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https://www.readbyqxmd.com/read/28441972/efficacy-of-olmesartan-amlodipine-in-colombian-hypertensive-patients-soat-study
#1
Richard Buendia, Monica Zambrano
BACKGROUND: Emerging evidence has shown a significant deficit in the control of hypertension (blood pressure <140/90 mmHg) among Hispanics or Latinos in about 65%. This study aims to determine the efficacy of the combination in fixed doses of olmesartan and amlodipine (20/5, 40/5, and 40/10 mg) in hypertensive patients treated in daily clinical practice by Colombian doctors. METHODS: This was an observational, retrospective, open-label, multi-center, non-comparative study...
April 26, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28294609/biseokeaniamides-a-b-and-c-sterol-o-acyltransferase-inhibitors-from-an-okeania-sp-marine-cyanobacterium
#2
Arihiro Iwasaki, Takato Tadenuma, Shimpei Sumimoto, Taichi Ohshiro, Kaori Ozaki, Keisuke Kobayashi, Toshiaki Teruya, Hiroshi Tomoda, Kiyotake Suenaga
Biseokeaniamides A, B, and C (1-3), structurally novel sterol O-acyltransferase (SOAT) inhibitors, were isolated from an Okeania sp. marine cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Biseokeaniamide B (2) exhibited moderate cytotoxicity against human HeLa cancer cells, and compounds 1-3 inhibited both SOAT1 and SOAT2, not only at an enzyme level but also at a cellular level. Biseokeaniamides (1-3) are the first linear lipopeptides that have been shown to exhibit SOAT-inhibitory activity...
March 15, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28242547/vicinal-diaryl-azole-based-urea-derivatives-as-potential-cholesterol-lowering-agents-acting-through-inhibition-of-soat-enzymes
#3
Palash Pal, Hardik P Gandhi, Ashish M Kanhed, Nirali R Patel, Niraj N Mankadia, Satish N Baldha, Mahesh A Barmade, Prashant R Murumkar, Mange Ram Yadav
A novel series of vicinal diaryl azole-urea derivatives were synthesized and evaluated for their potential to inhibit SOAT enzyme. Among the reported compounds, compound (12d) emerged as the most potent compound with an IC50 value of 2.43 μM. In polaxamer-407 induced lipoprotein lipase inhibition model, compound (12d) reduced triglyceride turnover in vivo. Compound (12d) also showed dose-dependent prevention of serum total cholesterol and prevention of LDL-C elevation at a dose of 30 mg/kg. Furthermore, compound (12d) showed potential to stop falling levels of serum HDL-C dose-dependently and improved the atherogenic index...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27936201/sterol-o-acyltransferase-2-contributes-to-the-yolk-cholesterol-trafficking-during-zebrafish-embryogenesis
#4
Nai-Yun Chang, Yen-Ju Chan, Shih-Torng Ding, Yen-Hua Lee, Wei-Chun HuangFu, I-Hsuan Liu
To elucidate whether Sterol O-acyltransferase (Soat) mediates the absorption and transportation of yolk lipids to the developing embryo, zebrafish soat1 and soat2 were cloned and studied. In the adult zebrafish, soat1 was detected ubiquitously while soat2 mRNA was detected specifically in the liver, intestine, brain and testis. Whole mount in situ hybridization demonstrated that both soat1 and soat2 expressed in the yolk syncytial layer, hatching gland and developing cardiovascular as well as digestive systems, suggesting that Soats may play important roles in the lipid trafficking and utilization during embryonic development...
2016: PloS One
https://www.readbyqxmd.com/read/27876317/discovery-of-soat2-inhibitors-from-synthetic-small-molecules
#5
Keisuke Kobayashi, Taichi Ohshiro, Hiroshi Tomoda, Feng Yin, Hai-Lei Cui, Pandurang V Chouthaiwale, Fujie Tanaka
Synthesis of new functionalized molecules and identification of biofunctional molecules can lead to the development of therapeutic leads and molecular tools for biomedical research. We have recently reported oxa-hetero-Diels-Alder reactions of enones with isatins to provide functionalized spirooxindole tetrahydropyran derivatives. Twenty-one compounds from the spirooxindole tetrahydropyran derivatives and related molecules were screened for inhibition of sterol O-acyltransferase (SOAT) isozymes SOAT1 and SOAT2...
December 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27465966/strategies-to-influence-rn-specialty-certification
#6
Deborah Solomon, Meredith Lahl, Marian Soat, James Bena, Mark McClelland
No abstract text is available yet for this article.
