that the susceptibility to oxidation is dependent on the primary, secondary, tertiary, and quaternary structure of the protein.

  3. Transgenic modification of gai or rg/1 causes dwarfing and alters gibberellins, root growth, and metabolite profiles in Populus

    SciTech Connect

    Tschaplinski, Timothy J; Busov, V.; Meilan, R; Pearce, D; Rood, s; Ma, C; Strauss, S

    2006-01-01

    In Arabidopsis and other plants, gibberellin (GA)-regulated responses are mediated by proteins including GAI, RGA and RGL1-3 that contain a functional DELLA domain. Through transgenic modification, we found that DELLA-less versions of GAI (gai) and RGL1 (rgl1) in a Populus tree have profound, dominant effects on phenotype, producing pleiotropic changes in morphology and metabolic profiles. Shoots were dwarfed, likely via constitutive repression of GA-induced elongation, whereas root growth was promoted two- to threefold in vitro. Applied GA{sub 3} inhibited adventitious root production in wild-type poplar, but gai/rgl1 poplars were unaffected by the inhibition. The concentrations of bioactive GA{sub 1} and GA{sub 4} in leaves of gai- and rgl1-expressing plants increased 12- to 64-fold, while the C{sub 19} precursors of GA{sub 1} (GA{sub 53}, GA{sub 44} and GA{sub 19}) decreased three- to ninefold, consistent with feedback regulation of GA 20-oxidase in the transgenic plants. The transgenic modifications elicited significant metabolic changes. In roots, metabolic profiling suggested increased respiration as a possible mechanism of the increased root growth. In leaves, we found metabolite changes suggesting reduced carbon flux through the lignin biosynthetic pathway and a shift towards allocation of secondary storage and defense metabolites, including various phenols, phenolic glucosides, and phenolic acid conjugates.

  4. Denys-Drash syndrome associated WT1 glutamine 369 mutants have altered sequence-preferences and altered responses to epigenetic modifications

    SciTech Connect

    Hashimoto, Hideharu; Zhang, Xing; Zheng, Yu; Wilson, Geoffrey G.; Cheng, Xiaodong

    2016-09-04

    Mutations in human zinc-finger transcription factor WT1 result in abnormal development of the kidneys and genitalia and an array of pediatric problems including nephropathy, blastoma, gonadal dysgenesis and genital discordance. Several overlapping phenotypes are associated with WT1 mutations, including Wilms tumors, Denys-Drash syndrome (DDS), Frasier syndrome (FS) and WAGR syndrome (Wilms tumor, aniridia, genitourinary malformations, and mental retardation). These conditions vary in severity from individual to individual; they can be fatal in early childhood, or relatively benign into adulthood. DDS mutations cluster predominantly in zinc fingers (ZF) 2 and 3 at the C-terminus of WT1, which together with ZF4 determine the sequence-specificity of DNA binding. We examined three DDS associated mutations in ZF2 of human WT1 where the normal glutamine at position 369 is replaced by arginine (Q369R), lysine (Q369K) or histidine (Q369H). These mutations alter the sequence-specificity of ZF2, we find, changing its affinity for certain bases and certain epigenetic forms of cytosine. X-ray crystallography of the DNA binding domains of normal WT1, Q369R and Q369H in complex with preferred sequences revealed the molecular interactions responsible for these affinity changes. DDS is inherited in an autosomal dominant fashion, implying a gain of function by mutant WT1 proteins. This gain, we speculate, might derive from the ability of the mutant proteins to sequester WT1 into unproductive oligomers, or to erroneously bind to variant target sequences.

  5. Denys-Drash syndrome associated WT1 glutamine 369 mutants have altered sequence-preferences and altered responses to epigenetic modifications

    PubMed Central

    Hashimoto, Hideharu; Zhang, Xing; Zheng, Yu; Wilson, Geoffrey G.; Cheng, Xiaodong

    2016-01-01

    Mutations in human zinc-finger transcription factor WT1 result in abnormal development of the kidneys and genitalia and an array of pediatric problems including nephropathy, blastoma, gonadal dysgenesis and genital discordance. Several overlapping phenotypes are associated with WT1 mutations, including Wilms tumors, Denys-Drash syndrome (DDS), Frasier syndrome (FS) and WAGR syndrome (Wilms tumor, aniridia, genitourinary malformations, and mental retardation). These conditions vary in severity from individual to individual; they can be fatal in early childhood, or relatively benign into adulthood. DDS mutations cluster predominantly in zinc fingers (ZF) 2 and 3 at the C-terminus of WT1, which together with ZF4 determine the sequence-specificity of DNA binding. We examined three DDS associated mutations in ZF2 of human WT1 where the normal glutamine at position 369 is replaced by arginine (Q369R), lysine (Q369K) or histidine (Q369H). These mutations alter the sequence-specificity of ZF2, we find, changing its affinity for certain bases and certain epigenetic forms of cytosine. X-ray crystallography of the DNA binding domains of normal WT1, Q369R and Q369H in complex with preferred sequences revealed the molecular interactions responsible for these affinity changes. DDS is inherited in an autosomal dominant fashion, implying a gain of function by mutant WT1 proteins. This gain, we speculate, might derive from the ability of the mutant proteins to sequester WT1 into unproductive oligomers, or to erroneously bind to variant target sequences. PMID:27596598

  6. Chronic but not acute antidepresant treatment alters serum zinc/copper ratio under pathological/zinc-deficient conditions in mice.

    PubMed

    Mlyniec, K; Ostachowicz, B; Krakowska, A; Reczynski, W; Opoka, W; Nowak, G

    2014-10-01

    Depression is the leading psychiatric disorder with a high risk of morbidity and mortality. Clinical studies report lower serum zinc in depressed patients, suggesting a strong link between zinc and mood disorders. Also copper as an antagonistic element to zinc seems to play a role in depression, where elevated concentration is observed. In the present study we investigated serum copper and zinc concentration after acute or chronic antidepressant (AD) treatment under pathological/zinc-deficient conditions. Zinc deficiency in mice was induced by a special diet administered for 6 weeks (zinc adequate diet - ZnA, contains 33.5 mgZn/kg; zinc deficient diet - ZnD, contains 0.2 mgZn/kg). Animals received acute or chronically saline (control), imipramine, escitalopram, reboxetine or bupropion. To evaluate changes in serum copper and zinc concentrations the total reflection X-ray fluorescence (TXRF) and flame atomic absorption spectrometry (FAAS) was performed. In ZnD animals serum zinc level was reduced after acute ADs treatment (similarly to vehicle treatment), however, as demonstrated in the previous study after chronic ADs administration no differences between both ZnA and ZnD groups were observed. Acute ADs in ZnD animals caused different changes in serum copper concentration with no changes after chronic ADs treatment. The calculated serum Zn/Cu ratio is reduced in ZnD animals (compared to ZnA subjects) treated with saline (acutely or chronically) and in animals treated acutely with ADs. However, chronic treatment with ADs normalized (by escitalopram, reboxetine or bupropion) or increased (by imipramine) this Zn/Cu ratio. Observed in this study normalization of serum Zn/Cu ratio in depression-like conditions by chronic (but not acute) antidepressants suggest that this ratio may be consider as a marker of depression or treatment efficacy.

  7. Serum visfatin and vaspin levels in prepubertal children: effect of obesity and weight loss after behavior modifications on their secretion and relationship with glucose metabolism.

    PubMed

    Martos-Moreno, G Á; Kratzsch, J; Körner, A; Barrios, V; Hawkins, F; Kiess, W; Argente, J

    2011-10-01

    To investigate the impact of obesity, weight loss and oral glucose ingestion on serum visfatin and vaspin levels in prepubertal children. A total of 100 prepubertal obese Caucasian children (OB) and 42 controls (C) were studied. The OB group was studied at baseline and after moderate (n=46) and extensive (n=14) body mass index (BMI) reduction by conservative treatment, undergoing body composition studies (dual-energy X-ray absorptiometry) and oral glucose tolerance tests (OGTTs). Serum visfatin and vaspin levels were studied throughout the OGTT, as were their relationships with insulin, leptin, leptin soluble receptor (sOB-R), adiponectin (total and high molecular weight), resistin, interleukin-6 (IL-6) and tumor necrosis factor-α levels at every time point. OB had higher visfatin (P<0.001), but similar vaspin than C. BMI reduction decreased visfatin levels (P<0.001), with BMI, waist circumference and the surrogate markers of body fat (leptin and sOB-R) showing significant correlations (P<0.05) with this peptide, but not with vaspin. Visfatin and vaspin decreased during the OGTT (P<0.001). Weight reduction did not alter visfatin dynamics in the OGTT, but decreased the area under the curve (AUC) for vaspin (P<0.001), with a correlation between the AUCs for vaspin and insulin after weight loss (P<0.05). Visfatin levels were positively correlated with resistin and IL-6, after controlling for BMI and HOMA (homeostatic model assessment) index at every time point in the study. Serum visfatin, but not vaspin, levels are influenced by body fat content in obese children, whereas both adipokines are modulated by glucose intake in a BMI-dependent manner.

  8. Altered serum levels of interleukin-3 in first-episode drug-naive and chronic medicated schizophrenia.

    PubMed

    Fu, Yin Yang; Zhang, Tong; Xiu, Mei Hong; Tang, Wei; Han, Mei; Yun, Long Tan; Chen, Da Chun; Chen, Song; Tan, Shu Ping; Soares, Jair C; Tang, Wen Jie; Zhang, Xiang Yang

    2016-10-01

    Elevated serum levels of Interleukin-3 (IL-3), a major component of the cytokines, have been observed in chronic and medicated patients with schizophrenia, but this elevation may reflect either or both medication and illness chronicity effects. Thus, we compared serum IL-3 levels in first-episode drug-naive (FEDN) to chronic medicated patients with schizophrenia and examined the association of IL-3 with their psychopathological symptoms. Serum IL-3 levels were assessed in 55 FEDN patients, 52 chronic medicated patients and 43 healthy controls. Schizophrenia symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS). Serum IL-3 levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). We found significantly lower IL-3 levels in FEDN patients than both chronic patients and healthy controls (both p<0.001), while IL-3 levels in chronic patients were markedly higher than in healthy controls. No significant association was observed between IL-3 and any clinical psychopathology in FEDN patients; however, we found a significant correlation between serum IL-3 levels and the PANSS general psychopathology subscore in chronic medicated patients (p<0.05). Decreased IL-3 levels in FEDN patients suggest that suppressed immune function may be associated with developing schizophrenia, but as the disease progresses IL-3 levels increase perhaps related to medication treatment or other factors that occur during chronic illness.

  9. Serum concentration and increased temperature alter Mayaro virus RNA and protein synthesis in Aedes albopictus (mosquito)-infected cells.

    PubMed

    Motta, M C; Fournier, M V; Carvalho, M G

    1995-01-01

    We have previously shown the inhibition of Mayaro virus multiplication in Aedes albopictus-infected cells maintained at a supraoptimal temperature for growth (37 degrees C) and a stimulation of virus production in response to high serum concentrations in the incubation medium. In the present study, we addressed the question of how the effect of continuous heat stress and high serum concentration soon after infection interfere with virus macromolecule synthesis. Cells maintained at 28 degrees C in the presence of 2% serum synthesized a viral genomic RNA of 12 kb and a subgenomic RNA of 5.2 kb 6 h postinfection. Analysis of the protein profile showed the presence of the viral nucleocapsid protein of 34 kDa (P34). However, if infected cells were maintained at 37 degrees C, a smear starting immediately below the 5.2-kb RNA was noticed and the viral P34 was not detected by SDS-PAGE. Addition of 10% serum to the growth medium of infected cells maintained at 37 degrees C results in a viral RNA profile and protein synthesis similar to those observed in cultures kept at 28 degrees C, i.e., the smear was not observed and the P34 protein was detected. The results suggest that the inhibition of virus multiplication by temperature may be related to the inhibition of viral nonstructural protein synthesis early during infection. The presence of high serum levels in the incubation medium protects macromolecule synthesis against heat stress.

  10. A longitudinal study of alterations of hippocampal volumes and serum BDNF levels in association to atypical antipsychotics in a sample of first-episode patients with schizophrenia.

    PubMed

    Rizos, Emmanouil; Papathanasiou, Matilda A; Michalopoulou, Panagiota G; Laskos, Efstathios; Mazioti, Aggeliki; Kastania, Anastasia; Vasilopoulou, Konstantina; Nikolaidou, Paraskevi; Margaritis, Dimitrios; Papageorgiou, Charalabos; Liappas, Ioannis

    2014-01-01

    Schizophrenia is associated with structural and functional abnormalities of the hippocampus, which have been suggested to play an important role in the formation and emergence of schizophrenia syndrome. Patients with schizophrenia exhibit significant bilateral hippocampal volume reduction and progressive hippocampal volume decrease in first-episode patients with schizophrenia has been shown in many neuroimaging studies. Dysfunction of the neurotrophic system has been implicated in the pathophysiology of schizophrenia. The initiation of antipsychotic medication alters the levels of serum Brain Derived Neurotrophic Factor (BDNF) levels. However it is unclear whether treatment with antipsychotics is associated with alterations of hippocampal volume and BDNF levels. In the present longitudinal study we investigated the association between serum BDNF levels and hippocampal volumes in a sample of fourteen first-episode drug-naïve patients with schizophrenia (FEP). MRI scans, BDNF and clinical measurements were performed twice: at baseline before the initiation of antipsychotic treatment and 8 months later, while the patients were receiving monotherapy with second generation antipsychotics (SGAs). We found that left hippocampal volume was decreased (corrected left HV [t = 2.977, df = 13, p = .011] at follow-up; We also found that the higher the BDNF levels change the higher were the differences of corrected left hippocampus after 8 months of treatment with atypical antipsychotics (Pearson r = 0.597, p = 0.024). The association of BDNF with hippocampal volume alterations in schizophrenia merits further investigation and replication in larger longitudinal studies.

  11. Anti-inflammatory Montelukast prevents toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin: Oxidative stress, histological alterations in liver, and serum cytokine levels.

    PubMed

    Bentli, Recep; Ciftci, Osman; Cetin, Asli; Otlu, Ali

    2016-05-01

    This study aimed to investigate the potential beneficial effects of the montelukast (ML) on oxidative stress and histological alterations in liver tissues and cytokine levels in rats intoxicated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were divided randomly into four equal groups (control, TCDD, ML, TCDD + ML). TCDD were administered by gavages dissolved in corn oil at the doses of 2 µg/kg/week, and ML was given intraperitoneally at the dose of 10 mg/kg/day. Oxidative status, histological alterations, and cytokine levels were analyzed on day 60. The results showed that although TCDD induced oxidative stress via significant increase in formation of thiobarbituric acid reactive substance, it caused a significant decline in glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels in liver. Besides, TCDD led to significant histopathological damage in liver and serum cytokine levels alterations (increase in tumor necrosis factor α and interleukin 1β levels). In contrast, ML treatment reversed oxidative effects of TCDD by increasing the levels of GSH, CAT, and SOD and decreasing the formation of TBARS. Also, it can normalize the levels of histological and cytokine alterations induced by TCDD. In conclusion, it was determined that TCDD exposure caused adverse effects on cytokine levels, histological alterations, and oxidative stress in rats. However, ML treatment partially eliminated toxic effects of TCDD. Thus, it was judged that coadministration of ML with TCDD may be useful to attenuate the negative effects of TCDD. © The Author(s) 2013.

  12. Canavanine Alters ROS/RNS Level and Leads to Post-translational Modification of Proteins in Roots of Tomato Seedlings

    PubMed Central

    Krasuska, Urszula; Andrzejczak, Olga; Staszek, Paweł; Bogatek, Renata; Gniazdowska, Agnieszka

    2016-01-01

    Canavanine (CAN), a structural analog of arginine (Arg), is used as a selective inhibitor of inducible NOS in mammals. CAN is incorporated into proteins’ structure in the place of Arg, leading to the formation of aberrant compounds. This non-protein amino acid is found in legumes, e.g., Canavalia ensiformis (L.) DC. or Sutherlandia frutescens (L.) R.Br. and acts as a strong toxin against herbivores or plants. Tomato (Solanum lycopersicum L.) seedlings were treated for 24–72 h with CAN (10 or 50 μM) inhibiting root growth by 50 or 100%, without lethal effect. We determined ROS level/production in root extracts, fluorescence of DAF-FM and APF derivatives corresponding to RNS level in roots of tomato seedlings and linked CAN-induced restriction of root growth to the post-translational modifications (PTMs) of proteins: carbonylation and nitration. Both PTMs are stable markers of nitro-oxidative stress, regarded as the plant’s secondary response to phytotoxins. CAN enhanced H2O2 content and superoxide radicals generation in extracts of tomato roots and stimulated formation of protein carbonyl groups. An elevated level of carbonylated proteins was characteristic for the plants after 72 h of the culture, mainly for the roots exposed to 10 μM CAN. The proteolytic activity was stimulated by tested non-protein amino acid. CAN treatment led to decline of fluorescence of DAF-FM derivatives, and transiently stimulated fluorescence of APF derivatives. Short-term exposure of tomato seedlings to CAN lowered the protein nitration level. Activity of peroxidase, polyamine oxidase and NADPH oxidase, enzymes acting as modulators of H2O2 concentration and governing root architecture and growth were determined. Activities of all enzymes were stimulated by CAN, but no strict CAN concentration dependence was observed. We conclude, that although CAN treatment led to a decline in the nitric oxide level, PTMs observed in roots of plants exposed to CAN are linked rather to the

  13. Genetic alterations of JAK/STAT cascade and histone modification in extranodal NK/T-cell lymphoma nasal type

    PubMed Central

    Kang, So Young; Kim, Seok Jin; Hwang, Jinha; Lee, Seungho; Kwak, Soo Heon; Park, Kyong Soo; Yoo, Hae Yong

    2015-01-01

    Extranodal NK/T-cell lymphoma nasal type (ENKL) is a rare type of non-Hodgkin lymphoma that more frequently occurs in East Asia and Latin America. Even though its molecular background has been discussed in the last few years, the current knowledge does not explain the disease pathogenesis in most cases of ENKL. Here, we performed multiple types of next-generation sequencing on 34 ENKL samples, including whole-exome sequencing (9 cancer tissues and 4 cancer cell lines), targeted sequencing (21 cancer tissues), and RNA sequencing (3 cancer tissues and 4 cancer cell lines). Mutations were found most frequently in 3 genes, STAT3, BCOR, and MLL2 (which were present in 9, 7, and 6 cancer samples, respectively), whereas there were only 2 cases of JAK3 mutation. In total, JAK/STAT pathway- and histone modification-related genes accounted for 55.9% and 38.2% of cancer samples, respectively, and their involvement in ENKL pathogenesis was also supported by gene expression analysis. In addition, we provided 177 genes upregulated only in cancer tissues, which appear to be linked with angiocentric and angiodestructive growth of ENKL. In this study, we propose several novel driver genes of ENKL, and show that these genes and their functional groups may be future therapeutic targets of this disease. PMID:25980440

  14. Modification of oil and glucosinolate content in canola seeds with altered expression of Brassica napus LEAFY COTYLEDON1.

    PubMed

    Elahi, Nosheen; Duncan, Robert W; Stasolla, Claudio

    2016-03-01

    Over the last few decades, research focusing on canola (Brassica napus L.) seed oil content and composition has expanded. Oil production and accumulation are influenced by genes participating in embryo and seed development. The Arabidopsis LEAFY COTYLEDON1 (LEC1) is a well characterized regulator of embryo development that also enhances the expression of genes involved in fatty acid (FA) synthesis. B. napus lines over-expressing or down-regulating BnLEC1 were successfully generated by Agrobacterium-mediated transformation. The constitutive expression of BnLEC1 in B. napus var. Polo, increased seed oil content by 7-16%, while the down-regulation of BnLEC1 in B. napus var. Topas reduced oil content by 9-12%. Experimental manipulation of BnLEC1 caused transcriptional changes in enzymes participating in sucrose metabolism, glycolysis, and FA biosynthesis, suggesting an enhanced carbon flux towards FA biosynthesis in tissues over-expressing BnLEC1. The increase in oil content induced by BnLEC1 was not accompanied by alterations in FA composition, oil nutritional value or glucosinolate (GLS) levels. Suppression of BnLEC1 reduced seed oil accumulation and elevated the level of GLS possibly through the transcriptional regulation of BnST5a (Sulphotransferase5a), the last GLS biosynthetic enzyme. Collectively, these findings demonstrate that experimental alterations of BnLEC1 expression can be used to influence oil production and quality in B. napus. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Alteration of serum levels of inflammatory cytokines and polysomnographic indices after uvulopalatal flap surgery in obstructive sleep apnea.

    PubMed

    Mutlu, Murad; Vuralkan, Erkan; Akin, Istemihan; Firat, Hikmet; Ardic, Sadik; Akaydin, Sevgi; Miser, Ece

    2017-02-01

    The aim of the current study was to compare the changes in polysomnographic indices and serum levels of C-reactive protein (CRP), cystatin C, tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) in patients with obstructive sleep apnea (OSA) who were treated surgically via a uvulopalatal flap (UPF) technique. Twenty-five patients (14 men, 11 women), average age 46.2 ± 9.3 years, who underwent UPF surgery were included in this study. Serum biochemical analyses and polysomnographic examinations were performed before and 6 months after the surgery. Pre- and postoperative values of apnea hypopnea index (AHI), oxygen desaturation index (ODI), and minimum oxygen concentrations, as well as serum levels of CRP, cystatin C, TNF-α, and ICAM-1 were compared. Comparison of variables before and after UPF surgery demonstrated that AHI (p = 0.001), ODI (p < 0.001) and oxygen saturation (p < 0.001) were significantly improved. In addition, serum levels of CRP (p = 0.036), cystatin C (p = 0.005), TNF-α (p < 0.001), and ICAM-1 (p < 0.001) were significantly reduced 6 months after surgery. Our results suggest that UPF is an effective surgical method that alleviates the severity of OSA. Moreover, it may have the potential to prevent the development of atherosclerosis by attenuating the inflammatory process induced by activation of inflammatory mediators such as CRP, TNF-α, ICAM-1, and cystatin C.

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

    USDA-ARS?s Scientific Manuscript database

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

  17. Altered extracellular ATP, ADP, and AMP hydrolysis in blood serum of sedentary individuals after an acute, aerobic, moderate exercise session.

    PubMed

    Moritz, Cesar Eduardo Jacintho; Teixeira, Bruno Costa; Rockenbach, Liliana; Reischak-Oliveira, Alvaro; Casali, Emerson André; Battastini, Ana Maria Oliveira

    2017-02-01

    Nucleotidases participate in the regulation of physiological and pathological events, such as inflammation and coagulation. Exercise promotes distinct adaptations, and can influence purinergic signaling. In the present study, we investigated soluble nucleotidase activities in the blood serum of sedentary young male adults at pre- and post-acute moderate aerobic exercise. In addition, we evaluated how this kind of exercise could influence adenine nucleotide concentrations in the blood serum. Sedentary individuals were submitted to moderate aerobic exercise on a treadmill; blood samples were collected pre- and post-exercise, and serum was separated for analysis. Results showed increases in ATP, ADP, and AMP hydrolysis post-exercise, compared to pre-exercise values. The ecto-nucleotide pyrophosphatase/phosphodiesterase was also evaluated, showing an increased activity post-exercise, compared to pre-exercise. Purine levels were analyzed by HPLC in the blood serum, pre- and post-exercise. Decreased levels of ATP and ADP were found post-exercise, in contrast with pre-exercise values. Conversely, post-exercise levels of adenosine and inosine increased compared to pre-exercise levels. Our results indicate an influence of acute exercise on ATP metabolism, modifying enzymatic behavior to promote a protective biological environment.

  18. A deafness-associated tRNAAsp mutation alters the m1G37 modification, aminoacylation and stability of tRNAAsp and mitochondrial function

    PubMed Central

    Wang, Meng; Peng, Yanyan; Zheng, Jing; Zheng, Binjiao; Jin, Xiaofen; Liu, Hao; Wang, Yong; Tang, Xiaowen; Huang, Taosheng; Jiang, Pingping; Guan, Min-Xin

    2016-01-01

    In this report, we investigated the pathogenic mechanism underlying the deafness-associated mitochondrial(mt) tRNAAsp 7551A > G mutation. The m.7551A > G mutation is localized at a highly conserved nucleotide(A37), adjacent (3′) to the anticodon, which is important for the fidelity of codon recognition and stabilization in functional tRNAs. It was anticipated that the m.7551A > G mutation altered the structure and function of mt-tRNAAsp. The primer extension assay demonstrated that the m.7551A > G mutation created the m1G37 modification of mt-tRNAAsp. Using cybrid cell lines generated by transferring mitochondria from lymphoblastoid cell lines derived from a Chinese family into mitochondrial DNA(mtDNA)-less (ρo) cells, we demonstrated the significant decreases in the efficiency of aminoacylation and steady-state level of mt-tRNAAsp in mutant cybrids, compared with control cybrids. A failure in metabolism of mt-tRNAAsp caused the variable reductions in mtDNA-encoded polypeptides in mutant cybrids. Impaired mitochondrial translation led to the respiratory phenotype in mutant cybrids. The respiratory deficiency lowed mitochondrial adenosine triphosphate production and increased the production of oxidative reactive species in mutant cybrids. Our data demonstrated that mitochondrial dysfunctions caused by the m.7551A > G mutation are associated with deafness. Our findings may provide new insights into the pathophysiology of maternally transmitted deafness that was manifested by altered nucleotide modification of mitochondrial tRNA. PMID:27536005

  19. Modification of the endogenous NO level influences apple embryos dormancy by alterations of nitrated and biotinylated protein patterns.

    PubMed

    Krasuska, Urszula; Ciacka, Katarzyna; Orzechowski, Sławomir; Fettke, Joerg; Bogatek, Renata; Gniazdowska, Agnieszka

    2016-10-01

    NO donors and Arg remove dormancy of apple embryos and stimulate germination. Compounds lowering NO level (cPTIO, L -NAME, CAN) strengthen dormancy. Embryo transition from dormancy state to germination is linked to increased nitric oxide synthase (NOS)-like activity. Germination of embryos is associated with declined level of biotin containing proteins and nitrated proteins in soluble protein fraction of root axis. Pattern of nitrated proteins suggest that storage proteins are putative targets of nitration. Nitric oxide (NO) acts as a key regulatory factor in removal of seed dormancy and is a signal necessary for seed transition from dormant state into germination. Modulation of NO concentration in apple (Malus domestica Borkh.) embryos by NO fumigation, treatment with NO donor (S-nitroso-N-acetyl-D,L-penicillamine, SNAP), application of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), N ω-nitro-L-arginine methyl ester (L-NAME), canavanine (CAN) or arginine (Arg) allowed us to investigate the NO impact on seed dormancy status. Arg analogs and NO scavenger strengthened embryo dormancy by lowering reactive nitrogen species level in embryonic axes. This effect was accompanied by strong inhibition of NOS-like activity, without significant influence on tissue NO2 (-) concentration. Germination sensu stricto of apple embryos initiated by dormancy breakage via short term NO treatment or Arg supplementation were linked to a reduced level of biotinylated proteins in root axis. Decrease of total soluble nitrated proteins was observed at the termination of germination sensu stricto. Also modulation of NO tissue status leads to modification in nitrated protein pattern. Among protein bands that correspond to molecular mass of approximately 95 kDa, storage proteins (legumin A-like and seed biotin-containing protein) were identified, and can be considered as good markers for seed dormancy status. Moreover, pattern of nitrated proteins suggest that

  20. Impact of the temporal stability of preexistent attentional bias for threat on its alteration through attention bias modification.

    PubMed

    Heeren, Alexandre; Philippot, Pierre; Koster, Ernst H W

    2015-12-01

    Attention bias modification (ABM) aims to reduce attentional bias for threat (AB), thereby diminishing anxiety symptoms. However, recent meta-analyses indicated mixed effects. Recent works suggest that the presence of AB prior to ABM can be considered as a critical moderating factor that may account for these mixed results. We assessed AB among highly trait-anxious individuals (n = 77) using both a face-version and a word-version of the dot-probe task at multiple time points: two weeks before ABM (t1), just prior to ABM (t2), and after ABM (t3). All participants were submitted to an ABM procedure including facial expressions. Analyses focused on 2 components of AB prior to ABM: a stable component, representing variance shared between the two baseline points (t1 and t2), and a dynamic component, representing variance that is specific to that point (t1 or t2). The stable component of AB at baseline predicted the intensity of AB after ABM (t3) while the dynamic component did not. The dynamic component of AB at baseline positively predicts performance improvement during ABM procedure, while the stable component negatively predicted it. The findings depicted above only appear with the face-version of the dot-probe task. The present results highlight the contribution of both the stable individual differences and dynamic components of preexistent AB. They also show the importance of moving the conceptualization of AB beyond the group-based analysis by integrating the notion and the assessment of within-person variability. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. A monounsaturated fatty acid-rich pecan-enriched diet favorably alters the serum lipid profile of healthy men and women.

    PubMed

    Rajaram, S; Burke, K; Connell, B; Myint, T; Sabaté, J

    2001-09-01

    Frequent consumption of nuts is associated with decreased risk of cardiovascular disease. We investigated the effect of pecans rich in monounsaturated fat as an alternative to the Step 1 diet in modifying serum lipids and lipoproteins in men and women with normal to moderately high serum cholesterol. In a single-blind, randomized, controlled, crossover feeding study, we assigned 23 subjects (mean age: 38 y; 9 women, 14 men) to follow two diets, each for 4 wk: a Step I diet and a pecan-enriched diet (accomplished by proportionately reducing all food items in a Step I diet by one fifth for a 20% isoenergetic replacement with pecans). The percentage of energy from fat in the two diets was 28.3 and 39.6%, respectively. Both diets improved the lipid profile; however, the pecan-enriched diet decreased both serum total and LDL cholesterol by 0.32 mmol/L (6.7 and 10.4%, respectively) and triglyceride by 0.14 mmol/L (11.1%) beyond the Step I diet, while increasing HDL cholesterol by 0.06 mmol/L (2.5 mg/dL). Serum apolipoprotein B and lipoprotein(a) decreased by 11.6 and 11.1%, respectively, and apolipoprotein A1 increased by 2.2% when subjects consumed the pecan compared with the Step I diet. These differences were all significant (P < 0.05). A 20% isoenergetic replacement of a Step I diet with pecans favorably altered the serum lipid profile beyond the Step I diet, without increasing body weight. Nuts such as pecans that are rich in monounsaturated fat may therefore be recommended as part of prescribed cholesterol-lowering diet of patients or habitual diet of healthy individuals.

  2. Modifications in high-density lipoprotein lipid composition and structure alter the plasma distribution of free and liposomal annamycin.

    PubMed

    Wasan, K M; Ng, S; Cassidy, S M

    1997-07-01

    Recent studies have shown that changes in lipoprotein cholesterol and triglyceride concentration alters the plasma distribution of free (Ann.) and liposomal annamycin (LAnn) and that the majority of Ann. is associated with high-density lipoproteins (HDL) following the incubation in plasma of LAnn. To demonstrate that alterations in HDL lipid composition and HDL structure may influence the plasma distribution of Ann. and LAnn, Ann. and LAnn (20 micrograms/mL) were incubated in plasma pretreated with dithionitrobenzoate (DTNB, a compound which inhibits the conversion of free cholesterol to esterified cholesterol) 18 h prior to the experiment or in untreated plasma for 60 min at 37 degrees C. In addition, Ann. and LAnn were co-incubated with DTNB in plasma for 60 min at 37 degrees C. Following incubation the plasma was separated into its HDL, low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and lipoprotein-deficient plasma (LPDP) fractions by ultracentrifugation and assayed for Ann. by fluorimetry. The HDL plasma cholesterol:triglyceride concentration ratio was significantly decreased following 18 h of DTNB pretreatment compared to untreated plasma controls. No significant differences in LDL/VLDL plasma cholesterol:triglyceride concentration ratio following 18 h of DTNB pretreatment was observed. An increased number of discoidal HDL particles were observed following 18 h of DTNB pretreatment. When Ann. was incubated in plasma pretreated with DTNB for 18 h the percentage of Ann. recovered in the HDL, LDL, and VLDL fractions significantly increased. However, the percentage of Ann. recovered within the LPDP fraction was significantly decreased. When LAnn was incubated in plasma pretreated with DTNB for 18 h the percentage of Ann. recovered in the HDL fraction significantly decreased. The percentage of Ann. recovered in the LPDP fraction significantly increased when LAnn was incubated in plasma pretreated with DTNB for 18 h. No significant differences

  3. High-fat diet alters serum fatty acid profiles in obesity prone rats: implications for in-vitro studies

    PubMed Central

    Liu, Tzu-Wen; Heden, Timothy D.; Morris, E. Matthew; Fritsche, Kevin L.; Vieira-Potter, Victoria J.; Thyfault, John P.

    2015-01-01

    High-fat diets (HFD) are commonly used in rodents to induce obesity, increase serum fatty acids, and induce lipotoxicity in various organs. In-vitro studies commonly utilize individual free fatty acids (FFA) to study lipid exposure in an effort to model what is occurring in-vivo, however, these approaches are not physiological as tissues are exposed to multiple fatty acids in-vivo. Here we characterize circulating lipids in obese-prone rats fed a HFD in both fasted and fed states with the goal of developing physiologically relevant fatty acid mixtures for subsequent in-vitro studies. Rats were fed a HFD (60% kcal fat) or a control diet (10% kcal fat) for 3 weeks; liver tissue, and both portal and systemic blood was collected. Fatty acid profiles and absolute concentrations of triglycerides (TAG) and FFA in the serum and TAG, diacylglycerol (DAG), and phospholipids (PL) in the liver were measured. Surprisingly, both systemic and portal serum TAG were ~40% lower in HFD-fed compared to controls. Overall, compared to the control diet, HFD feeding consistently induced an increase in the proportion of circulating polyunsaturated fatty acids (PUFA) with a concomitant decline in monounsaturated fatty acids (MUFA), and saturated fatty acids (SFA) in both serum TAG and FFA. The elevations of PUFA were mostly attributed to increases in n-6 PUFA, linoleic acid and arachidonic acid. In conclusion, fatty acid mixtures enriched with linoleic and arachidonic acid in addition to SFA and MUFA should be utilized for in-vitro studies attempting to model lipid exposures that occur during in-vivo HFD condition. PMID:26318121

  4. Zearalenone Altered the Serum Hormones, Morphologic and Apoptotic Measurements of Genital Organs in Post-weaning Gilts

    PubMed Central

    Chen, X. X.; Yang, C. W.; Huang, L. B.; Niu, Q. S.; Jiang, S. Z.; Chi, F.

