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https://www.readbyqxmd.com/read/28543538/clinical-and-histopathological-features-of-myofibrillar-myopathy-in-warmblood-horses
#1
S J Valberg, A M Nicholson, S S Lewis, R A Reardon, C J Finno
BACKGROUND: To report a novel exertional myopathy, myofibrillar myopathy (MFM), in Warmblood horses. OBJECTIVES: To 1) describe the distinctive clinical and myopathic features of MFM in Warmblood horses, 2) investigate the potential inheritance of MFM in a Warmblood family. STUDY DESIGN: Retrospective selection of MFM cases and prospective evaluation of a Warmblood family. METHODS: Retrospectively, muscle biopsies were selected from Warmblood horses diagnosed with MFM and clinical histories obtained (n = 10)...
May 22, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28504720/a-clinical-drug-library-screen-identifies-clobetasol-propionate-as-an-nrf2-inhibitor-with-potential-therapeutic-efficacy-in-keap1-mutant-lung-cancer
#2
E-J Choi, B-J Jung, S-H Lee, H-S Yoo, E-A Shin, H-J Ko, S Chang, S-Y Kim, S-M Jeon
The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2)pathway has a central role in cellular antioxidant defense. NRF2 activation due to KEAP1 or NRF2 mutations occurs frequently in many cancers, suggesting that NRF2 inhibition could be a promising therapeutic strategy. However, no potent NRF2 inhibitors are clinically available to date. To develop potent NRF2 inhibitors for therapeutic purpose, we screened ~4000 clinical compounds and determined clobetasol propionate (CP) as the most potent NRF2 inhibitor...
May 15, 2017: Oncogene
https://www.readbyqxmd.com/read/28500767/metformin-for-high-altitude-performance
#3
Martin Burtscher
Metformin has been introduced for treatment of type 2 diabetes but may also have ergogenic properties at high altitude by improving muscle glycogen repletion. However, very little information is available on potential risks associated with the (mis)use of metformin by healthy people. This article is protected by copyright. All rights reserved.
May 13, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28485573/radiosynthesis-and-in-vivo-evaluation-of-11-c-a1070722-a-high-affinity-gsk-3-pet-tracer-in-primate-brain
#4
Jaya Prabhakaran, Francesca Zanderigo, Kiran Kumar Solingapuram Sai, Harry Rubin-Falcone, Matthew J Jorgensen, Jay R Kaplan, Akiva Mintz, J John Mann, J S Dileep Kumar
Dysfunction of glycogen synthase kinase 3 (GSK-3) is implicated in the etiology of Alzheimer's disease, Parkinson's disease, diabetes, pain, and cancer. A radiotracer for functional positron emission tomography (PET) imaging could be used to study the kinase in brain disorders and to facilitate the development of small molecule inhibitors of GSK-3 for treatment. At present, there is no target-specific or validated PET tracer available for the in vivo monitoring of GSK-3. We radiolabeled the small molecule inhibitor [(11)C]1-(7-methoxy- quinolin-4-yl)-3-(6-(trifluoromethyl)pyridin-2-yl)urea ([(11)C]A1070722) with high affinity to GSK-3 (Ki = 0...
May 17, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28418865/anti-helminthic-niclosamide-inhibits-ras-driven-oncogenic-transformation-via-activation-of-gsk-3
#5
Sung Yong Ahn, Ji Hye Yang, Nam Hee Kim, Kyungro Lee, Yong Hoon Cha, Jun Seop Yun, Hee Eun Kang, Yoonmi Lee, Jiwon Choi, Hyun Sil Kim, Jong In Yook
Despite the importance of Ras oncogenes as a therapeutic target in human cancer, their 'undruggable' tertiary structures limit the effectiveness of anti-Ras drugs. Canonical Wnt signaling contributes to Ras activity by glycogen synthase kinase 3 (GSK-3)-dependent phosphorylation at the C-terminus and subsequent degradation. In the accompanying report, we show that the anti-helminthic niclosamide directly binds to GSK-3 and inhibits Axin functions in colon cancer cells, with reversion of Snail-mediated epithelial-mesenchymal transition...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28364639/the-impacts-of-emergent-pollutants-on-ruditapes-philippinarum-biochemical-responses-to-carbon-nanoparticles-exposure
#6
Lucia De Marchi, Victor Neto, Carlo Pretti, Etelvina Figueira, Federica Chiellini, Amadeu M V M Soares, Rosa Freitas
Multi-walled carbon nanotubes (MWCNTs) are one of the most important carbon Nanoparticles (NPs). The production and use of these NPs are increasing rapidly and, therefore, the need to assess their presence in the environment and associated risks has become of prime importance. Recent studies demonstrated the impacts of different NPs on bivalves, a taxonomic group where species tolerance to anthropogenic stressors, such as pollutants, is widely variable. The Manila clam Ruditapes philippinarum is one of the most commonly used bivalve species in environmental monitoring studies and ecotoxicology tests, however, to our knowledge, no information is available on biochemical alterations on this species due to MWCNTs exposure...
