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https://www.readbyqxmd.com/read/28302016/validation-of-tzd-scaffold-as-potential-aris-pharmacophore-modelling-atom-based-3d-qsar-and-docking-studies
#1
Lalita Dahiya, Manoj Kumar Mahapatra, Ramandeep Kaur, Vipin Kumar, Manoj Kumar
Metabolic disorders associated with diabetic patients are a serious concern. Aldose reductase (ALR2) has been identified as first rate-limiting enzyme in the polyol pathway which catalyzes the reduction of glucose to sorbitol. It represents one of the validated targets to develop potential new chemical entities for the prevention and subsequent progression of microvascular diabetic complications. In order to further understand the intricate structural prerequisites of molecules to act as ALR2 inhibitors, ligand-based pharmacophore model, atom-based 3D-QSAR and structure based drug design studies have been performed on a series of 2,4-thiazolidinedione derivatives with ALR2 inhibitory activity...
March 15, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28259841/enhancing-activity-and-selectivity-in-a-series-of-pyrrol-1-yl-1-hydroxypyrazole-based-aldose-reductase-inhibitors-the-case-of-trifluoroacetylation
#2
Nikolaos Papastavrou, Maria Chatzopoulou, Jana Ballekova, Mario Cappiello, Roberta Moschini, Francesco Balestri, Alexandros Patsilinakos, Rino Ragno, Milan Stefek, Ioannis Nicolaou
Aldose reductase (ALR2) has been the target of therapeutic intervention for over 40 years; first, for its role in long-term diabetic complications and more recently as a key mediator in inflammation and cancer. However, efforts to prepare small-molecule aldose reductase inhibitors (ARIs) have mostly yielded carboxylic acids with rather poor pharmacokinetics. To address this limitation, the 1-hydroxypyrazole moiety has been previously established as a bioisostere of acetic acid in a group of aroyl-substituted pyrrolyl derivatives...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28257804/characterization-and-cellular-localization-of-human-5-lipoxygenase-and-its-protein-isoforms-5-lo%C3%AE-13-5-lo%C3%AE-4-and-5-lop12
#3
Ann-Katrin Ball, Kim Beilstein, Sandra Wittmann, Duran Sürün, Meike J Saul, Frank Schnütgen, Nicolas Flamand, Ricardo Capelo, Astrid S Kahnt, Helena Frey, Liliana Schaefer, Rolf Marschalek, Ann-Kathrin Häfner, Dieter Steinhilber
Human 5-lipoxygenase (5-LO-WT) initiates the leukotriene (LT) biosynthesis. LTs play an important role in diseases like asthma, atherosclerosis and in many types of cancer. In this study, we investigated the 5-LO isoforms 5-LO∆13, 5-LO∆4 and 5-LOp12, lacking the exons 13, 4 or a part of exon 12, respectively. We were able to detect the mRNA of the isoforms 5-LO∆13 and 5-LOp12 in B and T cell lines as well as in primary B and T cells and monocytes. Furthermore, we found that expression of 5-LO and particularly of the 5-LO∆13 and 5-LOp12 isoforms is increased in monocytes from patients with rheumatoid arthritis and sepsis...
February 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28244665/fodmaps-food-composition-defining-cutoff-values-and-international-application
#4
REVIEW
Jane Varney, Jacqueline Barrett, Kate Scarlata, Patsy Catsos, Peter R Gibson, Jane G Muir
The low-FODMAP diet is a new dietary therapy for the management of irritable bowel syndrome that is gaining in popularity around the world. Developing the low-FODMAP diet required not only extensive food composition data but also the establishment of "cutoff values" to classify foods as low-FODMAP. These cutoff values relate to each particular FODMAP present in a food, including oligosaccharides (fructans and galacto-oligosaccharides), sugar polyols (mannitol and sorbitol), lactose, and fructose in excess of glucose...