    2015-01-01

    The present study was aimed at investigating the adverse effects of dietary zearalenone (ZEA) (1.1 to 3.2 mg/kg diet) on serum hormones, morphologic and apoptotic measurements of genital organs in post-weaning gilts. A total of twenty gilts (Landrace×Yorkshire×Duroc) weaned at 21 d with an average body weight of 10.36±1.21 kg were used in the study. Gilts were fed a basal diet with an addition of 0, 1.1, 2.0, or 3.2 mg/kg purified ZEA for 18 d ad libitum. Results showed that 3.2 mg/kg ZEA challenged gilts decreased (p<0.05) the serum levels of luteinizing hormone, however, serum levels of prolactin in gilts fed the diet containing 2.0 mg/kg ZEA or more were increased (p<0.05) compared to those in the control. Linear effects on all tested serum hormones except progesterone were observed as dietary ZEA levels increased (p<0.05). Gilts fed ZEA-contaminated diet showed increase (p<0.05) in genital organs size, hyperplasia of submucosal smooth muscles in the corpus uteri in a dose-dependent manner. However, the decreased numbers of follicles in the cortex and apoptotic cells in the ovarian were observed in gilts treated with ZEA in a dose-dependent manner. Degeneration and structural abnormalities of genital organs tissues were also observed in the gilts fed diet containing 1.1 mg/kg ZEA or more. Results suggested that dietary ZEA at 1.1 to 3.2 mg/kg can induce endocrine disturbance and damage genital organs in post-weaning gilts. PMID:25557812

  5. Evaluation of serum interleukin-10 levels as a predictor of glycemic alteration in chronic periodontitis and type 2 diabetes mellitus

    PubMed Central

    Acharya, Anirudh Balakrishna; Thakur, Srinath; Muddapur, Mahadevayya Veerayya

    2015-01-01

    Aim: Chronic periodontal disease (CPD) and type 2 diabetes mellitus (T2DM) share common pathogenic pathways. This study aimed to estimate levels of serum interleukin (IL-10), an anti-inflammatory cytokine also associated with T2DM and evaluate its association with hyperglycemia. Materials and Methods: This investigation involved sixty participants divided into four groups comprising 15 participants each: Group 1 (healthy controls), Group 2 (CPD patients), Group 3 (T2DM patients with CPD) and Group 4 (T2DM patients). Plaque index, gingival index, probing pocket depths (PPD), clinical attachment loss, bleeding on probing, random blood sugar, glycosylated hemoglobin (HbA1c), and serum IL-10 was measured. Results: Interleukin-10 was detected in all four groups. Statistically significant (P < 0.05) differences were observed in most of the variables in all groups. IL-10 correlated significantly with PPD in Group 1 and with HbA1c in Group 4. IL-10 regressed with PPD in Group 1 and with HbA1c in Group 4. IL-10 levels were lower in Group 3 when compared with Group 4 and was lowest in Group 2. Conclusion: Low IL-10 levels associated with high HbA1c. Pathogenic mechanisms of CPD seem to regulate IL-10. Serum IL-10 levels may be one of the predictors of glycemia. PMID:26392685

  6. Ubiquitin modifications

    PubMed Central

    Swatek, Kirby N; Komander, David

    2016-01-01

    Protein ubiquitination is a dynamic multifaceted post-translational modification involved in nearly all aspects of eukaryotic biology. Once attached to a substrate, the 76-amino acid protein ubiquitin is subjected to further modifications, creating a multitude of distinct signals with distinct cellular outcomes, referred to as the 'ubiquitin code'. Ubiquitin can be ubiquitinated on seven lysine (Lys) residues or on the N-terminus, leading to polyubiquitin chains that can encompass complex topologies. Alternatively or in addition, ubiquitin Lys residues can be modified by ubiquitin-like molecules (such as SUMO or NEDD8). Finally, ubiquitin can also be acetylated on Lys, or phosphorylated on Ser, Thr or Tyr residues, and each modification has the potential to dramatically alter the signaling outcome. While the number of distinctly modified ubiquitin species in cells is mind-boggling, much progress has been made to characterize the roles of distinct ubiquitin modifications, and many enzymes and receptors have been identified that create, recognize or remove these ubiquitin modifications. We here provide an overview of the various ubiquitin modifications present in cells, and highlight recent progress on ubiquitin chain biology. We then discuss the recent findings in the field of ubiquitin acetylation and phosphorylation, with a focus on Ser65-phosphorylation and its role in mitophagy and Parkin activation. PMID:27012465

  7. Increased serum hepcidin and alterations in blood iron parameters associated with asymptomatic P. falciparum and P. vivax malaria

    PubMed Central

    de Mast, Quirijn; Syafruddin, Din; Keijmel, Stephan; Riekerink, Teun Olde; Deky, Oktavian; Asih, Puji B.; Swinkels, Dorine W.; van der Ven, Andre J.

    2010-01-01

    Background Asymptomatic Plasmodium spp. infections and anemia are highly prevalent conditions in tropical regions. We studied whether asymptomatic parasitemia induces hepcidin- and/or cytokine-mediated iron maldistribution and anemia. Design and Methods A group of 1197 Indonesian schoolchildren, aged 5–15 years, were screened by microscopy for the presence of parasitemia. Concentrations of hemoglobin, serum hepcidin and parameters of iron status and inflammation were determined at baseline and 4 weeks after antimalarial treatment. Results Asymptomatic P. falciparum and P. vivax parasitemia were detected in 73 (6.1%) and 18 (1.5%) children, respectively, of whom 84% and 83% had a C-reactive protein concentration below 5 mg/L. Children with P. falciparum or P. vivax parasitemia had significantly lower hemoglobin concentrations than 17 aparasitemic controls (12.6 and 12.2 g/dL versus 14.4 g/dL; P<0.01), together with significantly higher serum hepcidin concentrations (5.2 and 5.6 nM versus 3.1 nM; P<0.05). The latter was associated with signs of iron maldistribution with higher ferritin concentrations and lower values of serum iron concentration, transferrin saturation and erythrocyte mean cell volume. Concentrations of growth differentiation factor 15 were similar across groups. Antimalarial treatment partly reversed these abnormalities and led to a significant increase in hemoglobin concentration. Conclusions Asymptomatic malarial parasitemia is associated with increased hepcidin concentrations and anemia, in the absence of a manifest acute phase response. Prolonged iron maldistribution may be an underestimated cause of anemia. Screening for parasitemia should be performed before starting iron supplementation, as iron therapy may be less effective and even hazardous in these circumstances. PMID:20133896

  8. Improvement in Serum Biochemical Alterations and Oxidative Stress of Liver and Pancreas following Use of Royal Jelly in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Ghanbari, Elham; Nejati, Vahid; Khazaei, Mozafar

    2016-01-01

    Objective This study aimed to evaluate the effects of royal jelly (RJ) on serum biochemical alterations and oxidative stress status in liver and pancreas of streptozotocin (STZ)- induced diabetic rats. Materials and Methods In this experimental study, thirty two male Wistar rats were divided into the following four groups (n=8/group): i. Control (C), ii. Diabetic (D), iii. Royal jelly (R), and iv. Royal jelly-treated diabetic (D/R) groups. Diabetes was induced by single intraperitoneal (IP) injection of STZ (60 mg/kg). The RJ [100 mg/kg body weight (BW)] was administered orally for 42 days. Blood samples were used to determine serum levels of insulin, high density lipoprotein cholesterol (HDL-c), total protein (TP), albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and fasting blood glucose (FBG). Also, the antioxidant status was evaluated by determining the levels of malondialdehyde (MDA), catalase (CAT) and ferric reducing antioxidant power (FRAP) in liver and pancreas. Data were analyzed by one-way analysis of variance (ANOVA) with P<0.05 as the significant level. Results STZ-induced diabetic rats showed a significant elevation in the serum levels of AST, ALT, ALP and FBG, whereas there was a significant decrease in serum levels of insulin, albumin, HDL-c and TP (P<0.05). Treatment of the diabetic rats with RJ restored the changes of the above parameters to their normal levels (P<0.05). In addition, RJ significantly improved reduced levels of FRAP and CAT as well as high MDA level in liver and pancreas (P<0.05). Conclusion RJ improves oxidative damage induced by STZ in the liver and pancreas of rats; therefore, it can be considered as an effective and alternative treatment for diabetes. PMID:27602318

  9. Deoxynivalenol in chicken feed alters the vaccinal immune response and clinical biochemical serum parameters but not the intestinal and carcass characteristics.

    PubMed

    Ghareeb, K; Awad, W A; Zebeli, Q; Böhm, J

    2016-02-01

    This study was conducted to investigate the impacts of deoxynivalenol (DON) feeding either alone or in combination with a microbial feed additive (MFA) on the immune response to a viral vaccine and serum clinical chemical parameters. Forty 1-day-old boiler chicks were weighed and randomly divided into four groups, 10 birds in each group: (i) control group fed with basal diet; (ii) DON group fed with basal diet artificially contaminated with 10 mg DON/kg feed; (iii) DON + MFA group fed with basal diet contaminated with 10 mg DON/kg feed and supplemented with 2.5 kg of MFA/ton feed; and (iv) MFA group fed with basal diet supplemented with 2.5 kg of MFA/ton feed. At 35 days of age, birds were slaughtered and blood was collected for investigating the antibody titre against infectious bronchitis virus (IBV) and clinical chemical parameters. The results showed that DON reduced (p = 0.032) the titre against IBV, decreased (p = 0.005) the level of alanine transaminase (ALT) (4.2 ± 0.5 U/l) compared with control birds (6.4 ± 0.5 U/l), increased (p = 0.002) the serum cholesterol concentration (144 ± 6 mg/dl) compared with their control counterparts (123 ± 5 mg/dl) and increased (p = 0.074) the amount of circulating triglycerides (62.25 ± 7.50 mg/dl) compared with controls (39.55 ± 4.74). These results indicate that dietary DON altered the humoral immune response to viral vaccine and affected the serum clinical biochemistry. However, DON in combination with MFA did not affect serum IBV titre. Taken together, DON in the feed of broilers produced an impairment of the success of IBV vaccine and affected the health of birds.

  10. A Longitudinal Study of Alterations of Hippocampal Volumes and Serum BDNF Levels in Association to Atypical Antipsychotics in a Sample of First-Episode Patients with Schizophrenia

    PubMed Central

    Rizos, Emmanouil; Papathanasiou, Matilda A.; Michalopoulou, Panagiota G.; Laskos, Efstathios; Mazioti, Aggeliki; Kastania, Anastasia; Vasilopoulou, Konstantina; Nikolaidou, Paraskevi; Margaritis, Dimitrios; Papageorgiou, Charalabos; Liappas, Ioannis

    2014-01-01

    Background Schizophrenia is associated with structural and functional abnormalities of the hippocampus, which have been suggested to play an important role in the formation and emergence of schizophrenia syndrome. Patients with schizophrenia exhibit significant bilateral hippocampal volume reduction and progressive hippocampal volume decrease in first-episode patients with schizophrenia has been shown in many neuroimaging studies. Dysfunction of the neurotrophic system has been implicated in the pathophysiology of schizophrenia. The initiation of antipsychotic medication alters the levels of serum Brain Derived Neurotrophic Factor (BDNF) levels. However it is unclear whether treatment with antipsychotics is associated with alterations of hippocampal volume and BDNF levels. Methods In the present longitudinal study we investigated the association between serum BDNF levels and hippocampal volumes in a sample of fourteen first-episode drug-naïve patients with schizophrenia (FEP). MRI scans, BDNF and clinical measurements were performed twice: at baseline before the initiation of antipsychotic treatment and 8 months later, while the patients were receiving monotherapy with second generation antipsychotics (SGAs). Results We found that left hippocampal volume was decreased (corrected left HV [t = 2.977, df = 13, p = .011] at follow-up; We also found that the higher the BDNF levels change the higher were the differences of corrected left hippocampus after 8 months of treatment with atypical antipsychotics (Pearson r = 0.597, p = 0.024). Conclusions The association of BDNF with hippocampal volume alterations in schizophrenia merits further investigation and replication in larger longitudinal studies. PMID:24551075

  11. Obestatin is present in saliva: alterations in obestatin and ghrelin levels of saliva and serum in ischemic heart disease.

    PubMed

    Ozbay, Yilmaz; Aydin, Suleyman; Dagli, A Ferda; Akbulut, Mehmet; Dagli, Necati; Kilic, Nermin; Rahman, Ali; Sahin, Ibrahim; Polat, Veli; Ozercan, H Ibrahim; Arslan, Nadi; Sensoy, Dogan

    2008-01-31

    Ghrelin and obestatin are a single gene products and are a multiple functional peptides that regulates energy homeostasis, and food intake. In the present work, we studied the secretion of ghrelin and its co-secreted peptide obestatin in 44 patients with ischemic heart disease with that of 27 healthy matched controls. Here we first conducted using an immunohistochemistry assay to screen whether human salivary glands have any obestatin immunoreactivity. Then, serum and saliva obestatin and acylated ghrelin levels were determined by using Radioimmunoassay. Our immunohistochemical analysis demonstrated that obestatin was localized in the striated and excretory duct of human salivary gland. We also report for the first time that obestatin, like ghrelin, is present in human salivary gland and saliva. No evidence of the role of obestatin or ghrelin saliva levels in the context of ischemic heart disease was found. Salivary ghrelin and obestatin levels are correlated in controls with the blood levels. Determination of salivary values could represent a non-invasive alternative to serum ones that can be useful in clinical practice.

  12. Alterations in selected serum biochemistry values of free-ranging Bornean leopard cats (Prionailurus bengalensis borneoensis) captured by box traps.

    PubMed

    Nájera, Fernando; Hearn, Andrew J; Ross, Joanna; Nathan, Senthivel; Revuelta, Luis

    2014-09-01

    Box-traps for capturing wild cats are widely used by researchers since it is one of the most effective methods for trapping these species. Although they are extensively utilised, the effects on the physiology of trapped felids remain unclear. Researchers frequently make judgements regarding the safety of such capture devices by examination of external injuries but often fail to take into consideration other physiological parameters. To assess the effects of capture events on selected serum biochemistry values of free-ranging Bornean leopard cats (Prionailurus bengalensis borneoensis) six free-ranging leopard cats (four males, two females) were trapped by using box-traps in Sabah, Malaysian Borneo. Blood was collected by jugular venipucture after chemical immobilization with a mixture of tiletamine and zolazepam. Blood was analysed for 17 serum biochemistry parameters. The most consistent and significantly higher value found in both sexes was aspartate aminotransferase (AST), followed by high mean value of alanine aminotransferase (ALT). Both mean values exceeded the upper limit of the reference range for captive leopard cats. These results demonstrate that captured leopard cats by box-traps undergo physical exertion and consequently some type of muscle injury/damage. Researchers and wildlife managers should be aware of the physiological response of trapped felids when using box-traps. Devices that facilitate the prompt removal of leopard cats from the traps would be useful for researchers to avoid further damage while live trapping this species.

  13. Low-selenium diet induces cell cycle arrest of thymocytes and alters serum IL-2 content in chickens.

    PubMed

    Peng, Xi; Cui, Hengmin; Yuan, Jingxin; Cui, Wei; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Pan, Kangcheng; Zhou, Yi; Lai, Weimin

    2011-12-01

    The purpose of this 42-day study was to investigate the effects of low selenium (Se) on cellular immune function by determining cell cycle of thymus, serum IL-2 content, and mitogenesis of peripheral blood T-lymphocytes. One hundred twenty 1-day-old Avian broilers were randomly assigned to two groups of 60 each and were fed on a low-Se diet (0.0342 mg/kg Se) or a control diet (0.2 mg/kg Se), respectively. Cell cycle analysis by flow cytometry showed that low-Se diet caused an increase in G(0)G(1) phase cells that corresponded to a decrease in S-phase cells in thymus. Ultrastructurally, mitochondria injury and increased apoptotic cells with condensed nuclei were observed. Low-Se diet decreased the serum IL-2 contents and mitogenesis of peripheral blood lymphocytes to concanavalin A in comparison with those of control group. These data indicate that low-Se diet inhibits the development of thymus by arresting the cell cycle and decreasing the IL-2 content.

  14. Histomorphometric alteration of knee articular cartilage and serum alkaline phosphatase in young female mice by chronic supplementation with soybean.

    PubMed

    Fazelipour, S; Tootian, Z; Matini, E; Hadipour-Jahromy, M

    2011-06-01

    The purpose of the present study was to examine the effect of soybean supplementation on cartilage thickness in the knee joint and serum levels of alkaline phosphatase (ALP) in mice. Forty female mice were fed for 6 months on one of four regimens: low protein, complete protein without soybean, and complete protein containing either 20% or 40% soybean. Body weight differences, histological and histomorphometric analysis, and ALP levels were determined and compared after 6 months. The results showed a significant increase in serum ALP activity and cartilage thickness in both groups fed on soybean-containing diets, compared with the other groups. Additionally, the number of chondrocytes was significantly increased (p < 0.001) in the group taking the 40% soybean regimen, and the proteoglycan content of the intracellular fluid in the tibia was higher in those groups taking soybean. In conclusion, the present study suggests that soybean supplementation is capable of stimulating ALP production and reducing cartilage loss in young female mice. Soybean supplementation during childhood may therefore be potentially useful in protecting joints. Copyright © 2010 John Wiley & Sons, Ltd.

  15. Influence of core and maltose surface modification of PEIs on their interaction with plasma proteins-Human serum albumin and lysozyme.

    PubMed

    Wrobel, Dominika; Marcinkowska, Monika; Janaszewska, Anna; Appelhans, Dietmar; Voit, Brigitte; Klajnert-Maculewicz, Barbara; Bryszewska, Maria; Štofik, Marcel; Herma, Regina; Duchnowicz, Piotr; Maly, Jan

    2017-04-01

    Regardless of the route of administration, some or all of a therapeutic agent will appear in the blood stream, where it can act on blood cells and other components of the plasma. Recently we have shown that poly(ethylene imines) (PEIs) which interact with plasma proteins are taken up into erythrocyte membranes. These observations led us to investigate the interactions between maltose functionalized hyperbranched PEIs (PEI-Mal) and plasma proteins. Two model proteins were chosen - human serum albumin (HSA) (albumins constitute ∼60% of all plasma proteins), and lysozyme. HSA is a negatively charged 66kDa protein at neutral pH, whereas lysozyme is a positively charged 14kDa protein. Fluorescence quenching and changes in the conformation of the amino acid tryptophan, diameter and zeta potential of proteins were investigated to evaluate the interaction of PEI-Mal with proteins. PEI-Mal interacts with both types of proteins. The strength of dendritic glycopolymer interactions was generally weak, especially with lysozyme. Greater changes were found with HSA, mainly triggered by hydrogen bonds and the electrostatic interaction properties of dendritic glycopolymers. Moreover, the structure and the size of PEI-Mal macromolecules affected these interactions; larger macromolecules with more sugar groups (95% maltose units) interacted more strongly with proteins than smaller ones with lower sugar modification (33% maltose units). Due to (i) the proven overall low toxicity of sugar-modified PEIs and, (ii) their ability to interact preferentially through hydrogen bonds with proteins of human plasma or possibly with other interesting protein targets, PEI-Mal is a good candidate for creating therapeutic nanoparticles in the fast developing field of nanomedicine.

  16. Modification of fos proteins: phosphorylation of c-fos, but not v-fos, is stimulated by 12-tetradecanoyl-phorbol-13-acetate and serum.

    PubMed Central

    Barber, J R; Verma, I M

    1987-01-01

    We have investigated the covalent modification of the proteins encoded by the murine fos proto-oncogene (c-fos) and that of the corresponding gene product of FBJ murine osteosarcoma virus (v-fos). Both proteins are posttranslationally processed in the cell, resulting in forms with lower electrophoretic mobilities than that of the initial translation product on sodium dodecyl sulfate-polyacrylamide gels. Treatment with alkaline phosphatase indicates that most, if not all, of this electrophoretic shift is due to phosphoesterification of both proteins. These phosphoryl groups stoichiometrically modify the v-fos and c-fos proteins on serine residues and turn over rapidly in vivo in the presence of protein kinase inhibitors (half-life, less than 15 min). Direct quantitative comparison of steady-state labeling studies with L-[35S]methionine and [32P]phosphate reveals that the c-fos protein is four- to fivefold more highly phosphorylated than the v-fos protein is. Comparison of tryptic fragments from [32P]phosphate-labeled proteins indicates that although the two proteins have several tryptic phosphopeptides in common, the c-fos protein contains unique major tryptic phosphopeptides that the v-fos protein lacks. These unique sites of c-fos phosphorylation have been tentatively localized to the carboxy-terminal 20 amino acid residues of the protein. Phosphorylation of the c-fos protein, but not the v-fos protein, can be stimulated at least fivefold in vivo by the addition of either 12-tetradecanoyl-phorbol-13-acetate or serum. This increase in the steady-state degree of phosphorylation of c-fos appears to be independent of protein kinase C since phosphorylation is Ca2+ and diacylglycerol independent. The possible role of phosphorylation of these proteins in cellular transformation is discussed. Images PMID:3110603

  17. Serum lipid alterations identified in chronic hepatitis B, hepatitis B virus-associated cirrhosis and carcinoma patients

    PubMed Central

    Wu, Tao; Zheng, Xiaojiao; Yang, Ming; Zhao, Aihua; Li, Meng; Chen, Tianlu; Panee, Jun; Jia, Wei; Ji, Guang

    2017-01-01

    The incidences of chronic hepatitis B (CHB), Hepatitis B virus (HBV)-associated cirrhosis and HBV-associated carcinoma are high and increasing. This study was designed to evaluate serum lipid metabolite changes that are associated with the progression from CHB to HBV-associated cirrhosis and ultimately to HBV-associated HCC. A targeted metabolomic assay was performed in fasting sera from 136 CHB patients, 104 HBV-associated cirrhosis, and 95 HBV-associated HCC using ultra-performance liquid chromatography triple quadrupole mass spectrometry. A total of 140 metabolites were identified. Clear separations between each two groups were obtained using the partial least squares discriminate analysis of 9 lipid metabolites. Progressively lower levels of long-chain lysophosphatidylcholines (lysoPC a C18:2, lysoPC a C20:3, lysoPC a C20:4) were observed from CHB to cirrhosis to carcinoma; lower levels of lysoPC a C20:4 were found in patients with higher model for end-stage liver disease in the same disease group; and lysoPC a C20:3 levels were lower in Child-Pugh Class C than in Class A and Class B in HBV-associated cirrhosis and HBV-associated HCC groups. The octadecadienyl carnitine level was higher in HBV-associated cirrhosis group than in other two groups. Serum levels of selected long-chain lysoPCs are promising markers for the progression of HBV-associated liver diseases. PMID:28198443

  18. Altered gene expression in human adipose stem cells cultured with fetal bovine serum compared to human supplements.

    PubMed

    Bieback, Karen; Ha, Viet Anh-Thu; Hecker, Andrea; Grassl, Melanie; Kinzebach, Sven; Solz, Hermann; Sticht, Carsten; Klüter, Harald; Bugert, Peter

    2010-11-01

    Mesenchymal stromal cells (MSCs) are promising candidates for innovative cell therapeutic applications. For clinical scale manufacturing regulatory agencies recommend to replace fetal bovine serum (FBS) commonly used in MSC expansion media as soon as equivalent alternative supplements are available. We already demonstrated that pooled blood group AB human serum (HS) and thrombin-activated platelet releasate plasma (tPRP) support the expansion of multipotent adipose tissue-derived MSCs (ASCs). Slight differences in size, growth pattern and adhesion prompted us to investigate the level of equivalence by compiling the transcriptional profiles of ASCs cultivated in these supplements. A whole genome gene expression analysis was performed and data verified by polymerase chain reaction and protein analyses. Microarray-based screening of 34,039 genes revealed 102 genes differentially expressed in ASCs cultured with FBS compared to HS or tPRP supplements. A significantly higher expression in FBS cultures was found for 90 genes (fold change ≥2). Only 12 of the 102 genes showed a lower expression in FBS compared to HS or tPRP cultures (fold change ≤0.5). Differences between cells cultivated in HS and tPRP were hardly evident. Supporting previous observations of reduced adhesion of cells cultivated in the human alternatives we detected a number of adhesion and extracellular matrix-associated molecules expressed at lower levels in ASCs cultivated with human supplements. Confirmative assays analyzing transcript or protein expression with selected genes supported these results. Likewise a number of mesodermal differentiation-associated genes were higher expressed in cells grown in FBS. Quantifying adipogenic and osteogenic differentiation lacked to demonstrate a clear correlation to the supplement due to donor-specific variances. Our results emphasize the necessity of comparability studies as they indicate that FBS induces a culture adaptation exceeding that of ex vivo

  19. Cruciferous vegetable supplementation in a controlled diet study alters the serum peptidome in a GSTM1-genotype dependent manner

    PubMed Central

    2011-01-01

    Background Cruciferous vegetable intake is inversely associated with the risk of several cancers. Isothiocyanates (ITC) are hypothesized to be the major bioactive constituents contributing to these cancer-preventive effects. The polymorphic glutathione-S-transferase (GST) gene family encodes several enzymes which catalyze ITC degradation in vivo. Methods We utilized high throughput proteomics methods to examine how human serum peptides (the "peptidome") change in response to cruciferous vegetable feeding in individuals of different GSTM1 genotypes. In two randomized, crossover, controlled feeding studies (EAT and 2EAT) participants consumed a fruit- and vegetable-free basal diet and the basal diet supplemented with cruciferous vegetables. Serum samples collected at the end of the feeding period were fractionated and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry spectra were obtained. Peak identification/alignment computer algorithms and mixed effects models were used to analyze the data. Results After analysis of spectra from EAT participants, 24 distinct peaks showed statistically significant differences associated with cruciferous vegetable intake. Twenty of these peaks were driven by their GSTM1 genotype (i.e., GSTM1+ or GSTM1- null). When data from EAT and 2EAT participants were compared by joint processing of spectra to align a common set, 6 peaks showed consistent changes in both studies in a genotype-dependent manner. The peaks at 6700 m/z and 9565 m/z were identified as an isoform of transthyretin (TTR) and a fragment of zinc α2-glycoprotein (ZAG), respectively. Conclusions Cruciferous vegetable intake in GSTM1+ individuals led to changes in circulating levels of several peptides/proteins, including TTR and a fragment of ZAG. TTR is a known marker of nutritional status and ZAG is an adipokine that plays a role in lipid mobilization. The results of this study present evidence that the GSTM1-genotype modulates the

  20. Serum cytokines are increased and circulating micronutrients are not altered in subjects with early compared to advanced knee osteoarthritis.

    PubMed

    Barker, Tyler; Rogers, Victoria E; Henriksen, Vanessa T; Aguirre, Dale; Trawick, Roy H; Rasmussen, G Lynn; Momberger, Nathan G

    2014-08-01

    Knee osteoarthritis (OA) is a leading cause of physical disability. At the early stage of knee OA, the increase in synovial fluid cytokine concentrations could contribute to the pathogenesis of OA by degrading articular cartilage. It is unknown, however, if inflammatory cytokines increase systemically at the early or advanced stage of knee OA. The systemic increase of inflammatory cytokines could be detrimental to the endogenous status of micronutrients that protect against excessive inflammation and cytokine-mediated events. The purpose of this study was to test the hypothesis that an increase in serum cytokines associate with a decrease in circulating micronutrients in subjects with early compared to advanced knee OA. Advanced knee OA subjects (n=14) displayed radiographic, pain, and muscular weakness symptoms of knee OA. Early knee OA subjects (n=14) were matched (age, gender, and body mass index) to the advanced OA group and displayed one or two of the aforementioned symptoms of knee OA. Inflammatory cytokines, vitamins C (ascorbic acid), D (25-hydroxyvitamin D), and E (α- and γ-tocopherols), and β-carotene were measured in fasting blood samples. In the early OA group, serum tumor necrosis factor (TNF)-α, interleukin (IL)-5, IL-6, IL-12, and IL-13 concentrations were significantly (all p<0.05) increased. Circulating ascorbic acid, 25-hydroxyvitamin D, α- and γ-tocopherol's, and β-carotene concentrations were not significantly different between groups. Based on these preliminary results, we conclude that the systemic increase of inflammatory cytokines is not associated with a decrease in circulating micronutrients in subjects with early compared to advanced knee OA.

  1. Tenofovir exposure alters associations of serum bicarbonate with chronic kidney disease risk in HIV-infected veterans.

    PubMed

    Kim, Julie E; Scherzer, Rebecca; Estrella, Michelle M; Ix, Joachim H; Shlipak, Michael G

    2016-04-24

    Among HIV-infected persons, tenofovir disoproxil fumarate (TDF) use is associated with higher risk of developing chronic kidney disease (CKD). Because lower serum bicarbonate concentrations may precede CKD onset, this study investigated the associations between TDF use and bicarbonate concentrations, and between bicarbonate with CKD risk among TDF users and nonusers. Retrospective cohort study of 16,070 HIV-infected US veterans who initiated antiretroviral therapy between 1997-2011. The association between TDF use with longitudinal bicarbonate concentrations and associations between bicarbonate with incident CKD stratified by TDF use (never, initial, and later user) were evaluated. Compared with TDF users, never users had faster declines in bicarbonate concentrations: change in bicarbonate -0.11 mmol/l per year (95% confidence interval -0.16, -0.05), compared with -0.04 mmol/l per year (-0.06, 0.05) in initial users and -0.02 mmol/l per year (-0.05, 0.01) in later users. Low baseline bicarbonate (<22 mmol/l) was significantly associated with CKD risk among TDF never users (1.80; 1.21, 2.68), but not among TDF users (0.98; 0.69, 1.38). Similarly, declining bicarbonate concentrations were associated with higher CKD risk among never users (hazard ratio 1.67 per mmol/l; 1.34, 2.08), but not among TDF users (1.09; 0.98, 1.22). Interactions were highly significant for both analyses (P value = 0.001). Despite associations with nephrotoxicity, TDF use was associated with higher serum bicarbonate concentrations longitudinally. Additionally, TDF use obscured the strong associations of bicarbonate with CKD risk in HIV-infected persons. Therefore, the role of bicarbonate concentrations as a tool to monitor kidney health in HIV-infected persons may be limited in the setting of TDF use.

  2. Tenofovir exposure alters associations of serum bicarbonate with chronic kidney disease risk in HIV-infected Veterans

    PubMed Central

    KIM, Julie; SCHERZER, Rebecca; ESTRELLA, Michelle; IX, Joachim; SHLIPAK, Michael G.

    2016-01-01

    Objective Among HIV-infected persons, tenofovir disoproxil fumarate (TDF) use is associated with higher risk of developing chronic kidney disease (CKD). Because lower serum bicarbonate concentrations may precede CKD onset, this study investigated the associations between TDF use and bicarbonate concentrations, and between bicarbonate with CKD risk among TDF users and non-users. Methods Retrospective cohort study of 16,070 HIV-infected US veterans who initiated antiretroviral therapy between 1997–2011. The association between TDF use with longitudinal bicarbonate concentrations and associations between bicarbonate with incident CKD stratified by TDF use (never, initial, and later user) were evaluated. Results Compared to TDF users, never users had faster declines in bicarbonate concentrations: change in bicarbonate −0.11 mmol/L/year (95% CI −0.16, −0.05), compared with −0.04 mmol/L/year (−0.06, 0.05) in initial users and −0.02 mmol/L/year (−0.05, 0.01) in later users. Low baseline bicarbonate (<22 mmol/L) was significantly associated with CKD risk among TDF never users (1.80; 1.21, 2.68), but not among TDF users (0.98; 0.69, 1.38). Similarly, declining bicarbonate concentrations were associated with higher CKD risk among never users(HR 1.67 per mmol/L; 1.34, 2.08), but not among TDF users (1.09; 0.98, 1.22). Interactions were highly significant for both analyses (p-value = 0.001). Conclusions Despite associations with nephrotoxicity, TDF use was associated with higher serum bicarbonate concentrations longitudinally. Additionally, TDF use obscured the strong associations of bicarbonate with CKD risk in HIV-infected persons. Therefore, the role of bicarbonate concentrations as a tool to monitor kidney health in HIV-infected persons may be limited in the setting of TDF use. PMID:26760455

  3. Periodontal disease and high doses of inhaled corticosteroids alter NTPDase activity in the blood serum of rats.

    PubMed

    Scarabelot, Vanessa L; Cavagni, Juliano; Medeiros, Liciane F; Detânico, Bernardo; Rozisky, Joanna R; de Souza, Andressa; Daudt, Luciana Dondonis; Gaio, Eduardo José; Ferreira, Maria Beatriz Cardoso; Rösing, Cassiano Kuchenbecker; Battastini, Ana Maria O; Torres, Iraci L S

    2014-08-01

    Certain drugs such as glucocorticoids may interfere with the modulation of periodontal disease. In contrast, corticosteroid treatment has been associated with a protective effect with regard to periodontal breakdown, depending on the dose, pathway, and exposure time. Considering the potential relevance of nucleotidases in coordinating the cardiovascular system and inflammation processes, the aim of this study was to investigate the nucleotidase activities in the blood serum of rats with periodontal disease exposed chronically to inhaled corticosteroids. Adult male Wistar rats (n=26) were randomly assigned to one of the following four study groups: a control group that received no intervention; a periodontal disease group that received saline solution; a 'low dose' group that received 30 μg of budesonide daily; and a corresponding 'high dose' group that received 100 μg daily over a 15-day time course. The hydrolysis of ATP, ADP, and AMP were analysed in blood serum. Periodontal disease diminished the hydrolysis of ATP and enhanced the hydrolysis of ADP. Repeated administration of either a low or high dose in the periodontal disease model of inhaled corticosteroids reversed the observed increase in ADP hydrolysis, and only the repeated administration of low doses of inhaled corticosteroids was able to reverse the decrease in the hydrolysis of ATP induced by periodontal disease. The variables investigated in this study may be involved in the pathophysiology of periodontal disease and may participate in the mechanisms that mediate the development of some of the side effects of inhaled corticosteroids. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. A novel HSP90 inhibitor delays castrate resistant prostate cancer without altering serum PSA levels and inhibits osteoclastogenesis

    PubMed Central

    Lamoureux, Francois; Thomas, Christian; Yin, Min-Jean; Kuruma, Hidetoshi; Fazli, Ladan; Gleave, Martin E; Zoubeidi, Amina

    2015-01-01

    Purpose Prostate cancer responds initially to anti-androgen therapies, however, progression to castration resistant disease frequently occurs. Therefore there is an urgent need for novel therapeutic agents that can prevent the emergence of castration resistant prostate cancer (CRPC). Hsp90 is a molecular chaperone involved in the stability of many client proteins including Akt and androgen receptor (AR). 17-AAG have been reported to inhibit tumor growth in various cancers, however induces tumor progression in the bone microenvironment. Methods Cell growth, apoptosis, and AR transactivation were examined by crystal violet assay, flow cytometry and luciferase assays respectively. The consequence of HSP90 therapy in vivo was evaluated in LNCaP xenograft model. The consequence of PF-04928473 therapy on bone metastasis was studied using an osteoclastogenesis in vitro assay. Results PF-04928473 inhibits cell growth in a panel of prostate cancer cells, induces cell cycle arrest at sub-G1 and leads to apoptosis and increased caspase-3 activity. These biologic events were accompanied by decreased activation of Akt and Erk as well as decreased expression of Her2, and decreased AR expression and activation in vitro. In contrast to 17-AAG, PF-04928473 abrogates RANKL-induced osteoclast differentiation by affecting NF-kB activation and Src phosphorylation. Finally, PF-04929113 inhibited tumor growth and prolonged survival compared to controls. Surprisingly, PF-04929113 did not reduce serum PSA levels in vivo in parallel these decreases in tumor volume. Conclusion These data identify significant anti-cancer activity of PF-04929113 in CRPC but suggest that serum PSA may not prove useful as pharmaco-dynamic tool for this drug. PMID:21349995

  5. Diet modification and its influence on metabolic and related pathological alterations in the SHR/NDmcr-cp rat, an animal model of the metabolic syndrome.

