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https://www.readbyqxmd.com/read/28106337/in-vivo-metabolomic-interpretation-of-the-anti-obesity-effects-of-hyacinth-bean-dolichos-lablab-l-administration-in-high-fat-diet-mice
#1
Dong Ho Suh, Hye Won Lee, Eun Sung Jung, Digar Singh, Seung-Hyung Kim, Choong Hwan Lee
SCOPE: The esoteric anti-obesity effects of hyacinth bean (Dolichos lablab L) have largely remained unexplored. Herein, we investigated the anti-obesity mechanisms of hyacinth bean compared to milk thistle, a natural herb employed for ameliorating obesity-related diseases, using high fat-diet (HFD) fed mice towards unfolding the perplexing mechanisms. METHODS AND RESULTS: C57BL/6J mice were orally administered hyacinth bean (25 mg/kg/day) and milk thistle (100 mg/kg/day) for 9 weeks along with HFD...
January 20, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28102864/transthyretin-v122i-pv142i-cardiac-amyloidosis-an-age-dependent-autosomal-dominant-cardiomyopathy-too-common-to-be-overlooked-as-a-cause-of-significant-heart-disease-in-elderly-african-americans
#2
REVIEW
Joel N Buxbaum, Frederick L Ruberg
Since the identification of a valine-to-isoleucine substitution at position 122 (TTR V122I; pV142I) in the transthyretin (TTR)-derived fibrils extracted from the heart of a patient with late-onset cardiac amyloidosis, it has become clear that the amyloidogenic mutation and the disease occur almost exclusively in individuals of identifiable African descent. In the United States, the amyloidogenic allele frequency is 0.0173 and is carried by 3.5% of community-dwelling African Americans. Genotyping across Africa indicates that the origin of the allele is in the West African countries that were the major source of the slave trade to North America...
January 19, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28091629/mapping-the-sequence-structure-relationships-of-simple-cyclic-hexapeptides
#3
Sean M McHugh, Hongtao Yu, Diana P Slough, Yu-Shan Lin
Cyclic peptides are promising protein-protein interaction modulators with high binding affinities and specificities, as well as enhanced stabilities and oral availabilities over linear analogs. Despite their relatively small size and cyclic architecture, it is currently difficult to predict the favored conformation(s) of most classes of cyclic peptides. An improved understanding of the sequence-structure relationships for cyclic peptides will offer an avenue for the rational design of cyclic peptides as possible therapeutics...
January 16, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28090046/an-isolated-case-of-late-onset-amyloidogenic-transthyretin-type-familial-amyloid-polyneuropathy-associated-with-a-mutant-transthyretin-substituting-methionine-for-valine-at-position-30-showing-latent-progressive-cardiac-involvement-confirmed-by-serial-annual
#4
Chikako Sato, Tomofumi Takaya, Shumpei Mori, Kohei Hasegawa, Fumitaka Soga, Hidekazu Tanaka, Yoshiaki Watanabe, Tatsuya Nishii, Atsushi K Kono, Yukiko Morinaga, Hatsue Ishibashi-Ueda, Ken-Ichi Hirata
Late-onset amyloidogenic transthyretin (ATTR) type familial amyloid polyneuropathy (FAP) shows features distinct from those of early-onset hereditary ATTR type FAP. We herein describe an asymptomatic 68-year-old man with late-onset ATTR type FAP whose serial annual electrocardiograms demonstrated progressive left bundle branch block. Latent but severe cardiac involvement seems to be one feature of late-onset ATTR type FAP, similar to senile systemic amyloidosis (SSA). Early differential diagnosis of late-onset ATTR type FAP from SSA is important because, currently, only the former has new therapeutic options available in Japan...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28089725/high-concentration-of-branched-chain-amino-acids-promotes-oxidative-stress-inflammation-and-migration-of-human-peripheral-blood-mononuclear-cells-via-mtorc1-activation
#5
Olha Zhenyukh, Esther Civantos, Marta Ruiz-Ortega, Maria Soledad Sánchez, Clotilde Vázquez, Concepción Peiró, Jesús Egido, Sebastián Mas
Leucine, isoleucine and valine are essential aminoacids termed branched-chain amino acids (BCAA) due to its aliphatic side-chain. In several pathological and physiological conditions increased BCAA plasma concentrations have been described. Elevated BCAA levels predict insulin resistance development. Moreover, BCAA levels higher than 2mmol/L are neurotoxic by inducing microglial activation in maple syrup urine disease. However, there are no studies about the direct effects of BCAA in circulating cells. We have explored whether BCAA could promote oxidative stress and pro-inflammatory status in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors...
