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https://www.readbyqxmd.com/read/28335566/profiling-and-preparation-of-metabolites-from-pyragrel-in-human-urine-by-online-solid-phase-extraction-coupled-with-high-performance-liquid-chromatography-tandem-mass-spectrometry-followed-by-a-macroporous-resin-based-purification-approach
#1
Xin Zhao, Jingjing Jiang, Guang Yang, Jie Huang, Guoping Yang, Guangwei He, Zhaoxing Chu, Taijun Hang, Guorong Fan
Pyragrel, a new anticoagulant drug, is derived from the molecular combination of ligustrazine and ferulic acid. Pyragrel showed significant inhibitory activity against platelet aggregation induced by adenosine diphosphate (ADP), and had been approved for a phase I clinical trial by CFDA. To characterize the metabolites of Pyragrel in human urine after intravenous administration, a reliable online solid-phase extraction couple with high performance liquid chromatography tandem mass spectrometry (online SPE-HPLC-MS(n)) method was conceived and applied...
March 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28335456/mosquito-traps-an-innovative-environmentally-friendly-technique-to-control-mosquitoes
#2
Brigitte Poulin, Gaëtan Lefebvre, Camille Muranyi-Kovacs, Samuel Hilaire
We tested the use of mosquito traps as an alternative to spraying insecticide in Camargue (France) following the significant impacts observed on the non-target fauna through Bti persistence and trophic perturbations. In a village of 600 inhabitants, 16 Techno Bam traps emitting CO₂ and using octenol lures were set from April to November 2016. Trap performance was estimated at 70% overall based on mosquitoes landing on human bait in areas with and without traps. The reduction of Ochlerotatus caspius and Oc...
March 18, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28335269/galactosylated-liposomes-for-targeted-co-delivery-of-doxorubicin-vimentin-sirna-to-hepatocellular-carcinoma
#3
Hea Ry Oh, Hyun-Young Jo, James S Park, Dong-Eun Kim, Je-Yoel Cho, Pyung-Hwan Kim, Keun-Sik Kim
The combination of therapeutic nucleic acids and chemotherapeutic drugs has shown great promise for cancer therapy. In this study, asialoglycoprotein receptors (ASGPR) targeting-ligand-based liposomes were tested to determine whether they can co-deliver vimentin siRNA and doxorubicin to hepatocellular carcinoma (HCC) selectively. To achieve this goal, we developed an ASGPR receptor targeted co-delivery system called gal-doxorubicin/vimentin siRNA liposome (Gal-DOX/siRNA-L). The Gal-DOX/siRNA-L was created via electrostatic interaction of galactose linked-cationic liposomal doxorubicin (Gal-DOX-L) on vimentin siRNA...
July 30, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28335006/a-platform-for-functional-assessment-of-large-variant-libraries-in-mammalian-cells
#4
Kenneth A Matreyek, Jason J Stephany, Douglas M Fowler
Sequencing-based, massively parallel genetic assays have revolutionized our ability to quantify the relationship between many genotypes and a phenotype of interest. Unfortunately, variant library expression platforms in mammalian cells are far from ideal, hindering the study of human gene variants in their physiologically relevant cellular contexts. Here, we describe a platform for phenotyping variant libraries in transfectable mammalian cell lines in two steps. First, a landing pad cell line with a genomically integrated, Tet-inducible cassette containing a Bxb1 recombination site is created...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334766/crystal-structure-of-the-n-terminal-domain-of-human-timeless-and-its-interaction-with-tipin
#5
Sandro Holzer, Gianluca Degliesposti, Mairi L Kilkenny, Sarah L Maslen, Dijana Matak-Vinkovíc, Mark Skehel, Luca Pellegrini
Human Timeless is involved in replication fork stabilization, S-phase checkpoint activation and establishment of sister chromatid cohesion. In the cell, Timeless forms a constitutive heterodimeric complex with Tipin. Here we present the 1.85 Å crystal structure of a large N-terminal segment of human Timeless, spanning amino acids 1-463, and we show that this region of human Timeless harbours a partial binding site for Tipin. Furthermore, we identify minimal regions of the two proteins that are required for the formation of a stable Timeless-Tipin complex and provide evidence that the Timeless-Tipin interaction is based on a composite binding interface comprising different domains of Timeless...
February 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334513/the-number-of-cag-and-ggn-triplet-repeats-in-the-androgen-receptor-gene-exert-combinatorial-effect-on-hormonal-and-sperm-parameters-in-young-men
#6
M Grigorova, M Punab, T Kahre, M Ivandi, N Tõnisson, O Poolamets, V Vihljajev, B Žilaitienė, J Erenpreiss, V Matulevičius, M Laan
Androgen receptor (AR) is a transcription factor that is activated upon binding to testosterone (T) and is implicated in regulating the expression of reproduction-related genes. The human AR gene (Xq11-12) spans 186,588 bp and eight exons. N-terminal transactivation domain of the encoded AR protein harbours two polymorphic stretches of identical amino acids, a polyglutamine tract (encoded by 8-37 CAG-repeats) and a polyglycine tract (encoded by 10-30 GGN-repeats). We set forward to analyse independent and combinatory effects of the length of these repetitive tracts on male reproductive hormones, testicular and sperm parameters in a population-based cohort of Baltic young men (n = 974; aged 20...