August 2016: Nursing Management
https://www.readbyqxmd.com/read/27392637/the-role-of-sulfated-steroid-hormones-in-reproductive-processes
#7
Joachim Geyer, Katharina Bakhaus, Rita Bernhardt, Carina Blaschka, Yaser Dezhkam, Daniela Fietz, Gary Grosser, Katja Hartmann, Michaela F Hartmann, Jens Neunzig, Dimitrios Papadopoulos, Alberto Sánchez-Guijo, Georgios Scheiner-Bobis, Gerhard Schuler, Mazen Shihan, Christine Wrenzycki, Stefan A Wudy, Martin Bergmann
Sulfated steroid hormones, such as dehydroepiandrosterone sulfate or estrone-3-sulfate, have long been regarded as inactive metabolites as they cannot activate classical steroid receptors. Some of them are present in the blood circulation at quite high concentrations, but generally sulfated steroids exhibit low membrane permeation due to their hydrophilic properties. However, sulfated steroid hormones can actively be imported into specific target cells via uptake carriers, such as the sodium-dependent organic anion transporter SOAT, and, after hydrolysis by the steroid sulfatase (so-called sulfatase pathway), contribute to the overall regulation of steroid responsive organs...
July 5, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27281560/inhibition-of-soat1-suppresses-glioblastoma-growth-via-blocking-srebp-1-mediated-lipogenesis
#8
Feng Geng, Xiang Cheng, Xiaoning Wu, Ji Young Yoo, Chunming Cheng, Jeffrey Yunhua Guo, Xiaokui Mo, Peng Ru, Brian Hurwitz, Sung-Hak Kim, Jose Otero, Vinay Puduvalli, Etienne Lefai, Jianjie Ma, Ichiro Nakano, Craig Horbinski, Balveen Kaur, Arnab Chakravarti, Deliang Guo
PURPOSE: Elevated lipogenesis regulated by sterol regulatory element-binding protein-1 (SREBP-1), a transcription factor playing a central role in lipid metabolism, is a novel characteristic of glioblastoma (GBM). The aim of this study was to identify effective approaches to suppress GBM growth by inhibition of SREBP-1. As SREBP activation is negatively regulated by endoplasmic reticulum (ER) cholesterol, we sought to determine whether suppression of sterol O-acyltransferase (SOAT), a key enzyme converting ER cholesterol to cholesterol esters (CE) to store in lipid droplets (LDs), effectively suppressed SREBP-1 and blocked GBM growth...
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27033324/identification-of-novel-inhibitors-of-the-steroid-sulfate-carrier-sodium-dependent-organic-anion-transporter-soat-slc10a6-by-pharmacophore-modelling
#9
Gary Grosser, Karl-Heinz Baringhaus, Barbara Döring, Werner Kramer, Ernst Petzinger, Joachim Geyer
The sodium-dependent organic anion transporter SOAT specifically transports sulfated steroid hormones and is supposed to play a role in testicular steroid regulation and male fertility. The present study aimed to identify novel specific SOAT inhibitors for further in vitro and in vivo studies on SOAT function. More than 100 compounds of different molecular structures were screened for inhibition of the SOAT-mediated transport of dehydroepiandrosterone sulfate in stably transfected SOAT-HEK293 cells. Twenty-five of these with IC50 values covering four orders of magnitude were selected as training set for 3D pharmacophore modelling...
June 15, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27020600/design-synthesis-and-biological-evaluation-of-beauveriolide-analogues-bearing-photoreactive-amino-acids
#10
Yuichi Masuda, Kazumasa Aoyama, Masahito Yoshida, Keisuke Kobayashi, Taichi Ohshiro, Hiroshi Tomoda, Takayuki Doi
Beauveriolides I and III, which are naturally occurring cyclodepsipeptides, have been reported to bind to sterol O-acyltransferase (SOAT), inhibiting its ability to synthesize cholesteryl esters. To facilitate an analysis of the binding site(s) of these compounds, we designed beauveriolide analogues 1a-d wherein the Leu or D-allo-Ile residue was replaced by photoreactive amino acids possessing methyldiazirine or trifluoromethyldiazirine in the side chains. The methyldiazirine moiety was installed by reaction of methyl ketones with liquid ammonia to provide imine intermediates, followed by treatment with hydroxylamine-O-sulfonic acid to provide the diaziridines...