January 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28079404/free-amino-acids-in-fibromyalgia-syndrome-relationship-with-clinical-picture
#6
Valeria Ruggiero, Massimiliano Mura, Enrico Cacace, Benedetta Era, Marcella Peri, Giuseppina Sanna, Antonella Fais
The objectives of our study were to evaluate free amino acid (FAA) concentrations in the serum of patients affected by fibromyalgia syndrome (FMS) and to determine the relationships between FAA levels and FMS clinical parameters. Thus, serum amino acid concentrations were quantified (HPLC analysis) in 23 females with fibromyalgia (according to the American College of Rheumatology classification criteria) and 20 healthy females. The results showed significantly higher serum concentrations of aspartate, cysteine, glutamate, glycine, isoleucine, leucine, methionine, ornithine, phenylalanine, sarcosine, serine, taurine, tyrosine and valine in FMS patients vs...
January 12, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28077967/integrated-omics-analyses-reveal-the-details-of-metabolic-adaptation-of-clostridium-thermocellum-to-lignocellulose-derived-growth-inhibitors-released-during-the-deconstruction-of-switchgrass
#7
Suresh Poudel, Richard J Giannone, Miguel Rodriguez, Babu Raman, Madhavi Z Martin, Nancy L Engle, Jonathan R Mielenz, Intawat Nookaew, Steven D Brown, Timothy J Tschaplinski, David Ussery, Robert L Hettich
BACKGROUND: Clostridium thermocellum is capable of solubilizing and converting lignocellulosic biomass into ethanol. Although much of the work-to-date has centered on characterizing this microbe's growth on model cellulosic substrates, such as cellobiose, Avicel, or filter paper, it is vitally important to understand its metabolism on more complex, lignocellulosic substrates to identify relevant industrial bottlenecks that could undermine efficient biofuel production. To this end, we have examined a time course progression of C...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28077676/a-ptk7-targeted-antibody-drug-conjugate-reduces-tumor-initiating-cells-and-induces-sustained-tumor-regressions
#8
Marc Damelin, Alexander Bankovich, Jeffrey Bernstein, Justin Lucas, Liang Chen, Samuel Williams, Albert Park, Jorge Aguilar, Elana Ernstoff, Manoj Charati, Russell Dushin, Monette Aujay, Christina Lee, Hanna Ramoth, Milly Milton, Johannes Hampl, Sasha Lazetic, Virginia Pulito, Edward Rosfjord, Yongliang Sun, Lindsay King, Frank Barletta, Alison Betts, Magali Guffroy, Hadi Falahatpisheh, Christopher J O'Donnell, Robert Stull, Marybeth Pysz, Paul Escarpe, David Liu, Orit Foord, Hans Peter Gerber, Puja Sapra, Scott J Dylla
Disease relapse after treatment is common in triple-negative breast cancer (TNBC), ovarian cancer (OVCA), and non-small cell lung cancer (NSCLC). Therapies that target tumor-initiating cells (TICs) should improve patient survival by eliminating the cells that can drive tumor recurrence and metastasis. We demonstrate that protein tyrosine kinase 7 (PTK7), a highly conserved but catalytically inactive receptor tyrosine kinase in the Wnt signaling pathway, is enriched on TICs in low-passage TNBC, OVCA, and NSCLC patient-derived xenografts (PDXs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077194/the-response-of-weaned-piglets-to-dietary-valine-and-leucine
#9
F Meyer, C Jansen van Rensburg, R M Gous
Valine (Val) is considered to be the fifth-limiting amino acid in a maize-soyabean meal diet for pigs. Excess leucine (Leu) levels often occur in commercial diets, which may attenuate the effect of Val deficiency because of an increased oxidation of Val. The objective of the present experiment was to determine the effect of increasing concentrations of Leu on the response of young piglets to dietary Val. In all, 75 Large White×Landrace entire male pigs, 44 days of age and with a mean starting weight of 13...
January 12, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28075591/discovery-of-potent-cyclophilin-inhibitors-based-on-structural-simplification-of-sanglifehrin-a
#10
Victoria A Steadman, Simon B Pettit, Karine G Poullennec, Linos Lazarides, Andrew J Keats, David K Dean, Steven J Stanway, Carol A Austin, Jonathan A Sanvoisin, Gregory M Watt, Hans G Fliri, Albert C Liclican, Debi Jin, Melanie H Wong, Stephanie A Leavitt, Yu-Jen Lee, Yang Tian, Christian R Frey, Todd C Appleby, Uli Schmitz, Petr Jansa, Richard L Mackman, Brian Edward Schultz
Cyclophilin inhibition has been a target for the treatment of hepatitis C and other diseases, but the generation of potent, drug-like molecules through chemical synthesis has been challenging. In this study, a set of macrocyclic cyclophilin inhibitors was synthesized based on the core structure of the natural product sanglifehrin A. Initial compound optimization identified the valine-m-tyrosine-piperazic acid tripeptide (Val-m-Tyr-Pip) in the sanglifehrin core, stereocenters at C14 and C15, and the hydroxyl group of the m-tyrosine (m-Tyr) residue as key contributors to compound potency...