    PubMed

    Kawai, Kouji; Sakairi, Tetsuya; Harada, Shuichi; Shinozuka, Junko; Ide, Mika; Sato, Hiroko; Tanaka, Masaharu; Toriumi, Wataru; Kume, Eisuke

    2012-05-01

    SHR/NDmcr-cp (SHR/NDcp) rats, which carry a nonsense mutation of the leptin receptor gene, are known to spontaneously develop hypertension, obesity and hyperlipidemia, and have therefore found use as an animal model of the metabolic syndrome and type 2 diabetes. However, some recent studies on SHR/NDcp rats revealed only mild elevation of blood glucose levels. To investigate whether metabolic factors including blood glucose and histopathological alterations of SHR/NDcp rats deteriorate with a diabetogenic diet, biochemical and histopathological examinations were conducted with animals fed normal or diabetogenic diets for 20 weeks. SHR/NDcp rats receiving the normal diet displayed obesity, hypertension, hyperlipidemia, and mild elevation of blood glucose and HbA1c levels. Urinary glucose excretion was noted in only 1 out of 6 animals. Histologically, macro- and micro-vesicular steatosis in the liver, glomerular and tubular damages in the kidney and islet hyperplasia mainly of beta cells in the pancreas were characteristically noted. In SHR/NDcp rats fed the diabetogenic diet, obesity was more severe, with higher blood glucose and HbA1c levels, increased numbers of animals with urinary glucose excretion, and more pronounced hepatic steatosis and renal tubular changes. However, elevation of blood glucose levels and urinary glucose excretion proved transient. These observations indicate that the diabetic state and associated histopathological alterations in SHR/NDcp rats are exacerbated by feeding a diabetogenic diet, but the effects are limited. Elevated islet function with compensative insulin secretion might be related to amelioration of the hyperglycemic state. Further diet modification could be needed to induce a more prominent and persistent diabetic state in SHR/NDcp rats. Copyright © 2010 Elsevier GmbH. All rights reserved.

  6. Il-6 Serum Levels and Production Is Related to an Altered Immune Response in Polycystic Ovary Syndrome Girls with Insulin Resistance

    PubMed Central

    Fulghesu, Anna M.; Sanna, Francesca; Uda, Sabrina; Magnini, Roberta; Portoghese, Elaine; Batetta, Barbara

    2011-01-01

    Polycystic ovarian syndrome (PCOS) is frequently characterized by obesity and metabolic diseases including hypertension, insulin resistance, and diabetes in adulthood, all leading to an increased risk of atherosclerosis. The present study aimed to evaluate serum and production of inflammatory markers in adolescent Sardinian PCOS. On the basis of HOMA findings, patients were divided into noninsulin resistant (NIR) and insulin resistant (IR), and were weight- and age-matched with healthy girls. Inflammatory cytokines (TNF-α, IL-6, Il-10, TGF-β) and lipokines (leptin, adiponectin), the reactant hs-CRP, and in vitro inflammatory lympho-monocyte response to microbial stimulus were evaluated. In healthy and PCOS subjects, leptin and hs-CRP were correlated with BMI, whereas adiponectin was significantly reduced in all PCOS groups. Although cytokines were similar in all groups, Interleukin-6 (IL-6) was significantly higher in IR PCOS. Moreover, in the latter group lipopolysaccharide-activated monocytes secreted significantly higher levels of IL-6 compared to NIR and control subjects. To conclude, IR PCOS displayed increased IL-6 serum levels and higher secretion in LPS-activated monocytes, whilst revealing no differences for other inflammatory cytokines. These results suggest that in PCOS patients an altered immune response to inflammatory stimuli is present in IR, likely contributing towards determining onset of a low grade inflammation. PMID:21547256

  7. Serum Proteome Alterations in Patients with Cognitive Impairment after Traumatic Brain Injury Revealed by iTRAQ-Based Quantitative Proteomics

    PubMed Central

    Liang, Qinghua; Zhang, Chunhu; Huang, Wei

    2017-01-01

    Background. Cognitive impairment is the leading cause of traumatic brain injury- (TBI-) related disability; however, the underlying pathogenesis of this dysfunction is not completely understood. Methods. Using an isobaric tagging for relative and absolute quantitation- (iTRAQ-) based quantitative proteomic approach, serum samples from healthy control subjects, TBI patients with cognitive impairment, and TBI patients without cognitive impairment were analysed to identify differentially expressed proteins (DEPs) related to post-TBI cognitive impairment. In addition, DEPs were further analysed using bioinformatic platforms and validated using enzyme-linked immunosorbent assays (ELISA). Results. A total of 56 DEPs were identified that were specifically related to TBI-induced cognitive impairment. Bioinformatic analysis revealed that a wide variety of cellular and metabolic processes and some signaling pathways were involved in the pathophysiology of cognitive deficits following TBI. Five randomly selected DEPs were validated using ELISA in an additional 105 cases, and the results also supported the experimental findings. Conclusions. Despite limitations, our findings will facilitate further studies of the pathological mechanisms underlying TBI-induced cognitive impairment and provide new methods for the research and development of neuroprotective agents. However, further investigation on a large cohort is warranted. PMID:28251161

  8. Alteration of Porcine Serum Albumin Levels in Pork Meat by Marination in Kiwi or Pineapple Juice and Subsequent Pan Broiling.

    PubMed

    Moon, Sung-Sil; Kim, Dongwook; Kim, Il-Suk; Ham, Jun-Sang; Park, Beom-Young; Jang, Aera

    2014-01-01

    This study was conducted to evaluate the changes in porcine serum albumin (PSA), a major allergen, which occur when raw pork ham is marinated with kiwi or pineapple juice, and/or when the ham is pan broiled at 300℃ for 4 min after marination. In this study, raw pork ham was soaked for 4 h or 8 h in marinades containing commercial marinating sauce only, commercial marinating sauce and 7% kiwi juice, or commercial marinating sauce and 7% pineapple juice. When the meat was marinated and then pan-broiled, pork ham meat protein was significantly denatured and hydrolyzed, and the level of PSA in the meat was significantly reduced. The PSA contents of pork broiled without marination, pork that had been marinated in commercial marinating sauce alone, pork that had been marinated in commercial marinating sauce with kiwi juice, and pork that had been marinated in commercial marinating sauce with pineapple juice, were 95.4, 43.3, 14.3, and 5.4 ng/mL, respectively (p<0.05). Marinating with pineapple juice was more effective than marinating with kiwi juice; and marination for 8 h was more effective than marinating for 4 h. These results indicate that the level of PSA in pork ham is effectively reduced, when the meat is first marinated in sauces that contain kiwi or pineapple extracts for 8 h, rather than 4 h, and then cooked. Further study is needed to determine whether marinated pork meat reduces allergenicity in vivo, as well.

  9. Genetic risk scores, sex and dietary factors interact to alter serum uric acid trajectory among African-American urban adults.

    PubMed

    Beydoun, May A; Canas, Jose-Atilio; Fanelli-Kuczmarski, Marie T; Tajuddin, Salman M; Evans, Michele K; Zonderman, Alan B

    2017-03-01

    Serum uric acid (SUA), a causative agent for gout among others, is affected by both genetic and dietary factors, perhaps differentially by sex. We evaluated cross-sectional (SUAbase) and longitudinal (SUArate) associations of SUA with a genetic risk score (GRS), diet and sex. We then tested the interactive effect of GRS, diet and sex on SUA. Longitudinal data on 766 African-American urban adults participating in the Healthy Aging in Neighborhood of Diversity across the Lifespan study were used. In all, three GRS for SUA were created from known SUA-associated SNP (GRSbase (n 12 SNP), GRSrate (n 3 SNP) and GRStotal (n 15 SNP)). Dietary factors included added sugar, total alcohol, red meat, total fish, legumes, dairy products, caffeine and vitamin C. Mixed-effects linear regression models were conducted. SUAbase was higher among men compared with that among women, and increased with GRStotal tertiles. SUArate was positively associated with legume intake in women (γ=+0·14; 95 % CI +0·06, +0·22, P=0·001) and inversely related to dairy product intake in both sexes combined (γ=-0·042; 95 % CI -0·075, -0·009), P=0·010). SUAbase was directly linked to alcohol consumption among women (γ=+0·154; 95 % CI +0·046, +0·262, P=0·005). GRSrate was linearly related to SUArate only among men. Legume consumption was also positively associated with SUArate within the GRStotal's lowest tertile. Among women, a synergistic interaction was observed between GRSrate and red meat intake in association with SUArate. Among men, a synergistic interaction between low vitamin C and genetic risk was found. In sum, sex-diet, sex-gene and gene-diet interactions were detected in determining SUA. Further similar studies are needed to replicate our findings.

  10. Altered fatty acid profile in the liver and serum of stroke-prone spontaneously hypertensive rats: reduced proportion of cis-vaccenic acid.

    PubMed

    Tanaka, Shizuyo; Kojiguchi, Chiho; Yamazaki, Tohru; Mitsumoto, Atsushi; Kobayashi, Daisuke; Kudo, Naomi; Kawashima, Yoichi

    2013-01-01

    Stroke-prone spontaneously hypertensive rats (SHRSP) are utilized as models for study of the pathogenesis of not only stroke and cardiovascular disorders but also atherosclerosis and metabolic syndrome. Basic information on the profiles of fatty acids and lipid classes in the liver is indispensable to use SHRSP as a model of disorder of lipid metabolism; nevertheless, detailed information on the metabolism of triacylglycerols (TAGs) and fatty acids in the liver of SHRSP is lacking. This study aimed to characterize profiles of lipid classes and fatty acids and to explore the mechanism underlying the characteristic alterations in metabolism of TAGs and fatty acids in the liver of SHRSP, in comparison with spontaneously hypertensive rats (SHR). The characteristic changes observed in SHRSP were (1) markedly lower hepatic TAG contents; (2) altered expressions of genes encoding three enzymes responsible for the control of TAG level, namely, adipose triglyceride lipase (for TAG degradation; up-regulated), carnitine palmitoyltransferase 1a (for fatty acid β-oxidation; up-regulated) and long-chain acyl-CoA synthetase 3 (for glycerolipid synthesis; down-regulated); (3) evidently lower contents and proportions of monounsaturated fatty acids, in particular cis-vaccenic acid (18:1n-7), in the liver and serum; and (4) down-regulation of palmitoleoyl-CoA chain elongase, which is necessary for the biosynthesis of 18:1n-7, in the liver. From the above observations, we concluded that there are significant differences in profiles of lipid classes and fatty acids between SHRSP and SHR, and that altered characteristics in SHRSP are likely responsible for increases in TAG hydrolysis and β-oxidation, and decreases in TAG synthesis and 18:1n-7 synthesis.

  11. TGF-B3 Dependent Modification of Radiosensitivity in Reporter Cells Exposed to Serum From Whole-Body Low Dose-Rate Irradiated Mice

    PubMed Central

    Altaner, Čestmír; Altanerova, Veronica; Ebbesen, Peter

    2015-01-01

    Prior findings in vitro of a TGF-β3 dependent mechanism induced by low dose-rate irradiation and resulting in increased radioresistance and removal of low dose hyper-radiosensitivity (HRS) was tested in an in vivo model. DBA/2 mice were given whole-body irradiation for 1 h at low dose-rates (LDR) of 0.3 or 0.03 Gy/h. Serum was harvested and added to RPMI (4% mouse serum and 6% bovine serum).This medium was transferred to reporter cells (T-47D breast cancer cells or T98G glioblastoma cells). The response to subsequent challenge irradiation of the reporter cells was measured by the colony assay. While serum from unirradiated control mice had no effect on the radiosensitivity in the reporter cells, serum from mice given 0.3 Gy/h or 0.03 Gy/h for 1 h removed HRS and also increased survival in response to doses up to 5 Gy. The effect lasted for at least 15 months after irradiation. TGF-β3 neutralizer added to the medium containing mouse serum inhibited the effect. Serum from mice given irradiation of 0.3 Gy/h for 1 h and subsequently treated with iNOS inhibitor 1400W did not affect radiosensitivity in reporter cells; neither did serum from the unirradiated progeny of mice given 1h LDR whole-body irradiation. PMID:26673923

  12. TGF-B3 Dependent Modification of Radiosensitivity in Reporter Cells Exposed to Serum From Whole-Body Low Dose-Rate Irradiated Mice.

    PubMed

    Edin, Nina Jeppesen; Altaner, Čestmír; Altanerova, Veronica; Ebbesen, Peter

    2015-01-01

    Prior findings in vitro of a TGF-β3 dependent mechanism induced by low dose-rate irradiation and resulting in increased radioresistance and removal of low dose hyper-radiosensitivity (HRS) was tested in an in vivo model. DBA/2 mice were given whole-body irradiation for 1 h at low dose-rates (LDR) of 0.3 or 0.03 Gy/h. Serum was harvested and added to RPMI (4% mouse serum and 6% bovine serum).This medium was transferred to reporter cells (T-47D breast cancer cells or T98G glioblastoma cells). The response to subsequent challenge irradiation of the reporter cells was measured by the colony assay. While serum from unirradiated control mice had no effect on the radiosensitivity in the reporter cells, serum from mice given 0.3 Gy/h or 0.03 Gy/h for 1 h removed HRS and also increased survival in response to doses up to 5 Gy. The effect lasted for at least 15 months after irradiation. TGF-β3 neutralizer added to the medium containing mouse serum inhibited the effect. Serum from mice given irradiation of 0.3 Gy/h for 1 h and subsequently treated with iNOS inhibitor 1400W did not affect radiosensitivity in reporter cells; neither did serum from the unirradiated progeny of mice given 1h LDR whole-body irradiation.

  13. Alteration of mélange-hosted chromitites from Korydallos, Pindos ophiolite complex, Greece: evidence for modification by a residual high-T post-magmatic fluid

    NASA Astrophysics Data System (ADS)

    Kapsiotis, Argyrios N.

    2014-12-01

    The peridotites from the area of Korydallos, in the Pindos ophiolitic massif, crop out as deformed slices of a rather dismembered sub-oceanic, lithospheric mantle section and are tectonically enclosed within the Avdella melange. The most sizeable block is a chromitite-bearing serpentinite showing a mesh texture. Accessory, subhedral to euhedral Cr-spinels in the serpentinite display Cr# [Cr/(Cr + Al)] values that range from 0.36 to 0.42 and Mg# [Mg/(Mg+ Fe2+ )] values that vary between 0.57 and 0.62, whereas the TiO2 content may be up to 0.47 wt.%. The serpentinite fragment is characterized by low abundances of magmaphile elements (Al2 O3 : 0.66 wt.%, CaO: 0.12 wt.%, Na2 O: 0.08 wt.%, TiO2 : 0.007 wt.%, Sc: 4 ppm) and enrichment in compatible elements (Cr: 2780 ppm and Ni: 2110 ppm). Overall data are in accordance with derivation of the serpentinite exotic block from a dunite that was formed in the mantle region underneath a back-arc basin before tectonic incorporation in the Korydallos melange. Two compositionally different chromitite pods are recognized in the studied serpentinite fragment, a Cr-rich chromitite and a high-Al chromitite, which have been ascribed to crystallization from a single, progressively differentiating MORB/IAT melt. Although both pods are fully serpentinized only the Al-rich one shows signs of limited Cr-spinel replacement by an opaque spinel phase and clinochlore across grain boundaries and fractures. Modification of the ore-making Cr-spinel is uneven among the Al-rich chromitite specimens. Textural features such as olivine replacement by clinochlore and clinochlore disruption by serpentine indicate that Cr-spinel alteration is not apparently related to serpentinization. From the unaltered Cr-spinel cores to their reworked boundaries the Al2 O3 and MgO abundances decrease, being mainly compensated by FeOt and Cr2 O3 increases. Such compositional variations are suggestive of restricted ferrian chromite (and minor magnetite) substitution for

  14. Blocking eIF5A Modification in Cervical Cancer Cells Alters the Expression of Cancer-Related Genes and Suppresses Cell Proliferation

    PubMed Central

    Mémin, Elisabeth; Hoque, Mainul; Jain, Mohit R.; Heller, Debra S.; Li, Hong; Cracchiolo, Bernadette; Hanauske-Abel, Hartmut M.; Pe’ery, Tsafi; Mathews, Michael B.

    2016-01-01

    Cancer etiology is influenced by alterations in protein synthesis that are not fully understood. In this study, we took a novel approach to investigate the role of the eukaryotic translation initiation factor eIF5A in human cervical cancers, where it is widely overexpressed. eIF5A contains the distinctive amino acid hypusine, which is formed by a posttranslational modification event requiring deoxyhypusine hydroxylase (DOHH), an enzyme that can be inhibited by the drugs ciclopirox and deferiprone. We found that proliferation of cervical cancer cells can be blocked by DOHH inhibition with either of these pharmacologic agents, as well as by RNA interference–mediated silencing of eIF5A, DOHH, or another enzyme in the hypusine pathway. Proteomic and RNA analyses in HeLa cervical cancer cells identified two groups of proteins in addition to eIF5A that were coordinately affected by ciclopirox and deferiprone. Group 1 proteins (Hsp27, NM23, and DJ-1) were downregulated at the translational level, whereas group 2 proteins (TrpRS and PRDX2) were upregulated at the mRNA level. Further investigations confirmed that eIF5A and DOHH are required for Hsp27 expression in cervical cancer cells and for regulation of its key target IκB and hence NF-κB. Our results argue that mature eIF5A controls a translational network of cancer-driving genes, termed the eIF5A regulon, at the levels of mRNA abundance and translation. In coordinating cell proliferation, the eIF5A regulon can be modulated by drugs such as ciclopirox or deferiprone, which might be repositioned to control cancer cell growth. PMID:24220243

  15. Protein restriction during gestation alters histone modifications at the glucose transporter 4 (GLUT4) promoter region and induces GLUT4 expression in skeletal muscle of female rat offspring.

    PubMed

    Zheng, Shasha; Rollet, Michelle; Pan, Yuan-Xiang

    2012-09-01

    Maternal nutrition during pregnancy is an intrauterine factor that results in alteration of the offspring genome and associates with disease risk in the offspring. We investigated the impact of a maternal low-protein (LP) diet on the expression of glucose transporter 4 (GLUT4) in offspring skeletal muscle. GLUT4 is an insulin-regulated glucose transporter involved in insulin sensitivity and carbohydrate metabolism in muscle cells. We observed sex-dependent GLUT4 mRNA expression and increased GLUT4 protein content in female pup skeletal muscle with maternal LP. Analysis of transcriptional and epigenetic regulation of increased skeletal muscle GLUT4 expression in offspring rats revealed the regulatory mechanisms involved. The protein level of myocyte enhancer factor 2A (MEF2A), which has been known as an activator of GLUT4 transcription via the ability to carry out specific binding to the GLUT4 MEF2 binding sequence, increased in female pups whose mothers were fed a LP diet. Modifications of chromatin structure, including acetylated histone H3, acetylated histone H4 and di-methylated histone H3 at lysine 4, were detected at a significantly increased level at the GLUT4 promoter region in female pup muscle following a maternal LP diet. Glycogen content was also detected as up-regulated, accompanied by increased glycogen synthase in LP female offspring muscle. These results document that maternal protein restriction during pregnancy induces GLUT4 expression in female offspring skeletal muscle but not in males, which may indicate sex-dependent adaptation of glucose metabolism to a maternal LP diet.

  16. Methionine and/or Methionine Sulfoxide Alter Ectoenzymes Activities in Lymphocytes and Inflammatory Parameters in Serum from Young Rats: Acute and Chronic Effects.

    PubMed

    Soares, Mayara Sandrielly Pereira; Zanusso Costa, Marcelo; da Silva, Tatiane Morgana; Gazal, Marta; Couto, Carlus Augustu Tavares do; Nogueira Debom, Gabriela; Rodrigues, Rodrigo; Hofstätter Azambuja, Juliana; André Casali, Emerson; Moritz, Cesar Eduardo Jacintho; Frescura Duarte, Marta; Braganhol, Elizandra; Moro Stefanello, Francieli; Maria Spanevello, Roselia

    2017-07-19

    In this study we investigated the effect of acute and chronic treatment with Met and/or methionine sulfoxide (MetO) on ectonucleotidases and cholinesterases activities from lymphocytes and purine derivatives compounds, C-protein reactive, interleukin-10, interleukin-6, and tumor necrosis factor-α levels in serum of young rats. Adenosine triphosphate hydrolysis was decreased in lymphocytes 1 h after treatment by MetO and Met + MetO. However, adenosine triphosphate and adenosine diphosphate hydrolysis in lymphocytes was increased in the groups MetO and Met + MetO and adenosine deaminase activity was increased in MetO 3 h after the treatment. Acetylcholinesterase activity was increased in lymphocytes after 3 h and 21 days of treatment by MetO and Met + MetO, while serum butyrycholinesterase activity was decreased after 1 h and 21 days of treatment in the same groups. In chronic treatment, interleukin-6 and tumor necrosis factor-α level were increased, while that interleukin-10 level was decreased by Met, MetO, and Met + MetO when compared to control group. C-protein reactive level was increased by MetO and Met + MetO. Adenosine triphosphate and adenosine monophosphate levels were reduced in all amino acids treated groups, while adenosine diphosphate and hypoxanthine were enhanced by MetO and Met + MetO. Adenosine and xanthine were reduced in the MetO group, whereas inosine levels were decreased in the MetO and Met + MetO groups. These findings help to understand the inflammatory alterations observed in hypermethioninemia.

  17. Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice

    PubMed Central

    Burns, Monika; Muthupalani, Sureshkumar; Ge, Zhongming; Wang, Timothy C.; Bakthavatchalu, Vasudevan; Cunningham, Catriona; Ennis, Kathleen; Georgieff, Michael; Fox, James G.

    2015-01-01

    Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world’s population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6–9 weeks of age, and were necropsied at 27–29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001). Infected mice had a lower red blood cell count (p<0.0001), hematocrit (p < 0.001), and hemoglobin concentration (p <0.0001) than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp) was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001). Expression of bone morphogenic protein 4 (Bmp4), a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001). Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th) (p = 0.02). Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp) and proteolipid protein 2 (Plp2)) was downregulated in infected mice (p = 0.001 and p = 0.02). Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3), Psd95 (a membrane associated guanylate kinase), and insulin-like growth factor 1 (Igf1)) was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively). Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use

  18. Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice.

    PubMed

    Burns, Monika; Muthupalani, Sureshkumar; Ge, Zhongming; Wang, Timothy C; Bakthavatchalu, Vasudevan; Cunningham, Catriona; Ennis, Kathleen; Georgieff, Michael; Fox, James G

    2015-01-01

    Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world's population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6-9 weeks of age, and were necropsied at 27-29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001). Infected mice had a lower red blood cell count (p<0.0001), hematocrit (p < 0.001), and hemoglobin concentration (p <0.0001) than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp) was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001). Expression of bone morphogenic protein 4 (Bmp4), a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001). Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th) (p = 0.02). Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp) and proteolipid protein 2 (Plp2)) was downregulated in infected mice (p = 0.001 and p = 0.02). Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3), Psd95 (a membrane associated guanylate kinase), and insulin-like growth factor 1 (Igf1)) was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively). Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use of Hp

  19. Structural, functional, and molecular alterations produced by aldosterone plus salt in rat heart: association with enhanced serum and glucocorticoid-regulated kinase-1 expression.

    PubMed

    Martín-Fernández, Beatriz; de las Heras, Natalia; Miana, María; Ballesteros, Sandra; Delgado, Carmen; Song, Su; Hintze, Thomas; Cachofeiro, Victoria; Lahera, Vicente

    2011-01-01

    We aimed to evaluate the structural, functional, inflammatory, and oxidative alterations, as well as serum and glucocorticoid-regulated kinase-1 (SGK-1) expression, produced in rat heart by aldosterone + salt administration. Fibrosis mediators such as connective tissue growth factor, matrix metalloproteinase 2, and tissue inhibitor of metalloproteinases 2 were also evaluated. Treatment with spironolactone was evaluated to prove mineralocorticoid mediation. Male Wistar rats received aldosterone (1 mg[middle dot]kg-1[middle dot]d-1) + 1% NaCl for 3 weeks. Half of the animals were treated with spironolactone (200 mg[middle dot]kg-1[middle dot]d-1). Systolic and diastolic blood pressures, left ventricle (LV) systolic pressure, and LV end-diastolic pressure were elevated (P < 0.05) in aldosterone + salt-treated rats. In aldosterone + salt-treated rats, -dP/dt decreased (P < 0.05), but +dP/dt was similar in all groups. Spironolactone normalized (P < 0.05) systolic blood pressure, diastolic blood pressure, LV systolic pressure, LV end-diastolic pressure, and -dP/dt. Relative heart weight, collagen content, messenger RNA expression of transforming growth factor beta, connective tissue growth factor, matrix metalloproteinase 2, tissue inhibitor of metalloproteinases 2, tumor necrosis factor alpha, interleukin-1[beta], p22phox, endothelial nitric oxide synhtase, and SGK-1 were increased (P < 0.05) in aldosterone + salt-treated rats, being reduced by spironolactone (P < 0.05). SGK-1 might be a key mediator in the structural, functional, and molecular cardiac alterations induced by aldosterone + salt in rats. All the observed changes and mediators are related with the activation of mineralocorticoid receptors.

  20. Alteration of the exDNA profile in blood serum of LLC-bearing mice under the decrease of tumour invasion potential by bovine pancreatic DNase I treatment

    PubMed Central

    Brenner, Evgenyi V.; Kurilshikov, Alexander M.; Patutina, Olga A.; Zenkova, Marina A.

    2017-01-01

    Taking into account recently obtained data indicating the participation of circulating extracellular DNA (exDNA) in tumorigenesis, enzymes with deoxyribonucleic activity have again been considered as potential antitumour and antimetastatic drugs. Previously, using murine Lewis lung carcinoma and hepatocellular carcinoma A1 tumour models, we have shown the antimetastatic activity of bovine DNase I, which correlates with an increase of DNase activity and a decrease of exDNA concentration in the blood serum of tumour-bearing mice. In this work, using next-generation sequencing on the ABS SOLiD™ 5.500 platform, we performed a search for molecular targets of DNase I by comparing the exDNA profiles of healthy animals, untreated animals with Lewis lung carcinoma (LLC) and those with LLC treated with DNase I. We found that upon DNase I treatment of LLC-bearing mice, together with inhibition of metastasis, a number of strong alterations in the patterns of exDNA were observed. The major differences in exDNA profiles between groups were: i) the level of GC-poor sequences increased during tumour development was reduced to that of healthy mice; ii) levels of sequences corresponding to tumour-associated genes Hmga2, Myc and Jun were reduced in the DNase I-treated group in comparison with non-treated mice; iii) 224 types of tandem repeat over-presented in untreated LLC-bearing mice were significantly reduced after DNase I treatment. The most important result obtained in the work is that DNase I decreased the level of B-subfamily repeats having homology to human ALU repeats, known as markers of carcinogenesis, to the level of healthy animals. Thus, the obtained data lead us to suppose that circulating exDNA plays a role in tumour dissemination, and alteration of multiple molecular targets in the bloodstream by DNase I reduces the invasive potential of tumours. PMID:28222152

  1. Cruciferous vegetable feeding alters UGT1A1 activity: diet- and genotype-dependent changes in serum bilirubin in a controlled feeding trial1

    PubMed Central

    Navarro, Sandi L.; Peterson, Sabrina; Chen, Chu; Makar, Karen W.; Schwarz, Yvonne; King, Irena B; Li, Shuying S.; Li, Lin; Kestin, Mark; Lampe, Johanna W.

    2009-01-01

    Chemoprevention by isothiocyanates from cruciferous vegetables occurs partly through up-regulation of phase-II conjugating enzymes, such as UDP-glucuronosyl-transferases (UGT). UGT1A1 glucuronidates bilirubin, estrogens, and several dietary carcinogens. The UGT1A1*28 polymorphism reduces transcription compared to the wild-type, resulting in decreased enzyme activity. Isothiocyanates are metabolized by glutathione-S-transferases (GST); variants may alter isothiocyanate clearance, such that response to crucifers may vary by genotype. We evaluated, in a randomized, controlled, cross-over feeding trial in humans (n=70), 3 test diets, (single- and double-“dose” cruciferous and cruciferous plus apiaceous) compared to a fruit-and-vegetable-free basal diet. We measured serum bilirubin concentrations on days 0, 7, 11 and 14 of each 2-week feeding period to monitor UGT1A1 activity, and determined effects of UGT1A1*28 and GSTM1/GSTT1-null variants on response. Aggregate bilirubin response to all vegetable-containing diets was statistically significantly lower compared to the basal diet (p<0.03 for all). Within each UGT1A1 genotype, lower bilirubin concentrations were seen in: *1/*1 in both single and double-dose cruciferous diets compared to basal (p<0.03 for both); *1/*28 in double-dose cruciferous and cruciferous plus apiaceous compared to basal, and cruciferous plus apiaceous compared to single-dose cruciferous (p<0.02 for all); and *28/*28 in all vegetable-containing diets compared to basal (p<0.02 for all). Evaluation of the effects of diet stratified by GST genotype revealed some statistically significant genotypic differences however, the magnitude was similar and not statistically significant between genotypes. These results may have implications for altering carcinogen metabolism through dietary intervention, particularly among UGT1A1*28/*28 individuals. PMID:19336732

  2. Correlates of risk of adipose tissue alterations and their modifications over time in HIV-1-infected women treated with antiretroviral therapy.

    PubMed

    Galli, Massimo; Ridolfo, Anna Lisa; Adorni, Fulvio; Cappelletti, Anna; Morelli, Paola; Massetto, Benedetta; Piazza, Manuela; Gianelli, Erika; Vaccarezza, Mauro; Gervasoni, Cristina; Moroni, Mauro

    2003-08-01

    To assess the correlates of risk of the different types of lipodystrophy and their modifications over time in a cohort of HIV-positive women receiving antiretroviral therapy (ART). A consecutive series of HIV-infected women receiving ART was prospectively enrolled between 1 and 31 March 1998, and followed up for 2 years. Adipose tissue alterations (ATAs) and their variations over time were assessed by means of clinical observation and anthropometric measurements, and logistic regression analysis was used to describe the associated risk factors identified by univariate and multivariate analyses. One-hundred-and-seventeen of the 212 women (55.2%) developed ATAs during the 24 months of follow-up. Central adiposity was observed in 95 patients and peripheral lipoatrophy in 91, with 21 patients (9.9%) showing pure lipoatrophy, 26 (12.3%) pure fat accumulation and 70 (33%) combined forms. Only six of the 223 regional adipose tissue alterations identified in 74 patients during the first 12 months of the study had disappeared by month 24. Of the 43 patients who developed breast enlargement during the first 12 months, 11 (25.6%) showed a decrease in breast size during the second year of follow-up that was unrelated to changes in therapy or therapeutic success. The development of ATAs during the first 12 months of follow-up independently correlated with protease inhibitor (PI) use (OR 2.81, P=0.002) but, by the end of the second year of follow-up, the only factor significantly related to the development of ATAs was the overall duration of ART (OR 1.85, P=0.041). The use of PI significantly increased the risk of developing central adiposity during the first 12 months of the study (OR 2.27, P=0.002), whereas the only variable significantly influencing the risk at month 24 was HIV-infection due to intravenous drug use, which proved to be protective (OR 0.53, P=0.043). During the first 12 months of follow-up, the development of peripheral lipoatrophy was significantly associated

  3. Changing the omega-6 to omega-3 fatty acid ratio in sow diets alters serum, colostrum, and milk fatty acid profiles, but has minimal impact on reproductive performance.

