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https://www.readbyqxmd.com/read/28303724/non-alcoholic-fatty-liver-disease-nafld-pathogenesis-classification-and-effect-on-drug-metabolizing-enzymes-and-transporters
#1
Enoch Cobbina, Fatemeh Akhlaghi
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. It is defined by the presence of steatosis in more than 5% of hepatocytes with little or no alcohol consumption. Insulin resistance, the metabolic syndrome or type 2 diabetes and genetic variants of PNPLA3 or TM6SF2 seem to play a role in the pathogenesis of NAFLD. The pathological progression of NAFLD follows tentatively a "three-hit" process namely steatosis, lipotoxicity and inflammation. The presence of steatosis, oxidative stress and inflammatory mediators like TNF-α and IL-6 has been implicated in the alterations of nuclear factors such as CAR, PXR, PPAR-α in NAFLD...
March 17, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28286122/regioselective-production-of-sulfated-polyphenols-using-human-cytosolic-sulfotransferase-expressing-escherichia-coli-cells
#2
Takehiko Shimohira, Katsuhisa Kurogi, Takuyu Hashiguchi, Ming-Cheh Liu, Masahito Suiko, Yoichi Sakakibara
Dietary polyphenols present in fruits and vegetables have been reported to manifest beneficial health effects on humans. Polyphenol metabolites including their sulfated derivatives have been shown to be biologically active. Primarily due to the difficulty in preparing regiospecific sulfated polyphenols for detailed investigations, the exact functions of sulfated polyphenols, however, remain unclear. The current study aimed to develop a procedure for the regioselective production of sulfated polyphenols using Escherichia coli cells expressing human cytosolic sulfotransferases (SULTs)...
March 9, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28278373/potential-metabolic-activation-of-a-representative-c4-alkylated-polycyclic-aromatic-hydrocarbon-retene-1-methyl-7-isopropyl-phenanthrene-associated-with-the-deepwater-horizon-oil-spill-in-human-hepatoma-hepg2-cells
#3
Meng Huang, Clementina A Mesaros, Linda C Hackfield, Richard P Hodge, Tianzhu Zang, Ian Alexander Blair, Trevor M Penning
Exposure to petrogenic polycyclic aromatic hydrocarbons (PPAHs) in the food-chain is the major human health hazard associated with the Deepwater Horizon oil spill. C4-Phenanthrenes are representative PPAHs present in the crude oil and could contaminate the seafood. We describe the metabolism of a C4-phenanthrene regioisomer retene (1-methyl-7-isopropyl-phenanthrene) in human HepG2 cells as a model for metabolism in human hepatocytes. Retene because of its sites of alkylation cannot be metabolized to a diol-epoxide...
March 9, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28250318/characterization-of-species-differences-in-xenobiotic-metabolism-in-non-experimental-animals
#4
Hazuki Mizukawa, Yoshinori Ikenaka, Mayu Kakehi, Shouta Nakayama, Mayumi Ishizuka
 The ability to metabolize xenobiotics in organisms has a wide degree of variation among organisms. This is caused by differences in the pattern of xenobiotic bioaccumulation among organisms, which affects their tolerance. It has been reported in the veterinary field that glucuronidation (UGT) activity in cats, acetylation activity in dogs and sulfation (SULT) activity in pigs are sub-vital in these species, respectively, and require close attention when prescribing the medicine. On the other hand, information about species differences in xenobiotics metabolism remains insufficient, especially in non-experimental animals...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28225918/the-aplication-of-cyanoacrilate-surgical-glue-on-skin-suture-in-rats
#5
João Ilgenfritz, Ricardo Dutra Aydos, Iandara Schettert Silva, Rondon Tosta Ramalho, João Ilgenfritz, Gerson Gattats Orro de Campos, Ricardo Kenithi Nakamura, Danilo M Zanello Guerisoli, Wilson de Barros Cantero
Purpose: To compare the use of a new cyanoacrylate-based surgical glue and suture with sepa-rate points in skin wounds closure. Methods: Thirty-six rats were subjected to a 4cm dorsal longitudinal incision. Twelve were sub-jected to simple suture with polyamide 6-0, 12 rats underwent wall synthesis using Dermabond(r) and 12 was performed cutaneous synthesis with N-2-Butyl-Cyanoacrylate. Twelve of each group was euthanized on the seventh postoperative day, their blood was taken to biochemical tests and a layer of skin and subcutaneous tissue surrounding the surgical scar was randomly divided in two segments, to the submission of tension tests and to histological study...
