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https://www.readbyqxmd.com/read/28643276/a-rapid-two-step-iduronate-2-sulfatatse-enzymatic-activity-assay-for-mpsii-pharmacokinetic-assessment
#1
Mitra Azadeh, Luying Pan, Yongchang Qiu, Ruben Boado
Clinical studies involving enzyme replacement therapies (ERTs) have increasingly utilized enzymatic activity assays to monitor efficacy and biofunction of the drug; as a result, these assays have become an important part of pharmacokinetic (PK) and pharmacodynamic assessments in ERT trials. This paper presents a two-step enzymatic activity assay for iduronate-2-sulfatase (I2S) (EC 3.1.6.13) which we have optimized to fit in 1 day and to complete in less than 6 h. The rapid assay presented here is a significant improvement over the original two-step method with run time of 24 h which spanned 2 days...
June 23, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28630303/how-members-of-the-human-gut-microbiota-overcome-the-sulfation-problem-posed-by-glycosaminoglycans
#2
Alan Cartmell, Elisabeth C Lowe, Arnaud Baslé, Susan J Firbank, Didier A Ndeh, Heath Murray, Nicolas Terrapon, Vincent Lombard, Bernard Henrissat, Jeremy E Turnbull, Mirjam Czjzek, Harry J Gilbert, David N Bolam
The human microbiota, which plays an important role in health and disease, uses complex carbohydrates as a major source of nutrients. Utilization hierarchy indicates that the host glycosaminoglycans heparin (Hep) and heparan sulfate (HS) are high-priority carbohydrates for Bacteroides thetaiotaomicron, a prominent member of the human microbiota. The sulfation patterns of these glycosaminoglycans are highly variable, which presents a significant enzymatic challenge to the polysaccharide lyases and sulfatases that mediate degradation...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28612226/iris-study-a-phase-ii-study-of-the-steroid-sulfatase-inhibitor-irosustat-when-added-to-an-aromatase-inhibitor-in-er-positive-breast-cancer-patients
#3
Carlo Palmieri, Rob C Stein, Xinxue Liu, Emma Hudson, Hanna Nicholas, Hironobu Sasano, Fouzia Guestini, Chris Holcombe, Sophie Barrett, Laura Kenny, Sadie Reed, Adrian Lim, Larry Hayward, Sacha Howell, R Charles Coombes
PURPOSE: Irosustat is a first-generation, orally active, irreversible steroid sulfatase inhibitor. We performed a multicentre, open label phase II trial of the addition of Irosustat to a first-line aromatase inhibitor (AI) in patients with advanced BC to evaluate the safety of the combination and to test the hypothesis that the addition of Irosustat to AI may further suppress estradiol levels and result in clinical benefit. EXPERIMENTAL DESIGN: Postmenopausal women with ER-positive locally advanced or metastatic breast cancer who had derived clinical benefit from a first-line AI and who subsequently progressed were enrolled...
June 13, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28593992/insights-into-hunter-syndrome-from-the-structure-of-iduronate-2-sulfatase
#4
Mykhaylo Demydchuk, Chris H Hill, Aiwu Zhou, Gábor Bunkóczi, Penelope E Stein, Denis Marchesan, Janet E Deane, Randy J Read
Hunter syndrome is a rare but devastating childhood disease caused by mutations in the IDS gene encoding iduronate-2-sulfatase, a crucial enzyme in the lysosomal degradation pathway of dermatan sulfate and heparan sulfate. These complex glycosaminoglycans have important roles in cell adhesion, growth, proliferation and repair, and their degradation and recycling in the lysosome is essential for cellular maintenance. A variety of disease-causing mutations have been identified throughout the IDS gene. However, understanding the molecular basis of the disease has been impaired by the lack of structural data...