June 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28360839/emerging-roles-for-glycogen-in-the-cns
#7
REVIEW
Alice E Waitt, Liam Reed, Bruce R Ransom, Angus M Brown
The ability of glycogen, the depot into which excess glucose is stored in mammals, to act as a source of rapidly available energy substrate, has been exploited by several organs for both general and local advantage. The liver, expressing the highest concentration of glycogen maintains systemic normoglycemia ensuring the brain receives a supply of glucose in excess of demand. However the brain also contains glycogen, although its role is more specialized. Brain glycogen is located exclusively in astrocytes in the adult, with the exception of pathological conditions, thus in order to benefit neurons, and energy conduit (lactate) is trafficked inter-cellularly...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28358334/glucose-plus-fructose-ingestion-for-post-exercise-recovery-greater-than-the-sum-of-its-parts
#8
REVIEW
Javier T Gonzalez, Cas J Fuchs, James A Betts, Luc J C van Loon
Carbohydrate availability in the form of muscle and liver glycogen is an important determinant of performance during prolonged bouts of moderate- to high-intensity exercise. Therefore, when effective endurance performance is an objective on multiple occasions within a 24-h period, the restoration of endogenous glycogen stores is the principal factor determining recovery. This review considers the role of glucose-fructose co-ingestion on liver and muscle glycogen repletion following prolonged exercise. Glucose and fructose are primarily absorbed by different intestinal transport proteins; by combining the ingestion of glucose with fructose, both transport pathways are utilised, which increases the total capacity for carbohydrate absorption...
March 30, 2017: Nutrients
https://www.readbyqxmd.com/read/28342896/neuroprotective-and-axonal-outgrowth-promoting-effects-of-tetramethylpyrazine-nitrone-in-chronic-cerebral-hypoperfusion-rats-and-primary-hippocampal-neurons-exposed-to-hypoxia
#9
Tao Zhang, Jianbo Gu, Liangmiao Wu, Ning Li, Yewei Sun, Pei Yu, Yuqiang Wang, Gaoxiao Zhang, Zaijun Zhang
Chronic cerebral hypoperfusion is an important risk factor for vascular dementia and other brain dysfunctions, for which there are currently no effective medications available. We investigated the neuroprotective and axonal outgrowth promoting effects of tetramethylpyrazine nitrone (TBN) in a permanent bilateral occlusion of the common carotid arteries (2VO) rat model and in primary hippocampal neurons exposed to oxygen glucose deprivation (OGD). At 6th week after 2VO, TBN increased the time spent in novel arms in the Y-maze test and improved the discrimination ratio in object reorganization task...
May 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28329151/caloric-restriction-and-rapamycin-differentially-alter-energy-metabolism-in-yeast
#10
Kyung-Mi Choi, Seok-Jin Hong, Jan M van Deursen, Sooah Kim, Kyoung Heon Kim, Cheol-Koo Lee
Rapamycin (RM), a drug that inhibits the mechanistic target of rapamycin (mTOR) pathway and responds to nutrient availability, seemingly mimics the effects of caloric restriction (CR) on healthy life span. However, the extent of the mechanistic overlap between RM and CR remains incompletely understood. Here, we compared the impact of CR and RM on cellular metabolic status. Both regimens maintained intracellular ATP through the chronological aging process and showed enhanced mitochondrial capacity. Comparative transcriptome analysis showed that CR had a stronger impact on global gene expression than RM...