March 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28241810/enhancing-the-thermostability-of-%C3%AE-l-rhamnosidase-from-aspergillus-terreus-and-the-enzymatic-conversion-of-rutin-to-isoquercitrin-by-adding-sorbitol
#5
Lin Ge, Anna Chen, Jianjun Pei, Linguo Zhao, Xianying Fang, Gang Ding, Zhenzhong Wang, Wei Xiao, Feng Tang
BACKGROUND: Thermally stable α-L-rhamnosidase with cleaving terminal α-L-rhamnose activity has great potential in industrial application. Therefore, it is necessary to find a proper method to improve the thermal stability of α-L-rhamnosidase. RESULTS: In this study, addition of sorbitol has been found to increase the thermostability of α-L-rhamnosidase from Aspergillus terreus at temperatures ranging from 65 °C to 80 °C. Half-life and activation free energy with addition of 2...
February 27, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28239653/the-human-brain-produces-fructose-from-glucose
#6
Janice J Hwang, Lihong Jiang, Muhammad Hamza, Feng Dai, Renata Belfort-DeAguiar, Gary Cline, Douglas L Rothman, Graeme Mason, Robert S Sherwin
Fructose has been implicated in the pathogenesis of obesity and type 2 diabetes. In contrast to glucose, CNS delivery of fructose in rodents promotes feeding behavior. However, because circulating plasma fructose levels are exceedingly low, it remains unclear to what extent fructose crosses the blood-brain barrier to exert CNS effects. To determine whether fructose can be endogenously generated from glucose via the polyol pathway (glucose → sorbitol → fructose) in human brain, 8 healthy subjects (4 women/4 men; age, 28...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28222384/direct-catalytic-production-of-sorbitol-from-waste-cellulosic-materials
#7
Lucília Sousa Ribeiro, José J de Melo Órfão, Manuel Fernando Ribeiro Pereira
Cotton wool, cotton textile, tissue paper and printing paper, all potential waste cellulosic materials, were directly converted to sorbitol using a Ru/CNT catalyst in the presence of H2 and using only water as solvent, without any acids. Conversions up to 38% were attained for the raw substrates, with sorbitol yields below 10%. Ball-milling of the materials disrupted their crystallinity, allowing reaching 100% conversion of cotton wool, cotton textile and tissue paper after 4h, with sorbitol yields around 50%...
February 8, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28220113/diverse-plant-associated-pleosporalean-fungi-from-saline-areas-ecological-tolerance-and-nitrogen-status-dependent-effects-on-plant-growth
#8
Yuan Qin, Xueyu Pan, Christian Kubicek, Irina Druzhinina, Komal Chenthamara, Jessy Labbé, Zhilin Yuan
Similar to mycorrhizal mutualists, the rhizospheric and endophytic fungi are also considered to act as active regulators of host fitness (e.g., nutrition and stress tolerance). Despite considerable work in selected model systems, it is generally poorly understood how plant-associated fungi are structured in habitats with extreme conditions and to what extent they contribute to improved plant performance. Here, we investigate the community composition of root and seed-associated fungi from six halophytes growing in saline areas of China, and found that the pleosporalean taxa (Ascomycota) were most frequently isolated across samples...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28209457/metabolomic-approach-reveals-the-biochemical-mechanisms-underlying-drought-stress-tolerance-in-thyme
#9
Parviz Moradi, Brian Ford-Lloyd, Jeremy Pritchard
Thyme as a perennial herb has been recognized globally for its antimicrobial, antiseptic and spasmolytic effects. In this investigation, we have used non-targeted metabolite and volatile profiling combined with the morpho-physiological parameters in order to understand the responses at the metabolite and physiological level in drought sensitive and tolerant thyme plant populations. The results at the metabolic level identified the significantly affected metabolites. Significant metabolites belonging to different chemical classes consisting amino acids, carbohydrates, organic acids and lipids have been compared in tolerant and sensitive plants...