June 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28588698/clinical-significance-of-the-estrogen-modifying-enzymes-steroid-sulfatase-and-estrogen-sulfotransferase-in-epithelial-ovarian-cancer
#5
Felicitas Mungenast, Stefanie Aust, Ignace Vergote, Adriaan Vanderstichele, Jalid Sehouli, Elena Braicu, Sven Mahner, Dan Cacsire Castillo-Tong, Robert Zeillinger, Theresia Thalhammer
17β-estradiol (E2) can contribute to the progression of epithelial ovarian cancer (EOC). Although the majority of patients with EOC are postmenopausal woman, when de novo estrogen production in the ovary has ceased, ovarian cancer cells remain exposed to estrogens synthesized locally in the cancer cells from inactive sulfonated steroid hormone precursors-such as estrone sulfate taken up from the circulation via the sulfatase pathway. An abundance of the estrogen-modifying enzymes, including estrogen-activating steroid sulfatase (STS) and estrogen-inactivating estrogen-sulfotransferase (SULT1E1), is important for providing active estrogen to EOC cells...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28588666/molecular-analysis-of-the-novel-ids-allele-in-a-thai-family-with-mucopolysaccharidosis-type-ii-the-c-928c-t-p-gln310-transcript-is-sensitive-to-nonsense-mediated-mrna-decay
#6
Lukana Ngiwsara, Kitiwan Rojnueangnit, Duangrurdee Wattanasirichaigoon, Thipwimol Tim-Aroon, Phannee Sawangareetrakul, Voraratt Champattanachai, James R Ketudat-Cairns, Jisnuson Svasti
Hunter syndrome (or mucopolysaccharidosis type II, MPS II) is an X-linked recessive disorder induced by a deficiency of the iduronate 2-sulfatase (IDS) enzyme, resulting in the accumulation of glycosaminoglycan substrates, heparan sulfate and dermatan sulfate, in the lysosomes. The progressive accumulation of undegraded metabolites induces cell and tissue dysfunction, leading to multi-systemic pathology. The heterogeneity of clinical phenotypes, ranging from mild to severe forms, results from different mutations in the IDS gene...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28573284/is-enzymatic-hydrolysis-a-reliable-analytical-strategy-to-quantify-glucuronidated-and-sulfated-polyphenol-metabolites-in-human-fluids
#7
Paola Quifer-Rada, Miriam Martínez-Huélamo, Rosa M Lamuela-Raventos
Phenolic compounds are present in human fluids (plasma and urine) mainly as glucuronidated and sulfated metabolites. Up to now, due to the unavailability of standards, enzymatic hydrolysis has been the method of choice in analytical chemistry to quantify these phase II phenolic metabolites. Enzymatic hydrolysis procedures vary in enzyme concentration, pH and temperature; however, there is a lack of knowledge about the stability of polyphenols in their free form during the process. In this study, we evaluated the stability of 7 phenolic acids, 2 flavonoids and 3 prenylflavanoids in urine during enzymatic hydrolysis to assess the suitability of this analytical procedure, using three different concentrations of β-glucuronidase/sulfatase enzymes from Helix pomatia...
June 2, 2017: Food & Function
https://www.readbyqxmd.com/read/28569426/structure-and-expression-of-sulfatase-and-sulfatase-modifying-factor-genes-in-the-diamondback-moth-plutella-xylostella-l
#8
Xiao-Li Ma, Wei-Yi He, Wei Chen, Xue-Jiao Xu, Wei-Ping Qi, Ming-Min Zou, Yan-Chun You, Simon W Baxter, Ping Wang, Min-Sheng You
The diamondback moth, Plutella xylostella (L.), uses sulfatases (SULF) to counteract the glucosinolate-myrosinase defensive system that cruciferous plants have evolved to deter insect feeding. Sulfatase activity is regulated by post-translational modification of a cysteine residue by sulfatase modifying factor 1 (SUMF1). We identified 12 SULF genes (PxylSulfs) and two SUMF1 genes (PxylSumf1s) in the P. xylostella genome. Phylogenetic analysis of SULFs and SUMFs from P. xylostella, Bombyx mori, Manduca sexta, Heliconius melpomene, Danaus plexippus, Drosophila melanogaster, Tetranychus urticae and Homo sapiens showed that the SULFs were clustered into five groups, and the SUMFs could be divided into two groups...
June 1, 2017: Insect Science
https://www.readbyqxmd.com/read/28566233/expanding-the-genetic-cause-of-multiple-sulfatase-deficiency-a-novel-sumf1-variant-in-a-patient-displaying-a-severe-late-infantile-form-of-the-disease
#9
Ilona Jaszczuk, Lars Schlotawa, Thomas Dierks, Andreas Ohlenbusch, Dominique Koppenhöfer, Mariusz Babicz, Monika Lejman, Karthikeyan Radhakrishnan, Agnieszka Ługowska
Multiple sulfatase deficiency (MSD) is a rare inherited metabolic disease caused by defective cellular sulfatases. Activity of sulfatases depends on post-translational modification catalyzed by formylglycine-generating enzyme (FGE), encoded by the SUMF1 gene. SUMF1 pathologic variants cause MSD, a syndrome presenting with a complex phenotype. We describe the first Polish patient with MSD caused by a yet undescribed pathologic variant c.337G>A [p.Glu113Lys] (i.e. p.E113K) in heterozygous combination with the known deletion allele c...
