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https://www.readbyqxmd.com/read/27911811/the-structure-of-the-catechin-binding-site-of-human-sulfotransferase-1a1
#1
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)...
November 23, 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
#2
Selvam Parasuraman, Nunna Vamsi Krishna
A novel intrinsic hydrolysis method was employed, for the first-time, to synthesize well-ordered H-AlSBA-15 with trivalent aluminium exclusively in tetrahedral framework structure of SBA-15. Unlike other methods, which involve incorporation of aluminum ions in, both, framework (Brønsted) and non-framework (Lewis) sites of the silicate matrix, the intrinsic hydroly-sis method isomorphously substitutes aluminium ions in the tetrahedral network even at high aluminium content. This unique approach relies mainly on hydrolysis rates of 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...
November 29, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27896399/cytochrome-p450-mediated-metabolism-of-triclosan-attenuates-its-cytotoxicity-in-hepatic-cells
#3
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
#4
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
#5
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 CUR as a feasible therapeutic agent. Piperine (PIP) has been reported to enhance the bioavailability of CUR, but the underlying mechanism remains poorly understood. In an attempt to find the mechanism by which PIP enhances the bioavailability of CUR, dosage ratio (CUR: PIP) and PIP pre-treatment are hypothesized as key factors for bioavailability improvement in this combination...
November 23, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27855415/instrumented-trail-making-task-to-differentiate-persons-with-no-cognitive-impairment-amnestic-mild-cognitive-impairment-and-alzheimer-disease-a-proof-of-concept-study
#6
He Zhou, Marwan Sabbagh, Rachel Wyman, Carolyn Liebsack, Mark E Kunik, Bijan Najafi
BACKGROUND: Objective and time-effective tools are needed to identify motor-cognitive impairment and facilitate early intervention. OBJECTIVE: We examined the feasibility, accuracy, and reliability of an instrumented trail-making task (iTMT) using a wearable sensor to identify motor-cognitive impairment among older adults. METHODS: Thirty subjects (age = 82.2 + 6.1 years, body mass index = 25.7 + 4.8, female = 43.3%) in 3 age-matched groups, 11 healthy, 10 with amnestic mild cognitive impairment (aMCI), and 9 with Alzheimer disease (AD), were recruited...
November 18, 2016: Gerontology
https://www.readbyqxmd.com/read/27849938/296-innovative-resuscitation-unit-expedited-critically-ill-transfers-from-outside-emergency-departments
#7
Quincy Tran, James O'Connor, Thomas Scalea, Leslie Sult, Ashley Aitken, Eric Lund, Theresa DiNardo, Lewis Rubinson
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27688058/current-insights-into-the-sulfatase-pathway-in-human-testis-and-cultured-sertoli-cells
#8
K Hartmann, J Bennien, B Wapelhorst, K Bakhaus, V Schumacher, S Kliesch, W Weidner, M Bergmann, J Geyer, D Fietz
Within the human testis, large amounts of sulfated steroid hormones are produced. As shown in breast tissue and placenta, these might not only be excretion intermediates, but re-activated in target cells by steroid sulfatase (STS). This process is called sulfatase pathway and may play a pivotal role in para- and/or intracrine regulation by creating a local supply for steroid hormones. This requires a facilitated transport via uptake carriers and efflux transporters as these hydrophilic molecules cannot pass the cell membrane...
September 29, 2016: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/27649811/updated-perspectives-on-the-cytosolic-sulfotransferases-sults-and-sult-mediated-sulfation
#9
Masahito Suiko, Katsuhisa Kurogi, Takuyu Hashiguchi, Yoichi Sakakibara, Ming-Cheh Liu
The cytosolic sulfotransferases (SULTs) are Phase II detoxifying enzymes that mediate the sulfate conjugation of numerous xenobiotic molecules. While the research on the SULTs has lagged behind the research on Phase I cytochrome P-450 enzymes and other Phase II conjugating enzymes, it has gained more momentum in recent years. This review aims to summarize information obtained in several fronts of the research on the SULTs, including the range of the SULTs in different life forms, concerted actions of the SULTs and other Phase II enzymes, insights into the structure-function relationships of the SULTs, regulation of SULT expression and activity, developmental expression of SULTs, as well as the use of a zebrafish model for studying the developmental pharmacology/toxicology...
September 21, 2016: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/27637483/role-of-exposure-recovery-schedule-in-micronuclei-induction-by-several-promutagens-in-v79-derived-cells-expressing-human-cyp2e1-and-sult1a1
#10
Hansi Jia, Chiteng Zhang, Hansruedi Glatt, Yungang Liu
The standard procedure for the micronucleus test in cell lines requires a short exposure (≤0.5 cell cycle) to the test compounds followed by a long recovery (≥1.5 cell cycle), and in case of negative or equivocal results, a second test with extended exposure (≥2 cell cycles) without or with a recovery time. In general the two procedures are advantageous for detecting clastogens and aneugens, respectively. However, whether the recommended procedures apply to micronucleus tests with promutagens in cell lines genetically engineered for expressing biotransformation enzymes has not been identified...