    PubMed

    Eastwood, L; Leterme, P; Beaulieu, A D

    2014-12-01

    This experiment tested the hypothesis that reducing the omega-6 (n-6) to omega-3 (n-3) fatty acid (FA) ratio in sow diets will improve performance, characterized by increased litter size, decreased preweaning mortality, and improved growth performance. Second, we determined if the FA profile in sow and piglet blood, colostrum, and milk are altered when sows are fed diets with varied n-6:n-3 ratios and if the dietary FA ratio impacts circulating concentrations of IgG, IgA, eicosapentaenoic (EPA), or docosahexaenoic (DHA) acid. Sows (n=150) were assigned to 1 of 5 treatments (each divided into gestation and lactation diets) on d 80 of gestation. Period 1 (P1) is defined as d 80 of gestation to weaning and Period 2 (P2) refers to the subsequent breeding to weaning. Diets were wheat and barley based (5% crude fat) and treatments consisted of a control (tallow), 3 diets with plant oil-based n-6:n-3 ratios (9:1P, 5:1P, and 1:1P), and a 5:1 fish oil diet (5:1F). Litter size was unaffected by treatment during P1 and P2 (P>0.10). In P1, birth weight was unaffected by diet (P>0.10); however, weaning weight (P=0.019) and ADG from birth to weaning (P=0.011) were greatest for piglets born to 9:1P and 5:1P sows. During P2, 5:1F sows consumed 10% less feed during lactation (P=0.036), tended to have reduced piglet birth weights (P=0.052), and piglet weaning weight was reduced by 0.8 kg (P=0.040) relative to the other diets. Colostrum and piglet serum IgA and IgG concentrations were unaffected by diet (P>0.10). Serum n-3 FA were greatest in sows (P<0.01) consuming 1:1P and 5:1F diets and in their offspring (P=0.014). Serum α-linolenic acid (ALA) was greatest in 1:1P sows and EPA and DHA were greatest in 5:1F sows (P<0.01). In pre-suckle piglet serum, ALA did not differ among treatment groups (P>0.10). Relative to piglets of sows consuming the control diet, EPA was 2.5-fold greater in the 1:1P group and 4-fold greater in 5:1F group (P<0.01) before suckling. In post-suckle samples

  4. O-METHYL PHOSPHORAMIDATE MODIFICATIONS ON THE CAPSULAR POLYSACCHARIDE OF CAMPYLOBACTER JEJUNI ARE INVOLVED IN SERUM RESISTANCE, INFECTION, AND INSECTICIDAL ACTIVITY

    USDA-ARS?s Scientific Manuscript database

    Campylobacter jejuni is the most commonly reported cause of bacterial foodborne illness in North America. C. jejuni decorates its surface polysaccharides with a variety of variable phosphorylated structures, including O-methyl phosphoramidate (MeOPN) modifications on the capsular polysaccharide. Alt...

  5. Alterations in serum microRNA in humans with alcohol use disorders impact cell proliferation and cell death pathways and predict structural and functional changes in brain.

    PubMed

    Ignacio, Cherry; Hicks, Steven D; Burke, Patrick; Lewis, Lambert; Szombathyne-Meszaros, Zsuzsa; Middleton, Frank A

    2015-09-05

    common genes, such as p53 and TNF, which stand out as potential keystone molecules. Lastly, we also examined the potential tissue origins of these biomarkers by quantifying their levels in 15 different tissue types and show that several are highly-enriched in the brain. Collectively, our results suggest that serum miRNA expression changes can directly relate to alterations in CNS structure and function, and may do so through effects on highly specific cellular pathways.

  6. A Nutrient-Driven tRNA Modification Alters Translational Fidelity and Genome-wide Protein Coding across an Animal Genus

    PubMed Central

    Zaborske, John M.; Bauer DuMont, Vanessa L.; Wallace, Edward W. J.; Pan, Tao; Aquadro, Charles F.; Drummond, D. Allan

    2014-01-01

    Natural selection favors efficient expression of encoded proteins, but the causes, mechanisms, and fitness consequences of evolved coding changes remain an area of aggressive inquiry. We report a large-scale reversal in the relative translational accuracy of codons across 12 fly species in the Drosophila/Sophophora genus. Because the reversal involves pairs of codons that are read by the same genomically encoded tRNAs, we hypothesize, and show by direct measurement, that a tRNA anticodon modification from guanosine to queuosine has coevolved with these genomic changes. Queuosine modification is present in most organisms but its function remains unclear. Modification levels vary across developmental stages in D. melanogaster, and, consistent with a causal effect, genes maximally expressed at each stage display selection for codons that are most accurate given stage-specific queuosine modification levels. In a kinetic model, the known increased affinity of queuosine-modified tRNA for ribosomes increases the accuracy of cognate codons while reducing the accuracy of near-cognate codons. Levels of queuosine modification in D. melanogaster reflect bioavailability of the precursor queuine, which eukaryotes scavenge from the tRNAs of bacteria and absorb in the gut. These results reveal a strikingly direct mechanism by which recoding of entire genomes results from changes in utilization of a nutrient. PMID:25489848

  7. Congenital alterations of glutamic acid 223 in the second NEMO alpha-helix result in Hypohidrotic Ectodermal Dysplasia and Immunodeficiency with Normal Serum IgG Levels

    PubMed Central

    Karamchandani-Patel, Gital; Hanson, Eric P.; Saltzman, Rushani; Kimball, C. Eve; Sorensen, Ricardo U.; Orange, Jordan S.

    2011-01-01

    Background Hypomorphic mutations in the NF-κB essential modulator (NEMO) gene result in a variable syndrome of somatic and immunological abnormalities. Clinically relevant genotype-phenotype associations are essential to understanding this complex disease. Objective Two unrelated boys with novel NEMO mutations altering codon 223 were studied for similarity in phenotype in consideration of potential genotype-phenotype associations. Methods Clinical and Laboratory features including cell counts, immunoglobulin quantity and quality, NK cell cytotoxicity, Toll-like and TNF receptor signaling were evaluated. Since both mutations affected NEMO codon 223 and were novel, consideration was given to new potential genotype-phenotype associations. Results Both patients were diagnosed with hypohydrotic ectodermal dysplasia and had severe or recurrent infections. One had recurrent sinopulmonary infections and the other necrotizing soft tissue MRSA infection and Streptococcus anginosus subdural empyema with bacteremia. NEMO gene sequence demonstrated a three-nucleotide deletion (c.667_669delGAG) in one patient and a substitution (667G>A) in the other. These predict either the deletion of NEMO glutamic acid 223 or it being replaced with lysine, respectively. Both patients had normal serum IgG levels but poor specific antibodies. NK cell cytotoxicity, Toll-like and TNF receptor signaling was also impaired. Serious bacterial infection did not occur in both patients after immunoglobulin replacement therapy. Conclusions Two different novel mutations affecting NEMO glutamic acid 223 resulted in clinically relevant similar phenotypes providing further evidence to support genotype-phenotype correlations in this disease. They suggest NEMO residue 223 is required for ectodermal development and immunity and is apparently dispensable for quantitative IgG production, but may be required for specific antibody production. PMID:21704885

  8. Congenital alterations of NEMO glutamic acid 223 result in hypohidrotic ectodermal dysplasia and immunodeficiency with normal serum IgG levels.

    PubMed

    Karamchandani-Patel, Gital; Hanson, Eric P; Saltzman, Rushani; Kimball, C Eve; Sorensen, Ricardo U; Orange, Jordan S

    2011-07-01

    Hypomorphic mutations in the nuclear factor-κB (NF-κB) essential modulator (NEMO) gene result in a variable syndrome of somatic and immunologic abnormalities. Clinically relevant genotype-phenotype associations are essential to understanding this complex disease. To study 2 unrelated boys with novel NEMO mutations altering codon 223 for similarity in phenotype in consideration of potential genotype-phenotype associations. Clinical and laboratory features, including cell counts, immunoglobulin quantity and quality, natural killer cell cytotoxicity, and Toll-like and tumor necrosis factor receptor signaling, were evaluated. Because both mutations affected NEMO codon 223 and were novel, consideration was given to new potential genotype-phenotype associations. Both patients were diagnosed as having hypohidrotic ectodermal dysplasia and had severe or recurrent infections. One had recurrent sinopulmonary infections and the other necrotizing soft tissue methicillin-resistant Staphylococcus aureus infection and Streptococcus anginosus subdural empyema with bacteremia. NEMO gene sequence demonstrated a 3-nucleotide deletion (c.667_669delGAG) in one patient and a substitution (667G>A) in the other. These findings predict either the deletion of NEMO glutamic acid 223 or it being replaced with lysine, respectively. Both patients had normal serum IgG levels but poor specific antibodies. Natural killer cell cytotoxicity and Toll-like and tumor necrosis factor receptor signaling were also impaired. Serious bacterial infection did not occur in both patients after immunoglobulin replacement therapy. Two different novel mutations affecting NEMO glutamic acid 223 resulted in clinically relevant similar phenotypes, providing further evidence to support genotype-phenotype correlations in this disease. They suggest NEMO residue 223 is required for ectodermal development and immunity and is apparently dispensable for quantitative IgG production but may be required for specific antibody

  9. Evidence of high polymeric IgA levels in serum of patients with Berger's disease and its modification with phenytoin treatment.

    PubMed

    Trascasa, M L; Egido, J; Sancho, J; Hernando, L

    1979-01-01

    High levels of polymeric IgA were found in the serum of patients with IgA glomerulonephritis. In four of the patients the IgA percentage distribution was established by ultracentrifugation in sucrose density gradients before and after six months of phenytoin treatment. A decrease in polymeric IgA, adopting a pattern similar to the controls, was observed. These findings may have both pathogenic and therapeutic implications.

  10. Diet Modification for Hyperlipidemia

    PubMed Central

    Mann, Heather D.; Piotrowski, Pamela

    1992-01-01

    Hyperlipidemia is a major risk factor associated with cardiovascular disease. Dietary modification is effective in achieving and maintaining improved serum lipid levels. Nutritional care provided by a dietitian includes individual dietary and lifestyle assessment, formulating an appropriate dietary regimen, education, and follow-up assessments. PMID:21221406

  11. Oncogenic RAS alters the global and gene-specific histone modification pattern during epithelial-mesenchymal transition in colorectal carcinoma cells.

    PubMed

    Peláez, Ignacio Mazón; Kalogeropoulou, Margarita; Ferraro, Angelo; Voulgari, Angeliki; Pankotai, Tibor; Boros, Imre; Pintzas, Alexander

    2010-06-01

    The presence of different forms of histone covalent modifications, such as phosphorylation, acetylation and methylation in localized promoter regions are markers for chromatin packing and transcription. Activation of RAS signalling pathways through oncogenic RAS mutations is a hallmark of colorectal cancer. Overexpression of Harvey-Ras oncogene induces epithelial-mesenchymal transition (EMT) in Caco-2 cells. We focused on the role of epigenetic modifications of histone H3 and its dependence on RAS signal transduction pathways and oncogenic transformation. Using cell lines stably overexpressing oncogenic Harvey-RAS with EMT phenotype, we studied the acquired changes in the H3 histone modification patterns. Two genes show inverse protein expression patterns after Ha-RAS overexpression: Cyclin D1, a cell cycle-related gene, and the EMT marker-gene E-cadherin. We report that these two genes demonstrate matching inverse histone repression patterns on their promoter, while histone markers associated with an active state of genes were affected by the RAS-activated signalling pathway MEK-ERK-MSK1. Furthermore, we show that though the level of methyltransferases enzymes was increased, the status of H3 three-methylation at lysine 27 (H3K27me(3)), associated with gene repression on the promoter of Cyclin D1, was lower. Together, these results suggest that histone covalent modifications can be affected by oncogenic RAS pathways to regulate the expression of target genes like Cyclin D1 or E-cadherin and that the dynamic balance of opposing histone-modifying enzymes is critical for the regulation of cell proliferation.

  12. Single ether group in a glycol-based ultra-thin layer prevents surface fouling from undiluted serum.

    PubMed

    Sheikh, Sonia; Yang, David Yi; Blaszykowski, Christophe; Thompson, Michael

    2012-01-30

    Through systematic structural modification, it is shown that the internal, single oxygen atom of simple monoethylene glycol-based organic films is essential for radically altering the fouling behaviour of quartz against undiluted serum, as characterized by the electromagnetic piezoelectric acoustic sensor. The synergy is strongest with distal hydroxyls.

  13. Effect of surface modification of poly(lactic acid) by low-pressure ammonia plasma on adsorption of human serum albumin

    NASA Astrophysics Data System (ADS)

    Sarapirom, S.; Yu, L. D.; Boonyawan, D.; Chaiwong, C.

    2014-08-01

    The final goal of the study was to promote understanding of mechanisms involved in cell attachment on biomedical polymer poly(lactic acid) (PLA). As the cell attachment on the material surface was preceded by blood protein adsorption which would critically affect subsequent cell adhesion, for the clinic application purpose, human serum albumin (HSA) was used in the investigation on its adsorption on PLA, which was however treated by low-pressure ammonia (NH3) plasma. The NH3-plasma-treated PLA was found to adsorb less HSA than the untreated PLA. The PLA was characterized using various techniques such as atomic force microscopy, contact angle and surface energy analysis and x-ray photoelectron spectroscopy. All of the characterization results indicated that due to NH3-plasma-induced polar groups the PLA enhanced its hydrophilicity which in turn inhibited the HSA adsorption. The decreased HSA adsorption would consequently increase the cell attachment because of the cell adhesion barrier reduced.

  14. Binding and modification of proteins by methylglyoxal under physiological conditions. A kinetic and mechanistic study with N alpha-acetylarginine, N alpha-acetylcysteine, and N alpha-acetyllysine, and bovine serum albumin.

    PubMed

    Lo, T W; Westwood, M E; McLellan, A C; Selwood, T; Thornalley, P J

    1994-12-23

    The physiological alpha-oxoaldehyde methylglyoxal binds and modifies arginine, lysine, and cysteine residues in proteins. The kinetics and mechanism of these reactions were investigated with N alpha-acetylamino acids and bovine serum albumin at pH 7.4 and 37 degrees C. The reaction of methylglyoxal with N alpha-acetylarginine involved the initial reversible formation of glycosylamine and 4,5-dihydroxy-5-methylimidazolidine derivatives, with further slow irreversible conversion to an imidazolone, N alpha-acetyl-N delta- (5-methyl-4-imidazolon-2-yl)ornithine. The imidazolone was fluorescent with an excitation lambda max value of 320 nm and an emission lambda max value of 398 nm. Methylglyoxal reacted reversibly with N alpha-acetyllysine to form glycosylamine and bisglycosylamine derivatives. Further reaction of these glycosylamines occurred to form brown, fluorescent oligomers that were not characterized. Methylglyoxal reacted rapidly and reversibly with N alpha-acetylcysteine to form the hemithioacetal adduct. The reaction of methylglyoxal with bovine serum albumin (BSA) at pH 7.4 and 37 degrees C involved the reversible and irreversible formation of methylglyoxal-BSA adducts. Irreversible modification of BSA occurred mainly on arginine residues to form imidazolone. The formation of methylglyoxal-modified proteins involves glycoxidation leading to advanced glycation end product-like fluorescence. It is expected to be increased in diabetes mellitus and may be linked to the development of diabetic complications.

  15. Supplementation with mixed tocopherols increases serum and blood cell gamma-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes.

    PubMed

    Clarke, Michael W; Ward, Natalie C; Wu, Jason H Y; Hodgson, Jonathan M; Puddey, Ian B; Croft, Kevin D

    2006-01-01

    Some studies have shown potential benefit of vitamin E on platelet function, but several clinical trials failed to show improved cardiovascular outcome with alpha-tocopherol supplementation. Gamma-tocopherol, a major dietary form of vitamin E, may have protective properties different from those of alpha-tocopherol. We compared the effects of supplementation with alpha-tocopherol (500 mg) and a gamma-tocopherol-rich compound (500 mg, containing 60% gamma-tocopherol) on serum and cellular tocopherol concentrations, urinary tocopherol metabolite excretion, and in vivo platelet activation in subjects with type 2 diabetes. Fifty-eight subjects were randomly assigned to receive either 500 mg alpha-tocopherol/d, 500 mg mixed tocopherols/d, or matching placebo. Serum, erythrocyte, and platelet tocopherol and urinary metabolite concentrations were measured at baseline and after the 6-wk intervention. Soluble CD40 ligand, urinary 11-dehydro-thromboxane B2, serum thromboxane B2, soluble P-selectin, and von Willebrand factor were measured as biomarkers of in vivo platelet activation. Serum alpha-tocopherol increased with both tocopherol treatments. Serum and cellular gamma-tocopherol increased 4-fold (P < 0.001) in the mixed tocopherol group, whereas red blood cell gamma-tocopherol decreased significantly after alpha-tocopherol supplementation. Excretion of alpha-carboxyethyl-hydroxychroman increased significantly after supplementation with alpha-tocopherol and mixed tocopherols. Excretion of gamma-carboxyethyl-hydroxychroman increased significantly after supplementation with mixed tocopherols and after that with alpha-tocopherol, which may reflect the displacement of gamma-tocopherol by alpha-tocopherol due to incorporation of the latter into lipoproteins in the liver. Neither treatment had any significant effect on markers of platelet activation. Supplementation with alpha-tocopherol decreased red blood cell gamma-tocopherol, whereas mixed tocopherols increased both serum

  16. Early life stress triggers sustained changes in histone deacetylase expression and histone H4 modifications that alter responsiveness to adolescent antidepressant treatment

    PubMed Central

    Levine, Amir; Worrell, Trent R.; Zimnisky, Ross; Schmauss, Claudia

    2011-01-01

    Early life stress can elicit long-lasting changes in gene expression and behavior. Recent studies on rodents suggest that these lasting effects depend on the genetic background. Whether epigenetic factors also play a role remains to be investigated. Here we exposed the stress-susceptible mouse strain Balb/c and the more resilient strain C57Bl/6 to a powerful early life stress paradigm, infant maternal separation. In Balb/c mice, infant maternal separation led to decreased expression of mRNA encoding the histone deacetylases (HDACs) 1, 3, 7, 8, and 10 in the forebrain neocortex in adulthood, an effect accompanied by increased expression of acetylated histone H4 proteins, especially acetylated H4K12 protein. These changes in HDAC expression and histone modifications were not detected in C57Bl/6 mice exposed to early life stress. Moreover, a reversal of the H4K12 hyperacetylation detected in infant maternally separated Balb/c mice (achieved with chronic adolescent treatment with a low dose of theophylline that only activates HDACs) worsened the abnormal emotional phenotype resulting from this early life stress exposure. In contrast, fluoxetine, a drug with potent antidepressant efficacy in infant maternally separated Balb/c mice, potentiated all histone modifications triggered by early life stress. Moreover, in non-stressed Balb/c mice, co-administration of an HDAC inhibitor and fluoxetine, but not fluoxetine alone, elicited antidepressant effects and also triggered changes in histone H4 expression that were similar to those provoked by fluoxetine treatment of mice exposed to early life stress. These results suggest that Balb/c mice develop epigenetic modifications after early life stress exposure that, in terms of the emotive phenotype, are of adaptive nature, and that enhance the efficacy of antidepressant drugs. PMID:21964251

  17. The chromatin remodeling complex NuRD establishes the poised state of rRNA genes characterized by bivalent histone modifications and altered nucleosome positions.

    PubMed

    Xie, Wenbing; Ling, Te; Zhou, Yonggang; Feng, Weijun; Zhu, Qiaoyun; Stunnenberg, Henk G; Grummt, Ingrid; Tao, Wei

    2012-05-22

    rRNA genes (rDNA) exist in two distinct epigenetic states, active promoters being unmethylated and marked by euchromatic histone modifications, whereas silent ones are methylated and exhibit heterochromatic features. Here we show that the nucleosome remodeling and deacetylation (NuRD) complex establishes a specific chromatin structure at rRNA genes that are poised for transcription activation. The promoter of poised rRNA genes is unmethylated, associated with components of the preinitiation complex, marked by bivalent histone modifications and covered by a nucleosome in the "off" position, which is refractory to transcription initiation. Repression of rDNA transcription in growth-arrested and differentiated cells correlates with elevated association of NuRD and increased levels of poised rRNA genes. Reactivation of transcription requires resetting the promoter-bound nucleosome into the "on" position by the DNA-dependent ATPase CSB (Cockayne syndrome protein B). The results uncover a unique mechanism by which ATP-dependent chromatin remodeling complexes with opposing activities establish a specific chromatin state and regulate transcription.

  18. 1,8-cineole protected human lipoproteins from modification by oxidation and glycation and exhibited serum lipid-lowering and anti-inflammatory activity in zebrafish.

    PubMed

    Cho, Kyung-Hyun

    2012-10-01

    We recently reported that a water extract of laurel or turmeric, 1,8-cineole enriched fractions, showed hypolipidemic activity in the zebrafish model. Therefore, the present study investigated the cineole's anti-oxidant and anti-inflammatory activities in lipoprotein metabolism in vitro and in vivo. Cineole had inhibitory effects on cupric ion-mediated oxidation of lipoproteins in general, while simultaneously enhancing ferric ion removal ability in high-density lipoprotein (HDL). Hypercholesterolemia was induced in zebrafish using cholesterol-feeding treatment, 4% cholesterol, for 3 weeks. After feeding with or without the addition of cineole, the results revealed that cineole possessed lipid-lowering and anti-inflammatory activities in hypercholesterolemic zebrafish. In addition, serum amyloid A and interleukin-6 levels were lowered and lipid accumulation was decreased in the liver. Conclusively, 1,8-cineole was found to have anti-oxidant activities in lipoprotein metabolism both in vitro and in vivo with simultaneous reduction of lipid accumulation in the liver of zebrafish.

  19. Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for pathogenesis.

    PubMed Central

    Poole, A R; Ionescu, M; Swan, A; Dieppe, P A

    1994-01-01

    The metabolism of the cartilage proteoglycan aggrecan was studied in patients with osteoarthritis (OA, n = 83), rheumatoid arthritis (RA, n = 127), and in controls (n = 117) using monoclonal antibody-based radioimmunoassays for glycosaminoglycans in the serum and synovial fluid (SF) to detect epitope 846 on chondroitin sulfate (probably only on recently synthesized molecules) and a keratan sulfate (KS) epitope AN9PI, present on intact and degraded molecules. Epitope 846 levels were always elevated in SF over serum (mean 38-fold in OA and 8.6-fold in RA) being highest in OA patients with the longest disease duration and greatest loss of cartilage, and lowest in RA joints with high leucocyte counts. Serum levels were more often elevated in RA (56%) than in OA (19%) and probably reflect increased aggrecan synthesis in diseased joints. KS levels were higher in SF than in serum in 69% of patients (up to 2.3-fold); levels were inversely (OA) and directly (RA) related to SF leucocyte counts. Serum KS was reduced in both diseases and in RA was inversely related to both systemic and joint inflammation markers. SF 846 levels were inversely related to SF KS in both diseases. These epitopes may provide a measure of the balance between cartilage synthesis and degradation in these diseases. PMID:7518830

  20. Alterations of irisin concentrations in saliva and serum of obese and normal-weight subjects, before and after 45 min of a Turkish bath or running.

    PubMed

    Aydin, Suleyman; Aydin, Suna; Kuloglu, Tuncay; Yilmaz, Musa; Kalayci, Mehmet; Sahin, Ibrahim; Cicek, Demet

    2013-12-01

    The purpose of this study was to ascertain (1) whether human saliva contains irisin and whether its level correlates with serum irisin concentration, (2) whether salivary glands, eccrine glands and sebaceous glands in human skin produce irisin, (3) how the changes in saliva and serum irisin concentrations after the Turkish bath at 47 ± 3°C compare with the changes caused by moderate exercise in obese and normal weight subjects. Seven obese male subjects and seven normal weight subjects were enrolled for Turkish bath. Seven obese male subjects and seven normal weight subjects were also enrolled for moderate outdoor exercise, and thirteen male normal weight subjects neither exercised nor showered at the Turkish bath. From each participant, 1.5 ml of saliva and 5 ml blood were collected simultaneously before and after the moderate exercise and Turkish bath. Salivary glands and eccrine and sebaceous glands in the skin were screened immunohistochemically for irisin while serum and saliva irisin were measured with an ELISA. Submandibular glands, eccrine glands and sebaceous glands in the human skin showed strong irisin immunoreactivity. Human saliva contained irisin and its level was significantly higher than the serum levels in both obese and normal weight subjects. However, irisin concentrations were more markedly increased in both saliva and serum samples from subjects who had showered at a Turkish bath than in obese subjects who had exercised or in normal weight subjects. Human submandibular glands, eccrine sweat glands and sebaceous glands synthesize irisin. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Sodium arsenite represses the expression of myogenin in C2C12 mouse myoblast cells through histone modifications and altered expression of Ezh2, Glp, and Igf-1

    SciTech Connect

    Hong, Gia-Ming

    2012-05-01

    Arsenic is a toxicant commonly found in water systems and chronic exposure can result in adverse developmental effects including increased neonatal death, stillbirths, and miscarriages, low birth weight, and altered locomotor activity. Previous studies indicate that 20 nM sodium arsenite exposure to C2C12 mouse myocyte cells delayed myoblast differentiation due to reduced myogenin expression, the transcription factor that differentiates myoblasts into myotubes. In this study, several mechanisms by which arsenic could alter myogenin expression were examined. Exposing differentiating C2C12 cells to 20 nM arsenic increased H3K9 dimethylation (H3K9me2) and H3K9 trimethylation (H3K9me3) by 3-fold near the transcription start site of myogenin, which is indicative of increased repressive marks, and reduced H3K9 acetylation (H3K9Ac) by 0.5-fold, indicative of reduced permissive marks. Protein expression of Glp or Ehmt1, a H3-K9 methyltransferase, was also increased by 1.6-fold in arsenic-exposed cells. In addition to the altered histone remodeling status on the myogenin promoter, protein and mRNA levels of Igf-1, a myogenic growth factor, were significantly repressed by arsenic exposure. Moreover, a 2-fold induction of Ezh2 expression, and an increased recruitment of Ezh2 (3.3-fold) and Dnmt3a (∼ 2-fold) to the myogenin promoter at the transcription start site (− 40 to + 42), were detected in the arsenic-treated cells. Together, we conclude that the repressed myogenin expression in arsenic-exposed C2C12 cells was likely due to a combination of reduced expression of Igf-1, enhanced nuclear expression and promoter recruitment of Ezh2, and altered histone remodeling status on myogenin promoter (− 40 to + 42). -- Highlights: ► Igf-1 expression is decreased in C2C12 cells after 20 nM arsenite exposure. ► Arsenic exposure alters histone remodeling on the myogenin promoter. ► Glp expression, a H3–K9 methyltransferase, was increased in arsenic-exposed cells. ► Ezh2

  2. Lithium ameliorates sleep deprivation-induced mania-like behavior, hypothalamic-pituitary-adrenal (HPA) axis alterations, oxidative stress and elevations of cytokine concentrations in the brain and serum of mice.

    PubMed

    Valvassori, Samira S; Resende, Wilson R; Dal-Pont, Gustavo; Sangaletti-Pereira, Heron; Gava, Fernanda F; Peterle, Bruna R; Carvalho, André F; Varela, Roger B; Dal-Pizzol, Felipe; Quevedo, João

    2017-06-01

    The goal of the present study was to investigate the effects of lithium administration on behavior, oxidative stress parameters and cytokine levels in the periphery and brain of mice subjected to an animal model of mania induced by paradoxical sleep deprivation (PSD). Male C57 mice were treated with saline or lithium for 7 days. The sleep deprivation protocol started on the 5th day during for the last 36 hours of the treatment period. Immediately after the sleep deprivation protocol, animals locomotor activity was evaluated and serum and brain samples was extracted to evaluation of corticosterone and adrenocorticotropic hormone circulating levels, oxidative stress parameters and citokynes levels. The results showed that PSD induced hyperactivity in mice, which is considered a mania-like behavior. PSD increased lipid peroxidation and oxidative damage to DNA, as well as causing alterations to antioxidant enzymes in the frontal cortex, hippocampus and serum of mice. In addition, PSD increased the levels of cytokines in the brains of mice. Treatment with lithium prevented the mania-like behavior, oxidative damage and cytokine alterations induced by PSD. Improving our understanding of oxidative damage in biomolecules, antioxidant mechanisms and the inflammatory system - alterations presented in the animal models of mania - is important in helping us to improve our knowledge concerning the pathophysiology of BD, and the mechanisms of action employed by mood stabilizers. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Serum starvation and thymidine double blocking achieved efficient cell cycle synchronization and altered the expression of p27, p53, bcl-2 in canine breast cancer cells.

    PubMed

    Tong, Jinjin; Sun, Dongdong; Yang, Chao; Wang, Yingxue; Sun, Sichao; Li, Qing; Bao, Jun; Liu, Yun

    2016-04-01

    Cell synchronization is an approach to obtain cell populations of the same stage, which is a prerequisite to studying the regulation of cell cycle progression in vivo. Serum starvation and thymidine double blocking (TdR) are two important practices in studying cell cycle synchronization. However, their effects on canine cancer cells as well as the regulatory mechanisms by these two methods are poorly understood. In this study, we determined the optimum conditions of serum starvation and TdR and their effects on cell cycle synchronization. We further explored the involvement of PI3K/Akt signaling pathway in the cell cycle synchronization by investigating the expression of three key genes (p27, p53 and bcl-2). Serum starvation resulted in a reversible cell cycle arrest and synchronously progress through G0/G1. The highest percentage of CHMm cells (87.47%) in G0/G1 stage was obtained after 42 h incubation with 0.5% fetal bovine serum (FBS). TdR double blocking could arrest 98.9% of CHMm cells in G1/S phase (0 h of release), and could arrest 93.74% of CHMm cells in S phase after 4h of release. We also found that the p27, p53, bcl-2 genes were most highly expressed in G0/G1 phase. Our current work revealed that serum starvation and TdR methods could achieve sufficient synchronization of CHMm cells. Moreover, the expression of p27, p53 and bcl-2 genes was related to cyclical movements and apoptosis. Our results will provide a new insight into cell cycle regulation and reprogramming of canine cancer cells induced by serum starvation and TdR blocking. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Short-term bisphosphonate treatment reduces serum 25(OH) vitamin D3 and alters values of parathyroid hormone, pentosidine, and bone metabolic markers

    PubMed Central

    Kamimura, Mikio; Uchiyama, Shigeharu; Nakamura, Yukio; Ikegami, Shota; Mukaiyama, Keijiro; Kato, Hiroyuki

    2017-01-01

    This study aimed to clarify the effects of short-term bisphosphonate (BP) administration in Japanese osteoporotic patients retrospectively. Daily minodronate (MIN) at 1 mg/day (MIN group) or weekly risedronate (RIS) at 17.5 mg/week (RIS group) was primarily prescribed for each patient. We analyzed the laboratory data of 35 cases (18 of MIN and 17 of RIS) before the start of treatment and at 4 months afterward. The changes in 25(OH)D3, whole parathyroid hormone (PTH), serum pentosidine, and the bone turnover markers urinary cross-linked N-telopeptide of type I collagen (NTX), serum tartrate-resistant acid phosphatase (TRACP)-5b, bone-specific alkaline phosphatase (BAP), and undercarboxylated osteocalcin were evaluated. Overall, serum 25(OH)D3 was significantly decreased from 21.8 to 18.4 ng/mL at 4 months, with a percent change of −14.7%. Whole PTH increased significantly from 23.4 to 30.0 pg/mL, with a percent change of 32.1%. Serum pentosidine rose from 0.0306 to 0.0337 μg/mL, with a percent change of 15.2%. In group comparisons, 25(OH)D3 and pentosidine showed comparable changes in both groups after 4 months of treatment, whereas whole PTH became significantly more increased in the MIN group. All bone turnover markers were significantly decreased at 4 months in both groups. Compared with the RIS group, the MIN group exhibited significantly larger value changes for urinary NTX, serum TRACP-5b, and BAP at the study end point. This study demonstrated that serum 25(OH)D3 became significantly decreased after only 4 months of BP treatment in Japanese osteoporotic patients and confirmed that MIN more strongly inhibited bone turnover as compared with RIS. PMID:28243105

  5. Serum sickness

    MedlinePlus

    Drug allergy - serum sickness; Allergic reaction - serum sickness; Allergy - serum sickness ... penicillin, cefaclor, and sulfa) can cause a similar reaction. Injected proteins such as antithymocyte globulin (used to ...

  6. A Study of Alterations in DNA Epigenetic Modifications (5mC and 5hmC) and Gene Expression Influenced by Simulated Microgravity in Human Lymphoblastoid Cells

    PubMed Central

    Wang, Zhiping; Liu, Yunlong; Lossie, Amy C.; Thimmapuram, Jyothi; Irudayaraj, Joseph

    2016-01-01

    Cells alter their gene expression in response to exposure to various environmental changes. Epigenetic mechanisms such as DNA methylation are believed to regulate the alterations in gene expression patterns. In vitro and in vivo studies have documented changes in cellular proliferation, cytoskeletal remodeling, signal transduction, bone mineralization and immune deficiency under the influence of microgravity conditions experienced in space. However microgravity induced changes in the epigenome have not been well characterized. In this study we have used Next-generation Sequencing (NGS) to profile ground-based “simulated” microgravity induced changes on DNA methylation (5-methylcytosine or 5mC), hydroxymethylation (5-hydroxymethylcytosine or 5hmC), and simultaneous gene expression in cultured human lymphoblastoid cells. Our results indicate that simulated microgravity induced alterations in the methylome (~60% of the differentially methylated regions or DMRs are hypomethylated and ~92% of the differentially hydroxymethylated regions or DHMRs are hyperhydroxymethylated). Simulated microgravity also induced differential expression in 370 transcripts that were associated with crucial biological processes such as oxidative stress response, carbohydrate metabolism and regulation of transcription. While we were not able to obtain any global trend correlating the changes of methylation/ hydroxylation with gene expression, we have been able to profile the simulated microgravity induced changes of 5mC over some of the differentially expressed genes that includes five genes undergoing differential methylation over their promoters and twenty five genes undergoing differential methylation over their gene-bodies. To the best of our knowledge, this is the first NGS-based study to profile epigenomic patterns induced by short time exposure of simulated microgravity and we believe that our findings can be a valuable resource for future explorations. PMID:26820575

  7. Alterations of serum zinc, copper, manganese, iron, calcium, and magnesium concentrations and the complexity of interelement relations in patients with obsessive-compulsive disorder.