January 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/28222028/expression-purification-and-characterization-of-human-cytosolic-sulfotransferase-sult-1c4
#6
Amber L Guidry, Zachary E Tibbs, Melissa Runge-Morris, Charles N Falany
Human cytosolic sulfotransferase 1C4 (hSULT1C4) is a dimeric Phase II drug-metabolizing enzyme primarily expressed in the developing fetus. SULTs facilitate the transfer of a hydrophilic sulfonate moiety from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) onto an acceptor substrate altering the substrate's biological activity and increasing the compound's water solubility. While several of the hSULTs' endogenous and xenobiotic substrates have been identified, the physiological function of hSULT1C4 remains unknown...
January 1, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28177672/a-reappraisal-of-the-6-o-desmethylnaproxen-sulfating-activity-of-the-human-cytosolic-sulfotransferases
#7
Fatemah Alherz, Daniyah A Almarghalani, Noor A Hussein, Katsuhisa Kurogi, Ming-Cheh Liu
In this study, we aimed to obtain a comprehensive account of the human cytosolic sulfotransferases (SULTs) that are capable of sulfating 6-<i>O</i>-desmethylnaproxen (<i>O</i>-DMN), a major metabolite of naproxen. Of the 13 known human SULTs tested, seven, SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C2, SULT1C4, and SULT1E1, displayed <i>O</i>-DMN-sulfating activity, when analyzed using an elevated substrate concentration (500 μM) together with 14 μM of the sulfate donor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS)...
January 22, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28160514/deep-learning-for-polyp-recognition-in-wireless-capsule-endoscopy-images
#8
Yixuan Yuan, Max Q-H Meng
PURPOSE: Wireless Capsule Endoscopy (WCE) enables physicians to examine the digestive tract without any surgical operations, at the cost of a large volume of images to be analyzed. In the computer-aided diagnosis of WCE images, the main challenge arisesfrom the difficulty of robust characterization of images. This study aims to provide dis-criminative description of WCE images and assist physicians to recognize polyp images automatically. METHODS: We propose a novel deep feature learning method, named stacked sparse autoencoder with image manifold constraint (SSAEIM), to recognize polyps in the WCE images...
February 4, 2017: Medical Physics
https://www.readbyqxmd.com/read/28160022/role-of-human-sulfotransferase-1a1-and-n-acetyltransferase-2-in-the-metabolic-activation-of-16-heterocyclic-amines-and-related-heterocyclics-to-genotoxicants-in-recombinant-v79-cells
#9
Matthieu Chevereau, Hansruedi Glatt, Daniel Zalko, Jean-Pierre Cravedi, Marc Audebert
Heterocyclic aromatic amines (HAAs) are primarily produced during the heating of meat or fish. HAAs are mutagenic and carcinogenic, and their toxicity in model systems depend on metabolic activation. This activation is mediated by cytochrome P450 (CYP) enzymes, in particular CYP1A2. Some studies have indicated a role of human sulfotransferase (SULT) 1A1 and N-acetyltransferase (NAT) 2 in the terminal activation of HAAs. In this study, we conducted a metabolism/genotoxicity relationship analysis for 16 HAAs and related heterocyclics...
February 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28070880/on-the-molecular-basis-underlying-the-metabolism-of-tapentadol-through-sulfation
#10
Ahsan F Bairam, Mohammed I Rasool, Katsuhisa Kurogi, Ming-Cheh Liu
BACKGROUND AND OBJECTIVES: Previous studies reported that tapentadol-sulfate represented one of the major metabolites of tapentadol excreted in urine. The current study aimed to identify the human cytosolic sulfotransferases (SULTs) that is(are) capable of sulfating tapentadol and to examine whether human cells and human organ specimens are capable of sulfating tapentadol. METHODS: Thirteen human SULTs, previously expressed and purified, as well as human organ cytosols, were analyzed for tapentadol-sulfating activity using an established sulfotransferase assay...
January 10, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28062095/the-liver-transcriptome-of-suckermouth-armoured-catfish-pterygoplichthys-anisitsi-loricariidae-identification-of-expansions-in-defensome-gene-families
#11
Thiago E Parente, Daniel A Moreira, Maithê G P Magalhães, Paula C C de Andrade, Carolina Furtado, Brian J Haas, John J Stegeman, Mark E Hahn
Pterygoplichthys is a genus of related suckermouth armoured catfishes native to South America, which have invaded tropical and subtropical regions worldwide. Physiological features, including an augmented resistance to organic xenobiotics, may have aided their settlement in foreign habitats. The liver transcriptome of Pterygoplichthys anisitsi was sequenced and used to characterize the diversity of mRNAs potentially involved in the responses to natural and anthropogenic chemicals. In total, 66,642 transcripts were assembled...
