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Bernhard H Monien, Benjamin Sachse, Walter Meinl, Klaus Abraham, Alfonso Lampen, Hansruedi Glatt
Furfuryl alcohol (FFA) is a heat-induced food contaminant. Conversion by sulfotransferases (SULT) yields 2-sulfoxymethylfuran, which is prone to react with DNA and proteins. In order to monitor the internal FFA exposure we developed a technique for the mass spectrometric quantification of the adduct N-((furan-2-yl)methyl)-valine (FFA-Val) after cleavage from the N-termini of hemoglobin. In the current study the method was applied to investigate the influence of different SULT forms on the adduct formation in wild-type mice and three genetically modified mouse models treated with FFA...
June 13, 2018: Toxicology Letters
Jessica Fernandes, M Vivek Ghate, Sanchari Basu Mallik, Shaila A Lewis
Saxagliptin (SAX) is dipeptidyl peptidase-4 enzyme inhibitor molecule now explored for its activity in the therapy of Alzheimer's disease. Being extremely hydrophilic, it is unable to permeate the blood-brain barrier by the conventional therapy modalities. Further repurposing the drug, SAX is associated with a reduction in the blood sugar level in the periphery. In the present study, the chitosan-L-valine conjugate was synthesized by carbodiimide chemistry. The conjugate was then used to prepare nanoparticles encapsulating SAX...
June 12, 2018: International Journal of Pharmaceutics
Michalina Gramatyka, Agnieszka Skorupa, Maria Sokół
Several lines of evidence indicate that exposure of heart to ionizing radiation increases the risk of cardiotoxicity manifested by heart dysfunction and cardiovascular diseases. It was initially believed that the heart is an organ relatively resistant to radiation. Currently, however, it is suspected that even low doses of radiation (< 2 Gy) may have a negative impact on the cardiovascular system. Cardiotoxicity of ionizing radiation is associated with metabolic changes observed in cardiac cells injured by radiation...
June 15, 2018: Acta Biochimica Polonica
Jagjit Kaur, Cheng Jiang, Guozhen Liu
Measurement of glycosylated hemoglobin (HbA1c) is a gold standard procedure for assessing long term glycemic control in individuals with diabetes mellitus as it gives the stable and reliable value of blood glucose levels for a period of 90-120 days. HbA1c is formed by the non-enzymatic glycation of terminal valine of hemoglobin. The analysis of HbA1c tends to be complicated because there are more than 300 different assay methods for measuring HbA1c which leads to variations in reported values from same samples...
June 7, 2018: Biosensors & Bioelectronics
Amany K Elshorbagy, Dorit Samocha-Bonet, Fredrik Jernerén, Cheryl Turner, Helga Refsum, Leonie K Heilbronn
Background: Plasma concentrations of branched-chain amino acids (BCAAs) and the sulfur-containing amino acid cysteine are associated with obesity and insulin resistance. BCAAs predict future diabetes. Objective: We investigated amino acid changes during food overconsumption. Methods: Forty healthy men and women with a body mass index (mean ± SEM) of 25.6 ± 0.6 were overfed by 1250 kcal/d for 28 d, increasing consumption of all macronutrients...
June 13, 2018: Journal of Nutrition
Anjaneya S Kathait, Paulo Puac, Mauricio Castillo
Maple syrup urine disease (MSUD) is a rare autosomal-recessive disorder that affects branched-chain amino acid (BCAA) metabolism. It is characterized by accumulation of BCAAs and corresponding branched-chain keto acids of leucine, isoleucine, and valine in plasma, urine, and cerebrospinal fluid. Leucine is toxic to brain cells, leading to cytotoxic edema affecting the myelinated white matter, and involving the corticospinal tracts, thalami, globus palladi, midbrain, dorsal brain stem, and cerebellum. We present a neonate with the classic subtype of MSUD and its imaging features on magnetic resonance imaging...
January 2018: Journal of Pediatric Neurosciences
F T Fellendorf, M Platzer, R Pilz, A Rieger, H P Kapfhammer, H Mangge, N Dalkner, S Zelzer, A Meinitzer, A Birner, S A Bengesser, R Queissner, C Hamm, R Hartleb, E Z Reininghaus
OBJECTIVES: An important aspect of bipolar disorder (BD) research is the identification of biomarkers pertaining to the somatic health state. The branched-chain essential amino acids (BCAAs), viz valine, leucine and isoleucine, have been proposed as biomarkers of an individual's health state, given their influence on protein synthesis and gluconeogenesis inhibition. METHODS: BCAA levels of 141 euthymic/subsyndromal individuals with BD and 141 matched healthy controls (HC) were analyzed by high-pressure lipid chromatography and correlated with clinical psychiatric, anthropometric and metabolic parameters...
