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https://www.readbyqxmd.com/read/27913581/a-proteomic-approach-to-analyse-the-aspirin-mediated-lysine-acetylome
#1
Michael H Tatham, Christian Cole, Paul Scullion, Ross Wilkie, Nicholas J Westwood, Lesley A Stark, Ronald T Hay
Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino-acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet unexplained drug actions or side-effects. Using isotopically labeled aspirin-d3, in combination with acetylated lysine purification and LC-MS/MS, we identified over 12000 sites of lysine acetylation from cultured human cells...
December 2, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27913183/nmr-strategies-to-support-medicinal-chemistry-workflows-for-primary-structure-determination
#2
Paul Oguadinma, Francois Bilodeau, Steven R LaPlante
Central to drug discovery is the correct characterization of the primary structures of compounds. In general, medicinal chemists make great synthetic and characterization efforts to deliver the intended compounds. However, there are occasions which incorrect compounds are presented, such as those reported for Bosutinib and TIC10. This may be due to a variety of reasons such as uncontrolled reaction schemes, reliance on limited characterization techniques (LC-MS and/or 1D 1H NMR spectra), or even the lack of availability or knowledge of characterization strategies...
November 24, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27913146/effects-of-high-fat-diet-on-plasma-profiles-of-eicosanoid-metabolites-in-mice
#3
Weicang Wang, Jun Yang, Haixia Yang, Katherine Z Sanidad, Bruce D Hammock, Daeyoung Kim, Guodong Zhang
Obesity is a serious health problem in the US and is associated with increased risks of various human diseases. To date, the mechanisms by which obesity increases the risks of a wide range of human diseases are not well understood. Here we used a LC-MS/MS-based lipidomics, which can analyze >100 bioactive lipid mediators produced by cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes, to analyze plasma profiles of lipid mediators in high-fat diet induced obesity in C57BL/6 mice. Our results showed that the plasma concentrations of epoxyoctadecenoic acids (EpOMEs, also termed as leukotoxins) were significantly increased in plasma of high-fat diet-fed mice, in addition, EpOMEs are among the most abundant lipid mediators detected in mouse plasma...
November 29, 2016: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/27913098/succinyl-coa-synthetase-sucla2-deficiency-in-two-siblings-with-impaired-activity-of-other-mitochondrial-oxidative-enzymes-in-skeletal-muscle-without-mitochondrial-dna-depletion
#4
Xiaoping Huang, Jirair K Bedoyan, Didem Demirbas, David J Harris, Alexander Miron, Simone Edelheit, George Grahame, Suzanne D DeBrosse, Lee-Jun Wong, Charles L Hoppel, Douglas S Kerr, Irina Anselm, Gerard T Berry
Mutations in SUCLA2 result in succinyl-CoA ligase (ATP-forming) or succinyl-CoA synthetase (ADP-forming) (A-SCS) deficiency, a mitochondrial tricarboxylic acid cycle disorder. The phenotype associated with this gene defect is largely encephalomyopathy. We describe two siblings compound heterozygous for SUCLA2 mutations, c.985A>G (p.M329V) and c.920C>T (p.A307V), with parents confirmed as carriers of each mutation. We developed a new LC-MS/MS based enzyme assay to demonstrate the decreased SCS activity in the siblings with this unique genotype...
November 12, 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27913096/a-sensitive-and-accurate-lc-ms-ms-assay-with-the-derivatization-of-1amino4methylpiperazine-applied-to-serum-allopregnanolone-pregnenolone-and-androsterone-in-pre-and-postmenopausal-women
#5
Yuyong Ke, Renaud Gonthier, Fernand Labrie
The concentrations of allopregnanolone (Allopreg), pregnenolone (Preg) and androsterone (ADT) are very low in the circulation, especially in postmenopausal women, resulting in a considerable challenge for their accurate measurements in serum or plasma. In this report, a sensitive and reliable LC-MS/MS assay method has been developed using a simple sample preparation and the 1-Amino-4-methylpiperazine (AMP) derivatization procedure. A 5pg/ml (0.1pg on column) of low limit of quantitation has been achieved for Allopreg, Preg and ADT, with a sensitivity comparable to data obtained with the commercial reagent...
