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https://www.readbyqxmd.com/read/28067100/effects-of-a-single-bout-of-strenuous-exercise-on-platelet-activation-in-female-apoe-ldlr-mice
#1
K Przyborowski, H Kassassir, M Wojewoda, K Kmiecik, B Sitek, K Siewiera, A Zakrzewska, A M Rudolf, R Kostogrys, C Watala, J A Zoladz, S Chlopicki
Strenuous physical exercise leads to platelet activation that is normally counterbalanced by the production of endothelium-derived anti-platelet mediators, including prostacyclin (PGI2) and nitric oxide (NO). However, in the case of endothelial dysfunction, e.g. in atherosclerosis, there exists an increased risk for intravascular thrombosis during exercise that might be due to an impairment in endothelial anti-platelet mechanisms. In the present work, we evaluated platelet activation at rest and following a single bout of strenuous treadmill exercise in female ApoE/LDLR(-)(/-) mice with early (3-month-old) and advanced (7-month-old) atherosclerosis compared to female age-matched WT mice...
January 9, 2017: Platelets
https://www.readbyqxmd.com/read/28007565/mechanism-of-degradation-of-an-%C3%AE-keto-epoxide-a-model-for-the-warhead-for-various-proteasome-inhibitor-anticancer-agents
#2
Kirsten M Phizackerley, Mouhannad Jumaa, Antonio Lopalco, Bradley H Wolfe, Christopher D Ablan, Valentino J Stella
The anti-cancer agent, carfilzomib has a unique α-keto-epoxide warhead. The model α-keto-epoxide, N-((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)pivalamide (1) along with a few of its degradation products were synthesized and studied. The kinetics of hydrolysis and identification of some of the degradation products of 1 were performed at pH values 2, 4, 5, 7 and 8 at 25°C, 40°C and 60°C and followed by HPLC and LC-MS, respectively. 1 degraded independent of pH between pH values 4 to 7 but showed some acid catalysis at pH 2 and base catalysis at pH 8...
December 19, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28003063/increased-potential-for-wound-activated-production-of-prostaglandin-e2-and-related-toxic-compounds-in-non-native-populations-of-gracilaria-vermiculophylla
#3
Mareike Hammann, Martin Rempt, Georg Pohnert, Gaoge Wang, Sung Min Boo, Florian Weinberger
The capacity of the East Asian seaweed Gracilaria vermiculophylla ("Ogonori") for production of prostaglandin E2 from arachidonic acid occasionally causes food poisoning after ingestion. During the last two decades the alga has been introduced to Europe and North America. Non-native populations have been shown to be generally less palatable to marine herbivores than native populations. We hypothesized that the difference in palatability among populations could be due to differences in the algal content of prostaglandins...
January 2016: Harmful Algae
https://www.readbyqxmd.com/read/27986991/recombinant-expression-and-characterization-of-a-l-amino-acid-oxidase-from-the-fungus-rhizoctonia-solani
#4
Katharina Hahn, Katrin Neumeister, Andreas Mix, Tilman Kottke, Harald Gröger, Gabriele Fischer von Mollard
L-Amino acid oxidases (L-AAOs) catalyze the oxidative deamination of L-amino acids to the corresponding α-keto acids, ammonia, and hydrogen peroxide. L-AAOs are homodimeric enzymes with FAD as a non-covalently bound cofactor. They are of potential interest for biotechnological applications. However, heterologous expression has not succeeded in producing large quantities of active recombinant L-AAOs with a broad substrate spectrum so far. Here, we report the heterologous expression of an active L-AAO from the fungus Rhizoctonia solani in Escherichia coli as a fusion protein with maltose-binding protein (MBP) as a solubility tag...
December 16, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27980494/in-vivo-osteoinduction-evaluating-2-beta-coxatene-as-an-immunoinductive-compound-and-novel-ingredient-for-joint-support
#5
Katherine Spinks, James J Scaffidi
CONTEXT: Osteoarthritis (OA) is a degenerative joint disease characterized by progressive loss of articular cartilage. Many treatments lack the ability to stimulate the growth of native cartilage tissue while they simultaneously increase joint comfort. For the past few decades, dietary supplements have been investigated for the ability to both address joint inflammation and stimulate cartilage tissue. OBJECTIVES: The present study intended to examine the supplement's in vivo osteoinductive capabilities and clinical efficacy for overall joint health...