June 14, 2018: World Journal of Biological Psychiatry
A Jasek, R E Latham, A Mañón, S Llamas-Moya, R Adhikari, R Poureslami, J T Lee
Exogenous enzymatic supplementation of poultry feeds, including α-galactosidase and xylanase, has been shown to increase metabolically available energy, although little information has been published on the impact on amino acid digestibility. An experiment was conducted to investigate a multicarbohydrase containing α-galactosidase and xylanase on amino acid digestibility, ileal digestible energy (IDE), and CP in male broiler chicks. The experiment was a 2 × 2 (diet × enzyme) factorial arrangement with 15 replicates of 8 male broilers per replicate raised for 21 d in a battery setting...
June 8, 2018: Poultry Science
Ting Shen, Yuyi You, Chitra Joseph, Mehdi Mirzaei, Alexander Klistorner, Stuart L Graham, Vivek Gupta
Brain-derived neurotrophic factor (BDNF) has a unique role in the neuronal development, differentiation, and survival in the developing and adult nervous system. A common single-nucleotide polymorphism in the pro-region of the human BDNF gene, resulting in a valine to methionine substitution (Val66Met), has been associated with the susceptibility, incidence, and clinical features of several neurodegenerative disorders. Much research has been dedicated to evaluating the effects of polymorphism in the past decade, and functional effects of this genetic variation...
June 2018: Aging and Disease
Yuqian Du, Chutong Tian, Menglin Wang, Di Huang, Wei Wei, Yan Liu, Lin Li, Bingjun Sun, Longfa Kou, Qiming Kan, Kexin Liu, Cong Luo, Jin Sun, Zhonggui He
Oligopeptide transporter 1 (PepT1) has been a striking prodrug-designing target. However, the underlying mechanism of PepT1 as a target to facilitate the oral absorption of nanoparticles (NPs) remains unclear. Herein, we modify Poly (lactic-co-glycolic acid) (PLGA) NPs with the conjugates of dipeptides (L-valine-valine, L-valine-phenylalanine) and polyoxyethylene (PEG Mw: 1000, 2000) stearate to facilitate oral delivery of docetaxel (DTX) to investigate the oral absorption mechanism and regulatory effects on PepT1 of the dipeptide-modified NPs...
November 2018: Drug Delivery
Fang-Hui Li, Tao Li, Jing-Yi Ai, Lei Sun, Zhu Min, Rui Duan, Ling Zhu, Yan-Ying Liu, Timon Cheng-Yi Liu
The effects of high-intensity interval (HIIT) and moderate-intensity continuous training (MICT) on basal autophagy and mitochondrial function in cardiac and skeletal muscle and plasma metabolic phenotypes have not been clearly characterized. Here, we investigated how 10-weeks HIIT and MICT differentially modify basal autophagy and mitochondrial markers in cardiac and skeletal muscle and conducted an untargeted metabolomics study with proton nuclear magnetic resonance (1 H NMR) spectroscopy and multivariate statistical analysis of plasma metabolic phenotypes...
2018: Frontiers in Physiology
Kuo-Liang Yang, Zheng-Zhong Zheng, Li-Yun Lin
Objective: HLA-B*40:247 is a low incidence allele in the HLA-B locus. The aim of this study is to confirm the ethnicity of B*40:247 and its deduced probable HLA- associated haplotype in Taiwanese individuals. Materials and Methods: A total of 2,329 unrelated Taiwanese individuals and 66,212 unrelated mainland Chinese individuals were tested for HLA using a sequence-based typing method. We confirmed the low incidence allele B*40:247 in Taiwanese. Polymerase chain reaction was performed to amplify exons 2, 3 and 4 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets...
April 2018: Ci Ji Yi Xue za Zhi, Tzu-chi Medical Journal
Sylvie Mavel, Antoine Lefèvre, David Bakhos, Diane Dufour-Rainfray, Hélène Blasco, Patrick Emond
Although there is some data from animal studies, the metabolome of inner ear fluid in humans remains unknown. Characterization of the metabolome of the perilymph would allow for better understanding of its role in auditory function and for identification of biomarkers that might allow prediction of response to therapeutics. There is a major technical challenge due to the small sample of perilymph fluid available for analysis (sub-microliter). The objectives of this study were to develop and validate a methodology for analysis of perilymph metabolome using liquid chromatography-high resolution mass spectrometry (LC-HRMS)...
May 22, 2018: Hearing Research
Mingxu Fang, Carl E Bauer
When faced with amino acid starvation, prokaryotic cells induce a stringent response that modulates their physiology. The stringent response is manifested by production of signaling molecules guanosine 5'-diphosphate,3'-diphosphate (ppGpp) and guanosine 5'-triphosphate,3'-diphosphate (pppGpp) that are also called alarmones. In many species, alarmone levels are regulated by a multidomain bifunctional alarmone synthetase/hydrolase called Rel. In this enzyme, there is an ACT domain at the carboxyl region that has an unknown function; however, similar ACT domains are present in other enzymes that have roles in controlling amino acid metabolism...