    PubMed

    Shohag, Hasanuzzaman; Ullah, Ashik; Qusar, Shalahuddin; Rahman, Mustafizur; Hasnat, Abul

    2012-09-01

    The purpose of the present study was to evaluate the status of serum trace elements: zinc, copper, manganese, iron, calcium, and magnesium concentrations in obsessive-compulsive disorder patients. Forty-eight obsessive-compulsive disorder patients and 48 healthy volunteers were included in this study. Patients were recruited from Bangabandhu Sheikh Mujib Medical University by random sampling. Serum trace element concentrations were determined using flame atomic absorption spectroscopy (for zinc, copper, iron, calcium, and magnesium) as well as graphite furnace atomic absorption spectroscopy (for manganese). Data were analyzed using independent t test, Pearson's correlation analysis, regression analysis, and ANOVA. Statistical analysis of these data showed a definite pattern of variation among certain elements in patients with obsessive-compulsive disorder compared to controls. In patients' serum, zinc, iron, and magnesium concentrations decreased significantly (p<0.05) compared to the controls. Serum manganese and calcium concentrations were significantly higher (p<0.05) in patients compared to the controls. These data showed a definite imbalance in the interelement relations in obsessive-compulsive disorder patients compared to controls and therefore suggest a disturbance in the element homeostasis.

  8. Serum factors alter the extent of dephosphorylation of ligands endocytosed via the mannose 6-phosphate/insulin-like growth factor II receptor

    PubMed Central

    1989-01-01

    Mouse L-cells that contain the cation-independent (CI) mannose 6- phosphate (Man 6-P)/insulin-like growth factor (IGF) II receptor endocytose acid hydrolases and deliver these enzymes to lysosomes. The postendocytic loss of the Man 6-P recognition marker from the cell- associated acid hydrolases was assessed by CI-Man 6-P receptor affinity chromatography. 125I-labeled acid hydrolases internalized by L-cells grown at high density were delivered to lysosomes but were not dephosphorylated. In contrast, the same 125I-labeled hydrolases internalized by L-cells maintained at low density were delivered to lysosomes and were extensively dephosphorylated. The dephosphorylation at low density required 5 h for completion suggesting that the phosphatase responsible for the dephosphorylation is located within the lysosomal compartment. Transition from the high to low density state was rapid and was not inhibited by cycloheximide. Medium substitution experiments indicated that serum factors were necessary to maintain the L-cells in the dephosphorylation-competent (low density) state, and that serum-free conditions led to a dephosphorylation-incompetent (high density) state. Addition of IGF II to cells in serum-free medium allowed acid hydrolases subsequently introduced by endocytosis to be dephosphorylated. The results indicate that the removal of the Man 6-P recognition marker from endocytosed acid hydrolases is regulated by serum factors in the growth medium, including IGF II. PMID:2549075

  9. Temperature Shift Alters DNA Methylation and Histone Modification Patterns in Gonadal Aromatase (cyp19a1) Gene in Species with Temperature-Dependent Sex Determination

    PubMed Central

    Hannigan, Brette; Crews, David

    2016-01-01

    The environment surrounding the embryos has a profound impact on the developmental process and phenotypic outcomes of the organism. In species with temperature-dependent sex determination, gonadal sex is determined by the incubation temperature of the eggs. A mechanistic link between temperature and transcriptional regulation of developmental genes, however, remains elusive. In this study, we examine the changes in DNA methylation and histone modification patterns of the aromatase (cyp19a1) gene in embryonic gonads of red-eared slider turtles (Trachemys scripta) subjected to a temperature shift during development. Shifting embryos from a male-producing temperature (MPT) to a female-producing temperature (FPT) at the beginning of the temperature-sensitive period (TSP) resulted in an increase in aromatase mRNA expression while a shift from FPT to MPT resulted in decreased expression. DNA methylation levels at CpG sites in the promoter of the aromatase gene were high (70–90%) at the beginning of TSP, but decreased in embryos that were incubated at constant FPT and those shifted from MPT to the FPT. This decrease in methylation in the promoter inversely correlated with the expected increase in aromatase expression at the FPT. The active demethylation under the FPT was especially prominent at the CpG site upstream of the gonad-specific TATA box at the beginning of TSP and spread downstream of the gene including exon1 as the gonad development progressed. In embryos incubated at FPT, the promoter region was also labeled by canonical transcriptional activation markers, H3K4me3 and RNA polymerase II. A transcriptional repression marker, H3K27me3, was observed in temperature-shifted gonads of both temperature groups, but was not maintained throughout the development in either group. Our findings suggest that DNA hypomethylation and H3K4me3 modification at the aromatase promoter may be a primary mechanism that releases a transcriptional block of aromatase to initiate a

  10. Temperature Shift Alters DNA Methylation and Histone Modification Patterns in Gonadal Aromatase (cyp19a1) Gene in Species with Temperature-Dependent Sex Determination.

    PubMed

    Matsumoto, Yuiko; Hannigan, Brette; Crews, David

    2016-01-01

    The environment surrounding the embryos has a profound impact on the developmental process and phenotypic outcomes of the organism. In species with temperature-dependent sex determination, gonadal sex is determined by the incubation temperature of the eggs. A mechanistic link between temperature and transcriptional regulation of developmental genes, however, remains elusive. In this study, we examine the changes in DNA methylation and histone modification patterns of the aromatase (cyp19a1) gene in embryonic gonads of red-eared slider turtles (Trachemys scripta) subjected to a temperature shift during development. Shifting embryos from a male-producing temperature (MPT) to a female-producing temperature (FPT) at the beginning of the temperature-sensitive period (TSP) resulted in an increase in aromatase mRNA expression while a shift from FPT to MPT resulted in decreased expression. DNA methylation levels at CpG sites in the promoter of the aromatase gene were high (70-90%) at the beginning of TSP, but decreased in embryos that were incubated at constant FPT and those shifted from MPT to the FPT. This decrease in methylation in the promoter inversely correlated with the expected increase in aromatase expression at the FPT. The active demethylation under the FPT was especially prominent at the CpG site upstream of the gonad-specific TATA box at the beginning of TSP and spread downstream of the gene including exon1 as the gonad development progressed. In embryos incubated at FPT, the promoter region was also labeled by canonical transcriptional activation markers, H3K4me3 and RNA polymerase II. A transcriptional repression marker, H3K27me3, was observed in temperature-shifted gonads of both temperature groups, but was not maintained throughout the development in either group. Our findings suggest that DNA hypomethylation and H3K4me3 modification at the aromatase promoter may be a primary mechanism that releases a transcriptional block of aromatase to initiate a

  11. Glycomic Alterations in the Highly-abundant and Lesser-abundant Blood Serum Protein Fractions for Patients Diagnosed with Hepatocellular Carcinoma.

    PubMed

    Kang, Pilsoo; Madera, Milan; Alley, William R; Goldman, Radoslav; Mechref, Yehia; Novotny, Milos V

    2011-08-15

    Hepatocellular cancer is a serious human disease with an unfortunately low survival rate. It further poses a significant epidemic threat to our society through its viral vectors associated with cirrhosis conditions preceding the cancer. A search for biomarkers of these diseases enlists analytical glycobiology, in general, and quantitative biomolecular mass spectrometry (MS), in particular, as valuable approaches to cancer research. The recent advances in quantitative glycan permethylation prior to MALDI-MS oligosaccharide profiling has enabled us to compare the glycan quantitative proportions in the small serum samples of cancer and cirrhotic patients against control individuals. We were further able to fractionate the major serum proteins from the minor components and compare statistically their differential glycosylation, elucidating some causes of quantitatively unusual glycosylation events. Numerous glycan structures were tentatively identified and connected with the origin proteins, with a particular emphasis on sialylated and fucosylated glycans.

  12. Glycomic Alterations in the Highly-abundant and Lesser-abundant Blood Serum Protein Fractions for Patients Diagnosed with Hepatocellular Carcinoma

    PubMed Central

    Kang, Pilsoo; Madera, Milan; Alley, William R.; Goldman, Radoslav; Mechref, Yehia; Novotny, Milos V.

    2011-01-01

    Hepatocellular cancer is a serious human disease with an unfortunately low survival rate. It further poses a significant epidemic threat to our society through its viral vectors associated with cirrhosis conditions preceding the cancer. A search for biomarkers of these diseases enlists analytical glycobiology, in general, and quantitative biomolecular mass spectrometry (MS), in particular, as valuable approaches to cancer research. The recent advances in quantitative glycan permethylation prior to MALDI-MS oligosaccharide profiling has enabled us to compare the glycan quantitative proportions in the small serum samples of cancer and cirrhotic patients against control individuals. We were further able to fractionate the major serum proteins from the minor components and compare statistically their differential glycosylation, elucidating some causes of quantitatively unusual glycosylation events. Numerous glycan structures were tentatively identified and connected with the origin proteins, with a particular emphasis on sialylated and fucosylated glycans. PMID:23788846

  13. Effect of vitamin E supplementation on arsenic induced alteration in blood biochemical profile, oxidant/antioxidant status, serum cortisol level and retention of arsenic and selenium in goats.

    PubMed

    Mohanta, Ranjan Kumar; Garg, Anil Kumar; Dass, Ram Sharan

    2015-01-01

    Arsenic (As) exerts oxidative stress with depletion of body selenium in monogastric animals. But in ruminants this fact is not yet verified. Vitamin E is an effective dietary antioxidant. Thus, in this experiment, the protective effect of vitamin E against arsenic toxicity induced by sodium arsenite (60mg As/kg diet) was investigated in goat kids. For this, 21 male kids were divided into three equal groups and fed either basal diet as such (control), or supplemented with 60mg As/kg diet and 60mg As/kg diet+250IU vitamin E/kg diet for 180 days. Vitamin E supplementation alleviated the toxic effects caused by arsenic on serum alanine aminotransferase and aspartate aminotransferase and lipid peroxidation. It also prevented the depletion of reduced glutathione content and reduction in activity of catalase, superoxide dismutase and glutathione-s-transferase in erythrocytes resulted from arsenic intoxication. The elevated levels of arsenic and reduced levels of selenium in the serum and tissues in arsenic treated animals were attenuated by vitamin E supplementation, though not completely. However, serum cortisol level was not affected by arsenic. It was concluded that arsenic exerts cortisol independent stressor mechanism and supplementation of vitamin E at a level of 250IU/kg diet was partially effective in reducing tissue accumulation of arsenic in the body and protect the kids from oxidative stress induced by arsenic. Copyright © 2014 Elsevier GmbH. All rights reserved.

  14. Alteration of the serum levels of the epidermal growth factor receptor and its ligands in patients with non-small cell lung cancer and head and neck carcinoma.

    PubMed

    Lemos-González, Y; Rodríguez-Berrocal, F J; Cordero, O J; Gómez, C; Páez de la Cadena, M

    2007-05-21

    Serum levels of the soluble epidermal growth factor receptor (sEGFR) and its ligands epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and amphiregulin (AR) were measured in healthy donors and patients with non-small cell lung cancer (NSCLC) and head and neck carcinoma (HNC). In NSCLC, we found sEGFR and EGF levels significantly lowered in patients with respect to healthy donors. In HNC patients, significantly diminished levels were found in the case of sEGFR, EGF and also AR. In both malignancies, no significant association was found between the serum levels of the molecules and the patients' gender, age or smoking habit. Only a significant association was found between the decrease of sEGFR and the absence of distant metastasis in NSCLC and the tumour stage in HNC. The most interesting result was that combining sEGFR and EGF, sensitivities of 88% in NSCLC and 100% in HNC were reached without losing specificity (97.8% in both cases). The use of discriminant analysis and logistic regression improved the sensitivity for NSCLC and the specificity for HNC. These data demonstrate a potentially interesting value of the serum levels of sEGFR and EGF, especially when combined, as markers for NSCLC and HNC.

  15. Neonatal paternal deprivation impairs social recognition and alters levels of oxytocin and estrogen receptor α mRNA expression in the MeA and NAcc, and serum oxytocin in mandarin voles.

    PubMed

    Cao, Yan; Wu, Ruiyong; Tai, Fadao; Zhang, Xia; Yu, Peng; An, Xiaolei; Qiao, Xufeng; Hao, Ping

    2014-01-01

    Paternal care is necessary for the healthy development of social behavior in monogamous rodents and social recognition underpins social behavior in these animals. The effects of paternal care on the development of social recognition and underlying neuroendocrine mechanisms, especially the involvement of oxytocin and estrogen pathways, remain poorly understood. We investigated the effects of paternal deprivation (PD: father was removed from neonatal pups and mother alone raised the offspring) on social recognition in mandarin voles (Microtus mandarinus), a socially monogamous rodent. Paternal deprivation was found to inhibit the development of social recognition in female and male offspring according to a habituation-dishabituation paradigm. Paternal deprivation resulted in increased inactivity and reduced investigation during new encounters with other animals. Paternal deprivation reduced oxytocin receptor (OTR) and estrogen receptor α (ERα) mRNA expression in the medial amygdala and nucleus accumbens. Paternal deprivation reduced serum oxytocin (OT) concentration in females, but had no effect on males. Our results provide substantial evidence that paternal deprivation inhibits the development of social recognition in female and male mandarin voles and alters social behavior later in life. This is possibly the result of altered expression of central OTR and ERα and serum OT levels caused by paternal deprivation.

  16. Maternal depression and anxiety are associated with altered gene expression in the human placenta without modification by antidepressant use: implications for fetal programming.

    PubMed

    Ponder, Kathryn L; Salisbury, Amy; McGonnigal, Bethany; Laliberte, Alyse; Lester, Barry; Padbury, James F

    2011-11-01

    We sought to determine if maternal depression, anxiety, and/or treatment with selective serotonin reuptake inhibitors (SSRIs) affect placental human serotonin transporter (SLC6A4), norepinephrine transporter (SLC6A2), and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) gene expression. Relative mRNA expression was compared among placental samples (n = 164) from healthy women, women with untreated depression and/or anxiety symptoms during pregnancy, and women who used SSRIs. SLC6A4 expression was significantly increased in placentas from women with untreated mood disorders and from women treated with SSRIs, compared to controls. SLC6A2 and 11β-HSD2 expression was increased in noncontrol groups, though the differences were not significant. SLC6A4, SLC6A2, and 11β-HSD2 expression levels were positively correlated. The finding that maternal depression/anxiety affects gene expression of placental SLC6A4 suggests a possible mechanism for the effect(s) of maternal mood on fetal neurodevelopmental programming. SSRI treatment does not further alter the elevated SLC6A4 expression levels observed with exposure to maternal depression or anxiety. Copyright © 2011 Wiley Periodicals, Inc.

  17. Glucosamine cardioprotection in perfused rat heart associated with increased O-Linked N-acetylglucosamine protein modification and altered p38 activation

    PubMed Central

    Fülöp, Norbert; Zhang, Zhenghao; Marchase, Richard B.; Chatham, John C.

    2010-01-01

    We have shown that in the perfused heart glucosamine improved functional recovery following ischemia and this appeared to be mediated via an increase in O-Linked N-acetylglucosamine (O-GlcNAc) levels on nucleocytoplasmic proteins. Several kinase pathways, specifically Akt and the mitogen activated protein kinases (MAPK) p38 and ERK1/2, which have been implicated in ischemic cardioprotection, have been reported to be modified in response to increased O-GlcNAc levels. Therefore, the goals of this study were to determine the effect of ischemia on O-GlcNAc levels and to evaluate whether the cardioprotection resulting from glucosamine treatment could be attributed to changes in ERK1/2, Akt and p38 phosphorylation. Isolated rat hearts were perfused with or without 5mM glucosamine and were subjected to 5, 10 or 30 min low flow ischemia (LFI) or 30 min LFI and 60min reperfusion. Glucosamine treatment attenuated ischemic contracture and improved functional recovery at the end of reperfusion. Glucosamine treatment increased flux through the hexosamine biosynthesis pathway and increased O-GlcNAc levels but had no effect on ATP levels. Glucosamine did not alter the response of either ERK1/2 or Akt to ischemia/reperfusion; however it significantly attenuated the ischemia-induced increase in p38 phosphorylation and paradoxically increased p38 phosphorylation at the end of reperfusion. These data support the notion that O-GlcNAc may play an important role as an internal stress response and that glucosamine-induced cardioprotection may be mediated via the p38 MAPK pathway. PMID:17208994

  18. Co-modification of class B genes TfDEF and TfGLO in Torenia fournieri Lind. alters both flower morphology and inflorescence architecture.

    PubMed

    Sasaki, Katsutomo; Yamaguchi, Hiroyasu; Nakayama, Masayoshi; Aida, Ryutaro; Ohtsubo, Norihiro

    2014-10-01

    The class B genes DEFICIENS (DEF)/APETALA3 (AP3) and GLOBOSA (GLO)/PISTILLATA (PI), encoding MADS-box transcription factors, and their functions in petal and stamen development have been intensely studied in Arabidopsis and Antirrhinum. However, the functions of class B genes in other plants, including ornamental species exhibiting floral morphology different from these model plants, have not received nearly as much attention. Here, we examine the cooperative functions of TfDEF and TfGLO on floral organ development in the ornamental plant torenia (Torenia fournieri Lind.). Torenia plants co-overexpressing TfDEF and TfGLO showed a morphological alteration of sepals to petaloid organs. Phenotypically, these petaloid sepals were nearly identical to petals but had no stamens or yellow patches like those of wild-type petals. Furthermore, the inflorescence architecture in the co-overexpressing torenias showed a characteristic change in which, unlike the wild-types, their flowers developed without peduncles. Evaluation of the petaloid sepals showed that these attained a petal-like nature in terms of floral organ phenotype, cell shape, pigment composition, and the expression patterns of anthocyanin biosynthesis-related genes. In contrast, torenias in which TfDEF and TfGLO were co-suppressed exhibited sepaloid petals in the second whorl. The sepaloid petals also attained a sepal-like nature, in the same way as the petaloid sepals. The results clearly demonstrate that TfDEF and TfGLO play important cooperative roles in petal development in torenia. Furthermore, the unique transgenic phenotypes produced create a valuable new way through which characteristics of petal development and inflorescence architecture can be investigated in torenia.

  19. Gestational hypermethioninaemia alters oxidative/nitrative status in skeletal muscle and biomarkers of muscular injury and inflammation in serum of rat offspring.

    PubMed

    Schweinberger, Bruna M; Turcatel, Elias; Rodrigues, André F; Wyse, Angela T S

    2015-10-01

    In this study we evaluated oxidative/nitrative stress parameters (reactive oxygen species production, lipid peroxidation, sulfhydryl content, superoxide dismutase, catalase and nitrite levels), as well as total protein content in the gastrocnemius skeletal muscle of the offspring of rats that had been subjected to gestational hypermethioninaemia. The occurrence of muscular injury and inflammation was also measured by creatine kinase activity, levels of creatinine, urea and C-reactive protein and the presence of cardiac troponin I in serum. Wistar female rats (70-90 days of age) received methionine (2.68 μmol/g body weight) or saline (control) twice a day by subcutaneous injections during the gestational period (21 days). After the rats gave birth, pups were killed at the twenty-first day of life for removal of muscle and serum. Methionine treatment increased reactive oxygen species production and lipid peroxidation and decreased sulfhydryl content, antioxidant enzymes activities and nitrite levels, as well as total protein content in skeletal muscle of the offspring. Creatine kinase activity was reduced and urea and C-reactive protein levels were increased in serum of pups. These results were accompanied by reduced muscle mass. Our findings showed that maternal gestational hypermethioninaemia induced changes in oxidative/nitrative status in gastrocnemius skeletal muscle of the offspring. This may represent a mechanism which can contribute to the myopathies and loss of muscular mass that is found in some hypermethioninaemic patients. In addition, we believe that these results may be relevant as gestational hypermethioninaemia could cause damage to the skeletal muscle during intrauterine life.

  20. Behavior modification.

    PubMed

    Pelham, W E; Fabiano, G A

    2000-07-01

    Attention deficit/hyperactivity disorder (ADHD) is a chronic and substantially impairing disorder. This means that treatment must also be chronic and substantial. Behavior Modification, and in many cases, the combination of behavior modification and stimulant medication, is a valid, useful treatment for reducing the pervasive impairment experienced by children with ADHD. Based on the research evidence reviewed, behavior modification should be the first line of treatment for children with ADHD.

  1. Alterations in serum levels of inflammatory cytokines (TNF, IL-1alpha, IL-1beta and IL-1Ra) 20 years after sulfur mustard exposure: Sardasht-Iran cohort study.

    PubMed

    Yaraee, Roya; Ghazanfari, Tooba; Ebtekar, Massoumeh; Ardestani, Sussan K; Rezaei, Abbas; Kariminia, Amina; Faghihzadeh, Soghrat; Mostafaie, Ali; Vaez-Mahdavi, Mohammad R; Mahmoudi, Mahmoud; Naghizadeh, Mohammad M; Soroush, Mohammad R; Hassan, Zuhair M

    2009-12-01

    Mustard gas, even in low doses, has the ability to inflict damage in multiple organs especially the skin, eyes, as well as the respiratory tract. This damage may cause many complications which persist during the lifespan of exposed subjects. Pro-inflammatory cytokines including TNF, IL-1alpha, IL-1beta and IL-1Ra cause systemic inflammatory reactions and numerous changes including altered cell signaling and migration, changes in cytokine production and fever. The aim of this study was to determine the serum levels of these cytokines in subjects who were exposed to mustard gas 20 years ago in comparison with an unexposed control group. In this historical cohort study 368 sulfur mustard (SM) exposed participants from Sardasht and 126 age-matched unexposed volunteers from Rabat (a nearby town) as controls were chosen by a random systematic sampling. The serum concentrations of IL-1alpha, IL-1beta, IL-1Ra and TNF were measured by a sandwich ELISA technique. Median of the serum levels of cytokines TNF, IL-1alpha, IL-1beta and IL-1Ra in the control group was 23.79, 1.89, 1.91 and 32.9 pg/ml respectively, while in the SM-exposed participants these values were 11.11, 0.81, 1.73 and 26.7 pg/ml respectively. The serum pro-inflammatory cytokine levels were significantly lower in the exposed group than in controls (p<0.01). There was also significant positive correlation between concentration of all of mentioned cytokines, the strongest being between IL-1beta and TNF (r=0.809 in the control group). The observed down-regulation of pro-inflammatory cytokines should be considered in interpretation of diagnosis and therapeutic measures taken to improve clinical complications.

  2. Enhancement of reproductive performances of Gangetic leaffish, Nandus nandus through up regulation of serum Ca²⁺ concentration, improved morphological alteration of liver and ovary with dietary polyunsaturated fatty acids.

    PubMed

    Reza, A H M M; Rakhi, S F; Hossen, M S; Takahashi, K; Hossain, Z

    2013-08-01

    Incorporation of polyunsaturated fatty acids (PUFAs) as biofunctional compounds with feed is an effective way for gonadal maturation without any hazardous effects on animal health, and thus it is possible to save the vulnerable species from the danger of extinction. In the present study sperm quality, level of Ca(2+) concentration in serum, histological structure of the liver and developmental stages of ovary of an endangered fish species, Nandus nandus were investigated for the confirmation of the positive effects of PUFAs in reproduction and gonadal maturation. Fishes were collected from Brahmaputra River, Mymensingh, Bangladesh. Treated group was fed 1% squid extracted phospholipid supplemented diet that was mixed with silver carp fish muscle where as controlled group was fed the same except phospholipid. For histology of liver and gonads, samples were dehydrated, cleaned and infiltrated, embedded in paraffin wax and sectioned. After that, the samples were stained with hematoxylin and eosin. The photomicrographs of the stained samples were taken by using light microscope. In comparison with the control group, treated group exhibited higher gonadal maturation which resulted in spontaneous spawning. Treated female demonstrated advanced gonadal developmental stages in comparison with the controlled female during different months. During spawning season, lipid granules and normal morphological alteration were observed in case of treated fish liver, whereas less lipid granules with more histological alteration of liver were observed in control group. Serum Ca(2+) concentration in treated female was found significantly higher (P < 0.01) in contrast to the controlled female during the breeding season which was an indicator of the augment of estrogen secretion during ovarian maturation. Better sperm quality, early maturation of oocytes, less histological alteration of liver hepatocytes and spontaneous spawning performances of PUFA-treated fish were as a result of the

  3. High-grade iron ore at Windarling, Yilgarn Craton: a product of syn-orogenic deformation, hypogene hydrothermal alteration and supergene modification in an Archean BIF-basalt lithostratigraphy

    NASA Astrophysics Data System (ADS)

    Angerer, Thomas; Hagemann, Steffen G.; Danyushevsky, Leonid

    2013-08-01

    , carbonate and quartz to form veins and breccia but did not generate significant volumes of iron ore. Ore stage 4 involved Mesozoic(?) to recent supergene oxidation and hydration in a weathering environment reaching down to depths of ˜100 to maximum 200 m below surface. Supergene ore formation involved goethite replacement of dolomite and quartz as well as martitisation. Important `ground preparation' for supergene modification and upgrade were mainly the formation of steep D1 to D4 structures, steep BIF/basalt margins and particularly the syn-D1 to syn-D2 carbonate alteration of BIF that is most susceptible to supergene dissolution. The Windarling deposits are structurally controlled, supergene-modified hydrothermal iron ore systems that share comparable physical, chemical and ore-forming characteristics to other iron ore deposits in the Yilgarn Craton (e.g. Koolyanobbing, Beebyn in the Weld Range, Mt. Gibson). However, the remarkable variety in pre-, syn- and post-deformational ore textures (relative to D1 and D2) has not been described elsewhere in the Yilgarn and are similar to the ore deposits in high-strain zones, such as of Brazil (Quadrilátero Ferrífero or Iron Quadrangle) and Nigeria. The overall similarity of alteration stages, i.e. the sequence of hydrothermal carbonate introduction and hypogene leaching, with other greenstone belt-hosted iron ore deposits supports the interpretation that syn-orogenic BIF alteration and upgrade was crucial in the formation of hypogene-supergene iron ore deposits in the Yilgarn Craton and possibly in other Archean/Paleoproterozoic greenstone belt settings worldwide.

  4. Serum metabolite profiles are altered by erlotinib treatment and the integrin α1-null genotype, but not by post traumatic osteoarthritis

    PubMed Central

    Mickiewicz, Beata; Shin, Sung Y.; Pozzi, Ambra; Vogel, Hans J.; Clark, Andrea L.

    2016-01-01

    The risk of developing post traumatic osteoarthritis (PTOA) following joint injury is high. Furthering our understanding of the molecular mechanisms underlying PTOA and/or identifying novel biomarkers for early detection may help improve treatment outcomes. Increased expression of integrin α1β1 and inhibition of epidermal growth factor receptor (EGFR) signaling protect the knee from spontaneous OA, however the impact of the integrin α1β1/EGFR axis on PTOA is currently unknown. We sought to determine metabolic changes in serum samples collected from wild type and integrin α1-null mice that underwent surgery to destabilize the medial meniscus and were treated with the EGFR inhibitor erlotinib. Following 1H nuclear magnetic resonance spectroscopy we generated multivariate statistical models that distinguished between the metabolic profiles of erlotinib- versus vehicle-treated mice, and the integrin α1-null versus wild type mouse genotype. Our results show the sex dependent effects of erlotinib treatment and highlight glutamine as a metabolite that counteracts this treatment. Furthermore, we identified a set of metabolites associated with increased reactive oxygen species production, susceptibility to OA and regulation of TRP channels in α1-null mice. Our study indicates that systemic pharmacological and genetic factors have a greater effect on serum metabolic profiles than site specific factors such as surgery. PMID:26784366

  5. Alterations in the blood glucose, serum lipids and renal oxidative stress in diabetic rats by supplementation of onion (Allium cepa. Linn).

    PubMed

    Bang, Mi-Ae; Kim, Hyeon-A; Cho, Young-Ja

    2009-01-01

    This study examined the anti-diabetic effect of onion (Allium cepa. Linn) in the streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into normal rats fed control diet or supplemented with onion powder (7% w/w) and diabetic rats fed control diet or supplemented with onion powder. Diabetes was induced by a single injection of STZ (60 mg/kg, ip) in citrate buffer. The animals were fed each of the experimental diet for 5 weeks. Blood glucose levels of rats supplemented with onion were lower than those of rats fed control diet in the diabetic rats. Onion also decreased the total serum lipid, triglyceride, and atherogenic index and increased HDL-cholesterol/total cholesterol ratio in the diabetic rats. Glutathione peroxidase, glutathione reductase and glutathione S-transferase activities were high in the diabetic rats compared to normal rats and reverted to near-control values by onion. These results indicate that onion decreased blood glucose, serum lipid levels and reduced renal oxidative stress in STZ-induced diabetic rats and this effect might exert the anti-diabetic effect of onion.

  6. Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats

    PubMed Central

    Hessner, Martin J.; Jia, Shuang; Åkesson, Lina; Stenlund, Hans; Moritz, Thomas; La Torre, Daria; Lernmark, Åke

    2017-01-01

    Type 1 diabetes is associated with abberations of fat metabolism before and after the clinical onset of disease. It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes. PMID:28192442

  7. miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes

    PubMed Central

    Marchand, Lucien; Jalabert, Audrey; Meugnier, Emmanuelle; Van den Hende, Kathleen; Fabien, Nicole; Nicolino, Marc; Madec, Anne-Marie; Thivolet, Charles; Rome, Sophie

    2016-01-01

    Background. The use of miRNAs as biomarkers for Type 1 Diabetes (T1D) risk is attractive as T1D is usually diagnosed in front of acute symptoms. As miR-375 is highly expressed in the endocrine pancreas, we postulated that its circulating level might reflect beta cell alterations and might be altered in the blood of T1D patients recently diagnosed. Methods. Sera were obtained from 22 T1D children at onset of the disease, before subcutaneous insulin treatment, and from 10 nondiabetic pediatric controls. MiR-375 seric level was quantified by stem-loop RT-PCR-based assay. MiRNAs regulations in isolated human islets in response to high glucose concentrations were determined by TaqMan Low-Density Array. Results. The abundance of miR-375, among the 410 miRNAs detected in human islets, mirrored its well-established role in rodent islet biology. Upregulated miRNAs targeted genes involved in islet homeostasis and regulation of beta cell mass. Downregulated miRNAs, including miR-375, were involved in pancreas secretion and protein turnover. Seric level of miR-375 was lower in T1D children versus age-matched controls, without any correlations with HbA1c, glycaemia, and number of autoantibodies. Conclusion. Altered circulating level of miR-375 at onset of T1D might be a general biomarker of metabolic alterations and inflammation associated with the disease. PMID:27314045

  8. Very early posttraumatic serum alterations are significantly associated to initial massive RBC substitution, injury severity, multiple organ failure and adverse clinical outcome in multiple injured patients

    PubMed Central

    2009-01-01

    Background Multiple severe trauma frequently leads to massive dysbalances of the human immune system. This phenomenon is known as "Systemic Inflammatory Response Syndrome (SIRS)". SIRS is connected to multiple organ failure and thereby entails higher morbidity and mortality in trauma patients. Pro-and anti-inflammatory cytokines such as Il-6, Il-8 and Il-10 seem to play a superior role in the development of SIRS. Several studies support the hypothesis that the very early cytokine release pattern determines the patients' subsequent clinical course. Most data about interleukins in trauma patients however refer to serum concentrations assessed sometime in the first 24 h, but there is only little information about release dynamics in a small-meshed time frame in the very initial post-trauma period. Patients and methods 58 multiple injured patients (Injury Severity Score > 16 points) were included. Blood samples were drawn on patient admission (not later then 90 minutes after trauma) and at 6 h, 12 h, 24 h, 48 h and 72 h. Il-6, Il-8 and Il-10 were measured using an automated chemiluminescence assay (IMMULITE, Siemens Healthcare Diagnostics GmbH). Interleukin levels were correlated to distinct epidemiological and clinical parameters. Results Interleukin serum concentrations are thoroughly elevated after trauma. Patients with haemorrhagic shock and consecutive massive RBC substitution (n = 27) exhibit higher Il-6, Il-8 and Il-10 levels as compared to patients with minor RBC transfusion extent (n = 31). Interleukin levels also differentiate patients with MOF (n = 43) from such without MOF (n = 15) already at the earliest post trauma time (90 minutes). Il-6, Il-8 and Il-10 concentrations also significantly distinguish patients with adverse outcome (n = 11) from such with favourable outcome (n = 47). Exclusively Il-10 has significant correlation to injury severity (ISS > 35). Conclusion The current study presents an image of the serum Il-6, 8 and 10 releases in multiple

  9. HMG Modifications and Nuclear Function

    PubMed Central

    Zhang, Qingchun; Wang, Yinsheng

    2009-01-01

    High mobility group (HMG) proteins assume important roles in regulating chromatin dynamics, transcriptional activities of genes and other cellular processes. Post-translational modifications of HMG proteins can alter their interactions with DNA and proteins, and consequently, affect their biological activities. Although the mechanisms through which these modifications are involved in regulating biological processes in different cellular contexts are not fully understood, new insights into these modification “codes” have emerged from the increasing appreciation of the functions of these proteins. In this review, we focus on the chemical modifications of mammalian HMG proteins and highlight their roles in nuclear functions. PMID:20123066

  10. Alterations of homocysteine serum levels during alcohol withdrawal are influenced by folate and riboflavin: results from the German Investigation on Neurobiology in Alcoholism (GINA).

    PubMed

    Heese, Peter; Linnebank, Michael; Semmler, Alexander; Muschler, Marc A N; Heberlein, Annemarie; Frieling, Helge; Stoffel-Wagner, Birgit; Kornhuber, Johannes; Banger, Markus; Bleich, Stefan; Hillemacher, Thomas

    2012-01-01

    Various studies have shown that plasma homocysteine (HCY) serum levels are elevated in actively drinking alcohol-dependent patients a during alcohol withdrawal, while rapidly declining during abstinence. Hyperhomocysteinemia has been associated not only with blood alcohol concentration (BAC), but also with deficiency of different B-vitamins, particularly folate, pyridoxine and cobalamin. Our study included 168 inpatients (110 men, 58 women) after admission for detoxification treatment. BAC, folate, cobalamin, pyridoxine, thiamine and riboflavin were obtained on admission (Day 1). HCY was assessed on Days 1, 7 and 11. HCY levels significantly declined during withdrawal. General linear models and linear regression analysis showed an influence of BAC, folate and riboflavin on the HCY levels on admission as well as on HCY changes occurring during alcohol withdrawal. No significant influence was found for thiamine, cobalamin and pyridoxine. These findings show that not only BAC and plasma folate levels, but also plasma levels of riboflavin influence HCY plasma levels in alcohol-dependent patients.