March 8, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28326005/bioactivity-of-food-peptides-biological-response-of-rats-to-bovine-milk-whey-peptides-following-acute-exercise
#11
Carolina Soares Moura, Pablo Christiano Barboza Lollo, Priscila Neder Morato, Eder Muller Risso, Jaime Amaya-Farfan
Background: Several physiologically beneficial effects of consuming a whey protein hydrolysate (WPH) have been attributed to the greater availability of bioactive peptides. Aims: The aim was to investigate the effect of four branched-chain amino acid- (BCAA-)containing dipeptides, present in WPH, on immune modulation, stimulation of HSP expression, muscle protein synthesis, glycogen content, satiety signals and the impact of these peptides on the plasma free amino acid profiles. Methods: The animals were divided in groups: control (rest, without gavage), vehicle (water), L-isoleucyl-L-leucine (lle-Leu), L-leucyl-L-isoleucine (Leu-lle), L-valyl-Lleucine (Val-Leu), L-leucyl-L-valine (Leu-Val) and WPH...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28290602/ajs1669-a-novel-small-molecule-muscle-glycogen-synthase-activator-improves-glucose-metabolism-and-reduces-body-fat-mass-in-mice
#12
Kazuhiro Nakano, Sen Takeshita, Noriko Kawasaki, Wataru Miyanaga, Yoriko Okamatsu, Mizuki Dohi, Tadakiyo Nakagawa
Impaired glycogen synthesis and turnover are common in insulin resistance and type 2 diabetes. As glycogen synthase (GS) is a key enzyme involved in the synthetic process, it presents a promising therapeutic target for the treatment of type 2 diabetes. In the present study, we identified a novel, potent and orally available GS activator AJS1669 {sodium 2-[[5-[[4-(4,5-difluoro-2-methylsulfanyl-phenyl)phenoxy] methyl]furan-2-carbonyl]-(2-furylmethyl)amino] acetate}. In vitro, we performed a glycogen synthase 1 (GYS1) activation assay for screening GS activators and identified that the activity of AJS1669 was further potentiated in the presence of glucose-6-phosphate (G6P)...
April 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28290249/in-vitro-and-in-silico-studies-of-mangiferin-from-aphloia-theiformis-on-key-enzymes-linked-to-diabetes-type-2-and-associated-complications
#13
Marie C N Picot, Gokhan Zengin, Adriano Mollica, Azzurra Stefanucci, Simone Carradori, Mohamad F Mahomoodally
BACKGROUND: Mangiferin, was identified in the crude methanol extract, ethyl acetate, and n-butanol fractions of Aphloia theiformis (Vahl.) Benn. OBJECTIVE: To study the plausible binding modes of mangiferin to key enzymes linked to diabetes type 2 (DT2), obesity, hypertension, Alzheimer's disease, and urolithiasis using molecular docking. METHOD: Crystallographic structures of α-amylase, α-glucosidase, glycogen phosphorylase (GP), pancreatic lipase, cholesterol esterase (CEase), angiotensin-I-converting enzyme (ACE), acetyl cholinesterase (AChE), and urease available on the Protein Databank database were docked to mangiferin using Gold 6...
March 7, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28284548/relationships-between-metal-compartmentalization-and-biomarkers-in-earthworms-exposed-to-field-contaminated-soils
#14
Léa Beaumelle, Mickaël Hedde, Franck Vandenbulcke, Isabelle Lamy
Partitioning tissue metal concentration into subcellular compartments reflecting toxicologically available pools may provide good descriptors of the toxicological effects of metals on organisms. Here we investigated the relationships between internal compartmentalization of Cd, Pb and Zn and biomarker responses in a model soil organism: the earthworm. The aim of this study was to identify metal fractions reflecting the toxic pressure in an endogeic, naturally occurring earthworm species (Aporrectodea caliginosa) exposed to realistic field-contaminated soils...
March 8, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28241986/short-fasting-does-not-protect-perfused-ex%C3%A2-vivo-rat-liver-against-ischemia-reperfusion-on-the-importance-of-a-minimal-cell-energy-charge
#15
Bérengère Papegay, Michaela Stadler, Vincent Nuyens, Véronique Kruys, Jean G Boogaerts, Joseph Vamecq
OBJECTIVE: Dietary restriction or reduced food intake was supported to protect against renal and hepatic ischemic injury. In this vein, short fasting was recently shown to protect in situ rat liver against ischemia-reperfusion. Here, perfused ex vivo instead of in situ livers were exposed to ischemia-reperfusion to study the impact of disconnecting liver from extrahepatic supply in energetic substrates on the protection given by short-term fasting. METHODS: Perfused ex vivo livers using short (18 h) fasted compared with fed rats were submitted to ischemia-reperfusion and studied for release of cytolysis markers in the perfusate...