January 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28075412/the-antagonistic-effect-of-mycotoxins-deoxynivalenol-and-zearalenone-on-metabolic-profiling-in-serum-and-liver-of-mice
#11
Jian Ji, Pei Zhu, Fangchao Cui, Fuwei Pi, Yinzhi Zhang, Yun Li, Jiasheng Wang, Xiulan Sun
Metabolic profiling in liver and serum of mice was studied for the combined toxic effects of deoxynivalenol (DON) and zearalenone (ZEN), through gas chromatography mass spectrum. The spectrum of serum and liver sample of mice, treated with individual 2 mg/kg DON, 20 mg/kg ZEN, and the combined DON + ZEN with final concentration 2 mg/kg DON and 20 mg/kg ZEN for 21 days, were deconvoluted, aligned and identified with MS DIAL. The data matrix was processed with univariate analysis and multivariate analysis for selection of metabolites with variable importance for the projection (VIP) > 1, t-test p value < 0...
January 10, 2017: Toxins
https://www.readbyqxmd.com/read/28074955/total-synthesis-and-biological-activity-of-dolastatin-16
#12
Loida O Casalme, Arisa Yamauchi, Akinori Sato, Julie G Petitbois, Yasuyuki Nogata, Erina Yoshimura, Tatsufumi Okino, Taiki Umezawa, Fuyuhiko Matsuda
The total synthesis of dolastatin 16, a macrocyclic depsipeptide first isolated from the sea hare Dolabella auricularia as a potential antineoplastic metabolite by Pettit et al., was achieved in a convergent manner. Dolastatin 16 was reported by Tan to exhibit strong antifouling activity, and thus shows promise for inhibiting the attachment of marine benthic organisms such as Amphibalanus amphitrite to ships and submerged artificial structures. Therefore, dolastatin 16 is a potential compound for a new, environmentally friendly antifouling material to replace banned tributyltin-based antifouling paints...
January 11, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28074650/revisiting-the-val-ile-mutation-in-mammalian-and-bacterial-nitric-oxide-synthases-a-spectroscopic-and-kinetic-study
#13
Marine Weisslocker-Schaetzel, Mehdi Lembrouk, Jérôme Santolini, Pierre Dorlet
Nitric oxide is produced in mammals by the nitric oxide synthase (NOS) isoforms at a catalytic site comprising a heme associated with a biopterin cofactor. Through genome sequencing, proteins that are highly homologous to the oxygenase domain of NOSs have been identified, in particular in bacteria. The active site is highly conserved except for a valine residue in the distal pocket that is replaced with an isoleucine in bacteria. This switch was previously reported to influence the kinetics of the reaction...
January 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28071792/thermal-stability-improvement-of-rice-bran-albumin-protein-incorporated-with-epigallocatechin-gallate
#14
Zhongkai Zhou, Jingjing Xu, Yuqian Liu, Demei Meng, Xiaoli Sun, Hong Yi, Yunjing Gao, Guoyu Sun, Padraig Strappe, Chris Blanchard, Rui Yang
Rice bran albumin protein (RAP) is sensitive to thermal changes and tends to degrade when exposed to high-temperature processing. In this work, RAP-epigallocatechin-3-gallate (EGCG) complex (RAPE) was prepared and the thermal stability was evaluated. Fluorescence results showed that EGCG could interact with RAP with a binding number n of 0.0885:1 (EGCG:RAP, w/w) and a binding constant K of 1.02 (± 0.002) ×10(4) /M, suggesting both hydrogen bonding and van der Waals forces played an important role. FTIR analysis demonstrated that EGCG could induce secondary structural changes in RAP above a ratio of 1...
January 10, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28070705/enzymatic-activation-of-double-targeted-5-o-l-valyl-decitabine-prodrug-by-biphenyl-hydrolase-like-protein-and-its-molecular-design-basis
#15
Wenhui Tao, Dongyang Zhao, Mengchi Sun, Meng Li, Xiangyu Zhang, Zhonggui He, Yinghua Sun, Jin Sun
A primary focus of this research was to explore the activation process and mechanism of decitabine (5-aza-2'-deoxycytidine, DAC) prodrug. Recently, it has been reported that biphenyl hydrolase-like protein (BPHL) can play an important role in the activation of some amino acid nucleoside prodrugs with a general preference for hydrophobic amino acids and 5'-esters. Therefore, we put forward a bold hypothesis that this novel enzyme may be primarily responsible for the activation process of DAC prodrug as well...