May 22, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28558253/sugar-sulfates-are-not-hydrolyzed-by-the-acid-inducible-sulfatase-asla-from-salmonella-enterica-enteritidis-nalr-and-kentucky-3795-at-ph-5-5
#10
Arpeeta Ganguly, Rolf Dieter Joerger
The open reading frames (ORFs), SEN0085 and SeKA_A4361, from Salmonella enterica Enteritidis NalR and Kentucky 3795, corresponding to the acid-inducible sulfatase gene, aslA from S. e Typhimurium, were previously suggested by microarray analysis to be differentially expressed under acid conditions. However, growth and enzyme activity tests in the present study demonstrated that both wild type strains exhibited sulfatase activity with 4-nitrophenyl sulfate and 5-bromo-4-chloro-3 indolyl sulfate at pH 5.5. The acid sulfatase does not appear to be involved in sugar sulfate, tyrosine sulfate and 4-hydroxy-3-methoxyphenylglycol sulfate, heparin or chondroitin sulfate hydrolysis at pH 5...
May 30, 2017: Canadian Journal of Microbiology
https://www.readbyqxmd.com/read/28552400/celecoxib-affects-estrogen-sulfonation-catalyzed-by-several-human-hepatic-sulfotransferases-but-does-not-stimulate-17-sulfonation-in-rat-liver
#11
Sriram Ambadapadi, Peter L Wang, Sergiu P Palii, Margaret O James
Celecoxib is known to alter the preferred position of SULT2A1-catalyzed sulfonation of 17β-estradiol (17β-E2) and other estrogens from the 3- to the 17-position. Understanding the effects of celecoxib on estrogen sulfonation is of interest in the context of the investigational use of celecoxib to treat breast cancer. This study examined the effects on celecoxib on cytosolic sulfotransferases in human and rat liver and on SULT enzymes known to be expressed in liver. Celecoxib's effects on the sulfonation of several steroids catalyzed by human liver cytosol were similar but not identical to those observed previously for SULT2A1...
May 24, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28547849/heparan-sulfate-alterations-in-extracellular-matrix-structures-and-fgf-2-signaling-impairment-in-the-aged-neurogenic-niche
#12
Taihei Yamada, Aurelien Kerever, Yusuke Yoshimura, Yuji Suzuki, Risa Nonaka, Kyohei Higashi, Toshihiko Toida, Frederic Mercier, Eri Arikawa-Hirasawa
Adult neurogenesis in the subventricular zone of the lateral ventricle decreases with age. In the subventricular zone, the specialized extracellular matrix structures, known as fractones, contact neural stem cells and regulate neurogenesis. Fractones are composed of extracellular matrix components, such as heparan sulfate proteoglycans. We previously found that fractones capture and store fibroblast growth factor 2 (FGF-2) via heparan sulfate binding, and may deliver FGF-2 to neural stem cells in a timely manner...
May 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28540353/kinetic-and-optical-properties-of-a-new-probe-for-sulfatase-activity-assay
#13
Hey Young Yoon, Jong-In Hong
A new probe for detecting sulfatase activity generated fluorescent N-methylisoindole when it was treated with sulfatase. Detailed synthetic procedures of reaction intermediates are described along with their spectral data. The Diels-Alder adduct of N-methylisoindole and N-phenylmaleimide was identified by LC-MS data. The fluorescence changes and kinetic values of the probe upon sulfatase treatment in the presence and absence of reducing agents were described. Inhibitory potency of EMATE was measured using the probe in the presence and absence of reducing agents...
June 2017: Data in Brief
https://www.readbyqxmd.com/read/28532150/synephrine-as-a-specific-marker-for-orange-consumption
#14
Matthias Bader, Tatjana Lang, Roman Lang, Thomas Hofmann
To validate the suitability of synephrine, known to be a highly abundant alkaloid in oranges, as a dietary biomarker for orange consumption, a highly sensitive and robust stable isotope dilution analysis (SIDA) as well as an ECHO method, using the analyte itself as a pseudointernal standard injected into the analysis run to provide an "echo peak" of the analyte, was developed to quantitate synephrine by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in citrus juices and human urine before and after the ingestion of orange juice...