March 2017: Nutrition
https://www.readbyqxmd.com/read/28216152/1-25-dihydroxyvitamin-d3-prevents-the-development-of-diabetic-cardiomyopathy-in-type-1-diabetic-rats-by-enhancing-autophagy-via-inhibiting-the-%C3%AE-catenin-tcf4-gsk-3%C3%AE-mtor-pathway
#16
Huili Wei, Hua Qu, Hang Wang, Baolan Ji, Yao Ding, Dan Liu, Yang Duan, Huimin Liang, Chuan Peng, Xiaoqiu Xiao, Huacong Deng
Diabetic cardiomyopathy (DCM) can increase the risk of heart failure and death in diabetic patients. However, no effective approaches are available to prevent its progression and development. Studies have shown that vitamin D is greatly implicated in cardiac hypertrophy and fibrosis, and there is a high prevalence of vitamin D deficiency in diabetic patients. In this study, we investigated whether 1,25-Dihydroxyvitamin-D3 (1,25D3) can improve DCM through a vitamin D receptor (VDR)-dependent mechanism associated with autophagy and the β-catenin/T-cell factor/lymphoid enhancer factor (TCF4)/glycogen synthase kinase-3β (GSK-3β)/mammalian target of rapamycin (mTOR) pathway...
April 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28215887/nitrogen-source-and-concentration-affect-utilization-of-glucose-by-mixed-ruminal-microbes-in-vitro
#17
M B Hall
The availability of rumen-degradable protein (RDP) changes the use of carbohydrates by ruminal microbes. However, the effects of RDP on the simultaneous use of carbohydrate and formation of microbial products are not well described, although such information is needed to understand the potential effect on nutrient supplies for ruminants. The objective of this in vitro study was to compare the effects of different levels of RDP (0.15, 0.31, 0.46 g of N/L) from tryptone (Tryp) or urea (Ur) on product formation from glucose in fermentations with mixed ruminal microbes...
April 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28176283/effect-of-nitrogen-availability-on-the-poly-3-d-hydroxybutyrate-accumulation-by-engineered-saccharomyces-cerevisiae
#18
Diogo J Portugal-Nunes, Sudhanshu S Pawar, Gunnar Lidén, Marie F Gorwa-Grauslund
Poly-3-D-hydroxybutyrate (or PHB) is a polyester which can be used in the production of biodegradable plastics from renewable resources. It is naturally produced by several bacteria as a response to nutrient starvation in the excess of a carbon source. The yeast Saccharomyces cerevisiae could be an alternative production host as it offers good inhibitor tolerance towards weak acids and phenolic compounds and does not depolymerize the produced PHB. As nitrogen limitation is known to boost the accumulation of PHB in bacteria, the present study aimed at investigating the effect of nitrogen availability on PHB accumulation in two recombinant S...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28167604/gs-dreadd-knock-in-mice-for-tissue-specific-temporal-stimulation-of-cyclic-amp-signaling
#19
Dmitry Akhmedov, Maria G Mendoza-Rodriguez, Kavitha Rajendran, Mario Rossi, Jürgen Wess, Rebecca Berdeaux
Hundreds of hormones and ligands stimulate cyclic AMP (cAMP) signaling in different tissues through the activation of G-protein-coupled receptors (GPCRs). Although the functions and individual effectors of cAMP signaling are well characterized in many tissues, pleiotropic effects of GPCR agonists limit investigations of physiological functions of cAMP signaling in individual cell types at different developmental stages in vivo To facilitate studies of cAMP signaling in specific cell populations in vivo, we harnessed the power of DREADD (designer receptors exclusively activated by designer drugs) technology by creating ROSA26-based knock-in mice for the conditional expression of a Gs-coupled DREADD (rM3Ds-green fluorescent protein [GFP], or "GsD")...
May 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28153019/the-effect-of-enhanced-acetate-influx-on-synechocystis-sp-pcc-6803-metabolism
#20
Kati Thiel, Eerika Vuorio, Eva-Mari Aro, Pauli Tapio Kallio
BACKGROUND: Acetate is a common microbial fermentative end-product, which can potentially be used as a supplementary carbon source to enhance the output of biotechnological production systems. This study focuses on the acetate metabolism of the photosynthetic cyanobacterium Synechocystis sp. PCC 6803 which is unable to grow on acetate as a sole carbon source but still can assimilate it via acetyl-CoA-derived metabolic intermediates. In order to gain insight into the acetate uptake, associated limitations and metabolic effects, a heterologous acetate transporter ActP from Escherichia coli was introduced into Synechocystis to facilitate the transport of supplemented acetate from the medium into the cell...
February 2, 2017: Microbial Cell Factories
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