February 14, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28208627/phytochemical-analysis-of-agrimonia-pilosa-ledeb-its-antioxidant-activity-and-aldose-reductase-inhibitory-potential
#10
Set Byeol Kim, Seung Hwan Hwang, Hong-Won Suh, Soon Sung Lim
The aim of this study was to determine aldose reductase (AR) inhibitory activity and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity of compounds from Agrimonia pilosa Ledeb (AP). We isolated agrimoniin (AM), four flavonoid glucosides and two flavonoid glucuronides from the n-butanol fraction of AP 50% methanol extract. In addition to isolated compounds, the AR-inhibitory activity and the DPPH free radical scavenging activity of catechin, 5-flavonoids, and 4-flavonoid glucosides (known components of AP) against rat lens AR (RLAR) and DPPH assay were measured...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207877/selective-inhibition-of-aggregation-fibrillation-of-bovine-serum-albumin-by-osmolytes-mechanistic-and-energetics-insights
#11
Moumita Dasgupta, Nand Kishore
Bovine serum albumin (BSA) is an important transport protein of the blood and its aggregation/fibrillation would adversely affect its transport ability leading to metabolic disorder. Therefore, understanding the mechanism of fibrillation/aggregation of BSA and design of suitable inhibitor molecules for stabilizing its native conformation, are of utmost importance. The qualitative and quantitative aspects of the effect of osmolytes (proline, hydroxyproline, glycine betaine, sarcosine and sorbitol) on heat induced aggregation/fibrillation of BSA at physiological pH (pH 7...
2017: PloS One
https://www.readbyqxmd.com/read/28207302/characteristics-of-shiga-toxin-producing-escherichia-coli-o157-in-slaughtered-reindeer-from-northern-finland
#12
Claudio Zweifel, Lisa Fierz, Nicole Cernela, Sauli Laaksonen, Maria Fredriksson-Ahomaa, Roger Stephan
Fecal samples collected from 470 slaughtered reindeer 6 to 7 months of age were screened by real-time PCR (after enrichment) for Shiga toxin genes (stx) and then for Escherichia coli serogroup O157. Shiga toxin genes were found frequently (>30% of samples), and serogroup O157 was detected in 20% of the stx-positive samples. From these samples, a total of 25 E. coli O157:H(-) isolates (nonmotile but PCR positive for fliCH7) were obtained. Twenty-four of these E. coli O157:H(-) isolates did not ferment sorbitol and originated from one geographic area...
February 16, 2017: Journal of Food Protection
https://www.readbyqxmd.com/read/28194018/protective-role-of-fructokinase-blockade-in-the-pathogenesis-of-acute-kidney-injury-in-mice
#13
Ana Andres-Hernando, Nanxing Li, Christina Cicerchi, Shinichiro Inaba, Wei Chen, Carlos Roncal-Jimenez, Myphuong T Le, Michael F Wempe, Tamara Milagres, Takuji Ishimoto, Mehdi Fini, Takahiko Nakagawa, Richard J Johnson, Miguel A Lanaspa
Acute kidney injury is associated with high mortality, especially in intensive care unit patients. The polyol pathway is a metabolic route able to convert glucose into fructose. Here we show the detrimental role of endogenous fructose production by the polyol pathway and its metabolism through fructokinase in the pathogenesis of ischaemic acute kidney injury (iAKI). Consistent with elevated urinary fructose in AKI patients, mice undergoing iAKI show significant polyol pathway activation in the kidney cortex characterized by high levels of aldose reductase, sorbitol and endogenous fructose...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28191945/engineered-surface-immobilized-enzyme-that-retains-high-levels-of-catalytic-activity-in-air
#14
Somayesadat Badieyan, Qiuming Wang, Xingquan Zou, Yaoxin Li, Maggie Herron, Nicholas L Abbott, Zhan Chen, E Neil G Marsh
In the absence of aqueous buffer, most enzymes retain little or no activity; however, "water-free" enzymes would have many diverse applications. Here, we describe the chemically precise immobilization of an enzyme on an engineered surface designed to support catalytic activity in air at ambient humidity. Covalent immobilization of haloalkane dehalogenase on a surface support displaying poly(sorbitol methacrylate) chains resulted in ∼40-fold increase in activity over lyophilized enzyme powders for the gas-phase dehalogenation of 1-bromopropane...
February 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28177738/sorbitol-increases-muscle-glucose-uptake-ex-vivo-and-inhibits-intestinal-glucose-absorption-ex-vivo-and-in-normal-and-type-2-diabetic-rats
#15
Chika I Chukwuma, Md Shahidul Islam
Previous studies have suggested that sorbitol, a known polyol sweetener possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using <i>ex vivo </i>and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC<sub>50</sub> = 14...