June 4, 2018: Proceedings of the National Academy of Sciences of the United States of America
Efstathia Papada, Ljilja Torović, Charalampia Amerikanou, Nikolaos Kalogeropoulos, Ilias Smyrnioudis, Andriana C Kaliora
We aimed to explore whether plasma-free amino acids are modified in response to terpenes administration in healthy humans. In this open-label, single-arm acute trial, seventeen healthy male volunteers were administered with a naturally occurring product of known terpenes-namely mastiha-after overnight fasting. Blood samples were collected at different time points before and after ingestion. We aimed at identifying and quantifying 60 free amino acids in plasma applying Gas Chromatography-Mass Spectrometry. A total of 24 free amino acids were quantified...
June 3, 2018: Nutrients
Yu Saito, Yuji Morine, Shuichi Iwahashi, Tetsuya Ikemoto, Satoru Imura, Hisami Yamanaka-Okumura, Akiyoshi Hirayama, Tomoyoshi Soga, Masaru Tomita, Mitsuo Shimada
Background: Metabolome analysis is one of the omics which investigates the final product of a central dogma. Changes of liver metabolites during liver regeneration following hepatectomy (Hx) continue to remain unclear. The aim of the present study was to investigate the changes of liver metabolites following Hx with ischemia reperfusion (I/R) towards liver regeneration. Methods: Twenty-three patients who underwent Hx were enrolled in this study. Non-tumor tissues were sampled immediately before and after Hx and a comparison was made between the liver samples taken before and after Hx using capillary electrophoresis (CE)-time-of-flight mass spectrometry (TOFMS) as metabolome analysis...
May 2018: Annals of gastroenterological surgery
Omid Fallahzadeh, Zohreh Dehghani-Bidgoli, Mohammad Assarian
Pathology as a common diagnostic test of cancer is an invasive, time-consuming, and partially subjective method. Therefore, optical techniques, especially Raman spectroscopy, have attracted the attention of cancer diagnosis researchers. However, as Raman spectra contain numerous peaks involved in molecular bounds of the sample, finding the best features related to cancerous changes can improve the accuracy of diagnosis in this method. The present research attempted to improve the power of Raman-based cancer diagnosis by finding the best Raman features using the ACO algorithm...
June 4, 2018: Lasers in Medical Science
Mathilde Lescanne, Puneet Ahuja, Anneloes Blok, Monika Timmer, Tomas Akerud, Marcellus Ubbink
Liquid-state NMR spectroscopy is a powerful technique to elucidate binding properties of ligands on proteins. Ligands binding in hydrophobic pockets are often in close proximity to methyl groups and binding can lead to subtle displacements of methyl containing side chains to accommodate the ligand. To establish whether pseudocontact shifts can be used to characterize ligand binding and the effects on methyl groups, the N-terminal domain of HSP90 was tagged with caged lanthanoid NMR probe 5 at three positions and titrated with a ligand...
June 2, 2018: Journal of Biomolecular NMR
Jean-Michel Molina, Sebastien Gallien, Marie-Laure Chaix, El Mountacer El Abbassi, Isabelle Madelaine, Christine Katlama, Nadia Valin, Pierre Delobel, Kristell Desseaux, Gilles Peytavin, Juliette Saillard, François Raffi, Sylvie Chevret
Objectives: To assess whether low-dose ritonavir-boosted darunavir (darunavir/r) in combination with two NRTIs could maintain virological suppression in patients on a standard regimen of darunavir/r + two NRTIs. Design: A multicentre, Phase II, non-comparative, single-arm, open-label study. Setting: Tertiary care hospitals in France. Subjects: One hundred HIV-1-infected adults with no darunavir or NRTI resistance-associated mutations (RAMs) and a plasma HIV RNA level ≤50 copies/mL for ≥12 months on once-daily darunavir/r (800/100 mg) + two NRTIs for ≥6 months were switched to darunavir/r 400/100 mg with the same NRTIs...
June 1, 2018: Journal of Antimicrobial Chemotherapy
Natthaporn Takpho, Daisuke Watanabe, Hiroshi Takagi
In the yeast Saccharomyces cerevisiae , the branched-chain amino acid aminotransferases (BCATs) Bat1 and Bat2 catalyze the conversion of α-ketoisovalerate, α-keto-β-methylvalerate, and α-ketoisokaproate and into valine, isoleucine, and leucine, respectively, as the final step of branched-chain amino acid biosynthesis. Bat1 and Bat2 are homologous proteins that share 77% identity, but Bat1 localizes in the mitochondria and Bat2 in the cytosol. Based on our preliminary finding that only disruption of the BAT1 gene led to slow-growth phenotype, we hypothesized that Bat1 and Bat2 play distinct roles in valine biosynthesis and the regulation of cell growth...
March 21, 2018: Microbial Cell
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