  11. On the alterations in serum concentration of somatotropin and insuline-like growth factor 1 in lactating cows after the treatment with a little studied recombinant bovine somatotropin.

    PubMed

    Castigliego, L; Grifoni, G; Rosati, R; Iannone, G; Armani, A; Gianfaldoni, D; Guidi, A

    2009-08-01

    A study was performed to delineate bST and IGF-1 variation, over a whole lactation, in cows treated with a nowadays widely commercialised but little studied sustained release formulation of recombinant bST. Total bST levels were found to be exceptionally high in the first days after administration, but decreased rapidly in the second week after injection. The increase in the IGF-1 serum concentration was significant for almost the entire biweekly cycle. Based on this study, the peaks of ST (often above 100 ng/ml) are considered particularly unlikely to be found in non-treated bovines, even under pathological conditions, especially when detected in a number of animals within a herd. Notwithstanding the great heterogeneity of results on this topic, these data suggest that tests against fraud involving the use of rbST in dairy products may be regarded as a feasible possibility.

  12. A novel antibody-antigen based impedimetric immunosensor for low level detection of HER2 in serum samples of breast cancer patients via modification of a gold nanoparticles decorated multiwall carbon nanotube-ionic liquid electrode.

    PubMed

    Arkan, Elham; Saber, Reza; Karimi, Ziba; Shamsipur, Mojtaba

    2015-05-18

    A highly sensitive impedimetric immunosensor based on a gold nanoparticles/multiwall carbon nanotube-ionic liquid electrode (AuNPs/MW-CILE) was developed for the determination of human epidermal growth factor receptor 2 (HER2). Gold nanoparticles were used to enhance the extent of immobilization and to retain the immunoactivity of the antibody Herceptin on the electrode. Cyclic voltammetry and electrochemical impedance spectroscopy were employed for characterization of various layers coated onto the AuNPs/MW-CILE. The impedance measurements at different steps were based on the charge transfer kinetics of the [Fe(CN)6](3-/4-) redox pair. The immobilization of antibody and the corresponding antigen-antibody interaction at the electrode surface altered the interfacial electron transfer. The interactions of antibody with various concentrations of antigen were also monitored via the change of impedance response. The results showed that the charge transfer resistance increases linearly with increasing concentrations of HER2 antigen. The linear range and limit of detection were found as 10-110 ng mL(-1) and 7.4 ng mL(-1), respectively. The sensitivity and specificity of the immunosensor were validated. The results showed that the prepared immunosensor is a useful tool for screening of trace amounts of HER2 in serum samples of breast cancer patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Berberine alters epigenetic modifications, disrupts microtubule network, and modulates HPV-18 E6-E7 oncoproteins by targeting p53 in cervical cancer cell HeLa: a mechanistic study including molecular docking.

    PubMed

    Saha, Santu Kumar; Khuda-Bukhsh, Anisur Rahman

    2014-12-05

    Increased evidence of chemo-resistance, toxicity and carcinogenicity necessitates search for alternative approaches for determining next generation cancer therapeutics and targets. We therefore tested the efficacy of plant alkaloid berberine on human papilloma virus (HPV) -18 positive cervical cancer cell HeLa systematically-involving certain cellular, viral and epigenetic factors. We observed disruptions of microtubule network and changes in membrane topology due to berberine influx through confocal and atomic force microscopies (AFM). We examined nuclear uptake, internucleosomal DNA damages, mitochondrial membrane potential (MMP) alterations and cell migration assays to validate possible mode of cell death events. Analytical data on interactions of berberine with pBR322 through fourier transform infrared (FTIR) and gel migration assay strengthen berberine׳s biologically significant DNA binding abilities. We measured cellular uptake, DNA ploidy and DNA strand-breaks through fluorescence activated cell sorting (FACS). To elucidate epigenetic modifications, in support of DNA binding associated processes, if any, we conducted methylation-specific restriction enzyme (RE) assay, methylation specific-PCR (MSP) and expression studies of histone proteins. We also analyzed differential interactions and localization of cellular tumor suppressor p53 and viral oncoproteins HPV-18 E6-E7 through siRNA approach. We further made in-silico approaches to determine possible binding sites of berberine on histone proteins. Overall results indicated cellular uptake of berberine through cell membrane depolarization causing disruption of microtubule networks and its biological DNA binding abilities that probably contributed to epigenetic modifications. Results of modulation in p53 and viral oncoproteins HPV-18 E6-E7 by berberine further proved its potential as a promising chemotherapeutic agent in cervical cancer.

  14. Alterations in BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) serum levels in bipolar disorder: The role of lithium.

    PubMed

    Tunca, Zeliha; Ozerdem, Aysegul; Ceylan, Deniz; Yalçın, Yaprak; Can, Güneş; Resmi, Halil; Akan, Pınar; Ergör, Gül; Aydemir, Omer; Cengisiz, Cengiz; Kerim, Doyuran

    2014-09-01

    Brain-derived neurotrophic factor (BDNF) has been consistently reported to be decreased in mania or depression in bipolar disorders. Evidence suggests that Glial cell line-derived neurotrophic factor (GDNF) has a role in the pathogenesis of mood disorders. Whether GDNF and BDNF act in the same way across different episodes in bipolar disorders is unclear. BDNF and GDNF serum levels were measured simultaneously by enzyme-linked immunosorbent assay (ELISA) method in 96 patients diagnosed with bipolar disorder according to DSM-IV (37 euthymic, 33 manic, 26 depressed) in comparison to 61 healthy volunteers. SCID- I and SCID-non patient version were used for clinical evaluation of the patients and healthy volunteers respectively. Correlations between the two trophic factor levels, and medication dose, duration and serum levels of lithium or valproate were studied across different episodes of illness. Patients had significantly lower BDNF levels during mania and depression compared to euthymic patients and healthy controls. GDNF levels were not distinctive. However GDNF/BDNF ratio was higher in manic state compared to euthymia and healthy controls. Significant negative correlation was observed between BDNF and GDNF levels in euthymic patients. While BDNF levels correlated positively, GDNF levels correlated negatively with lithium levels. Regression analysis confirmed that lithium levels predicted only GDNF levels positively in mania, and negatively in euthymia. Small sample size in different episodes and drug-free patients was the limitation of thestudy. Current data suggests that lithium exerts its therapeutic action by an inverse effect on BDNF and GDNF levels, possibly by up-regulating BDNF and down-regulating GDNF to achieve euthymia. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Modifications in Lipid Levels Are Independent of Serum TNF-α in Rheumatoid Arthritis: Results of an Observational 24-Week Cohort Study Comparing Patients Receiving Etanercept Plus Methotrexate or Methotrexate as Monotherapy

    PubMed Central

    Rodriguez-Jimenez, Norma Alejandra; Garcia-Gonzalez, Carlos E.; Ayala-Lopez, Karina Patricia; Trujillo-Hernandez, Benjamin; Aguilar-Chavez, Erika Anita; Rocha-Muñoz, Alberto Daniel; Vasquez-Jimenez, Jose Clemente; Olivas-Flores, Eva; Salazar-Paramo, Mario; Corona-Sanchez, Esther Guadalupe; Vazquez-Del Mercado, Monica; Varon-Villalpando, Evangelina; Cota-Sanchez, Adolfo; Cardona-Muñoz, Ernesto German; Gamez-Nava, Jorge I.; Gonzalez-Lopez, Laura

    2014-01-01

    Objective. To compare the modifications in lipids between patients with rheumatoid arthritis (RA) receiving etanercept plus methotrexate (ETA + MTX) versus methotrexate (MTX) and their relationship with serum levels of tumor necrosis factor-alpha (TNF-α). Methods. In an observational cohort study, we compared changes in lipid levels in patients receiving ETA + MTX versus MTX in RA. These groups were assessed at baseline and at 4 and 24 weeks, measuring clinical outcomes, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and TNF-α. Results. Baseline values for lipid levels were similar in both groups. HDL-C levels increased significantly only in the ETA + MTX group (from 45.5 to 50.0 mg/dL at 4 weeks, a 10.2% increase, P < 0.001, and to 56.0 mg/dL at 24 weeks, a 25.1% increase, P < 0.001), while other lipids underwent no significant changes. ETA + MTX also exhibited a significant increase in TNF-α (44.8 pg/mL at baseline versus 281.4 pg/mL at 24 weeks, P < 0.001). The MTX group had no significant changes in lipids or TNF-α. Significant differences in HDL-C between groups were observed at 24 weeks (P = 0.04) and also in TNF-α  (P = 0.01). Conclusion. HDL-C levels increased significantly following treatment with ETA + MTX, without a relationship with decrease of TNF-α. PMID:25243145

  16. Altered exosomal protein expression in the serum of NF-κB knockout mice following skeletal muscle ischemia-reperfusion injury.

    PubMed

    Yang, Johnson Chia-Shen; Lin, Ming-Wei; Rau, Cheng-Shyuan; Jeng, Seng-Feng; Lu, Tsu-Hsiang; Wu, Yi-Chan; Chen, Yi-Chun; Tzeng, Siou-Ling; Wu, Chia-Jung; Hsieh, Ching-Hua

    2015-06-10

    The NF-κB signaling pathway plays a role in local and remote tissue damage following ischemia-reperfusion (I/R) injury to skeletal muscles. Evidence suggests that exosomes can act as intercellular communicators by transporting active proteins to remote cells and may play a role in regulating inflammatory processes. This study aimed to profile the exosomal protein expression in the serum of NF-κB knockout mice following skeletal muscle ischemia-reperfusion injury. To investigate the potential changes in protein expression mediated by NF-κB in secreted exosomes in the serum following I/R injury, the levels of circulating exosomal proteomes in C57BL/6 and NF-κB(-/-) mice were compared using two dimensional differential in-gel electrophoresis (2-DE), liquid chromatography tandem mass spectrometry (LC-MS/MS), and proteomic analysis. In C57BL/6 mice, the levels of circulating exosomal proteins, including complement component C3 prepropeptide, PK-120 precursor, alpha-amylase one precursor, beta-enolase isoform 1, and adenylosuccinate synthetase isozyme 1, increased following I/R injury. However, in the NF-κB(-/-) mice, the expression of the following was upregulated in the exosomes: protease, serine 1; glyceraldehyde-3-phosphate dehydrogenase-like isoform 1; glyceraldehyde-3-phosphate dehydrogenase; and pregnancy zone protein. In contrast, the expression of apolipoprotein B, complement component C3 prepropeptide, and immunoglobulin kappa light chain variable region was downregulated in NF-κB(-/-) mice. Bioinformatic annotation using the Protein Analysis Through Evolutionary Relationships (PANTHER) database revealed that the expression of the exosomal proteins that participate in metabolic processes and in biological regulation was lower in NF-κB(-/-) mice than in C57BL/6 mice, whereas the expression of proteins that participate in the response to stimuli, in cellular processes, and in the immune system was higher. The data presented in this study suggest that NF

  17. Correlation between serum reactivity to Demodex-associated Bacillus oleronius proteins, and altered sebum levels and Demodex populations in erythematotelangiectatic rosacea patients.

    PubMed

    Jarmuda, Stanislaw; McMahon, Fred; Zaba, Ryszard; O'Reilly, Niamh; Jakubowicz, Oliwia; Holland, Ashling; Szkaradkiewicz, Andrzej; Kavanagh, Kevin

    2014-02-01

    Rosacea is a chronic inflammatory condition that affects the skin of the face and the eyes. The aetiology of rosacea is not clearly established but increasing evidence suggests a potential role for bacteria in the induction of the condition. A role for Bacillus oleronius, originally isolated from within a Demodex folliculorum mite, in the aetiology of the condition has been suggested. The aim of the study was to determine whether a correlation existed between the level of sebum and the density of D. folliculorum in the skin of erythematotelangiectatic rosacea patients, and the reactivity of these patients' sera to proteins of B. oleronius. Serum reactivity to the 62 and 83 kDa B. oleronius proteins was found in 82.6 % (62/75) of the rosacea patients and in 26.9 % (14/52) of controls (P = 0.0016). In the group of rosacea patients whose sera reacted to B. oleronius proteins, the level of sebum was statistically lower than in controls (P = 0.01). The density of D. folliculorum on the face of Bacillus positive rosacea patients was statistically higher than controls (P = 0.0001). Rosacea patients demonstrated increased Demodex populations on their faces and reduced sebum levels. Their sera also showed reactivity to B. oleronius proteins, suggesting a potential role for this bacterium in the aetiology of rosacea.

  18. Inflammatory and apoptotic alterations in serum and injured tissue after experimental polytrauma in mice: distinct early response compared with single trauma or "double-hit" injury.

    PubMed

    Weckbach, Sebastian; Hohmann, Christoph; Braumueller, Sonja; Denk, Stephanie; Klohs, Bettina; Stahel, Philip F; Gebhard, Florian; Huber-Lang, Markus S; Perl, Mario

    2013-02-01

    The exact alterations of the immune system after polytrauma leading to sepsis and multiple-organ failure are poorly understood. Thus, the early local and systemic inflammatory and apoptotic response was characterized in a new polytrauma model and compared with the alterations seen after single or combined injuries. Anesthetized C57BL/6 mice were subjected to either blunt bilateral chest trauma (Tx), closed head injury, right femur fracture including contralateral soft tissue injury, or a combination of injuries (PTx). After 2 hours or 6 hours, animals were sacrificed, and the systemic as well as the local pulmonary immune response (bronchoalveolar lavage [BAL]/plasma cytokines, lung myeloperoxidase [MPO] activity, and alveolocapillary barrier dysfunction) were evaluated along with lung/brain apoptosis (lung caspase 3 Western blotting, immunohistochemistry, and polymorphonuclear leukocytes [PMN] Annexin V). Hemoglobin, PO2 saturation, and pH did not differ between the experimental groups. Local BAL cytokines/chemokines were significantly increased in almost all groups, which included Tx. There was no further enhancement of this local inflammatory response in the lungs in case of PTx. At 2 hours, all groups except sham and closed head injury alone revealed an increased activity of lung MPO. However, 6 hours after injury, lung MPO remained increased only in the PTx group. Increased BAL protein levels were found, reflecting enhanced lung leakage in all groups with Tx 6 hours after trauma. Only after PTx was neutrophil apoptosis significantly decreased, whereas lung caspase 3 and plasma interleukin 6/keratinocyte chemoattractant (KC) were substantially increased. The combination of different injuries leads to an earlier systemic inflammatory response when compared with the single insults. Interestingly, only after PTx but not after single or double hits was lung apoptosis increased, and PMN apoptosis was decreased along with a prolonged presence of neutrophils in the

  19. Dehydrated citrus pulp alters feedlot performance of crossbred heifers during the receiving period and modulates serum metabolite concentrations before and after an endotoxin challenge.

    PubMed

    Cribbs, J T; Bernhard, B C; Young, T R; Jennings, M A; Burdick Sanchez, N C; Carroll, J A; Callaway, T R; Schmidt, T B; Johnson, B J; Rathmann, R J

    2015-12-01

    English × Continental heifers ( = 180) were sourced in 2 loads (219.3 ± 16.0 and 221.4 ± 16.4 kg, respectively) from commercial auction barns to study the effects of feeding dehydrated citrus pulp (DCP) on feedlot performance of newly received heifers. A completely randomized block design was used with BW nested within arrival load and blocked by BW into 3 dietary treatments (36 pens, 5 heifers/pen, 12 blocks, 3 pens/block, and 12 pens/treatment). Treatment diets contained 1) 0% DCP (control diet [CON]), 2) 10% DCP, or 3) 20% DCP on a DM basis. Diets containing DCP were exchanged with steam-flaked corn on a 1:1 basis. Cattle were fed a 63, 73, and 83% concentrate diet from d 0 to 28, d 28 to 42, and d 42 to 56, respectively. Over the 56-d trial period, as the amount of dietary DCP increased, DMI decreased ( = 0.01), ADG decreased ( < 0.01), and G:F decreased ( = 0.02). From d 0 to 28, there was no difference in the observed minus the predicted NEg of the diet ( = 0.73); from d 28 to 42, there was a linear increase in NEg favoring DCP treatments ( < 0.01); and from d 42 to 56, there was a linear decrease in NEg against the DCP treatments ( < 0.01). At the conclusion of the trial, a subset of heifers ( = 22; 307.89 ± 3.32 kg on d 63) were used to evaluate blood metabolite concentrations before and after a lipopolysaccharide (LPS) challenge. On d 63, heifers were fitted with jugular catheters and moved into individual stalls. On d 64, heifers were intravenously challenged with LPS (0.5 μg/kg BW), and blood samples were collected every 0.5 h from -2 to 8 h and at 24 h relative to the LPS challenge (0 h). Serum glucose, serum urea nitrogen (SUN), and NEFA concentrations were determined. Cattle lost less weight at both 24 and 72 h after the LPS challenge with increasing DCP percentage ( < 0.01). Glucose ( = 0.12) and NEFA ( = 0.13) concentrations did not differ before the LPS challenge; however, there was a treatment effect for SUN, with elevated concentrations of

  20. Spironolactone prevents alterations associated with cardiac hypertrophy produced by isoproterenol in rats: involvement of serum- and glucocorticoid-regulated kinase type 1.

    PubMed

    Martín-Fernández, Beatriz; de las Heras, Natalia; Miana, María; Ballesteros, Sandra; Valero-Muñoz, María; Vassallo, Dalton; Davel, Ana Paula; Rossoni, Luciana Venturini; Cachofeiro, Victoria; Lahera, Vicente

    2012-06-01

    Persistent β-adrenergic receptor stimulation with isoproterenol is associated with cardiac hypertrophy as well as cardiac synthesis of angiotensin II. Serum- and glucocorticoid-regulated kinase type 1 (SGK-1) is a key mediator in structural, functional and molecular cardiac effects of aldosterone in rats. This study was designed to investigate the cardiac effects of the mineralocorticoid receptor antagonist spironolactone on the response to isoproterenol treatment in rats, as well as the involvement of the main mediator of cellular aldosterone action, SGK-1, in the heart. Male Wistar rats received isoproterenol (3 mg kg(-1) day(-1)) or vehicle for 15 days. Half of the animals in each group were simultaneously treated with spironolactone (200 mg kg(-1) day(-1)). Systolic and diastolic blood pressures were not significantly different among groups. Treatment with spironolactone normalized the increased left ventricular end-diastolic pressure observed in isoproterenol-treated rats. Isoproterenol treatment induced cardiac hypertrophy and increased collagen content, both of which were normalized by spironolactone treatment. The mRNA levels of transforming growth factor β, connective tissue growth factor, matrix metalloprotease 2, matrix metalloprotease inhibitor 2, tumour necrosis factor α, interleukin 1β, p22phox and xanthine dehydrogenase were increased (P < 0.05) in isoproterenol-treated rats, and this effect was prevented by spironolactone (P < 0.05). Spironolactone also reduced the elevated SGK-1 expression in isoproterenol-treated rats. The observed reduction of the principal mediator of aldosterone cellular actions, SGK-1, by spironolactone in hearts from isoproterenol-treated rats suggests a role of mineralocorticoids in the cardiac hypertrophy, fibrosis, inflammation, oxidation and diastolic dysfunction induced by isoproterenol treatment in rats.

  1. Altered serum glyceraldehyde-derived advanced glycation end product (AGE) and soluble AGE receptor levels indicate carbonyl stress in patients with schizophrenia.

    PubMed

    Takeda, Mayu; Ohnuma, Tohru; Takeuchi, Masayoshi; Katsuta, Narimasa; Maeshima, Hitoshi; Takebayashi, Yuto; Higa, Motoyuki; Nakamura, Toru; Nishimon, Shohei; Sannohe, Takahiro; Hotta, Yuri; Hanzawa, Ryo; Higashiyama, Ryoko; Shibata, Nobuto; Gohda, Tomohito; Suzuki, Yusuke; Yamagishi, Sho-ichi; Tomino, Yasuhiko; Arai, Heii

    2015-04-23

    Recent cross-sectional and longitudinal studies indicate that measurements of peripheral blood carbonyl stress markers such as the advanced glycation end product (AGE) pentosidine and the reactive carbonyl-detoxifying B6 vitamin pyridoxal could be used as therapeutic biological markers in subpopulations of schizophrenia patients. Glyceraldehyde-derived AGEs (Glycer-AGE) have strong neurotoxicity, and soluble receptors for AGEs (sRAGE) may ameliorate the effects of AGEs. In the present study, we measured Glycer-AGEs and sRAGE levels to determine their potential as diagnostic, therapeutic, or clinical biological markers in patients with schizophrenia. After enrollment of 61 admitted Japanese patients with acute schizophrenia and 39 healthy volunteers, 54 patients were followed up from the acute stage to remission. Serum biomarkers were measured in blood samples taken before breakfast using competitive enzyme-linked immunosorbent assays, and Glycer-AGEs were significantly higher and sRAGE levels were significantly lower in patients with acute schizophrenia than in healthy controls. Glycer-AGEs/sRAGE ratios were also higher in schizophrenia patients and were stable during the clinical course. Furthermore, discriminant analyses confirmed that Glycer-AGEs and Glycer-AGEs/sRAGE ratios are significant diagnostic markers for schizophrenia, and distinguished between patients and healthy controls in 70.0% of cases. However, these markers of carbonyl stress were not correlated with clinical features, including disease severity, or with daily chlorpromazine doses. These data indicate the potential of Glycer-AGEs, RAGEs, and their relative ratios as diagnostic markers for patients with schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Phenotype and function of CXCR5+CD45RA-CD4+ T cells were altered in HBV-related hepatocellular carcinoma and elevated serum CXCL13 predicted better prognosis.

    PubMed

    Duan, Zhaojun; Gao, Jian; Zhang, Ling; Liang, Hua; Huang, Xiangbo; Xu, Qiang; Zhang, Yu; Shen, Tao; Lu, Fengmin

    2015-12-29

    The present study reveals an immunological characterization of circulating and tumor-infiltrating T follicular helper cells (Tfh), namely CXCR5+CD45RA-CD4+ T cells, and their related cytokines in hepatitis B virus-related hepatocellular carcinoma (HCC) patients. In HCC patients, circulating Tfh cells showed a CCR7+ and/or ICOS+ phenotype with increased Th2-like cells and decreased Th1-like and Th17-like subsets. Although the bulk frequency of circulating Tfh cells was not altered in HCC patients, the frequency of infiltrated CXCR5+CD45RA-CD4+ CD3+cells was higher in tumor than in para-tumor tissues, and Th1-like cells were the predominant phenotype. Circulating Tfh cells in HCC patients were defective in the production of IL-21 in vitro, which was in accordance with lower IL-21 levels in tumor tissues than in para-tumor tissues. Serum CXCL13 was increased in HCC patients and associated with recurrence-free survival after hepatectomy. This was confirmed in an additional HCC cohort of 111 patients with up to 5 years follow-up. Immunohistochemical staining indicated that the percentage of CXCR5+ or CXCL13+ cells was higher in poorly differentiated than in well-differentiated tumors. In conclusion, patients with HBV-related HCC showed altered phenotypes and impaired function of Tfh cells or subpopulations. CXCL13 could be a potential biomarker for predicting recurrence in HCC patients after hepatectomy.

  3. Public perceptions of hurricane modification.

    PubMed

    Klima, Kelly; Bruine de Bruin, Wändi; Morgan, M Granger; Grossmann, Iris

    2012-07-01

    If hurricane modification were to become a feasible strategy for potentially reducing hurricane damages, it would likely generate public discourse about whether to support its implementation. To facilitate an informed and constructive discourse, policymakers need to understand how people perceive hurricane modification. Here, we examine Florida residents' perceptions of hurricane modification techniques that aim to alter path and wind speed. Following the mental models approach, we conducted a survey study about public perceptions of hurricane modification that was guided by formative interviews on the topic. We report a set of four primary findings. First, hurricane modification was perceived as a relatively ineffective strategy for damage reduction, compared to other strategies for damage reduction. Second, hurricane modification was expected to lead to changes in projected hurricane path, but not necessarily to the successful reduction of projected hurricane strength. Third, more anger was evoked when a hurricane was described as having changed from the initially forecasted path or strength after an attempted modification. Fourth, unlike what we expected, participants who more strongly agreed with statements that recognized the uncertainty inherent in forecasts reported more rather than less anger at scientists across hurricane modification scenarios. If the efficacy of intensity-reduction techniques can be increased, people may be willing to support hurricane modification. However, such an effort would need to be combined with open and honest communications to members of the general public. © 2011 Society for Risk Analysis.

  4. Response modification in carcinogenesis.

    PubMed Central

    Cerutti, P A

    1989-01-01

    A major goal in multistep carcinogenesis research is the integration of recent findings obtained by sophisticated molecular-genetic and cytogenetic analysis of cancer into the more descriptive concepts of experimental pathology. It is proposed that the creation of a promotable cell in carcinogenic initiation requires a response modification to extracellular or intercellular signals. Different types of response modification can be distinguished: changes in the receptors for growth and differentiation factors and their cytoplasmic and nuclear signal transduction pathways; increased resistance of initiated cells to cytotoxic agents; alterations in junctional cell-to-cell communications. The challenge of a response-modified cell to an appropriate promoter results in its selection and clonal expansion, usually to a benign tumor. In addition, for malignancy, chromosomal changes are required that affect cellular functions that can play a role early or late in tumorigenesis. These concepts are illustrated with examples from oncogene research and oxidant promotion. PMID:2667983

  5. Biological effects of static electric field: Plasma/serum proteome analysis of rats.

    PubMed

    Harutyunyan, Hayk; Artsruni, Gagik

    2013-03-01

    The external static electric field (SEF) of man-made origin brings to the substantially increased SEF background in a human environment the biological activity of which is a moot question. The paper reports on rats blood plasma/serum proteome modifications by means of 1D polyacrilamide gel electrophoresis and clotting process alterations after the short- and long-term SEF exposures of 200 kV/m. The results indicate decrease of fast α1 and α2 globular proteins in plasma coinciding with clotting acceleration after the short-term SEF, and attenuation of clotting-dependent proteome modifications reflected with incomplete coagulation after the long-term SEF exposure. Increased lysozyme activity in serum unlike plasma was observed after both SEF exposures. Applied model of the high-voltage SEF environment indicates dependence of biological systems functioning on the external SEF.

  6. HHMD: the human histone modification database.

    PubMed

    Zhang, Yan; Lv, Jie; Liu, Hongbo; Zhu, Jiang; Su, Jianzhong; Wu, Qiong; Qi, Yunfeng; Wang, Fang; Li, Xia

    2010-01-01

    Histone modifications play important roles in chromatin remodeling, gene transcriptional regulation, stem cell maintenance and differentiation. Alterations in histone modifications may be linked to human diseases especially cancer. Histone modifications including methylation, acetylation and ubiquitylation probed by ChIP-seq, ChIP-chip and qChIP have become widely available. Mining and integration of histone modification data can be beneficial to novel biological discoveries. There has been no comprehensive data repository that is exclusive for human histone modifications. Therefore, we developed a relatively comprehensive database for human histone modifications. Human Histone Modification Database (HHMD, http://bioinfo.hrbmu.edu.cn/hhmd) focuses on the storage and integration of histone modification datasets that were obtained from laboratory experiments. The latest release of HHMD incorporates 43 location-specific histone modifications in human. To facilitate data extraction, flexible search options are built in HHMD. It can be searched by histone modification, gene ID, functional categories, chromosome location and cancer name. HHMD also includes a user-friendly visualization tool named HisModView, by which genome-wide histone modification map can be shown. HisModView facilitates the acquisition and visualization of histone modifications. The database also has manually curated information of histone modification dysregulation in nine human cancers.

  7. Serum ferritin.

    PubMed

    Worwood, M

    1979-01-01

    (1) Brief introduction to iron metabolism and the biochemistry of ferritin. (2) Early studies of circulating ferritin. (3) Methods for measuring serum ferritin concentrations -- immunoradiometric, radioimmuno- and enzyme-linked immuno assays based on liver or spleen ferritin -- an evaluation of these techniques. (4) Serum ferritin concentrations in normal subjects -- definition of normality -- relationship between storage iron and serum ferritin concentrations -- changes during development from birth to old age -- iron deficiency -- variability of serum ferritin concentration -- evaluation of use of ferritin assay for assessment of storage iron levels. (5) Serum ferritin concentrations in disease -- hemochromatosis -- secondary iron overload -- liver damage -- infection and chronic disease -- cancer. (6) Assay of serum ferritin with antibodies to ferritins other than liver or spleen -- ferritinemia and cancer. (7) Properties of serum ferritin -- molecular weight -- iron content -- isoelectric focusing patterns -- carbohydrate content -- immunological properties. (8) Physiology of circulating ferritin -- release of ferritin from tissues -- origin of circulating ferritin -- clearance from the plasma -- iron and protein turnover. (9) Summary -- factors influencing serum ferritin concentrations and clinical use of ferritin estimations.

  8. Epigenetic modifications and diabetic retinopathy.

    PubMed

    Kowluru, Renu A; Santos, Julia M; Mishra, Manish

    2013-01-01

    Diabetic retinopathy remains one of the most debilitating chronic complications, but despite extensive research in the field, the exact mechanism(s) responsible for how retina is damaged in diabetes remains ambiguous. Many metabolic pathways have been implicated in its development, and genes associated with these pathways are altered. Diabetic environment also facilitates epigenetics modifications, which can alter the gene expression without permanent changes in DNA sequence. The role of epigenetics in diabetic retinopathy is now an emerging area, and recent work has shown that genes encoding mitochondrial superoxide dismutase (Sod2) and matrix metalloproteinase-9 (MMP-9) are epigenetically modified, activates of epigenetic modification enzymes, histone lysine demethylase 1 (LSD1), and DNA methyltransferase are increased, and the micro RNAs responsible for regulating nuclear transcriptional factor and VEGF are upregulated. With the growing evidence of epigenetic modifications in diabetic retinopathy, better understanding of these modifications has potential to identify novel targets to inhibit this devastating disease. Fortunately, the inhibitors and mimics targeted towards histone modification, DNA methylation, and miRNAs are now being tried for cancer and other chronic diseases, and better understanding of the role of epigenetics in diabetic retinopathy will open the door for their possible use in combating this blinding disease.

  9. [Lung cancer and epigenetic modifications].

    PubMed

    Darılmaz Yüce, Gülbahar; Ortaç Ersoy, Ebru

    2016-06-01

    Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA expression, have been reported to play a major role in the genesis of lung cancer. DNA methylation, histone modifications, and RNA expression are epigenetic markers in assesment of early detection, prognosis and evaluation of treatment of lung cancer. In this rewiev we summarize the common epigenetic changes associated with lung cancer to give some clarity to its etiology, and to provide an overview of the potential translational applications of these changes, including applications for early detection, diagnosis, prognostication, and therapeutics.

  10. Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis

    PubMed Central

    Wiese, Dawn M.; Horst, Sara N.; Brown, Caroline T.; Allaman, Margaret M.; Hodges, Mallary E.; Slaughter, James C.; Druce, Jennifer P.; Beaulieu, Dawn B.; Schwartz, David A.; Wilson, Keith T.; Coburn, Lori A.

    2016-01-01

    Background and Aims Ulcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines. Methods Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography. Results UC subjects had increased total fat and oleic acid (OA) intake, but decreased arachidonic acid (AA) intake vs controls. In serum, there was less percent saturated fatty acid (SFA) and AA, with higher monounsaturated fatty acids (MUFA), linoleic acid, OA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations. Conclusions In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC. PMID:27227540

  11. Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis.

    PubMed

    Wiese, Dawn M; Horst, Sara N; Brown, Caroline T; Allaman, Margaret M; Hodges, Mallary E; Slaughter, James C; Druce, Jennifer P; Beaulieu, Dawn B; Schwartz, David A; Wilson, Keith T; Coburn, Lori A

    2016-01-01

    Ulcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines. Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography. UC subjects had increased total fat and oleic acid (OA) intake, but decreased arachidonic acid (AA) intake vs controls. In serum, there was less percent saturated fatty acid (SFA) and AA, with higher monounsaturated fatty acids (MUFA), linoleic acid, OA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations. In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.

  12. Seasonal influence over serum and urine metabolic markers in submariners during prolonged patrols

    PubMed Central

    Holy, Xavier; Bégot, Laurent; Renault, Sylvie; Butigieg, Xavier; André, Catherine; Bonneau, Dominique; Savourey, Gustave; Collombet, Jean-Marc

    2015-01-01

    Within the framework of earlier publications, we have consistently dedicated our investigations to eliciting the effects of both seasonal vitamin D deficiency and submarine-induced hypercapnia on serum parameters for acid–base balance and bone metabolism in submariners over a 2-month winter (WP) or summer (SP) patrols. The latest findings reported herein, contribute further evidence with regard to overall physiological regulations in the same submariner populations that underwent past scrutiny. Hence, urine and blood samples were collected in WP and SP submariners at control prepatrol time as well as on submarine patrol days 20, 41, and 58. Several urine and serum metabolic markers were quantified, namely, deoxypyridinoline (DPD), lactate, albumin, creatinine, nonesterified fatty acids (NEFA), and ionized sodium (Na+) or potassium (K+), with a view to assessing bone, muscle, liver, or kidney metabolisms. We evidenced bone metabolism alteration (urine DPD, calcium, and phosphorus) previously recorded in submarine crewmembers under prolonged patrols. We also highlighted transitory modifications in liver metabolism (serum albumin) occurring within the first 20 days of submersion. We further evidenced changes in submariners’ renal physiology (serum creatinine) throughout the entire patrol time span. Measurements of ionic homeostasis (serum Na+ and K+) displayed potential seasonal impact over active ionic pumps in submariners. Finally, there is some evidence that submersion provides beneficial conditions prone to fend off seasonal lactic acidosis (serum lactate) detected in WP submariners. PMID:26265754

  13. Ecological Effects of Weather Modification: A Problem Analysis.

    ERIC Educational Resources Information Center

    Cooper, Charles F.; Jolly, William C.