July 1, 2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/26980608/7-chlorofolipastatin-an-inhibitor-of-sterol-o-acyltransferase-produced-by-marine-derived-aspergillus-ungui-nkh-007
#11
Ryuji Uchida, Kento Nakajyo, Keisuke Kobayashi, Taichi Ohshiro, Takeshi Terahara, Chiaki Imada, Hiroshi Tomoda
A new depsidone, named 7-chlorofolipastatin, and five known structurally related depsidones were isolated from the culture broth of the marine-derived fungus Aspergillus ungui NKM-007 by solvent extraction and HPLC using an octadecylsilyl column. The structure of 7-chlorofolipastatin was elucidated by various spectroscopic data including 1D and 2D NMR spectroscopy. 7-Chlorofolipastatin inhibited sterol O-acyltransferase (SOAT) 1 and 2 isozymes in cell-based and enzyme assays using SOAT1- and SOAT2-expressing Chinese hamster ovary (CHO) cells...
August 2016: Journal of Antibiotics
https://www.readbyqxmd.com/read/26321246/dysregulated-expression-of-sterol-o-acyltransferase-1-soat1-in-the-hair-shaft-of-hoxc13-null-mice
#12
Christopher S Potter, Michael J Kern, Mary Ann Baybo, Nathanael D Pruett, Alan R Godwin, John P Sundberg, Alexander Awgulewitsch
The cholesterol-metabolizing enzyme sterol O-acetyltransferase (SOAT1) is implicated in an increasing number of biological and pathological processes in a number of organ systems, including the differentiation of the hair shaft. While the functional and regulatory mechanisms underlying these diverse functional roles remain poorly understood, the compartment of the hair shaft known as medulla, affected by mutations in Soat1, may serve as a suitable model for defining some of these mechanisms. A comparative analysis of mRNA and protein expression patterns of Soat1/SOAT1 and the transcriptional regulator Hoxc13/HOXC13 in postnatal skin of FVB/NTac mice indicated co-expression in the most proximal cells of the differentiating medulla...
December 2015: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/26283692/prd125-a-potent-and-selective-inhibitor-of-sterol-o-acyltransferase-2-markedly-reduces-hepatic-cholesteryl-ester-accumulation-and-improves-liver-function-in-lysosomal-acid-lipase-deficient-mice
#13
Adam M Lopez, Jen-Chieh Chuang, Kenneth S Posey, Taichi Ohshiro, Hiroshi Tomoda, Lawrence L Rudel, Stephen D Turley
In most organs, the bulk of cholesterol is unesterified, although nearly all possess a varying capability of esterifying cholesterol through the action of either sterol O-acyltransferase (SOAT) 1 or, in the case of hepatocytes and enterocytes, SOAT2. Esterified cholesterol (EC) carried in plasma lipoproteins is hydrolyzed by lysosomal acid lipase (LAL) when they are cleared from the circulation. Loss-of-function mutations in LIPA, the gene that encodes LAL, result in Wolman disease or cholesteryl ester storage disease (CESD)...
November 2015: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/26220175/atp-binding-cassette-transporters-and-sterol-o-acyltransferases-interact-at-membrane-microdomains-to-modulate-sterol-uptake-and-esterification
#14
Sonia Gulati, Dina Balderes, Christine Kim, Zhongmin A Guo, Lisa Wilcox, Estela Area-Gomez, Jamie Snider, Heimo Wolinski, Igor Stagljar, Juliana T Granato, Kelly V Ruggles, Joseph A DeGiorgis, Sepp D Kohlwein, Eric A Schon, Stephen L Sturley
A key component of eukaryotic lipid homeostasis is the esterification of sterols with fatty acids by sterol O-acyltransferases (SOATs). The esterification reactions are allosterically activated by their sterol substrates, the majority of which accumulate at the plasma membrane. We demonstrate that in yeast, sterol transport from the plasma membrane to the site of esterification is associated with the physical interaction of the major SOAT, acyl-coenzyme A:cholesterol acyltransferase (ACAT)-related enzyme (Are)2p, with 2 plasma membrane ATP-binding cassette (ABC) transporters: Aus1p and Pdr11p...
November 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/25899123/clonoamide-a-new-inhibitor-of-sterol-o-acyltransferase-produced-by-clonostachys-sp-bf-0131
#15
Keisuke Kobayashi, Nobuaki Tsukasaki, Ryuji Uchida, Yuichi Yamaguchi, Hiroshi Tomoda
A new compound designated as clonoamide was isolated from a culture broth of the fungus Clonostachys sp. BF-0131 by solvent extraction, Diaion HP20 column chromatography, octadecylsilyl column chromatography and preparative HPLC as an inhibitor of sterol O-acyltransferase (SOAT). The structure of clonoamide was elucidated as 2-oxo-9E,11E-tridecandienyl acetamide by various spectral analyses including NMR. The compound inhibited SOAT1 and SOAT2 isozymes with IC50 values of 39 and 110 μm, respectively, in a cell-based assay using SOAT1- and SOAT2-expressing Chinese hamster ovary cells...