December 12, 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28177569/the-oxidized-thiol-proteome-in-aging-and-cataractous-mouse-and-human-lens-revealed-by-icat-labeling
#16
Benlian Wang, Grant Hom, Sheng Zhou, Minfei Guo, Binbin Li, Jing Yang, Vincent M Monnier, Xingjun Fan
Age-related cataractogenesis is associated with disulfide-linked high molecular weight (HMW) crystallin aggregates. We recently found that the lens crystallin disulfidome was evolutionarily conserved in human and glutathione-depleted mouse (LEGSKO) cataracts and that it could be mimicked by oxidation in vitro (Mol. Cell Proteomics, 14, 3211-23 (2015)). To obtain a comprehensive blueprint of the oxidized key regulatory and cytoskeletal proteins underlying cataractogenesis, we have now used the same approach to determine, in the same specimens, all the disulfide-forming noncrystallin proteins identified by ICAT proteomics...
April 2017: Aging Cell
https://www.readbyqxmd.com/read/28171819/mobilisation-of-microbial-indicators-microbial-source-tracking-markers-and-pathogens-after-rainfall-events
#17
Cristina García-Aljaro, Julia Martín-Díaz, Enric Viñas-Balada, William Calero-Cáceres, Francisco Lucena, Anicet R Blanch
Climate change is expected to affect the Mediterranean region by causing an increase in the number of heavy rainfall events. The aim of this study was to assess the effect of extreme river flow variations due to rainfall on the persistence and mobilisation of various microorganisms. These included faecal pollution indicators (Escherichia coli (EC), somatic coliphages (SOMCPH) and sulphite reducing clostridia spores (SRC)), microbial source tracking indicators (Bacteroides thetaiotaomicron GA17 strain phages (GA17PH) and sorbitol fermenting bifidobacteria (SFBIF)), and two pathogens (Salmonella spp and Enterovirus)...
February 2, 2017: Water Research
https://www.readbyqxmd.com/read/28157063/safe-excipient-exposure-in-neonates-and-small-children-protocol-for-the-seen-project
#18
Kristine Svinning Valeur, Steen Axel Hertel, Kaare Engell Lundstrøm, Helle Holst
INTRODUCTION: The pharmacokinetics of excipients in neonates differs from that of older children. In a recent pan--European survey, two thirds of neonates received at least one potentially harmful excipient, such as ethanol and benzoates. The content of sweeteners varied by route of administration (more common by enteral than parenteral route), and regional differences were revealed. The survey did not identify if the content of excipients was more pronounced in medications prescribed for specific medical diseases, e...
February 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/28153595/phenolic-compounds-the-inhibition-effect-on-polyol-pathway-enzymes
#19
Hatice Esra Aslan, Şükrü Beydemir
The polyol pathway called as sorbitol way is a small part of glycose metabolism. The pathway is regarded as an important element in the pathogenesis of various diabetic complications in individuals with diabetes mellitus. The pathway plays a crucial role in hyperglycemia. The polyol pathway contains two enzymes as aldose reductase (AR) and sorbitol dehydrogenase (SDH). In the present study, AR and SDH were purified from sheep liver by using simple chromatographic methods. AR was purified with a yield of 2.11% and approximately 162 fold and SDH was purified with a yield of 0...
March 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28144651/switching-chirality-in-the-assemblies-of-bio-based-amphiphiles-solely-by-varying-their-alkyl-chain-length
#20
Pei Zhang, Jun Ma, Xinchen Kang, Huizhen Liu, Chunjun Chen, Zhanrong Zhang, Jianling Zhang, Buxing Han
Here we show that chirality inversion can be realized solely by changing the alkyl chain length of sorbitol-alkylamine surfactants. The chirality switch phenomenon is attributed to twisting of a headgroup, which depends on the balance between hydrophobic interaction and torsional stress, resulting in various orientational orders in assemblies and chirality inversion.
February 9, 2017: Chemical Communications: Chem Comm
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