    This publication reviews the potential hazards to the environment of weather modification techniques as they eventually become capable of producing large scale weather pattern modifications. Such weather modifications could result in ecological changes which would generally require several years to be fully evident, including the alteration of…

  14. Surface modification for corrosion resistance

    SciTech Connect

    Natesan, K.

    1993-06-01

    The raw gas environments that arise from coal gasification have chemical compositions that are low in pO{sub 2} and moderate-to-high in pS{sub 2}. Metallic materials for service in such an environment undergo predominantly sulfidation attack at temperatures of 400 to 700{degree}C. Modification of alloy compositions in bulk can alter the scaling processes and lead to improvements in corrosion resistance, but the benefits can only be attained at temperatures much higher than the service temperatures of the components. Modification of surfaces of structural components by several of the coating techniques examined in this study showed substantial benefit in corrosion resistance when tested in simulated coal gasification environments. The paper presents several examples of surface modification and their corrosion performance.

  15. Histone modifications in cancer biology and prognosis.

    PubMed

    Kurdistani, Siavash K

    2011-01-01

    Cancer is a disease of genome sequence alterations as well as epigenetic changes. Epigenetics refers in part to the mechanisms by which histones affect various DNA-based processes, such as gene regulation. Histones are proteins around which the DNA wraps itself to form chromatin--the physiologically relevant form of the human genome. Histones are modified extensively by posttranslational modifications that alter chromatin structure and serve to recruit to or exclude protein complexes from DNA. Aberrations in histone modifications occur frequently in cancer including changes in their levels and distribution at gene promoters, gene coding regions, repetitive DNA sequences, and other genomic elements. Locus-specific alterations in histone modifications may have adverse effects on expression of nearby genes but so far have not been shown to have clinical utility. Cancer cells also exhibit alterations in global levels of specific histone modifications, generating an additional layer of epigenetic heterogeneity at the cellular level in tumor tissues. Unlike locus-specific changes, the cellular epigenetic heterogeneity can be used to define previously unrecognized subsets of cancer patients with distinct clinical outcomes. In general, increased prevalence of cells with lower global levels of histone modifications is prognostic of poorer clinical outcome such as increased risk of tumor recurrence and/or decreased survival probability. Prognostic utility of histone modifications has been demonstrated independently for multiple cancers including those of prostate, lung, kidney, breast, ovary, and pancreas, suggesting a fundamental association between global histone modification levels and tumor aggressiveness, regardless of cancer tissue of origin. Cellular levels of histone modifications may also predict response to certain chemotherapeutic agents, serving as predictive biomarkers that could inform clinical decisions on choice and course of therapy. The challenge before us

  16. Sleep Deprivation Alters Rat Ventral Prostate Morphology, Leading to Glandular Atrophy: A Microscopic Study Contrasted with the Hormonal Assays

    PubMed Central

    Venâncio, Daniel P.; Andersen, Monica L.; Vilamaior, Patricia S. L.; Santos, Fernanda C.; Zager, Adriano; Tufik, Sérgio; Taboga, Sebastião R.; De Mello, Marco T.

    2012-01-01

    We investigated the effect of 96 h paradoxical sleep deprivation (PSD) and 21-day sleep restriction (SR) on prostate morphology using stereological assays in male rats. After euthanasia, the rat ventral prostate was removed, weighed, and prepared for conventional light microscopy. Microscopic analysis of the prostate reveals that morphology of this gland was altered after 96 h of PSD and 21 days of SR, with the most important alterations occurring in the epithelium and stroma in the course of both procedures compared with the control group. Both 96 h PSD and 21-day SR rats showed lower serum testosterone and higher corticosterone levels than control rats. The significance of our result referring to the sleep deprivation was responsible for deep morphological alterations in ventral prostate tissue, like to castration microscopic modifications. This result is due to the marked alterations in hormonal status caused by PSD and SR. PMID:22927719

  17. Calorimetric investigation of diclofenac drug binding to a panel of moderately glycated serum albumins.

    PubMed

    Indurthi, Venkata S K; Leclerc, Estelle; Vetter, Stefan W

    2014-08-01

    Glycation alters the drug binding properties of serum proteins and could affect free drug concentrations in diabetic patients with elevated glycation levels. We investigated the effect of bovine serum albumin glycation by eight physiologically relevant glycation reagents (glucose, ribose, carboxymethyllysine, acetoin, methylglyoxal, glyceraldehyde, diacetyl and glycolaldehyde) on diclofenac drug binding. We used this non-steroidal anti-inflammatory drug diclofenac as a paradigm for acidic drugs with high serum binding and because of its potential cardiovascular risks in diabetic patients. Isothermal titration calorimetry showed that glycation reduced the binding affinity Ka of serum albumin and diclofenac 2 to 6-fold by reducing structural rigidity of albumin. Glycation affected the number of drug binding sites in a glycation reagent dependent manner and lead to a 25% decrease for most reagent, expect for ribose, with decreased by 60% and for the CML-modification, increased the number of binding sites by 60%. Using isothermal titration calorimetry and differential scanning calorimetry we derived the complete thermodynamic characterization of diclofenac binding to all glycated BSA samples. Our results suggest that glycation in diabetic patients could significantly alter the pharmacokinetics of the widely used over-the-counter NSDAI drug diclofenac and with possibly negative implications for patients.

  18. Abnormal serum thyroid hormones concentration with healthy functional gland: a review on the metabolic role of thyroid hormones transporter proteins.

    PubMed

    Azad, Reza Mansourian

    2011-03-01

    Laboratory findings can definitely help the patients not to enter into status, where the damage might be happen due to a miss-diagnosis based on clinical assessment alone. The secondary disease accompanied with thyroid patients should also carefully check out due to the interference which some diseases can cause in the amount of serum thyroid hormone, particularly the free thyroxin. The dilemma over thyroid clinical diagnosis occur due to variation on serum thyroid hormone which initiated by other non-thyroidal disorders which can play an important roles in metabolic disorders of thyroid hormone due to the alteration which occur on the serum level of thyroid hormone transporter proteins. The majority of serum thyroid hormones of up to 95-99% are bound to the carrier proteins mainly to Thyroxin-Binding Globulins (TBG), some transthyretin already known as pre-albumin and albumin which are all synthesis in the liver and any modification which alter their production may alter the status of thyroid hormones. It seems TBG, transthyretin and albumin carries 75, 20, 5% of thyroid hormones within blood circulation, respectively. The dilemma facing the thyroid hormones following disruption of thyroid hormone transporter protein synthesis originate from this fact that any alteration of these protein contribute to the alteration of total thyroid and free serum thyroid hormones which are in fact the biologically active form of thyroid hormones. The subsequent of latter implication result in miss-understanding and miss-diagnosis of thyroid function tests, with possible wrongly thyroid clinical care, followed by undesired therapy of otherwise healthy thyroid.

  19. Differences in both matrix metalloproteinase 9 concentration and zymographic profile between plasma and serum with clot activators are due to the presence of amorphous silica or silicate salts in blood collection devices.

    PubMed

    Mannello, Ferdinando; Tanus-Santos, Jose E; Meschiari, Cesar A; Tonti, Gaetana A

    2008-03-01

    Matrix metalloproteinases (MMPs) are promising diagnostic tools, and blood sampling/handling alters MMP concentrations between plasma and serum and between serum with and without clot activators. To explain the higher MMP-9 expression in serum collected with clot accelerators relative to serum with no additives and to plasma, we analyzed the effects of increasing amounts of silica and silicates (components of clot activators) in citrate plasma, serum, and buffy coats collected in both plastic and glass tubes from 50 healthy donors, and we analyzed the effects of silica and silicate on cultured leukemia cells. The levels of MMP-2 did not show significant changes between glass and plastic tubes, between serum and plasma, between serum with and without clot accelerators, or between silica and silicate treatments. No modification of MMP-9 expression was obtained by the addition of silica or silicate to previously separated plasma and serum. Increasing the amounts of nonsoluble silica and soluble silicate added to citrate and empty tubes prior to blood collection resulted in increasing levels of MMP-9 relative to citrate plasma and serum. Silica and silicate added to buffy coats and leukemia cells significantly induced MMP-9 release/secretion, demonstrating that both silica and silicate induce the release of pro- and complexed MMP-9 forms. We recommend limiting the misuse of serum and avoiding the interfering effects of clot activators.

  20. Dietary rapeseed/canola-oil supplementation reduces serum lipids and liver enzymes and alters postprandial inflammatory responses in adipose tissue compared to olive-oil supplementation in obese men.

    PubMed

    Kruse, Michael; von Loeffelholz, Christian; Hoffmann, Daniela; Pohlmann, Antje; Seltmann, Anne-Cathrin; Osterhoff, Martin; Hornemann, Silke; Pivovarova, Olga; Rohn, Sascha; Jahreis, Gerhard; Pfeiffer, Andreas F H

    2015-03-01

    Obesity is associated with hyperlipidemia, hepatic steatosis, and low-grade inflammation. Studies have shown that MUFA as well as PUFA have beneficial effects on blood lipids and the inflammatory state. This study investigates the effects of a daily supplementation of either 50 g of rapeseed/canola (RA) or olive (OL) oil over 4 wk on serum lipids, serum liver enzymes, and inflammatory gene expression in subcutaneous (s. c.) adipose tissue in obese men. Consuming RA resulted in increased serum n-3 fatty acids and a reduction in total cholesterol, LDL cholesterol, and serum aspartate aminotransferase compared to OL. In s. c. adipose tissue, gene expression of the pro-inflammatory cytokine IL6 was reduced in RA compared to OL. However, after 4 h after a test meal, containing the appropriate oil, white bread, and 400 mL of liquid diet drink (835 kcal in total), gene expression of IL6, IL1B, and EMR1 (egf-like module containing Mucin-like hormone receptor-like 1) was increased in RA and of monocyte chemoattractant protein-1 (CCL2) in both RA and OL. This demonstrates that consuming RA for 4 wk improves serum lipids, liver enzymes, and basal inflammation in s. c. adipose tissue, but it mediates an acute pro-inflammatory response in adipose tissue upon consuming a meal. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Serum Metabolomic Biomarkers of Dementia

    PubMed Central

    Mousavi, Malahat; Jonsson, Pär; Antti, Henrik; Adolfsson, Rolf; Nordin, Annelie; Bergdahl, Jan; Eriksson, Kåre; Moritz, Thomas; Nilsson, Lars-Göran; Nyberg, Lars

    2014-01-01

    Aims: This study compared serum metabolites of demented patients (Alzheimer's disease and vascular dementia) and controls, and explored serum metabolite profiles of nondemented individuals 5 years preceding the diagnosis. Methods: Cognitively healthy participants were followed up for 5-20 years. Cognitive assessment, serum sampling, and diagnosis were completed every 5 years. Multivariate analyses were conducted on the metabolite profiles generated by gas chromatography/time-of-flight mass spectrometry. Results: A significant group separation was found between demented patients and controls, and between incident cases and controls. Metabolites that contributed in both analyses were 3,4-dihydroxybutanoic acid, docosapentaenoic acid, and uric acid. Conclusions: Serum metabolite profiles are altered in demented patients, and detectable up to 5 years preceding the diagnosis. Blood sampling can make an important contribution to the early prediction of conversion to dementia. PMID:25177334

  2. Enzymatically Modified Starch Ameliorates Postprandial Serum Triglycerides and Lipid Metabolome in Growing Pigs

    PubMed Central

    Metzler-Zebeli, Barbara U.; Eberspächer, Eva; Grüll, Dietmar; Kowalczyk, Lidia; Molnar, Timea; Zebeli, Qendrim

    2015-01-01

    Developing host digestion-resistant starches to promote human health is of great research interest. Chemically modified starches (CMS) are widely used in processed foods and although the modification of the starch molecule allows specific reduction in digestibility, the metabolic effects of CMS have been less well described. This short-term study evaluated the impact of enzymatically modified starch (EMS) on fasting and postprandial profiles of blood glucose, insulin and lipids, and serum metabolome in growing pigs. Eight jugular-vein catheterized pigs (initial body weight, 37.4 kg; 4 months of age) were fed 2 diets containing 72% purified starch (EMS or waxy corn starch (control)) in a cross-over design for 7 days. On day 8, an 8-hour meal tolerance test (MTT) was performed with serial blood samplings. Besides biochemical analysis, serum was analysed for 201 metabolites through targeted mass spectrometry-based metabolomic approaches. Pigs fed the EMS diet showed increased (P<0.05) immediate serum insulin and plasma glucose response compared to pigs fed the control diet; however, area-under-the-curves for insulin and glucose were not different among diets. Results from MTT indicated reduced postprandial serum triglycerides with EMS versus control diet (P<0.05). Likewise, serum metabolome profiling identified characteristic changes in glycerophospholipid, lysophospholipids, sphingomyelins and amino acid metabolome profiles with EMS diet compared to control diet. Results showed rapid adaptations of blood metabolites to dietary starch shifts within 7 days. In conclusion, EMS ingestion showed potential to attenuate postprandial raise in serum lipids and suggested constant alteration in the synthesis or breakdown of sphingolipids and phospholipids which might be a health benefit of EMS consumption. Because serum insulin was not lowered, more research is warranted to reveal possible underlying mechanisms behind the observed changes in the profile of serum lipid

  3. Modification of polystyrene surface in aqueous solutions.

    PubMed

    Mielczarski, J A; Jeyachandran, Y L; Mielczarski, E; Rai, B

    2011-10-15

    Herein, we report our analysis of the surface modification of polystyrene (PS) when treated under ambient conditions with a common biological buffer such as phosphate buffered saline (PBS) or aqueous solutions of the ionic constituents of PBS. Attenuated total reflection Fourier transform infrared spectroscopy was used for the analysis because the resultant spectra are very sensitive to minor changes in the chemical and structural properties of PS films. In addition, ultraviolet-visible spectroscopy was applied to characterize the surface modifications of PS. Treatment with PBS resulted in the most significant chemical and structural surface modifications of the PS films, as compared with each of the solutions of the constituents of PBS, which were tested separately. A multistep mechanism for the wet modification of PS is discussed. We postulate that the observed surface modifications are the result of photo-oxidation/reduction, swelling, and conformational changes and re-arrangement of the polymer chain. The resultant surface modifications could be similar to those produced by commonly used dry processes such as plasma treatments and electron, ion or ultraviolet irradiation. We found that the modifications that occurred in PBS were more stable than those initiated by dry processes. The formation of active groups on the surface of PS can be controlled by adsorption of bovine serum albumin or thermal annealing of PS before PBS treatment. This approach provides a simple and efficient method for the surface modification of PS for biomedical applications. Copyright © 2011. Published by Elsevier Inc.

  4. The pivotal regulatory landscape of RNA modifications.

    PubMed

    Li, Sheng; Mason, Christopher E

    2014-01-01

    Posttranscriptionally modified nucleosides in RNA play integral roles in the cellular control of biological information that is encoded in DNA. The modifications of RNA span all three phylogenetic domains (Archaea, Bacteria, and Eukarya) and are pervasive across RNA types, including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and (less frequently) small nuclear RNA (snRNA) and microRNA (miRNA). Nucleotide modifications are also one of the most evolutionarily conserved properties of RNAs, and the sites of modification are under strong selective pressure. However, many of these modifications, as well as their prevalence and impact, have only recently been discovered. Here, we examine both labile and permanent modifications, from simple methylation to complex transcript alteration (RNA editing and intron retention); detail the models for their processing; and highlight remaining questions in the field of the epitranscriptome.

  5. Herbal formula menoprogen alters insulin-like growth factor-1 and insulin-like growth factor binding protein-1 levels in the serum and ovaries of an aged female rat model of menopause.

    PubMed

    Wei, Min; Zheng, Sheng Z; Lu, Ye; Liu, Daniel; Ma, Hong; Mahady, Gail B

    2015-10-01

    Menoprogen (MPG), a traditional Chinese medicine formula for menopause, improves menopausal symptoms; however, its mechanism remains unknown. Previous studies have shown that MPG is not directly estrogenic; thus, the goal of this study was to investigate the effects of MPG on insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-1 (IGFBP-1) levels in an aged female rat model of menopause. In a six-arm study, 14-month-old female Sprague-Dawley rats (n = 8 per arm) were randomly divided into the following groups: untreated aged, 17β-estradiol-treated aged (estradiol [E2]), and three arms with increasing doses of MPG (162, 324, or 648 mg/kg/d). The sixth arm contained 4-month-old female Sprague-Dawley rats as a normal comparison group. Four weeks after MPG or E2 administration, animals were killed after blood draws, and ovarian tissues were excised. Levels of E2 and progesterone (P4) were determined by radioimmunoassay. Serum and ovarian tissue levels of IGF-1, IGFBP-1, and IGF-1 receptor were determined by enzyme-linked immunosorbent assay. Compared with the normal group, aged rats had significantly reduced serum levels of E2, P4, and IGF-1, and increased serum and ovarian tissue levels of IGFBP-1. MPG restored serum IGF-1 and IGFBP-1 levels and down-regulated ovarian levels of IGFBP-1, which were closely related to increases in E2 and P4 levels in aged rats. No significant differences in either IGF-1 or IGFBP-1 were observed between the three doses of MPG. MPG exerts a direct in vivo effect on aged female rats by positively regulating serum and ovarian IGF-1 and IGFBP-1 levels.

  6. Epigenetic modifications in rheumatoid arthritis.

    PubMed

    Strietholt, Simon; Maurer, Britta; Peters, Marvin A; Pap, Thomas; Gay, Steffen

    2008-01-01

    Over the last decades, genetic factors for rheumatoid diseases like the HLA haplotypes have been studied extensively. However, during the past years of research, it has become more and more evident that the influence of epigenetic processes on the development of rheumatic diseases is probably as strong as the genetic background of a patient. Epigenetic processes are heritable changes in gene expression without alteration of the nucleotide sequence. Such modifications include chromatin methylation and post-translational modification of histones or other chromatin-associated proteins. The latter comprise the addition of methyl, acetyl, and phosphoryl groups or even larger moieties such as binding of ubiquitin or small ubiquitin-like modifier. The combinatory nature of these processes forms a complex network of epigenetic modifications that regulate gene expression through activation or silencing of genes. This review provides insight into the role of epigenetic alterations in the pathogenesis of rheumatoid arthritis and points out how a better understanding of such mechanisms may lead to novel therapeutic strategies.

  7. Epigenetic modifications as novel therapeutic targets for Huntington's disease.

    PubMed

    Wang, Fengli; Fischhaber, Paula L; Guo, Caixia; Tang, Tie-Shan

    2014-06-01

    Huntington's disease is a late-onset, autosomal dominant neurodegenerative disorder characterized by motor, cognitive and psychiatric symptomatology. The earliest stage of Huntington's disease is marked by alterations in gene expression, which partially results from dysregulated epigenetic modifications. In past decades, altered epigenetic markers including histone modifications (acetylation, methylation, ubiquitylation and phosphorylation) and DNA modifications (cytosine methylation and hydroxymethylation) have been reported as important epigenetic features in patients and multiple animal models of Huntington's disease. Drugs aimed to correct some of those alterations have shown promise in treating Huntington's disease. This article discusses the field of epigenetics for potential Huntington's disease interventions and presents the most recent findings in this area.

  8. Modification of chemotherapy by nitroimidazoles

    SciTech Connect

    Siemann, D.W.

    1984-09-01

    The potentiation of chemotherapeutic agents by radiation sensitizers has been extensively studied for several years. There is little doubt that the effectiveness of certain anti-cancer drugs, primarily alkylating agents, can readily be enhanced both in vitro and in vivo through the addition of a sensitizer. While enhanced effects have been observed in certain critical normal tissues, in general most animal model studies have demonstrated a therapeutic gain at large sensitizer doses. This approach to combination therapies therefore appears promising. Yet many questions concerning the interaction between chemotherapeutic agents and radiosensitizers, particularly in the aspects of modification of chemotherapy by nitroimidazoles are reviewed and discussed. These address the importance in chemopotentiation of (i) hypoxia, (ii) alterations in DNA damage and/or repair, (iii) depletion of intracellular sulfhydryls and (iv) modification of drug pharmacokinetics.

  9. Medicinal values of fruit peels from Citrus sinensis, Punica granatum, and Musa paradisiaca with respect to alterations in tissue lipid peroxidation and serum concentration of glucose, insulin, and thyroid hormones.

    PubMed

    Parmar, Hamendra Singh; Kar, Anand

    2008-06-01

    Peel extracts from Citrus sinensis, Punica granatum, and Musa paradisiaca were investigated for their effects on tissue lipid peroxidation (LPO) and on the concentration of thyroid hormones, insulin, and glucose in male rats. In vitro inhibition of H(2)O(2)-induced LPO in red blood cells of rats by 0.25, 0.50, 1.0, and 2.0 microg/mL C. sinensis, P. granatum, and M. paradisiaca peel extracts was observed in a dose-specific manner. Maximum inhibition was observed at 0.50 microg/mL C. sinensis, 2.0 microg/mL P. granatum, and 1.0 microg/mL M. paradisiaca. In the in vivo investigation, out of four different concentrations of each peel extract, 25, 200, and 100 mg/kg C. sinensis, P. granatum, and M. paradisiaca, respectively, were found to maximally inhibit hepatic LPO. The most effective doses were further evaluated for effects on serum triiodothyronine (T(3)), thyroxine (T(4)), insulin, and glucose concentrations. C. sinensis exhibited antithyroidal, hypoglycemic, and insulin stimulatory activities, in addition to inhibition of LPO, as it significantly decreased the serum T(4) (P < .05) and glucose (P < .001) concentrations with a concomitant increase in insulin levels (P < .05). P. granatum decreased LPO in hepatic, cardiac, and renal tissues (P < .01, P < .001, and P < .05, respectively) and serum glucose concentration (P < .01). M. paradisiaca strongly inhibited the serum level of thyroid hormones (P < .01 for both T(3) and T(4)) but increased the level of glucose (P < .05). These findings reveal the hitherto unknown potential of the tested peel extracts in the regulation of thyroid function and glucose metabolism. Besides antiperoxidative activity, C. sinensis extract has antithyroidal, hypoglycemic, and insulin stimulatory properties, which suggest its potential to ameliorate both hyperthyroidism and diabetes mellitus.

  10. Lifestyle modification and endothelial function in obese subjects.

    PubMed

    Hamdy, Osama

    2005-03-01

    The metabolic syndrome is a cluster of metabolic and vascular abnormalities that include central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk of coronary and cerebral vascular disease. These metabolic and vascular abnormalities are the main cause of cardiovascular mortality in western societies. Endothelial dysfunction, an early step in the development of atherosclerosis, has been reported in obese nondiabetic individuals and in patients with Type 2 diabetes. It has also been observed in individuals at high risk for Type 2 diabetes, including those with impaired glucose tolerance and the normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence points to adipocytes as a complex and active endocrine tissue whose secretory products, including free fatty acids and several cytokines (i.e., leptin, adiponectin, tissue necrosis factor-alpha, interleukin-6, and resistin) play a major role in the regulation of human metabolic and vascular biology. These adipocytokines have been claimed to be the missing link between insulin resistance and cardiovascular disease. Interventions designed to improve endothelial and/or adipose-tissue functions may reduce cardiovascular events in obese individuals with either the metabolic syndrome or Type 2 diabetes. Lifestyle modification in the form of caloric restriction and increased physical activity are the most common modalities used for treating those individuals at risk and is unanimously agreed to be the initial step in managing Type 2 diabetes. Several recent studies have demonstrated favorable impacts of lifestyle modifications in improving endothelial function and insulin sensitivity, in addition to altering serum levels of adipocytokines and possibly reducing cardiovascular events. This review discusses current knowledge of the role of lifestyle modifications in ameliorating cardiovascular risk in obese subjects with

  11. Protein modification by adenine propenal.

    PubMed

    Shuck, Sarah C; Wauchope, Orrette R; Rose, Kristie L; Kingsley, Philip J; Rouzer, Carol A; Shell, Steven M; Sugitani, Norie; Chazin, Walter J; Zagol-Ikapitte, Irene; Boutaud, Olivier; Oates, John A; Galligan, James J; Beavers, William N; Marnett, Lawrence J

    2014-10-20

    Base propenals are products of the reaction of DNA with oxidants such as peroxynitrite and bleomycin. The most reactive base propenal, adenine propenal, is mutagenic in Escherichia coli and reacts with DNA to form covalent adducts; however, the reaction of adenine propenal with protein has not yet been investigated. A survey of the reaction of adenine propenal with amino acids revealed that lysine and cysteine form adducts, whereas histidine and arginine do not. N(ε)-Oxopropenyllysine, a lysine-lysine cross-link, and S-oxopropenyl cysteine are the major products. Comprehensive profiling of the reaction of adenine propenal with human serum albumin and the DNA repair protein, XPA, revealed that the only stable adduct is N(ε)-oxopropenyllysine. The most reactive sites for modification in human albumin are K190 and K351. Three sites of modification of XPA are in the DNA-binding domain, and two sites are subject to regulatory acetylation. Modification by adenine propenal dramatically reduces XPA's ability to bind to a DNA substrate.

  12. Serum N-glycome characterization and anti-carbohydrate antibody profiling in oral squamous cell carcinoma patients

    PubMed Central

    Chang, Su-Chieh; Wang, Rei-Jing; Hung, Ling-Yi; Fang, Po-Jan; Tang, Wei-Chien; Yu, Peiwen

    2017-01-01

    Glycosylation is a protein post translational modification which plays important role in protein function, stabilization, trafficking, and turnover. Alteration of protein glycosylation is a common phenomenon during tumor progression, migration, invasion, angiogenesis, as well as metastasis. Hence, aberrant glycan structures and the induced corresponding anti-carbohydrate antibodies are potential biomarkers for cancer diagnosis. In this study, serum N-glycomes and anti-carbohydrate antibodies from normal populations and oral squamous cell carcinoma (OSCC) patients were investigated. Total serum proteins were lyophilized and subjected to chemical reduction, alkylation and trypsin digestion. The N-glycans were released, purified, permethylated, and analyzed using MALDI-TOF-Mass spectrometry. In addition, the serum anti-carbohydrate antibody profiles were also investigated by carbohydrate microarray. We found that the relative abundances of seven N-glycans were decreased or increased in serum of OSCC with diagnostic accuracy greater than 75%. The relative abundances of total tri-antennary and tetra-antennary glycans with varying degrees of fucosylation and sialylation were also increased in serum N-glycomes of OSCC. In an independent validation group of forty-eight OCCC patients, most of the high-molecular weight serum N-glycans showed significantly high sensitivity and specificity according to the identified cutoff values. Furthermore, the serum levels of two IgM antibodies were elevated accompanied with the decreased levels of nine IgG antibodies in patient serum. Taken together, these serum N-glycans and antibodies identified in this study should be considered as the candidates of potential biomarkers for OSCC diagnosis. PMID:28594851

  13. Behavior Modification is not...

    ERIC Educational Resources Information Center

    Tawney, James W.; And Others

    1973-01-01

    Identified are misconceptions of behavior modification procedures according to which behavior modification is connected mistakenly with noncontingent reinforcement, partial change of a teacher's behavior, decelerations of inappropriate behaviors only, dependency producing technology, teacher dominated activity, a single type of classroom…

  14. Behavior Modification in Coaching.

    ERIC Educational Resources Information Center

    Lynch, Annette Rutt; Stillman, Stephen M.

    1979-01-01

    An example of behavior modification used in athletic coaching is presented. The case study involves a member of a women's basketball team and details the use of behavior modification for both weight reduction and skill improvement. (JMF)

  15. Behavior Modification is not...

    ERIC Educational Resources Information Center

    Tawney, James W.; And Others

    1973-01-01

    Identified are misconceptions of behavior modification procedures according to which behavior modification is connected mistakenly with noncontingent reinforcement, partial change of a teacher's behavior, decelerations of inappropriate behaviors only, dependency producing technology, teacher dominated activity, a single type of classroom…

  16. Readers of histone modifications

    PubMed Central

    Yun, Miyong; Wu, Jun; Workman, Jerry L; Li, Bing

    2011-01-01

    Histone modifications not only play important roles in regulating chromatin structure and nuclear processes but also can be passed to daughter cells as epigenetic marks. Accumulating evidence suggests that the key function of histone modifications is to signal for recruitment or activity of downstream effectors. Here, we discuss the latest discovery of histone-modification readers and how the modification language is interpreted. PMID:21423274

  17. Mutant p53 proteins alter cancer cell secretome and tumour microenvironment: Involvement in cancer invasion and metastasis.

    PubMed

    Cordani, Marco; Pacchiana, Raffaella; Butera, Giovanna; D'Orazi, Gabriella; Scarpa, Aldo; Donadelli, Massimo

    2016-07-01

    An ever-increasing number of studies highlight the role of mutant p53 proteins in the alteration of cancer cell secretome and in the modification of tumour microenvironment, sustaining an invasive phenotype of cancer cell. The knowledge of the molecular mechanisms underlying the interplay between mutant p53 proteins and the microenvironment is becoming fundamental for the identification of both efficient anticancer therapeutic strategies and novel serum biomarkers. In this review, we summarize the novel findings concerning the regulation of secreted molecules by cancer cells bearing mutant TP53 gene. In particular, we highlight data from available literature, suggesting that mutant p53 proteins are able to (i) alter the secretion of enzymes involved in the modulation of extracellular matrix components; (ii) alter the secretion of inflammatory cytokines; (iii) increase the extracellular acidification; and (iv) regulate the crosstalk between cancer and stromal cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. A hyperspectral and toxicological analysis of protein corona impact on silver nanoparticle properties, intracellular modifications, and macrophage activation

    PubMed Central

    Shannahan, Jonathan H; Podila, Ramakrishna; Brown, Jared M

    2015-01-01

    The inevitable adsorption of biomolecules on nanomaterials results in the formation of a protein corona (PC), which modifies the nanoparticle (NP)–cell interface resulting in modified uptake, activity, clearance, and toxicity. While the physicochemical properties of the NP govern the composition of PC, the formation of PC in turn alters the characteristics of the NP by imparting a new unique “biological” identity. To assess how the PC influences AgNP properties, intracellular modifications, and cellular responses, we utilized a combination of hyperspectral and toxicological analyses. AgNPs were coated with a complex PC (multiple proteins, eg, 10% fetal bovine serum) or a simple PC (single protein, eg, bovine serum albumin [BSA]) and evaluated by hyperspectral and dynamic light scattering for modifications in AgNP properties. Mouse macrophages were exposed to AgNPs with PCs and examined for differences in uptake, cytotoxicity, and cell activation. Hyperspectral imaging revealed intracellular modifications to AgNPs that were found to spectrally match alterations in AgNPs following incubation in lysosomal fluid. Addition of the PC influenced AgNP uptake and cytotoxicity; however, hydrodynamic size and surface charge did not contribute to these responses. Assessments of all endpoints demonstrated differences between complex and BSA PC, suggesting that these responses are not purely driven by the primary protein component of the complex PC (ie, BSA). Alterations in cellular–NP uptake/interactions may be driven through cell surface receptor recognition of protein constituents that make up the PC rather than the physicochemical differences in AgNPs. PMID:26508856

  19. Novel utilization of serum in tissue decellularization.

    PubMed

    Gui, Liqiong; Chan, Stephen A; Breuer, Christopher K; Niklason, Laura E

    2010-04-01

    Decellularization of native tissues is a promising technique with numerous applications in tissue engineering and regenerative medicine. However, there are various limitations of currently available decellularization methods, such as alteration of extracellular matrix mechanics and restricted use on certain tissues. This study was conducted to explore the effect of serum on the decellularization of various types of tissues. Fetal bovine serum-containing cell culture medium endothelial growth media-2 removed DNA but not cellular beta-actin from human umbilical artery after detergent treatment, without compromising the tissue mechanical strength assessed by burst pressure. In addition, the effect of serum-containing endothelial growth media-2 on DNA removal was replicated in other types of tissues such as tissue-engineered vessels and myocardium. Other types of serum, including human serum, were also shown to remove DNA from detergent-pretreated tissues. In conclusion, we describe a novel utilization of serum that may have broad applications in tissue decellularization.

  20. Modification of the theophylline radioimmunoassay

    SciTech Connect

    Reed, R.C.; Burkett, E.S.; Myers, C.M.; Schwartz, H.J.; Salazar, R.

    1984-01-01

    The routine utilization of a commercially available radioimmunoassay (RIA) for theophylline (GammaDab), although reliable, is currently prohibited by the high cost of the reagents. In an effort to reduce these costs we have diluted the (/sup 125/I)theophylline tracer and theophylline antiserum reagents by one-half, contrary to the manufacturer's recommendations. We have demonstrated that an excellent correlation exists (r . 0.968) between our modified RIA method and a conventional high-performance liquid chromatographic technique, despite reagent dilution. Accordingly, our reagent costs have been reduced by half. We conclude that the GammaDab kit reagents can be diluted twofold and still provide an accurate determination of serum theophylline. We must also emphasize that any further alteration(s) of this theophylline RIA procedure would require a thorough evaluation before its routine use could be substantiated.

  1. Microneutralization assay for swine influenza virus in swine serum

    USDA-ARS?s Scientific Manuscript database

    The microneutralization (MN) assay is a modification of the serum virus neutralization assay and is a serological test to detect the presence of functional systemic antibodies that prevent infectivity of virus. When infectious virus is mixed with serum antibody, the virus infectivity can be "neutral...

  2. 48 CFR 217.7103-6 - Modification of master agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise...