October 2016: Integrative Medicine
https://www.readbyqxmd.com/read/27979258/carotenoids-and-carotenoid-esters-of-orange-and-yellow-fleshed-mamey-sapote-pouteria-sapota-jacq-h-e-moore-stearn-fruit-and-their-post-prandial-absorption-in-humans
#6
Tania Chacón-Ordóñez, Ralf M Schweiggert, Anja Bosy-Westphal, Víctor M Jiménez, Reinhold Carle, Patricia Esquivel
Although different genotypes of mamey sapote with distinct pulp colors are consumed in countries from Central to South America, in-depth knowledge on genotype-related differences of their carotenoid profile is lacking. Since the fruit was found to contain the potentially vitamin A-active keto-carotenoids sapotexanthin and cryptocapsin, we sought to qualitatively and quantitatively describe the carotenoid profile of different genotypes by HPLC-DAD-MS(n). Sapotexanthin and cryptocapsin were present in all genotypes...
April 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/27951728/effects-of-astaxanthin-on-blood-coagulation-fibrinolysis-and-platelet-aggregation-in-hyperlipidemic-rats
#7
Zu-Yue Deng, Wei-Guang Shan, Shen-Feng Wang, Meng-Mei Hu, Yan Chen
CONTEXT: Astaxanthin (ASTX) is a xanthophyll carotenoid that reduces hemostasis in hyperlipidemic organisms. Its antihemostatic mechanisms remain unclear. OBJECTIVE: The effects of ASTX on coagulation, the fibrinolytic system and platelet aggregation were investigated in hyperlipidemic rats. MATERIALS AND METHODS: Different doses of ASTX (5, 10 and 30 mg/kg/day, p.o.) were administered for four weeks to high-fat diet-induced hyperlipidemic rats...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27940118/screening-of-luzula-species-native-to-the-carpathian-basin-for-anti-inflammatory-activity-and-bioactivity-guided-isolation-of-compounds-from-luzula-luzuloides-lam-dandy-wilmott
#8
Barbara Tóth, Fang-Rong Chang, Tsong-Long Hwang, Ádám Szappanos, Attila Mándi, Attila Hunyadi, Tibor Kurtán, Gusztáv Jakab, Judit Hohmann, Andrea Vasas
The present study focused on the anti-inflammatory screening of Luzula species native to the Carpathian Basin and bioactivity-guided isolation of compounds of Luzula luzuloides (Lam.) Dandy & Wilmott. The anti-inflammatory properties of extracts with different polarity prepared from Luzula species were determined. Among them, the CH2Cl2-soluble fraction of L. luzuloides possessed strong inhibitory effects on superoxide anion generation (99.39±0.37%) and elastase release (114.22±3.13%) in fMLP/CB-induced human neutrophils at concentration of 10μg/mL...
January 2017: Fitoterapia
https://www.readbyqxmd.com/read/27935701/cobalt-catalyzed-6-2-cycloaddition-of-alkynes-with-1-3-5-7-cyclooctatetraene-as-a-key-element-in-the-direct-construction-of-substituted-bicyclo-4-3-1-decanes
#9
Vladimir A D'yakonov, Gulnara N Kadikova, Lilya U Dzhemileva, Guzel F Gazizullina, Ilfir R Ramazanov, Usein M Dzhemilev
A new, effective catalytic system based on Co(acac)2 has been developed for [6 + 2] cycloaddition of terminal alkynes to 1,3,5,7-cyclooctatetraene to give substituted bicyclo[4.2.2]deca-2,4,7,9-tetraenes in high yields (68-85%). The electrophilic activation of double bonds in the bicyclic products with m-CPBA is an efficient method for the synthesis of substituted bicyclo[4.3.1]deca-2,4,8-triene-7,10-diols, which form the key structural moieties of numerous natural biologically active compounds. The structures of the obtained compounds were reliably proven by modern spectral methods and X-ray diffraction...
December 20, 2016: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/27933795/potent-inhibition-of-3-deoxy-d-arabinoheptulosonate-7-phosphate-dahp-synthase-by-dahp-oxime-a-phosphate-group-mimic
#10
Naresh Balachandran, Maren Heimhalt, Peter Liuni, Frederick To, Derek J Wilson, Murray S Junop, Paul J Berti
3-Deoxy-d-arabinoheptulosonate-7-phosphate (DAHP) synthase catalyzes the first step in the shikimate pathway. It catalyzes an aldol-like reaction of phosphoenolpyruvate (PEP) with erythrose 4-phosphate (E4P) to form DAHP. The kinetic mechanism was rapid equilibrium sequential ordered ter ter, with the essential divalent metal ion, Mn(2+), binding first, followed by PEP and E4P. DAHP oxime, in which an oxime group replaces the keto oxygen, was a potent inhibitor, with Ki = 1.5 ± 0.4 μM, though with residual activity at high inhibitor concentrations...