November 29, 2016: Steroids
https://www.readbyqxmd.com/read/27912907/bioactivity-guided-isolation-of-anti-inflammatory-triterpenoids-from-the-sclerotia-of-poria-cocos-using-lps-stimulated-raw264-7-cells
#6
Seoung Rak Lee, Seulah Lee, Eunjung Moon, Hye-Jin Park, Hyun Bong Park, Ki Hyun Kim
Poria cocos Wolf (Polyporaceae) has been used as a medicinal fungus to treat various diseases since ancient times. This study aimed to investigate the anti-inflammatory chemical constituents of the sclerotia of P. cocos. Based on bioassay-guided fractionation using lipopolysaccharide (LPS)-stimulated Raw264.7 cells, chemical investigation of the EtOH extract of the sclerotia of P. cocos resulted in the isolation and identification of eight compounds including six triterpenoids, namely poricoic acid A (1), 3-O-acetyl-16α-hydroxydehydrotrametenolic acid (2), polyporenic acid C (3), 3β-hydroxylanosta-7,9(11),24-trien-21-oic acid (4), trametenolic acid (5), and dehydroeburicoic acid (6), as well as (-)-pinoresinol (7) and protocatechualdehyde (8)...
November 23, 2016: Bioorganic Chemistry
https://www.readbyqxmd.com/read/27911932/chemical-and-cellular-assays-combined-with-in-vitro-digestion-to-determine-the-antioxidant-activity-of-flavonoids-from-chinese-bayberry-myrica-rubra-sieb-et-zucc-leaves
#7
Yu Zhang, Shiguo Chen, Chaoyang Wei, Hui Gong, Lanqi Li, Xingqian Ye
Oxidative stress is highly associated with the development of cardiovascular diseases and cancer and has drawn great attention. Natural products suggest a potential role in prevention of these disorders. The aim of this study was to investigate the antioxidant and anti-cancer properties of Chinese bayberry leaves (Myrica rubra Sieb. et Zucc.) flavonoids (BLF) comprehensively through the combination of in vitro digestion, chemical and cellular antioxidant assays. Based on the LC/MS data, the major flavonoids of BLF were myricitrin and quercetin 3-rhamnoside...
2016: PloS One
https://www.readbyqxmd.com/read/27911435/detecting-biomarkers-of-secondhand-marijuana-smoke-in-young-children
#8
Karen M Wilson, Michelle R Torok, Binnian Wei, Lanqing Wang, Michelle Robinson, Connie S Sosnoff, Benjamin C Blount
BACKGROUND: The impact of secondhand marijuana smoke exposure on children is unknown. New methods allow detection of secondhand marijuana smoke in children. METHODS: We studied children ages 1 month to 2 years hospitalized with bronchiolitis in Colorado from 2013-2015. Parents completed a survey, and urine samples were analyzed for cotinine using LC/MS/MS (LOD 0.03 ng/ml) and marijuana metabolites including COOH-THC (LOD 0.015 ng/ml). RESULTS: A total of 43 subjects had urine samples available for analysis...
December 2, 2016: Pediatric Research
https://www.readbyqxmd.com/read/27911021/a-rapid-and-simple-liquid-chromatography-tandem-mass-spectrometry-method-for-the-measurement-of-testosterone-androstenedione-and-dehydroepiandrosterone-in-human-serum
#9
Wenjuan Xu, Huijun Li, Qing Guan, Ying Shen, Liming Cheng
BACKGROUND: The assay of androgens plays an important role for the differential diagnosis of androgen-related endocrine diseases. We developed a rapid and simple liquid chromatography tandem mass spectrometry (LC-MS/MS) method with small sample volume and simple sample preparation for simultaneous determination of serum testosterone, androstenedione and dehydroepiandrosterone (DHEA) in adults. METHODS: We spiked 100 μL of serum with 200 μL of internal standard solution, which was prepared in methanol, for matrix effect relief and protein precipitation...
December 2, 2016: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/27910164/hplc-uv-and-lc-ms-analyses-of-acylquinic-acids-in-geigeria-alata-dc-oliv-hiern-and-their-contribution-to-antioxidant-and-antimicrobial-capacity
#10
Dimitrina Zheleva-Dimitrova, Reneta Gevrenova, Maya M Zaharieva, Hristo Najdenski, Silviya Ruseva, Valentin Lozanov, Vessela Balabanova, Sakina Yagi, Georgi Momekov, Vanio Mitev
INTRODUCTION: Geigeria alata is a traditional plant used in Sudanese folk medicine for treatment of diabetes, cough, epilepsy and intestinal complaints. OBJECTIVE: To analyze phenolic acids in Geigeria alata roots and leaves and to evaluate their antioxidant and antimicrobial activities. METHODOLOGY: Phenolic acids in the aqueous-methanol extracts were identified by LC-MS. Major compounds were isolated using low-pressure liquid chromatography...