February 15, 2017: Marine Pollution Bulletin
https://www.readbyqxmd.com/read/28055299/guiding-bispecific-monovalent-antibody-formation-through-proteolysis-of-igg1-single-chain
#12
Nazzareno Dimasi, Ryan Fleming, Kris F Sachsenmeier, Binyam Bezabeh, Carl Hay, Jincheng Wu, Erin Sult, Saravanan Rajan, Li Zhuang, Peter Cariuk, Andrew Buchanan, Michael A Bowen, Herren Wu, Changshou Gao
We developed an IgG1 domain-tethering approach to guide the correct assembly of two light and two heavy chains, derived from two different antibodies, to form bispecific monovalent antibodies in IgG1 format. We show here that assembling two different light and heavy chains by sequentially connecting them with protease-cleavable polypeptide linkers results in the generation of monovalent bispecific antibodies that have IgG1 sequence, structure and functional properties. This approach was used to generate a bispecific monovalent antibody targeting the epidermal growth factor receptor and the type I insulin-like growth factor receptor that: 1) can be produced and purified using standard IgG1 techniques; 2) exhibits stability and structural features comparable to IgG1; 3) binds both targets simultaneously; and 4) has potent anti-tumor activity...
January 5, 2017: MAbs
https://www.readbyqxmd.com/read/28050713/metabolic-profiling-of-human-long-term-liver-models-and-hepatic-clearance-predictions-from-in-vitro-data-using-nonlinear-mixed-effects-modeling
#13
Nicole A Kratochwil, Christophe Meille, Stephen Fowler, Florian Klammers, Aynur Ekiciler, Birgit Molitor, Sandrine Simon, Isabelle Walter, Claudia McGinnis, Johanna Walther, Brian Leonard, Miriam Triyatni, Hassan Javanbakht, Christoph Funk, Franz Schuler, Thierry Lavé, Neil J Parrott
Early prediction of human clearance is often challenging, in particular for the growing number of low-clearance compounds. Long-term in vitro models have been developed which enable sophisticated hepatic drug disposition studies and improved clearance predictions. Here, the cell line HepG2, iPSC-derived hepatocytes (iCell®), the hepatic stem cell line HepaRG™, and human hepatocyte co-cultures (HμREL™ and HepatoPac®) were compared to primary hepatocyte suspension cultures with respect to their key metabolic activities...
March 2017: AAPS Journal
https://www.readbyqxmd.com/read/28040644/transcriptional-changes-in-oysters-crassostrea-brasiliana-exposed-to-phenanthrene-at-different-salinities
#14
Flávia Lucena Zacchi, Daína de Lima, Fabrício Flores-Nunes, Jacó Joaquim Mattos, Karim Hahn Lüchmann, Carlos Henrique Araújo de Miranda Gomes, Márcia Caruso Bícego, Satie Taniguchi, Silvio Tarou Sasaki, Afonso Celso Dias Bainy
Euryhaline animals from estuaries, such as the oyster Crassostrea brasiliana, show physiological mechanisms of adaptation to tolerate salinity changes. These ecosystems receive constant input of xenobiotics from urban areas, including polycyclic aromatic hydrocarbons (PAHs), such as phenanthrene (PHE). In order to understand the influence of salinity on the molecular responses of C. brasiliana exposed to PHE, oysters were acclimatized to different salinities (35, 25 and 10) for 15days and then exposed to 100μgL(-1) PHE for 24h and 96h...
February 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28001382/bifunctional-photocatalysts-for-enantioselective-aerobic-oxidation-of-%C3%AE-ketoesters
#15
Wei Ding, Liang-Qiu Lu, Quan-Quan Zhou, Yi Wei, Jia-Rong Chen, Wen-Jing Xiao
A novel visible-light-responsive chiral ligand has been developed by grafting a triplet state photosensitizer to chiral bisoxazoline ligands. Complexation of this ligand with Ni(acac)2 results in a powerful catalyst for the asymmetric oxidation reaction of β-ketoesters, which uses oxygen or air as the green oxidant and visible light or sunlight as the ideal driving force. Using this protocol, products containing the α-hydroxy-β-dicarbonyl motif are produced in high yields and with excellent enantiopurities...