December 6, 2016: Biochemistry
https://www.readbyqxmd.com/read/27911816/rapid-emergence-and-mechanisms-of-resistance-by-u87-glioblastoma-cells-to-doxorubicin-in-an-in-vitro-tumor-microfluidic-ecology
#11
Jeonghun Han, Yukyung Jun, So Hyun Kim, Hong-Hoa Hoang, Yeonjoo Jung, Suyeon Kim, Jaesang Kim, Robert H Austin, Sanghyuk Lee, Sungsu Park
In vitro prediction of the probable rapid emergence of resistance to a drug in tumors could act to winnow out potential candidates for further costly development. We have developed a microfluidic device consisting of ∼500 hexagonal microcompartments that provides a complex ecology with wide ranges of drug and nutrient gradients and local populations. This ecology of a fragmented metapopulation induced the drug resistance in stage IV U87 glioblastoma cells to doxorubicin in 7 d. Exome and transcriptome sequencing of the resistant cells identified mutations and differentially expressed genes...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27901143/a-butterfly-motion-of-formic-acid-and-cyclobutanone-in-the-1%C3%A2-%C3%A2-1-hydrogen-bonded-molecular-cluster
#12
Luca Evangelisti, Lorenzo Spada, Weixing Li, Susana Blanco, Juan Carlos López, Alberto Lesarri, Jens-Uwe Grabow, Walther Caminati
Upon supersonic expansion, formic acid and cyclobutanone (CBU) form a molecular cluster in which the two constituent molecules, linked by OHO and CHO hydrogen bonds, undergo a rapid interconversion between two equivalent forms. The tunneling motion takes place through the rupture and reformation of the C-HO hydrogen bond between the carbonyl oxygen of HCOOH and one of the two hydrogen atoms of the methylenic group adjacent to the cyclobutanone keto group. From the microwave spectra, tunneling energy splittings (ΔE01) have been determined for the parent (1122...
December 21, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27871908/acetylated-deoxycholic-dca-and-cholic-ca-acids-are-potent-ligands-of-pregnane-x-pxr-receptor
#13
Alejandro Carazo, Lucie Hyrsova, Jan Dusek, Hana Chodounska, Alzbeta Horvatova, Karel Berka, Vaclav Bazgier, Hongying Gan-Schreier, Waleé Chamulitrat, Eva Kudova, Petr Pavek
The Pregnane X (PXR), Vitamin D (VDR) and Farnesoid X (FXR) nuclear receptors have been shown to be receptors of bile acids controlling their detoxification or synthesis. Chenodeoxycholic (CDCA) and lithocholic (LCA) acids are ligands of FXR and VDR, respectively, whereas 3-keto and acetylated derivates of LCA have been described as ligands for all three receptors. In this study, we hypothesized that oxidation or acetylation at position 3, 7 and 12 of bile acids DCA (deoxycholic acid), LCA, CA (cholic acid), and CDCA by detoxification enzymes or microbiome may have an effect on the interactions with bile acid nuclear receptors...
January 4, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/27855668/identification-and-characterization-of-two-new-5-keto-4-deoxy-d-glucarate-dehydratases-decarboxylases
#14
André Pick, Barbara Beer, Risa Hemmi, Rena Momma, Jochen Schmid, Kenji Miyamoto, Volker Sieber
BACKGROUND: Hexuronic acids such as D-galacturonic acid and D-glucuronic acid can be utilized via different pathways within the metabolism of microorganisms. One representative, the oxidative pathway, generates α-keto-glutarate as the direct link entering towards the citric acid cycle. The penultimate enzyme, keto-deoxy glucarate dehydratase/decarboxylase, catalyses the dehydration and decarboxylation of keto-deoxy glucarate to α-keto-glutarate semialdehyde. This enzymatic reaction can be tracked continuously by applying a pH-shift assay...
November 17, 2016: BMC Biotechnology
https://www.readbyqxmd.com/read/27854034/efficient-preparation-of-s-n-boc-3-hydroxylpiperidine-through-bioreduction-by-a-thermostable-aldo-ketoreductase
#15
Mengyan He, Shuo Zhou, Maolin Cui, Xiaolu Jin, Dunyue Lai, Shuangling Zhang, Zhiguo Wang, Zhenming Chen
(S)-N-Boc-3-hydroxypiperidine ((S)-NBHP) is a key pharmaceutical intermediate and the chiral source in synthesizing Imbruvica, which is a newly approved drug in lymphoma therapy by targeting Bruton's tyrosine kinase (BTK). Current chemical synthesis of (S)-NBHP suffered from the need of noble metal catalyst and low yield. The single reported bioconversion of (S)-NBHP was achieved by using recombinant ketoreductase, but enzyme sequence was kept confidential and the catalytic process suffered from the thermodeactivation and substrate inhibition...