December 1, 2016: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/27909777/quantitative-determination-of-the-neurotoxin-%C3%AE-n-methylamino-l-alanine-bmaa-by-capillary-electrophoresis-tandem-mass-spectrometry
#11
Elliott S Kerrin, Robert L White, Michael A Quilliam
Recent reports of the widespread occurrence of the neurotoxin β-N-methylamino-L-alanine (BMAA) in cyanobacteria and particularly seafood have raised concerns for public health. LC-MS/MS is currently the analytical method of choice for BMAA determinations but incomplete separation of isomeric and isobaric compounds, matrix suppression and conjugated forms are plausible limitations. In this study, capillary electrophoresis (CE) coupled with MS/MS has been developed as an alternative method for the quantitative determination of free BMAA...
December 1, 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/27909398/an-amyloid-like-pathological-conformation-of-tdp-43-is-stabilized-by-hypercooperative-hydrogen-bonds
#12
Miguel Mompeán, Marco Baralle, Emanuele Buratti, Douglas V Laurents
TDP-43 is an essential RNA-binding protein forming aggregates in almost all cases of sporadic amyotrophic lateral sclerosis (ALS) and many cases of frontotemporal lobar dementia (FTLD) and other neurodegenerative diseases. TDP-43 consists of a folded N-terminal domain with a singular structure, two RRM RNA-binding domains, and a long disordered C-terminal region which plays roles in functional RNA regulatory assemblies as well as pernicious aggregation. Evidence from pathological mutations and seeding experiments strongly suggest that TDP-43 aggregates are pathologically relevant through toxic gain-of-harmful-function and/or harmful loss-of-native-function mechanisms...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27908912/a-deep-proteome-analysis-identifies-the-complete-secretome-as-the-functional-unit-of-human-cardiac-progenitor-cells
#13
Sudhish Sharma, Rachana Mishra, Grace E Bigham, Brody Wehman, Mohd M Khan, Huichun Xu, Progyaparamita Saha, Young Ah Goo, Srinivisa R Datla, Ling Chen, Mohan E Tulapurkar, Bradley S Taylor, Peixin Yang, Sotirios K Karathanasis, David R Goodlett, Sunjay Kaushal
RATIONALE: Cardiac progenitor cells are an attractive cell type for tissue regeneration but their mechanism for myocardial remodeling is still unclear. OBJECTIVE: This investigation determines how chronological age influences the phenotypic characteristics and the secretome of human cardiac progenitor cells (CPCs), as well as their potential to recover injured myocardium. METHODS AND RESULTS: Adult (aCPCs) and neonatal (nCPCs) cells were derived from patients more than 40 years or less than one month of age, respectively, and their functional potential was determined in a rodent myocardial infarction (MI) model...
December 1, 2016: Circulation Research
https://www.readbyqxmd.com/read/27908826/itraq-based-quantitative-proteomic-analysis-of-midgut-in-silkworm-infected-with-bombyx-mori-cytoplasmic-polyhedrosis-virus
#14
Kun Gao, Xiang-Yuan Deng, Meng-Ke Shang, Guang-Xing Qin, Cheng-Xiang Hou, Xi-Jie Guo
: Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) specifically infects the epithelial cells in the midgut of silkworm and causes them to death, which negatively affects the sericulture industry. In order to determine the midgut response at the protein levels to the virus infection, differential proteomes of the silkworm midgut responsive to BmCPV infection were identified with isobaric tags for relative and absolute quantitation (iTRAQ) labeling followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
November 28, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/27908627/validation-of-a-two-generational-reproduction-test-in-daphnia-magna-an-interlaboratory-exercise
#15
Carlos Barata, Bruno Campos, Claudia Rivetti, Gerald A LeBlanc, Stephanie Eytcheson, Stephanie McKnight, Marysia Tobor-Kaplon, Selinda de Vries Buitenweg, Suhyon Choi, Jinhee Choi, Elena I Sarapultseva, Marie-Agnès Coutellec, Maïra Coke, Pascal Pandard, Arnaud Chaumot, Hervé Quéau, Nicolas Delorme, Olivier Geffard, Fernando Martínez-Jerónimo, Haruna Watanabe, Norihisa Tatarazako, Isabel Lopes, João L T Pestana, Amadeu M V M Soares, Cecilia Manuela Pereira, Karel De Schamphelaere
Effects observed within one generation disregard potential detrimental effects that may appear across generations. Previously we have developed a two generation Daphnia magna reproduction test using the OECD TG 211 protocol with a few amendments, including initiating the second generation with third brood neonates produced from first generation individuals. Here we showed the results of an inter-laboratory calibration exercise among 12 partners that aimed to test the robustness and consistency of a two generation Daphnia magna reproduction test...