September 15, 2016: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
https://www.readbyqxmd.com/read/27633141/the-natural-anthraquinones-from-rheum-palmatum-induced-the-metabolic-disorder-of-melatonin-by-inhibiting-human-cyp-and-sult-enzymes
#11
Weiru Jiang, Xiangge Tian, Yan Wang, Zheng Sun, Peipei Dong, Chao Wang, Xiaokui Huo, Baojing Zhang, Shanshan Huang, Sa Deng, Xiaobo Wang, Xiaochi Ma
Melatonin (Mel) as an endogenous hormone, has been widely used in clinic for multiple therapeutic purposes. Further, the natural anthraquinones were widespread in various plants including herbs, foods, and some flavoring agents. The present work aims to evaluate the metabolic disorder of Mel caused by various common herbs and further identify their underlying mechanism. More importantly, the relationships between inhibitory activity and their structures were also investigated. Our results demonstrate that some herbs containing anthraquinone derivatives exhibited strong inhibition on Mel metabolism...
September 12, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27627846/the-detoxification-responses-damage-effects-and-bioaccumulation-in-the-scallop-chlamys-farreri-exposed-to-single-and-mixtures-of-benzo-a-pyrene-and-chrysene
#12
Ruiming Guo, Luqing Pan, Pengfei Lin, Lei Zheng
This study aimed to investigate the detoxification responses, damage effects and biotransformation in scallop Chlamys farreri exposed to benzo[a]pyrene (BaP) (0.1, 1μg/L), chrysene (CHR) (0.1, 1μg/L) and BaP+CHR (0.1+0.1, 1+1μg/L) for 15days. Results demonstrated that BaP and CHR concentration (BaP<CHR) in tissues increased rapidly in a time and dose effect. The mRNA expression of aryl hydrocarbon receptor (AhR), cytochrome P450 1A1 (CYP1A1), CYP1B1, multidrug resistance protein 1 (MRP1/ABCC1), breast cancer resistance protein (BCRP/ABCG2) and P-glycoprotein (P-gp) were induced especially in the mixtures of BaP and CHR...
September 11, 2016: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/27622332/co-inhibition-of-cd73-and-a2ar-adenosine-signaling-improves-anti-tumor-immune-responses
#13
Arabella Young, Shin Foong Ngiow, Deborah S Barkauskas, Erin Sult, Carl Hay, Stephen J Blake, Qihui Huang, Jing Liu, Kazuyoshi Takeda, Michele W L Teng, Kris Sachsenmeier, Mark J Smyth
Preclinical studies targeting the adenosinergic pathway have gained much attention for their clinical potential in overcoming tumor-induced immunosuppression. Here, we have identified that co-blockade of the ectonucleotidase that generates adenosine CD73 and the A2A adenosine receptor (A2AR) that mediates adenosine signaling in leuokocytes, by using compound gene-targeted mice or therapeutics that target these molecules, limits tumor initiation, growth, and metastasis. This tumor control requires effector lymphocytes and interferon-γ, while antibodies targeting CD73 promote an optimal therapeutic response in vivo when engaging activating Fc receptors...
September 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27622077/targeting-cd73-in-the-tumor-microenvironment-with-medi9447
#14
Carl M Hay, Erin Sult, Qihui Huang, Kathy Mulgrew, Stacy R Fuhrmann, Kelly A McGlinchey, Scott A Hammond, Raymond Rothstein, Jonathan Rios-Doria, Edmund Poon, Nick Holoweckyj, Nicholas M Durham, Ching Ching Leow, Gundo Diedrich, Melissa Damschroder, Ronald Herbst, Robert E Hollingsworth, Kris F Sachsenmeier
MEDI9447 is a human monoclonal antibody that is specific for the ectoenzyme CD73 and currently undergoing Phase I clinical trials. Here we show that MEDI9447 is a potent inhibitor of CD73 ectonucleotidase activity, with wide ranging immune regulatory consequences. MEDI9447 results in relief from adenosine monophosphate (AMP)-mediated lymphocyte suppression in vitro and inhibition of mouse syngeneic tumor growth in vivo. In contrast with other cancer immunotherapy agents such as checkpoint inhibitors or T-cell agonists, MEDI9447 drives changes in both myeloid and lymphoid infiltrating leukocyte populations within the tumor microenvironment of mouse models...