November 16, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27834752/cyclooxygenase-2-derived-prostaglandins-mediate-cerebral-microcirculation-in-a-juvenile-ischemic-rat-model
#16
Pierre-Louis Leger, Julien Pansiot, Valerie Besson, Bruno Palmier, Sylvain Renolleau, Olivier Baud, Bruno Cauli, Christiane Charriaut-Marlangue
BACKGROUND AND PURPOSE: We previously showed that the selective neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) increases cerebral microcirculation in a juvenile ischemic rat model. We address the roles of cyclooxygenase (COX)-elaborated prostaglandins in collateral recruitment and blood supply. METHODS: Fourteen-day-old rats were subjected to ischemia-reperfusion and treated with either PBS or 7-NI (25 mg/kg) at the reperfusion onset. Six-keto-prostaglandin F1α was measured using ELISA...
December 2016: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/27815364/predictors-of-variation-in-cyp2a6-mrna-protein-and-enzyme-activity-in-a-human-liver-bank-influence-of-genetic-and-nongenetic-factors
#17
Julie-Anne Tanner, Bhagwat Prasad, Katrina G Claw, Patricia Stapleton, Amarjit Chaudhry, Erin G Schuetz, Kenneth E Thummel, Rachel F Tyndale
Cytochrome P450 2A6 CYP2A6: metabolizes several clinically relevant substrates, including nicotine, the primary psychoactive component in cigarette smoke. Smokers vary widely in their rate of inactivation and clearance of nicotine, altering numerous smoking phenotypes. We aimed to characterize independent and shared impact of genetic and nongenetic sources of variation in CYP2A6 mRNA, protein, and enzyme activity in a human liver bank (n = 360). For the assessment of genetic factors, we quantified levels of CYP2A6, cytochrome P450 oxidoreductase (POR), and aldo-keto reductase 1D1 (AKR1D1) mRNA, and CYP2A6 and POR proteins...
January 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27791305/radical-mediated-1-2-formyl-carbonyl-functionalization-of-alkenes-and-application-to-the-construction-of-medium-sized-rings
#18
Zhong-Liang Li, Xiao-Hua Li, Na Wang, Ning-Yuan Yang, Xin-Yuan Liu
A novel radical 1,2-formylfunctionalization of alkenes involving 1,2(4,5)-formyl migration triggered by addition of various carbon- and heteroatom-centered radicals to alkenes has been developed for the first time, thus providing straightforward access to diverse β-functionalized aldehydes with good efficiency, remarkable selectivity, and excellent functional group tolerance. Analogous transformations mediated by a keto-carbonyl migration have also been effected under similar conditions. This method was used to access ring systems including various benzannulated nine-, ten-, and eleven-membered rings, complex 6-5(6,7)-6(5) fused rings, and bridged rings with diverse functionalities...
October 28, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27782055/quantitative-determination-of-3-o-acetyl-11-keto-%C3%AE-boswellic-acid-akba-and-other-boswellic-acids-in-boswellia-sacra-flueck-syn-b-carteri-birdw-and-boswellia-serrata-roxb
#19
Giuseppe Mannino, Andrea Occhipinti, Massimo E Maffei
Boswellia serrata and Boswellia sacra (syn. B. carteri) are important medicinal plants widely used for their content of bioactive lipophilic triterpenes. The qualitative and quantitative determination of boswellic acids (BAs) is important for their use in dietary supplements aimed to provide a support for osteoarthritic and inflammatory diseases. We used High Performance Liquid Chromatography (HPLC)-Diode Array Detector (DAD) coupled to ElectroSpray Ionization and tandem Mass Spectrometry (ESI-MS/MS) for the qualitative and quantitative determination of BAs extracted from the gum resins of B...
October 6, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27762589/hpma-copolymer-based-polymer-conjugates-for-the-delivery-and-controlled-release-of-retinoids
#20
O Lidický, M Šírová, T Etrych
In this paper, we describe the synthesis, physicochemical characterization, drug release kinetics and preliminary biological evaluation of several N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer-retinoid conjugates designed for solid tumor immunotherapy. The conjugates are supposed to inhibit the immunosuppressive activity of myeloid-derived suppressor cells (MDSC) accumulated in the solid tumor microenvironment. All-trans retinoic acid (ATRA) was derivatized to hydrazide (AtrHy) and then attached to the polymer backbone via a spacer that is stable at the normal pH of blood (7...
October 20, 2016: Physiological Research
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