October 2015: Journal of Antibiotics
https://www.readbyqxmd.com/read/25319728/transport-of-the-soy-isoflavone-daidzein-and-its-conjugative-metabolites-by-the-carriers-soat-ntcp-oat4-and-oatp2b1
#16
Gary Grosser, Barbara Döring, Bernhard Ugele, Joachim Geyer, Sabine E Kulling, Sebastian T Soukup
Soy isoflavones (IF) are phytoestrogens, which interact with estrogen receptors. They are extensively metabolized by glucuronosyltransferases and sulfotransferases, leading to the modulation of their estrogenic activity. It can be assumed that this biotransformation also has a crucial impact on the uptake of IF by active or passive cellular transport mechanisms, but little is known about the transport of IF phase II metabolites into the cell. Therefore, transport assays for phase II metabolites of daidzein (DAI) were carried out using HEK293 cell lines transfected with five human candidate carriers, i...
December 2015: Archives of Toxicology
https://www.readbyqxmd.com/read/25295561/capture-of-knowledge-work-of-clinical-nurse-specialists-using-a-role-tracking-tool
#17
Jennifer P Colwill, Colin O'Rourke, Lydia Booher, Marian Soat, Deborah Solomon, Nancy M Albert
PURPOSE: The aim of this study was to quantify clinical nurse specialist (CNS) work and determine if competencies are associated with personal characteristics, priorities, and quality outcomes. BACKGROUND: The work of a CNS is difficult to quantify. Nurse leaders need quantifiable data to understand the impact of CNS work. DESIGN: A prospective, single-center, correlational study with a convenience sample was conducted. SETTING AND SAMPLE: The study was conducted in a 1200-bed quaternary care medical center in Northeast Ohio, using CNSs...
November 2014: Clinical Nurse Specialist CNS
https://www.readbyqxmd.com/read/25218443/acyl-coa-cholesterol-acyltransferases-acats-soats-enzymes-with-multiple-sterols-as-substrates-and-as-activators
#18
REVIEW
Maximillian A Rogers, Jay Liu, Bao-Liang Song, Bo-Liang Li, Catherine C Y Chang, Ta-Yuan Chang
Cholesterol is essential to the growth and viability of cells. The metabolites of cholesterol include: steroids, oxysterols, and bile acids, all of which play important physiological functions. Cholesterol and its metabolites have been implicated in the pathogenesis of multiple human diseases, including: atherosclerosis, cancer, neurodegenerative diseases, and diabetes. Thus, understanding how cells maintain the homeostasis of cholesterol and its metabolites is an important area of study. Acyl-coenzyme A:cholesterol acyltransferases (ACATs, also abbreviated as SOATs) converts cholesterol to cholesteryl esters and play key roles in the regulation of cellular cholesterol homeostasis...
July 2015: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/25196914/assessment-of-epithelial-innate-antimicrobial-factors-in-sinus-tissue-from-patients-with-and-without-chronic-rhinosinusitis
#19
Jivianne T Lee, Oswaldo H Escobar, Rabin Anouseyan, Agnieszka Janisiewicz, Edward Eivers, Keith E Blackwell, David B Keschner, Rohit Garg, Edith Porter
BACKGROUND: Airway secretions contain endogenous antimicrobial factors (AMFs) that contribute to the innate host defense of the respiratory tract. Antibacterial peptides as well as host-derived lipids including cholesteryl esters have been detected in maxillary lavage fluid. Sterol O-acyltransferase 1 (SOAT1) is a key enzyme in cholesteryl ester production. The purpose of this study is to determine if such intrinsic microbicidal molecules are acutely expressed within sinus tissue and to compare levels of expression between patients with and without chronic rhinosinusitis (CRS)...
November 2014: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/25038322/a-steroidogenic-pathway-for-sulfonated-steroids-the-metabolism-of-pregnenolone-sulfate
#20
J Neunzig, A Sánchez-Guijo, A Mosa, M F Hartmann, J Geyer, S A Wudy, R Bernhardt
In many tissues sulfonated steroids exceed the concentration of free steroids and recently they were also shown to fulfill important physiological functions. While it was previously demonstrated that cholesterol sulfate (CS) is converted by CYP11A1 to pregnenolone sulfate (PregS), further conversion of PregS has not been studied in detail. To investigate whether a steroidogenic pathway for sulfonated steroids exists similar to the one described for free steroids, we examined the interaction of PregS with CYP17A1 in a reconstituted in-vitro system...
October 2014: Journal of Steroid Biochemistry and Molecular Biology
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