May 30, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28525382/sulfatase-1-overexpression-indicates-poor-prognosis-in-urothelial-carcinoma-of-the-urinary-bladder-and-upper-tract
#15
Hsiang-Ying Lee, Bi-Wen Yeh, Ti-Chun Chan, Kei-Fu Yang, Wei-Ming Li, Chun-Nung Huang, Hung-Lung Ke, Ching-Chia Li, Hsin-Chih Yeh, Peir-In Liang, Yow-Ling Shiue, Wen-Jeng Wu, Chien-Feng Li
Urothelial carcinoma (UC), arising from the urothelium of the urinary tract, can occur in the upper (UTUC) and the urinary bladder (UBUC). A representative molecular aberration for UC characteristics and prognosis remains unclear. Data mining of Gene Expression Omnibus focusing on UBUC, we identified sulfatase-1 (SULF1) upregulation is associated with UC progression. SULF1 controls the sulfation status of heparan sulfate proteoglycans and plays a role in tumor growth and metastasis, while its role is unexplored in UC...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521442/mrna-expression-of-steroidogenic-enzymes-steroid-hormone-receptors-and-their-coregulators-in-gastric-cancer
#16
Bartosz Adam Frycz, Dawid Murawa, Maciej Borejsza-Wysocki, Mateusz Wichtowski, Arkadiusz Spychała, Ryszard Marciniak, Paweł Murawa, Michał Drews, Paweł Piotr Jagodziński
Epidemiological and experimental findings suggest that the development of gastric cancer (GC) is regulated by steroid hormones. In postmenopausal women and older men, the majority of steroid hormones are produced locally in peripheral tissue through the enzymatic conversion of steroid precursors. Therefore, using reverse transcription-quantitative polymerase chain reaction analysis, the mRNA expression of genes encoding steroidogenic enzymes, including steroid sulfatase (STS), hydroxy-delta-5-steroid dehydrogenase 3 beta- and steroid delta-isomerase 1 (HSD3B1), 17β-hydroxysteroid dehydrogenase type 7 and aromatase (CYP19A1), was investigated in primary tumoral and adjacent healthy gastric mucosa from 60 patients with GC...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28508966/recurrent-purple-urine-bag-syndrome-presenting-with-full-spectrum-of-disease-severity-case-report-and-review-of-literature
#17
Junzhi Lin, Martha Hlafka, Omar Vargas, Mukul Bhattarai
Purple urine bag syndrome (PUBS) is a unique phenomenon characterized by purple discoloration of the urinary catheter bag and tubing following urinary catheterization lasting for hours to days. The purple discoloration is a mixture of indirubin dissolved in plastic with indigo on its surface. PUBS is most commonly associated with urinary tract infection (UTI) caused by bacteria with indoxyl phosphatase/sulfatase activity. It occurs predominantly in chronically catheterized, constipated elderly female patients...
November 2016: CEN Case Reports
https://www.readbyqxmd.com/read/28490013/sulfatase-2-modulates-fate-change-from-motor-neurons-to-oligodendrocyte-precursor-cells-through-coordinated-regulation-of-shh-signaling-with-sulfatase-1
#18
Wen Jiang, Yugo Ishino, Hirokazu Hashimoto, Kazuko Keino-Masu, Masayuki Masu, Kenji Uchimura, Kenji Kadomatsu, Takeshi Yoshimura, Kazuhiro Ikenaka
Sulfatases (Sulfs) are a group of endosulfatases consisting of Sulf1 and Sulf2, which specifically remove sulfate from heparan sulfate proteoglycans. Although several studies have shown that Sulf1 acts as a regulator of sonic hedgehog (Shh) signaling during embryonic ventral spinal cord development, the detailed expression pattern and function of Sulf2 in the spinal cord remains to be determined. In this study, we found that Sulf2 also modulates the cell fate change from motor neurons (MNs) to oligodendrocyte precursor cells (OPCs) by regulating Shh signaling in the mouse ventral spinal cord in coordination with Sulf1...
May 11, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28487826/oxidative-profile-exhibited-by-mucopolysaccharidosis-type-iva-patients-at-diagnosis-increased-keratan-urinary-levels
#19
Bruna Donida, Desirèe P Marchetti, Carlos Eduardo Diaz Jacques, Graziela Ribas, Marion Deon, Paula Manini, Helen Tais da Rosa, Dinara Jaqueline Moura, Jenifer Saffi, Roberto Giugliani, Carmen Regla Vargas
Morquio A disease (Mucopolysaccharidosis type IVA, MPS IVA) is one of the 11 mucopolysaccharidoses (MPSs), a heterogeneous group of inherited lysosomal storage disorders (LSDs) caused by deficiency in enzymes need to degrade glycosaminoglycans (GAGs). Morquio A is characterized by a decrease in N-acetylgalactosamine-6-sulfatase activity and subsequent accumulation of keratan sulfate and chondroitin 6-sulfate in cells and body fluids. As the pathophysiology of this LSD is not completely understood and considering the previous results of our group concerning oxidative stress in Morquio A patients receiving enzyme replacement therapy (ERT), the aim of this study was to investigate oxidative stress parameters in Morquio A patients at diagnosis...
June 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28482050/parallel-assessment-of-the-effects-of-bisphenol-a-and-several-of-its-analogs-on-the-adult-human-testis
#20
C Desdoits-Lethimonier, L Lesné, P Gaudriault, D Zalko, J P Antignac, Y Deceuninck, C Platel, N Dejucq-Rainsford, S Mazaud-Guittot, B Jégou
STUDY QUESTION: Are bisphenol A (BPA) and BPA analogs (BPA-A) safe for male human reproductive function? SUMMARY ANSWER: The endocrine function of human testes explants [assessed by measuring testosterone and insulin-like factor 3 (INSL3)] was impacted by exposure of the human adult testis explants to BPA/BPA-A. WHAT IS KNOWN ALREADY: The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption...
May 8, 2017: Human Reproduction
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