December 28, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27911811/the-structure-of-the-catechin-binding-site-of-human-sulfotransferase-1a1
#16
Ian Cook, Ting Wang, Mark Girvin, Thomas S Leyh
We are just beginning to understand the allosteric regulation of the human cytosolic sulfotransferase (SULTs) family-13 disease-relevant enzymes that regulate the activities of hundreds, if not thousands, of signaling small molecules. SULT1A1, the predominant isoform in adult liver, harbors two noninteracting allosteric sites, each of which binds a different molecular family: the catechins (naturally occurring flavonols) and nonsteroidal antiinflammatory drugs (NSAIDs). Here, we present the structure of an SULT allosteric binding site-the catechin-binding site of SULT1A1 bound to epigallocatechin gallate (EGCG)...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27897396/acid-mediated-synthesis-of-ordered-mesoporous-aluminosilicates-the-challenge-and-the-promise
#17
Nunna V Krishna, Parasuraman Selvam
A new intrinsic hydrolysis method was employed, for the first-time, to synthesize well-ordered H-AlSBA-15 with trivalent aluminium exclusively in the tetrahedral framework structure of SBA-15. Unlike other methods, which involve incorporation of aluminium ions in both the framework (Brønsted) and non-framework (Lewis) sites of the silicate matrix, the intrinsic hydrolysis method isomorphously substitutes aluminium ions in the tetrahedral network even at high aluminium content. This unique approach relies mainly on the hydrolysis rates of the inorganic (silicon and aluminium) precursors used for the preparation in such a way that the condensation occurs simultaneously so as to overcome the usually encountered difficulties in stabilizing aluminium ions in the silicate matrix...
January 31, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27896399/cytochrome-p450-mediated-metabolism-of-triclosan-attenuates-its-cytotoxicity-in-hepatic-cells
#18
Yuanfeng Wu, Priyanka Chitranshi, Lucie Loukotková, Gonçalo Gamboa da Costa, Frederick A Beland, Jie Zhang, Jia-Long Fang
Triclosan is a widely used broad-spectrum anti-bacterial agent. The objectives of this study were to identify which cytochrome P450 (CYP) isoforms metabolize triclosan and to examine the effects of CYP-mediated metabolism on triclosan-induced cytotoxicity. A panel of HepG2-derived cell lines was established, each of which overexpressed a single CYP isoform, including CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A7, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP3A7, CYP4A11, and CYP4B1...
November 28, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27884139/brominated-flame-retardants-in-placental-tissues-associations-with-infant-sex-and-thyroid-hormone-endpoints
#19
Christopher Leonetti, Craig M Butt, Kate Hoffman, Stephanie C Hammel, Marie Lynn Miranda, Heather M Stapleton
BACKGROUND: Brominated flame retardants (BFRs) are endocrine disruptors that bioaccumulate in the placenta, but it remains unclear if they disrupt tissue thyroid hormone (TH) metabolism. Our primary goal was to investigate associations between placental BFRs, TH levels, Type 3 deiodinase (DIO3) activity and TH sulfotransferase (SULT) activities. METHODS: Placenta samples collected from 95 women who delivered term (>37 weeks) infants in Durham, NC, USA (enrolled 2010-2011) were analyzed for polybrominated diphenyl ethers (PBDEs), 2,4,6-tribromophenol (2,4,6-TBP), THs (T4, T3 and rT3), and DIO3 and TH SULT activities...
November 25, 2016: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/27882569/selective-reduction-in-the-expression-of-ugts-and-sults-a-novel-mechanism-by-which-piperine-enhances-the-bioavailability-of-curcumin-in-rat
#20
Xiaohui Zeng, Dake Cai, Qiaohuang Zeng, Zhao Chen, Guoping Zhong, Juncheng Zhuo, Haining Gan, Xuejun Huang, Ziming Zhao, Nan Yao, Dane Huang, Chengzhe Zhang, Dongmei Sun, Yuxing Chen
Curcumin (CUR) is known to exert numerous health-promoting effects in pharmacological studies, but its low bioavailability hinders the development of curcumin as a feasible therapeutic agent. Piperine (PIP) has been reported to enhance the bioavailability of curcumin, but the underlying mechanism remains poorly understood. In an attempt to find the mechanism by which piperine enhances the bioavailability of curcumin, the dosage ratio (CUR: PIP) and pre-treatment with piperine were hypothesized as key factors for improving the bioavailability in this combination...
January 2017: Biopharmaceutics & Drug Disposition
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