  3. Spectroscopic Studies on the Molecular Ageing of Serum Albumin.

    PubMed

    Chudzik, Mariola; Maciążek-Jurczyk, Małgorzata; Pawełczak, Bartosz; Sułkowska, Anna

    2016-12-27

    Pathological states in the organism, e.g., renal or hepatic diseases, cataract, dysfunction of coronary artery, diabetes mellitus, and also intensive workout, induce the structural modification of proteins called molecular ageing or N-A isomerization. The aim of this study was to analyze the structural changes of serum albumin caused by alkaline ageing using absorption, spectrofluorescence, and circular dichroism spectroscopy. The N-A isomerization generates significant changes in bovine (BSA) and human (HSA) serum albumin subdomains-the greatest changes were observed close to the tryptophanyl (Trp) and tyrosyl (Tyr) residue regions while a smaller change was observed in phenyloalanine (Phe) environment. Moreover, the changes in the polarity of the Trp neighborhood as well as the impact of the ageing process on α-helix, β-sheet content, and albumin molecule rotation degree have been analyzed. Based on the spectrofluorescence study, the alterations in metoprolol binding affinity to the specific sites that increase the toxicity of the drug were investigated.

  4. Protein electrophoresis - serum

    MedlinePlus

    ... Hemolysis Hyperimmunization Immunoelectrophoresis - blood Immunofixation blood test Liver disease Malignancy Malnutrition Nephrotic syndrome Rheumatoid arthritis Serum globulin electrophoresis Serum iron test Systemic lupus erythematosus ...

  5. Effect of supplemental vitamin D and calcium on serum sclerostin levels

    USDA-ARS?s Scientific Manuscript database

    Serum sclerostin has been inversely associated with serum 25OHD concentration, but the effect of supplementation with vitamin D and calcium on serum sclerostin is unknown. This study was done to determine whether supplementation altered serum sclerostin levels in healthy older adults. We measured s...

  6. Application of metabolomics based on direct mass spectrometry analysis for the elucidation of altered metabolic pathways in serum from the APP/PS1 transgenic model of Alzheimer's disease.

    PubMed

    González-Domínguez, Raúl; García-Barrera, Tamara; Vitorica, Javier; Gómez-Ariza, José Luis

    2015-03-25

    Metabolomic analysis of brain tissue from transgenic mouse models of Alzheimer's disease has demonstrated a great potential for the study of pathological mechanisms and the development of new therapies and biomarkers for diagnosis. However, in order to translate these investigations to the clinical practice it is necessary to corroborate these findings in peripheral samples. To this end, this work considers the application of a novel metabolomic platform based on the combination of a two-steps extraction procedure with complementary analysis by direct infusion electrospray mass spectrometry and flow infusion atmospheric pressure photoionization mass spectrometry for a holistic investigation of metabolic abnormalities in serum samples from APP/PS1 mice. A number of metabolites were found to be perturbed in this mouse model, including increased levels of di- and tri-acylglycerols, eicosanoids, inosine, choline and glycerophosphoethanolamine; reduced content of cholesteryl esters, free fatty acids, lysophosphocholines, amino acids, energy-related metabolites, phosphoethanolamine and urea, as well as abnormal distribution of phosphocholines depending on the fatty acid linked to the molecular moiety. This allowed the elucidation of possible pathways disturbed underlying to disease (abnormal homeostasis of phospholipids leading to membrane breakdown, energy-related failures, hyperammonemia and hyperlipidemia, among others), thus demonstrating the utility of peripheral samples to investigate pathology in the APP/PS1 model.

  7. Modifications of mitosis

    SciTech Connect

    1993-12-31

    Chapter 15, discusses modifications of mitosis, including endoreduplication, polyteny, endomitosis, C-mitosis, restitution, amitosis and multipolar mitoses. Apart from multipolar mitosis, all other mitotic modifications are characterized by an absent or defective spindle, and in most cases these result in the duplication of the chromosome number. 29 refs., 4 figs.

  8. Permit application modifications

    SciTech Connect

    1995-11-01

    This document contains the Permit Application Modifications for the Y-12 Industrial Landfill V site on the Oak Ridge Reservation. These modifications include the assessment of stability of the proposed Landfill V under static and loading conditions. Analyses performed include the general slope stability, veneer stability of the bottom liner and cover system, and a liquefaction potential assessment of the foundation soils.

  9. Basic Behavior Modification.

    ERIC Educational Resources Information Center

    Mehrabian, Albert

    This monograph examines the component parts of behavior modification, initially defining the problem behavior and drawing a difference between specific observable behaviors (the focus of behavior modification), and the interest of Freudian and similar psychologies in unobservable internal processes. Instrumental learning related to shaping in…

  10. CEL-2000: A therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model.

    PubMed

    Zimmerman, Daniel H; Taylor, Patricia; Bendele, Alison; Carambula, Roy; Duzant, Yvonne; Lowe, Valeria; O'Neill, Sean P; Talor, Eyal; Rosenthal, Kenneth S

    2010-04-01

    The mouse model of collagen induced arthritis (CIA) effectively mimics human disease and thus is useful for testing and development of rheumatoid arthritis (RA) therapies. We developed a Ligand Epitope Antigen Presentation System (LEAPS) peptide hetero-conjugate vaccine containing an epitope of human collagen type II (CEL-2000) that acted as a therapeutic vaccine in the collagen induced arthritis (CIA) mouse model. LEAPS technology converts a small peptide containing a disease specific epitope into an immunogen by attaching it to an immune or T cell binding peptide (I/TCBL). For CEL-2000, a peptide from human collagen type II (254-273) is attached to the I/TCBL peptide from human beta2 microglobulin (J). Treatment with CEL-2000 limited disease (CIA) progression, as demonstrated by reduced Arthritic Index (AI) score, and footpad swelling. Efficacy was confirmed by histopathological microscopic examination of tissues at the end of the study. CEL-2000 limited disease progression as well or better than the etanercept (Enbrel) therapeutic control with significantly better histopathological results than the etanercept treated mice. Most interestingly, CEL-2000 therapy modulated serum cytokine levels with an increase in IL-12p70 and IL-10, which are not seen with etanercept therapy, and reduced IL-17 and TNF-alpha, also seen with etanercept, among other cytokines studied. CEL-2000 was safe and well tolerated for the mice that received 5 injections given every 2weeks in a 90day study supporting its potential usage for long term therapy. These studies demonstrate that fewer treatments with CEL-2000 provide therapy at least as effective as etanercept by specifically modulating the disease producing autoimmune response.

  11. Characterizing serum metabolic alterations of Alzheimer's disease and intervention of Shengmai-San by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry.

    PubMed

    Lu, Shengwen; Han, Ying; Chu, Hang; Kong, Ling; Zhang, Aihua; Yan, Guangli; Sun, Hui; Wang, Ping; Wang, Xijun

    2017-04-05

    Alzheimer's disease (AD) is a chronic and multi-factor-induced neurodegenerative disorder. The development of a single-target treatment strategy for AD has not been successful. Shengmai-San (SMS), a traditional Chinese medicine containing multi-active components, has been reported to be effective for treating AD. However, the mechanism of SMS is still unclear, and as a multicomponent combination therapy, there is a lack of appropriate evaluation. Thereby, metabolomics was applied to investigate the multi-target intervention of SMS by monitoring the fold changes of metabolites in serum. An AD model was successfully replicated by treating rats with oral aluminum chloride (AlCl3) and an intraperitoneal injection of d-galactose (d-gal) for 105 days. The intervention group was treated with SMS during the whole modeling process. The results of classical experiments showed that SMS could alleviate Aβ1-40 deposition, protect neurons in the CA3 region of the hippocampus and improve spatial learning and memory impairment compared with the model group. Based on these curative effects, a metabolomics study was implemented using the UPLC-Q/TOF-MS method. A heatmap of AD-associated metabolites (P < 0.05) was set up to target the most relevant metabolic network and to evaluate the comprehensive effects of SMS. Based on this AD-associated metabolic network, the total regulation-of-metabolites' coverage rate of SMS was 51.35% and the gross metabolites' recovery proportion was 72.32%. Lipid peroxidation was the main mechanism of SMS intervention in AD, including inhibition of the generation of linoleic acid hydroperoxides, such as 13-HPODE, 9-HPODE and 9-OxoODE.

  12. Serum selenium assay following serum ferritin assay

    SciTech Connect

    Stevens, R.G.; Morris, J.S.; Hann, H.L.; Pulsipher, B.; Stahlhut, M.W.

    1986-08-01

    Stored serum samples can be an important research resource into the etiology of cancer. These sera cannot be replaced and should therefore be used to best advantage. In previous epidemiologic studies, only single serum constituents have been assayed in individual serum samples. For example, serum ferritin has been examined in samples stored for as long as 10 years at -20C for a possible relation with general mortality (1) and cancer death (2). Ferritin is the tissue iron-storage protein and is therefore subject to denaturation. Serum selenium has also been examined in relation to cancer risk in a prospective manner by using stored frozen serum samples (3, 4). The interactions of a variety of serum factors in relation to cancer risk would be a desirable research goal, except that the amounts of serum typically available in frozen serum banks are less than 1 ml. It was the purpose of this investigation to determine if a radioimmunoassay for ferritin affected a subsequent neutron activation assay for selenium on the same 0.1 ml serum sample.

  13. Regulation of the cardiac Na+ channel NaV1.5 by post-translational modifications.

    PubMed

    Marionneau, Céline; Abriel, Hugues

    2015-05-01

    The cardiac voltage-gated Na(+) channel, Na(V)1.5, is responsible for the upstroke of the action potential in cardiomyocytes and for efficient propagation of the electrical impulse in the myocardium. Even subtle alterations of Na(V)1.5 function, as caused by mutations in its gene SCN5A, may lead to many different arrhythmic phenotypes in carrier patients. In addition, acquired malfunctions of Na(V)1.5 that are secondary to cardiac disorders such as heart failure and cardiomyopathies, may also play significant roles in arrhythmogenesis. While it is clear that the regulation of Na(V)1.5 protein expression and function tightly depends on genetic mechanisms, recent studies have demonstrated that Na(V)1.5 is the target of various post-translational modifications that are pivotal not only in physiological conditions, but also in disease. In this review, we examine the recent literature demonstrating glycosylation, phosphorylation by Protein Kinases A and C, Ca(2+)/Calmodulin-dependent protein Kinase II, Phosphatidylinositol 3-Kinase, Serum- and Glucocorticoid-inducible Kinases, Fyn and Adenosine Monophosphate-activated Protein Kinase, methylation, acetylation, redox modifications, and ubiquitylation of Na(V)1.5. Modern and sensitive mass spectrometry approaches, applied directly to channel proteins that were purified from native cardiac tissues, have enabled the determination of the precise location of post-translational modification sites, thus providing essential information for understanding the mechanistic details of these regulations. The current challenge is first, to understand the roles of these modifications on the expression and the function of Na(V)1.5, and second, to further identify other chemical modifications. It is postulated that the diversity of phenotypes observed with Na(V)1.5-dependent disorders may partially arise from the complex post-translational modifications of channel protein components.

  14. Epigenetic Modifications of Major Depressive Disorder

    PubMed Central

    Saavedra, Kathleen; Molina-Márquez, Ana María; Saavedra, Nicolás; Zambrano, Tomás; Salazar, Luis A.

    2016-01-01

    Major depressive disorder (MDD) is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders. PMID:27527165

  15. Epigenetic Modifications of Major Depressive Disorder.

    PubMed

    Saavedra, Kathleen; Molina-Márquez, Ana María; Saavedra, Nicolás; Zambrano, Tomás; Salazar, Luis A

    2016-08-05

    Major depressive disorder (MDD) is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders.

  16. 49 CFR 180.513 - Repairs, alterations, conversions, and modifications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... § 171.7 of this subchapter). (b) Unless the exterior tank car shell or interior tank car jacket has a protective coating, after a repair that requires the complete removal of the tank car jacket, the exterior tank car shell and the interior tank car jacket must have a protective coating applied to prevent the...

  17. 49 CFR 180.513 - Repairs, alterations, conversions, and modifications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... this subchapter). (b) Unless the exterior tank car shell or interior tank car jacket has a protective coating, after a repair that requires the complete removal of the tank car jacket, the exterior tank car shell and the interior tank car jacket must have a protective coating applied to prevent the...

  18. Epigenetic alterations in depression and antidepressant treatment.

    PubMed

    Menke, Andreas; Binder, Elisabeth B

    2014-09-01

    Epigenetic modifications control chromatin structure and function, and thus mediate changes in gene expression, ultimately influencing protein levels. Recent research indicates that environmental events can induce epigenetic changes and, by this, contribute to long-term changes in neural circuits and endocrine systems associated with altered risk for stress-related psychiatric disorders such as major depression. In this review, we describe recent approaches investigating epigenetic modifications associated with altered risk for major depression or response to antidepressant drugs, both on the candidate gene levels as well as the genome-wide level. In this review we focus on DNA methylation, as this is the most investigated epigenetic change in depression research.

  19. Accurate determination of serum ASAT isoenzymes.

    PubMed

    Konttinen, A; Ojala, K

    1978-01-01

    An improved electrophoretic modification for measuring aspartate aminotransferase (ASAT) isoenzymes is presented. This method fulfils the clinical requirements for sensitivity and allows the detection of 1 U/l mitochondria ASAT activity at 25 degree C. The procedure is relatively simple, requiring about one hour for a series of 8 determinations. Mitochondrial ASAT activity was found in all patients suffering from acute myocardial infarction pathological activity was observed for several days longer than that of total serum ASAT enzyme. None of the 25 healthy people studied had mitochondrial ASAT in their serum.

  20. On the genetic modification of psychology, personality, and behavior.

    PubMed

    Neitzke, Alex B

    2012-12-01

    I argue that the use of heritable modifications for psychology, personality, and behavior should be limited to the reversal or prevention of relatively unambiguous instances of pathology or likely harm (e.g. sociopathy). Most of the likely modifications of psychological personality would not be of this nature, however, and parents therefore should not have the freedom to make such modifications to future children. I argue by examining the viewpoints of both the individual and society. For individuals, modifications would interfere with their capacity for self-determination in a way that undermines the very concept of self-determination. I argue that modification of psychology and personality is unlike present parenting in morally significant ways. For society, modification offers a medium for power to manipulate the makeup of persons and populations, possibly causing biological harm to the species and altering our conceptions of social responsibility.

  1. Influence of cattle temperament on blood serum fatty acid content

    USDA-ARS?s Scientific Manuscript database

    Cattle temperament has been reported to influence blood metabolites. Specifically, temperament was related with increased circulation of serum NEFA, decreased blood urea nitrogen, and reduced insulin sensitivity. Metabolic alterations such as these may impact cattle immune function, performance trai...

  2. Metal-catalyzed oxidation of human serum albumin: conformational and functional changes. Implications in protein aging.

    PubMed

    Meucci, E; Mordente, A; Martorana, G E

    1991-03-15

    Mild oxidative stress, as elicited by ascorbate, oxygen, and trace metals, affects the binding properties of human serum albumin via purely conformational changes. In fact, no gross alteration can be observed in the electrophoretic and chromatographic patterns of albumin, whereas localized modifications are indicated by the changes in absorption and fluorescence spectra and in polarization degree. The oxidized protein presents a small increase of bityrosine production and a time-dependent increase in the content of carbonyl groups, whereas proteolytic susceptibility is unchanged. A higher affinity for cis-parinaric acid and a slight loss of solubility in high salt indicate a greater surface hydrophobicity. Pinpoint denaturation of the albumin molecule is also suggested by a decreased "esterase" activity in the presence of p-nitrophenyl acetate. Conformational stability evaluated through thermal shock and addition of moderate amounts of guanidine indicate that the oxidized protein is more heat-resistant, less flexible, and more rigid than the native one. Although limited, structural damages afforded by the oxidative stress cause alterations of albumin binding properties as documented by experiments with probes and physiological ligands. The loss of biological activity of human serum albumin induced by ascorbate system appears of medical relevance, because it can affect drug metabolism and particularly drug tolerance in the elderly.

  3. Enzymatic modification of schizophyllan

    USDA-ARS?s Scientific Manuscript database

    An enzymatic method was developed for the progressive modification of the polysaccharide schizophyllan. Fungal strains Hypocrea nigricans NRRL 62555, Penicillium crustosum NRRL 62558, and Penicillium simplicissimum NRRL 62550 were previously identified as novel sources of ß-endoglucanase with specif...

  4. Calorimetric markers of Bence Jones and nonsecretory multiple myeloma serum proteome.

    PubMed

    Todinova, Svetla; Krumova, Sashka; Radoeva, Ralitsa; Gartcheva, Lidia; Taneva, Stefka G

    2014-12-16

    The present work provides a thermodynamic description of blood serum from patients diagnosed with Bence Jones myeloma (BJMM) and nonsecretory myeloma (NSMM) by means of differential scanning calorimetry (DSC), serum protein electrophoresis, and free light chain assay. Specific alterations in the thermodynamic behavior of both BJMM and NSMM proteome have been revealed. On the basis of the transition temperature of the main transition in the calorimetric profiles and the shape similarity criterion, we defined BJMM and NSMM sets/subsets of thermograms with very similar thermodynamic features. We show that some of the BJMM and NSMM subsets correlate with previously defined secretory myeloma subsets (Todinova et al. Anal. Chem. 2011, 83, 7992). The established analogies strongly suggest that common molecular markers contribute to the calorimetric profiles of the different, secretory and nonsecretory, myeloma types; our data show robust evidence that these are ligands stabilizing the major serum proteins. We demonstrate that the DSC approach might be highly beneficial, especially for NSMM patients, since the characteristic modifications in the DSC profiles might serve as calorimetric markers when no monoclonal proteins can be detected in the bloodstream and the diagnosis heavily relies on invasive methods.

  5. Surface modification of solids

    SciTech Connect

    Appleton, B.R.

    1984-05-01

    The use of ion beam and pulsed laser processing is reviewed for the near-surface modification of a wide range of materials. The techniques of ion implantation doping, ion beam and laser mixing, and pulsed-laser annealing are stressed with particular emphasis on the nonequilibrium aspects of these processing techniques and on new materials properties which can result. Examples are presented illustrating the utility of these techniques for fundamental materials research as well as practical surface modifications.

  6. Epigenetics in the development, modification, and prevention of cardiovascular disease.

    PubMed

    Whayne, Thomas F

    2015-04-01

    Epigenetics has major relevance to all disease processes; cardiovascular (CV) disease and its related conditions are no exception. Epigenetics is defined as the study of heritable alterations in gene expression, or cellular phenotype, and goes far beyond a pure genetic approach. A more precise definition is that epigenetics represents all the meiotically and mitotically inherited changes in gene expression that are not encoded on the deoxyribonucleic acid (DNA) sequence itself. Major epigenetic mechanisms are modifications of histone proteins in chromatin and DNA methylation (which does not alter the DNA sequence). There is increasing evidence for the involvement of epigenetics in human disease such as cancer, inflammatory disease and CV disease. Other chronic diseases are also susceptible to epigenetic modification such as metabolic diseases including obesity, metabolic syndrome, and diabetes mellitus. There is much evidence for the modification of epigenetics by nutrition and exercise. Through these modifications, there is infinite potential for benefit for the fetus, the newborn, and the individual as well as population effects. Association with CV disease, including coronary heart disease and peripheral vascular disease, is evident through epigenetic relationships and modification by major CV risk factors such as tobacco abuse. Aging itself may be altered by epigenetic modification. Knowledge of epigenetics and its relevance to the development, modification, and prevention of CV disease is in a very preliminary stage but has an infinite future.

  7. Human Rights and Behavior Modification

    ERIC Educational Resources Information Center

    Roos, Philip

    1974-01-01

    Criticisms of behavior modification, which charge that it violates ethical and legal principles, are discussed and reasons are presented to explain behavior modification's susceptibility to attack. (GW)

  8. Serum herpes simplex antibodies

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003352.htm Serum herpes simplex antibodies To use the sharing features on this page, please enable JavaScript. Serum herpes simplex antibodies is a blood test that looks for ...

  9. Enzymatic modifications of exopolysaccharides enhance bacterial persistence

    PubMed Central

    Whitfield, Gregory B.; Marmont, Lindsey S.; Howell, P. Lynne

    2015-01-01

    Biofilms are surface-attached communities of bacterial cells embedded in a self-produced matrix that are found ubiquitously in nature. The biofilm matrix is composed of various extracellular polymeric substances, which confer advantages to the encapsulated bacteria by protecting them from eradication. The matrix composition varies between species and is dependent on the environmental niche that the bacteria inhabit. Exopolysaccharides (EPS) play a variety of important roles in biofilm formation in numerous bacterial species. The ability of bacteria to thrive in a broad range of environmental settings is reflected in part by the structural diversity of the EPS produced both within individual bacterial strains as well as by different species. This variability is achieved through polymerization of distinct sugar moieties into homo- or hetero-polymers, as well as post-polymerization modification of the polysaccharide. Specific enzymes that are unique to the production of each polymer can transfer or remove non-carbohydrate moieties, or in other cases, epimerize the sugar units. These modifications alter the physicochemical properties of the polymer, which in turn can affect bacterial pathogenicity, virulence, and environmental adaptability. Herein, we review the diversity of modifications that the EPS alginate, the Pel polysaccharide, Vibrio polysaccharide, cepacian, glycosaminoglycans, and poly-N-acetyl-glucosamine undergo during biosynthesis. These are EPS produced by human pathogenic bacteria for which studies have begun to unravel the effect modifications have on their physicochemical and biological properties. The biological advantages these polymer modifications confer to the bacteria that produce them will be discussed. The expanding list of identified modifications will allow future efforts to focus on linking these modifications to specific biosynthetic genes and biofilm phenotypes. PMID:26029200

  10. Serum sickness syndrome.

    PubMed

    Lin, R Y

    1986-01-01

    Numerous agents are known to cause serum sickness reactions. Although generally a benign disorder, serum sickness must be distinguished from various rheumatic and infectious disorders. The causative agent must be identified in order to avoid subsequent reactions. With the introduction of new drugs and biotechnically produced hormones and antibodies, new causes of serum sickness reactions are likely.

  11. Epigenetic alterations underlying autoimmune diseases.

    PubMed

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein

    2016-01-01

    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases.

  12. Readers of PCNA modifications.

    PubMed

    Ulrich, Helle D; Takahashi, Tomio

    2013-08-01

    The eukaryotic sliding clamp, proliferating cell nuclear antigen (PCNA), acts as a central coordinator of DNA transactions by providing a multivalent interaction surface for factors involved in DNA replication, repair, chromatin dynamics and cell cycle regulation. Posttranslational modifications (PTMs), such as mono- and polyubiquitylation, sumoylation, phosphorylation and acetylation, further expand the repertoire of PCNA's binding partners. These modifications affect PCNA's activity in the bypass of lesions during DNA replication, the regulation of alternative damage processing pathways such as homologous recombination and DNA interstrand cross-link repair, or impact on the stability of PCNA itself. In this review, we summarise our current knowledge about how the PTMs are "read" by downstream effector proteins that mediate the appropriate action. Given the variety of interaction partners responding to PCNA's modified forms, the ensemble of PCNA modifications serves as an instructive model for the study of biological signalling through PTMs in general.

  13. Results from the Atherosclerosis Risk in Communities study suggest that low serum magnesium is associated with incident kidney disease

    PubMed Central

    Tin, Adrienne; Grams, Morgan E.; Maruthur, Nisa M.; Astor, Brad C.; Couper, David; Mosley, Thomas H.; Selvin, Elizabeth; Coresh, Josef; Linda Kao, Wen Hong

    2014-01-01

    Low serum magnesium has been associated with kidney function decline in persons with diabetes as well as cardiovascular disease in the general population. Since the association of serum magnesium with incident kidney disease in the general population is unknown, we assessed this in 13,226 participants (aged 45 to 65) in the Atherosclerosis Risk in Communities study with baseline estimated glomerular filtration rate of at least 60 ml/min/1.73m2 in years 1987–89 and followed through 2010. The risks for incident chronic kidney disease (CKD) and end-stage renal disease (ESRD) associated with baseline total serum magnesium levels were evaluated using Cox regression. There were 1,965 CKD and 208 ESRD events during a median follow-up of 21 years. In adjusted analysis, low serum magnesium levels (0.7mmol/L or less) had significant associations with incident CKD and ESRD compared with the highest quartile with adjusted hazard ratio of 1.58 (95% CI: 1.35–1.87) for CKD and 2.39 (95% CI: 1.61–3.56) for ESRD. These associations remained significant after excluding users of diuretics and across subgroups stratified by hypertension, diabetes, and self-reported race. Thus, in a large sample of middle-aged adults, low total serum magnesium was independently associated with incident CKD and ESRD. Further studies are needed to determine whether modification of serum magnesium levels might alter subsequent incident kidney disease rates. PMID:25272232

  14. Alterations of lipid metabolism in Wilson disease

    PubMed Central

    2011-01-01

    Introduction Wilson disease (WD) is an inherited disorder of human copper metabolism, characterised by accumulation of copper predominantly in the liver and brain, leading to severe hepatic and neurological disease. Interesting findings in animal models of WD (Atp7b-/- and LEC rats) showed altered lipid metabolism with a decrease in the amount of triglycerides and cholesterol in the serum. However, serum lipid profile has not been investigated in large human WD patient cohorts to date. Patients and Methods This cohort study involved 251 patients examined at the Heidelberg and Dresden (Germany) University Hospitals. Patients were analysed on routine follow-up examinations for serum lipid profile, including triglycerides, cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL). Data on these parameters at time of diagnosis were retrieved by chart review where available. For statistical testing, patients were subgrouped by sex, manifestation (hepatic, neurological, mixed and asymptomatic) and treatment (D-penicillamine, trientine, zinc or combination). Results A significant difference in total serum cholesterol was found in patients with hepatic symptoms, which diminished under therapy. No alterations were observed for HDL, LDL and triglycerides. Conclusion Contradictory to previous reports using WD animal models (Atp7b-/- and LEC rats), the most obvious alteration in our cohort was a lower serum cholesterol level in hepatic-affected patients, which might be related to liver injury. Our data suggested unimpaired cholesterol metabolism in Wilson disease under therapy, independent of the applied medical treatment. PMID:21595966

  15. Programming for articularion modification.

    PubMed

    Gerber, A

    1977-02-01

    Within the past decade, principles and techniques of programmed instruction have been applied to the procedures of articulation modification in a number of preconstructed programs. The analysis of nine of these programs reveals that the majority of them are characterized by precisely stated objectives, ordered sequences of materials and procedures, clearly established criteria and rigorously controlled methods of reinforcement and recording of responses. Evaluation of the preconstructed programs raises some questions about the appropriateness of certain aspects of the technology to the process of articulation modification.

  16. Impact of protein modification on the protein corona on nanoparticles and nanoparticle-cell interactions.

    PubMed

    Treuel, Lennart; Brandholt, Stefan; Maffre, Pauline; Wiegele, Sarah; Shang, Li; Nienhaus, G Ulrich

    2014-01-28

    Recent studies have firmly established that cellular uptake of nanoparticles is strongly affected by the presence and the physicochemical properties of a protein adsorption layer around these nanoparticles. Here, we have modified human serum albumin (HSA), a serum protein often used in model studies of protein adsorption onto nanoparticles, to alter its surface charge distribution and investigated the consequences for protein corona formation around small (radius ∼5 nm), dihydrolipoic acid-coated quantum dots (DHLA-QDs) by using fluorescence correlation spectroscopy. HSA modified by succinic anhydride (HSAsuc) to generate additional carboxyl groups on the protein surface showed a 3-fold decreased binding affinity toward the nanoparticles. A 1000-fold enhanced affinity was observed for HSA modified by ethylenediamine (HSAam) to increase the number of amino functions on the protein surface. Remarkably, HSAsuc formed a much thicker protein adsorption layer (8.1 nm) than native HSA (3.3 nm), indicating that it binds in a distinctly different orientation on the nanoparticle, whereas the HSAam corona (4.6 nm) is only slightly thicker. Notably, protein binding to DHLA-QDs was found to be entirely reversible, independent of the modification. We have also measured the extent and kinetics of internalization of these nanoparticles without and with adsorbed native and modified HSA by HeLa cells. Pronounced variations were observed, indicating that even small physicochemical changes of the protein corona may affect biological responses.

  17. Mutant TP53 Posttranslational Modifications: Challenges and Opportunities

    PubMed Central

    Nguyen, Thuy-Ai; Menendez, Daniel; Resnick, Michael A.; Anderson, Carl W.

    2014-01-01

    The wild-type human p53 (TP53) tumor suppressor can be posttranslationally modified at over 60 of its 393 residues. These modifications contribute to changes in TP53 stability and in its activity as a transcription factor in response to a wide variety of intrinsic and extrinsic stresses in part through regulation of protein-protein and protein-DNA interactions. The TP53 gene frequently is mutated in cancers, and in contrast to most other tumor suppressors the mutations are mostly missense often resulting in the accumulation of mutant protein, which may have novel or altered functions. Most mutant TP53s can be posttranslationally modified at the same residues as in wild-type TP53. Strikingly, however, codons for modified residues are rarely mutated in human tumors, suggesting that TP53 modifications are not essential for tumor suppression activity. Nevertheless, these modifications might alter mutant TP53 activity and contribute to a gain-of-function leading to increased metastasis and tumor progression. Furthermore, many of the signal transduction pathways that result in TP53 modifications are altered or disrupted in cancers. Understanding the signaling pathways that result in TP53 modification and the functions of these modifications in both wild-type TP53 and its many mutant forms may contribute to more effective cancer therapies. PMID:24395704

  18. Mutant TP53 posttranslational modifications: challenges and opportunities.

    PubMed

    Nguyen, Thuy-Ai; Menendez, Daniel; Resnick, Michael A; Anderson, Carl W

    2014-06-01

    The wild-type (WT) human p53 (TP53) tumor suppressor can be posttranslationally modified at over 60 of its 393 residues. These modifications contribute to changes in TP53 stability and in its activity as a transcription factor in response to a wide variety of intrinsic and extrinsic stresses in part through regulation of protein-protein and protein-DNA interactions. The TP53 gene frequently is mutated in cancers, and in contrast to most other tumor suppressors, the mutations are mostly missense often resulting in the accumulation of mutant (MUT) protein, which may have novel or altered functions. Most MUT TP53s can be posttranslationally modified at the same residues as in WT TP53. Strikingly, however, codons for modified residues are rarely mutated in human tumors, suggesting that TP53 modifications are not essential for tumor suppression activity. Nevertheless, these modifications might alter MUT TP53 activity and contribute to a gain-of-function leading to increased metastasis and tumor progression. Furthermore, many of the signal transduction pathways that result in TP53 modifications are altered or disrupted in cancers. Understanding the signaling pathways that result in TP53 modification and the functions of these modifications in both WT TP53 and its many MUT forms may contribute to more effective cancer therapies. Published 2014. Wiley Periodicals, Inc. **This article is a U.S. Government work and is in the public domain in the USA.

  19. Surface chemical modification of waxy maize starch nanocrystals.

    PubMed

    Angellier, Hélène; Molina-Boisseau, Sonia; Belgacem, Mohamed Naceur; Dufresne, Alain

    2005-03-15

    The surface of waxy maize starch nanocrystals obtained from sulfuric acid hydrolysis of native waxy maize starch granules was chemically modified using two different reagents, namely, alkenyl succinic anhydride and phenyl isocyanate. The occurrence of chemical modification was evaluated by FTIR and X-ray photoelectron spectroscopies. Contact angle measurements from which the surface energy of the materials under investigation was deduced showed that chemical modification led to more hydrophobic particles. Chemical modification altered the morphology of particles, as shown by observation by transmission electron microscopy, but not their crystallinity (X-ray diffraction analysis).

  20. Biblical behavior modification.

    PubMed

    Lasure, L C; Mikulas, W L

    1996-07-01

    Although we may have formalized and systematized the field of behavior modification in the last few decades, people around the world have been using behavioral change strategies throughout history. Premack's (1965) theory of reinforcement is often called "Grandma's rule" because grandmothers have long been using it (e.g. You must finish your vegetables before you may go out and play). Franks (1969, p. 4), in one of the first behavioral texts, gave historical examples from China, Turkey, France, and Italy. Knapp and Shodahl (1974) showed how Benjamin Franklin used behavior modification. And de Silva (1984, 1985) gave examples of behavior modification by the Buddha and other early Buddhists. Conspicuously absent from our literature are examples from the Judeo-Christian tradition. In this paper, we provide a number of behavior modification examples from the Bible (New International Version). Footnotes provide references for many more examples. In the discussion, we explore implications for education and therapy. Examples are grouped by the following categories: operant conditioning, respondent conditioning, modeling, and cognitive interventions. However, the Biblical examples, like contemporary case studies, do not always fall neatly into discrete categories. They often are a combination, particularly operant and respondent conditioning interweaving.

  1. Teachers and Behavior Modification.

    ERIC Educational Resources Information Center

    Frey, Sherman

    This survey of 406 educators attending the 1973 summer session at Northern Illinois University sought to determine educators' familiarity with behavior modification, including the nature of their exposure to it and the extent to which they have integrated it into their own behavior. The survey also sought subjects' opinion of the value of being…

  2. Behavior Modification: Education's Watergate.

    ERIC Educational Resources Information Center

    Carrison, Muriel Paskin

    Several of the theoretical and experimental assumptions relating to behavior modification are examined and criticized: (1) the human mind can only be understood by observing and measuring the functional behavior it causes, (2) performance can be equated with learning, (3) reward systems and token economies improve intrinsic learning, and (4) all…

  3. THE MODIFICATION OF STUTTERING.

    ERIC Educational Resources Information Center

    BRUTTEN, EUGENE J.; SHOEMAKER, DONALD J.

    INTENDED FOR BOTH THE COLLEGE STUDENT AND THE PROFESSIONAL SPEECH PATHOLOGIST, THE BOOK PRESENTS CURRENT LEARNING THEORIES CONCERNING STUTTERING, DATA IMPORTANT TO THE THEORIES, AND A 2-PROCESS THEORY OF LEARNING FOR THEORETICAL INTEGRATION OF THE DATA ON STUTTERING AND FOR THERAPEUTIC MODIFICATION. INFORMATION PRESENTED ABOUT BEHAVIORISTIC…

  4. Behavior Modification with Children

    ERIC Educational Resources Information Center

    Brown, Daniel G.

    1972-01-01

    The author urges wider use of positive reinforcement theories in helping emotionally disturbed and mentally handicapped children. Underlining the influence of environment on behavior, he also notes that behavior modification programs utilize fewer trained personnel more effectively and, like Tennessee's Re-Education Treatment, allow for therapy in…