January 9, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28064091/dose-response-characteristics-of-clematis-triterpenoid-saponins-and-clematichinenoside-ar-in-rheumatoid-arthritis-rats-by-liquid-chromatography-mass-spectrometry-based-serum-and-urine-metabolomics
#16
Rui Li, Lin-Xiu Guo, Yi Li, Wen-Qi Chang, Jian-Qun Liu, Li-Fang Liu, Gui-Zhong Xin
Clematidis Radix et Rhizoma is a traditional Chinese medicine widely used for treating arthritic disease. Clematis triterpenoid saponins (TS) and clematichinenoside AR (C-AR) have been considered to be responsible for its antiarthritic effects. However, the underling mechanism is still unclear because of their low bioavailability. To address of this issue, metabolomics tools were performed to determine metabolic variations associated with rheumatoid arthritis (RA) and responses to Clematis TS, C-AR and positive drug (Triptolide, TP) treatments...
December 29, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28062376/a-biotin-enrichment-strategy-identifies-novel-carbonylated-amino-acids-in-proteins-from-human-plasma
#17
Jesper F Havelund, Katarzyna Wojdyla, Michael J Davies, Ole N Jensen, Ian Max Møller, Adelina Rogowska-Wrzesinska
: Protein carbonylation is an irreversible protein oxidation correlated with oxidative stress, various diseases and ageing. Here we describe a peptide-centric approach for identification and characterisation of up to 14 different types of carbonylated amino acids in proteins. The modified residues are derivatised with biotin-hydrazide, enriched and characterised by tandem mass spectrometry. The strength of the method lies in an improved elution of biotinylated peptides from monomeric avidin resin using hot water (95°C) and increased sensitivity achieved by reduction of analyte losses during sample preparation and chromatography...
January 3, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28058725/urinary-metabolomics-of-complete-freund-s-adjuvant-induced-hyperalgesia-in-rats
#18
Yang Liu, Hui Chen, Jun Lu, Youshui Jiang, Rui Yang, Songyan Gao, Xin Dong, Wei Chen
The aim of this study was to demonstrate the differences of metabolomics changes in a hyperalgesia model and find potent biomarkers of hyperalgesia. Seven rats were placed in metabolic cages. An emulsion containing 500 μg of Complete Freund's adjuvant (CFA) was used to induce hyperalgesia. Urine samples were collected prior to the injection of CFA and on post-injection days 1, 3 and 7. Ultraperformance liquid chromatography, coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS), was used for a quantitative analysis of urinary metabolic changes in the CFA-induced hyperalgesia model...
November 5, 2016: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28053874/long-term-outcome-of-isobutyryl-coa-dehydrogenase-deficiency-diagnosed-following-an-episode-of-ketotic-hypoglycaemia
#19
S Santra, A Macdonald, M A Preece, R K Olsen, B S Andresen
Isobutyryl-CoA Dehydrogenase Deficiency (IBDD) is an inherited disorder of valine metabolism caused by mutations in ACAD8. Most reported patients have been diagnosed through newborn screening programmes due to elevated C4-carnitine levels and appear clinically asymptomatic. One reported non-screened patient had dilated cardiomyopathy and anaemia at the age of two years. We report a 13 month old girl diagnosed with IBDD after developing hypoglycaemic encephalopathy (blood glucose 1.9 mmol/l) during an episode of rotavirus-induced gastroenteritis...
March 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28043640/alternate-efflux-pump-mechanism-may-contribute-to-drug-resistance-in-extensively-drug-resistant-isolates-of-mycobacterium-tuberculosis
#20
Akbar Kanji, Rumina Hasan, Ambreen Zaver, Asho Ali, Kehkashan Imtiaz, Mussarat Ashraf, Taane G Clark, Ruth McNerney, Samreen Shafiq, Zahra Hasan
INTRODUCTION: Extensively drug-resistant tuberculosis (XDR-TB) has emerged as one of the biggest threats to public health and TB control programs worldwide. XDR-TB is caused by Mycobacterium tuberculosis (MTB) strains resistant to rifampin and isoniazid, as well as to a fluoroquinolone and to at least one injectable aminoglycoside. Drug resistance in MTB has primarily been associated with single nucleotide polymorphisms (SNPs) in particular genes. However, it has also been shown that efflux pumps may play a role in resistance of MTB...
December 2016: International Journal of Mycobacteriology
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