August 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27593531/age-related-change-of-hepatic-uridine-diphosphate-glucuronosyltransferase-and-sulfotransferase-activities-in-male-chickens-and-pigs
#15
S X Hu
The hepatic activities of uridine diphosphate glucuronosyltransferase (UGT) and sulfotransferase (SULT) of male Ross 708 broiler chickens at the age of 1, 7, 14, 28, and 56 days and male Camborough-29 pigs at the age of 1 day and 2, 5, 10, and 20 weeks were investigated. Glucuronidation and sulfation of 4-nitrophenol were used to evaluate the activities. Porcine hepatic UGT and SULT activities were low at birth, peaked at around 5-10 weeks, and then declined. Both hepatic UGT and SULT activities of chickens were high at hatch and declined...
September 4, 2016: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27582324/human-cytosolic-sulfotransferase-sult1a3-mediates-the-sulfation-of-dextrorphan
#16
Akihiro Yamamoto, Katsuhisa Kurogi, Isaac Thomas Schiefer, Ming-Yih Liu, Yoichi Sakakibara, Masahito Suiko, Ming-Cheh Liu
Dextrorphan, an active metabolite of the antitussive dextromethorphan, has been shown to be subjected to sulfation by several zebrafish cytosolic sulfotransferases (SULTs). We were interested in finding out which of the human SULT(s) is(are) capable of catalyzing the sulfation of dextrorphan, and to verify whether sulfation of dextrorphan may occur in cultured human cells and human organ cytosols. Data from the enzymatic assays showed that, of all thirteen known human SULTs, SULT1A3 displayed the strongest dextrorphan-sulfating activity...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27572079/the-role-of-metabolizing-enzymes-and-transporters-in-antiretroviral-therapy
#17
Ling Ye, Chuqi Hou, Shuwen Liu
Patients with human immunodeficiency virus (HIV) receive antiretroviral therapy (ART) through the use of antiretroviral drugs. A combination of at least three drugs that suppreses HIV replication is used as standard treatment, and this is often called "highly active antiretroviral therapy" (HAART). Virus resistance is less likely when three or more drugs are used. A complication of anti-HIV drugs has a complex pharmacokinetic profile which is involved with extensive metabolism and transport by drug metabolizing enzymes (e...
August 29, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27565680/transcriptional-regulation-of-human-cytosolic-sulfotransferase-1c3-by-peroxisome-proliferator-activated-receptor-%C3%AE-in-ls180-human-colorectal-adenocarcinoma-cells
#18
Sarah Dubaisi, Hailin Fang, Thomas A Kocarek, Melissa Runge-Morris
Cytosolic sulfotransferase 1C3 (SULT1C3) is the least characterized of the three human SULT1C subfamily members. Originally identified as an orphan SULT by computational analysis of the human genome, we recently reported that SULT1C3 is expressed in human intestine and LS180 colorectal adenocarcinoma cells and is upregulated by agonists of peroxisome proliferator-activated receptor (PPAR) α and γ To determine the mechanism responsible for PPAR-mediated upregulation, we prepared reporter plasmids containing fragments of the SULT1C3 5'-flanking region...
November 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27491884/estimation-of-bisphenol-a-human-toxicity-by-3d-cell-culture-arrays-high-throughput-alternatives-to-animal-tests
#19
Dong Woo Lee, Woo-Yeon Oh, Sang Hyun Yi, Bosung Ku, Moo-Yeal Lee, Yoon Hee Cho, Mihi Yang
Bisphenol A (BPA) has been widely used for manufacturing polycarbonate plastics and epoxy resins and has been extensively tested in animals to predict human toxicity. In order to reduce the use of animals for toxicity assessment and provide further accurate information on BPA toxicity in humans, we encapsulated Hep3B human hepatoma cells in alginate and cultured them in three dimensions (3D) on a micropillar chip coupled to a panel of metabolic enzymes on a microwell chip. As a result, we were able to assess the toxicity of BPA under various metabolic enzyme conditions using a high-throughput and micro assay; sample volumes were nearly 2,000 times less than that required for a 96-well plate...
September 30, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27449410/identification-and-characterization-of-the-human-cytosolic-sulfotransferases-mediating-the-sulfation-of-clioquinol-and-iodoquinol
#20
Katsuhisa Kurogi, Ying Hui, Yoichi Sakakibara, Masahito Suiko, Ming-Cheh Liu
The aim of the current study was to identify the human cytosolic sulfotransferases (SULTs) that are capable of sulfating clioquinol and iodoquinol, and to verify the presence of clioquinol/iodoquinol-sulfating activity in human organ homogenates. A systematic analysis revealed that six of the thirteen known human SULTs, SULT1A1 SULT1A2, SULTA3, SULT1B1, SULT1C4, and SULT1E1 showed considerable clioquinol/iodoquinol-sulfating activity. Kinetic parameters of the sulfation of clioquinol and iodoquinol by three SULTs, SULT1A1, SULT1A3, and SULT1C4, that showed the strongest clioquinol/iodoquinol-sulfating activity were determined...
July 19, 2016: Drug Metabolism Letters
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