November 28, 2016: Science of the Total Environment
https://www.readbyqxmd.com/read/27908259/a-novel-liquid-chromatography-tandem-mass-spectrometry-method-for-the-estimation-of-bilirubin-glucuronides-and-its-application-to-in-vitro-enzyme-assays
#16
Siva Prasad Putluru, Murali Krishna Matta, Deepak Ahire, Murali Subramanian, Michael Sinz, Sandhya Mandlekar
Bilirubin is a toxic waste product of metabolism, eliminated mainly through UGT1A1 mediated conjugation to mono- and di-glucuronides. Due to the potentially low Km value of bilirubin glucuronidation, the quantitative sensitivity obtained with most UV/visible light detection methods are not sufficient to accurately calculate UGT1A1 enzyme kinetics and inhibition properties of new chemical entities at low bilirubin concentrations. In addition, bilirubin, as well as its metabolites, are unstable during sample preparation and bioanalysis...
November 24, 2016: Drug Metabolism Letters
https://www.readbyqxmd.com/read/27907855/lc-ms-ms-assay-for-the-quantitation-of-the-tyrosine-kinase-inhibitor-neratinib-in-human-plasma
#17
Brian F Kiesel, Robert A Parise, Alvin Wong, Kiana Keyvanjah, Samuel Jacobs, Jan H Beumer
Neratinib is an orally available tyrosine kinase inhibitor targeting HER2 (ERBB2) and EGFR (ERBB). It is being clinically evaluated for the treatment of breast and other solid tumors types as a single agent or in combination with other chemotherapies. In support of several phase I/II clinical trials investigating neratinib combinations, we developed and validated a novel LC-MS/MS assay for the quantification of neratinib in 100μL of human plasma with a stable isotopic internal standard. Analytes were extracted from plasma using protein precipitation and evaporation of the resulting supernatant followed by resuspension...
November 22, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27907185/antioxidant-antimicrobial-and-cytotoxic-properties-as-well-as-the-phenolic-content-of-the-extract-from-hancornia-speciosa-gomes
#18
Uilson P Santos, Jaqueline F Campos, Heron Fernandes V Torquato, Edgar Julian Paredes-Gamero, Carlos Alexandre Carollo, Leticia M Estevinho, Kely de Picoli Souza, Edson Lucas Dos Santos
Hancornia speciosa Gomes (Apocynaceae) is a fruit tree, popularly known as mangabeira, and it is widely distributed throughout Brazil. Several parts of the plant are used in folk medicine, and the leaf and bark extracts have anti-inflammatory, antihypertensive, antidiabetic, and antimicrobial properties. In this study, we investigated the chemical composition of the ethanolic extract of Hancornia speciosa leaves (EEHS) and its antioxidant, antimicrobial, and cytotoxic activities as well as the mechanisms involved in cell death...
2016: PloS One
https://www.readbyqxmd.com/read/27907126/variability-in-the-sxt-gene-clusters-of-psp-toxin-producing-aphanizomenon-gracile-strains-from-norway-spain-germany-and-north-america
#19
Andreas Ballot, Leonardo Cerasino, Vladyslava Hostyeva, Samuel Cirés
Paralytic shellfish poisoning (PSP) toxin production has been detected worldwide in the cyanobacterial genera Anabaena, Lyngbya, Scytonema, Cuspidothrix and Aphanizomenon. In Europe Aphanizomenon gracile and Cuspidothrix issatschenkoi are the only known producers of PSP toxins and are found in Southwest and Central European freshwater bodies. In this study the PSP toxin producing Aphanizomenon sp. strain NIVA-CYA 851 was isolated from the Norwegian Lake Hillestadvannet. In a polyphasic approach NIVA-CYA 851 was morphologically and phylogenetically classified, and investigated for toxin production...
2016: PloS One
https://www.readbyqxmd.com/read/27906622/sensitive-liquid-chromatography-mass-spectrometry-lc-ms-assay-reveals-novel-insights-on-dna-methylation-and-incorporation-of-gemcitabine-its-metabolite-difluorodeoxyuridine-deoxyuridine-and-rx-3117-into-dna
#20
Richard J Honeywell, Dzjemma Sarkisjan, Ietje Kathmann, Michael H Kristensen, Godefridus J Peters
Antimetabolites are incorporated into DNA and RNA, affecting their function. Liquid-chromatography-mass-spectrometry (LC-MS-MS) permits the sensitive, selective analysis of normal nucleosides. The method was adapted to measure the incorporation of deoxyuridine, gemcitabine (difluorodeoxycytidine), its metabolite difluorodeoxyuridine (dFdU), and the novel compound fluorocyclopentenylcytosine (RX3117). DNA was degraded to its deoxynucleotides for quantification by LC-MS-MS, gradient chromatography on a Phenomenex prodigy-3-ODS with positive ionization...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
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