March 23, 2017: Andrology
https://www.readbyqxmd.com/read/28333153/a-novel-inhibitor-idpp-interferes-with-entry-and-egress-of-hcv-by-targeting-glycoprotein-e1-in-a-genotype-specific-manner
#7
Myungeun Lee, Jaewon Yang, Eunji Jo, Ji-Young Lee, Hee-Young Kim, Ralf Bartenschlager, Eui-Cheol Shin, Yong-Soo Bae, Marc P Windisch
Despite recent advances in curing chronic hepatitis C (CHC), the high economic burden to therapy, viral drug resistance, difficult to treat hepatitis C virus (HCV) genotypes and patient groups are still of concern. To address this unmet medical needs, we devised strategies to identify novel viral interventions through target-free high-throughput screening of small molecules utilizing a phenotypic-based HCV infection assay. Thereby, a very potent (EC50 46 ± 26 pM) iminodipyridinopyrimidine (IDPP) drug candidate was selected, and confirmed in primary human hepatocytes (EC50 0...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331958/nucleic-acid-sensing-with-enzyme-dna-binding-protein-conjugates-cascade-and-simple-dna-nanostructures
#8
Gülsen Betül Aktas, Vasso Skouridou, Lluis Masip
A versatile and universal DNA sensing platform is presented based on enzyme-DNA binding protein tags conjugates and simple DNA nanostructures. Two enzyme conjugates were thus prepared, with horseradish peroxidase linked to the dimeric single-chain bacteriophage Cro repressor protein (HRP-scCro) and glucose oxidase linked to the dimeric headpiece domain of Escherichia coli LacI repressor protein (GOx-dHP), and used in conjunction with a hybrid ssDNA-dsDNA detection probe. This probe served as a simple DNA nanostructure allowing first for target recognition through its target-complementary single-stranded DNA (ssDNA) part and then for signal generation after conjugate binding on the double-stranded DNA (dsDNA) containing the specific binding sites for the dHP and scCro DNA binding proteins...
March 22, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28331163/in-vitro-evaluation-of-candidate-bacillus-spp-for-animal-feed
#9
Sirima Mingmongkolchai, Watanalai Panbangred
The aim of this study was to select aerobic spore-formers for animal feed based on their in vitro probiotic potential, including their enzyme-producing ability and safety assessment. Seven isolates out of 187 spore-forming bacteria were selected for their ability to produce cellulase (89.21-1668.32 U/ml), xylanase (1399.68-4351.10 U/ml), and phytase (2.72-28.70 U/ml). Among seven isolates, five had activities towards a broad range of p-nitrophenyl esters with acyl chain lengths from C2 to C12. The probiotic properties of all selected isolates varied with respect to their acid and bile salt tolerance under simulated gastrointestinal tract (GIT) conditions, and their adherence ability to human intestinal cell lines (Caco-2 and HT-29)...
March 22, 2017: Journal of General and Applied Microbiology
https://www.readbyqxmd.com/read/28331093/structural-characterization-of-hcov-nl63-n-protein
#10
Bozena Szelazek, Wojciech Kabala, Krzysztof Kus, Michal Zdzalik, Aleksandra Twarda-Clapa, Przemyslaw Golik, Michal Burmistrz, Dominik Florek, Benedykt Wladyka, Krzysztof Pyrc, Grzegorz Dubin
Coronaviruses are responsible for upper and lower respiratory tract infections in humans. It is estimated that 1-10% of the population suffers annually from cold-like symptoms related to infection with HCoV-NL63, an alphacoronavirus. The nucleocapsid (N) protein, the major structural component of the capsid, facilitates RNA packing, links the capsid to the envelope and is also involved in multiple other processes including viral replication and evasion of the immune system. Although the role of N protein in viral replication is relatively well described, no structural data are currently available regarding the N proteins of alphacoronaviruses...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28331001/quantitative-tyrosine-phosphoproteomics-of-egfr-tyrosine-kinase-inhibitor-treated-lung-adenocarcinoma-cells-reveals-potential-novel-biomarkers-of-therapeutic-response
#11
Xu Zhang, Tapan Maity, Manoj K Kashyap, Mukesh Bansal, Abhilash Venugopalan, Sahib Singh, Shivangi Awasthi, Arivusudar Marimuthu, Harrys Kishore Charles Jacob, Natalya Belkina, Stephanie Pitts, Constance M Cultraro, Shaojian Gao, Fatos Kirkali, Romi Biswas, Raghothama Chaerkady, Andrea Califano, Akhilesh Pandey, Udayan Guha
Mutations in the Epidermal growth factor receptor (EGFR) kinase domain, such as the L858R missense mutation and deletions spanning the conserved sequence 747LREA750, are sensitive to tyrosine kinase inhibitors (TKIs). The gatekeeper site residue mutation, T790M accounts for around 60% of acquired resistance to EGFR TKIs. The first generation EGFR TKIs, erlotinib and gefitinib, and the second generation inhibitor, afatinib are FDA approved for initial treatment of EGFR mutated lung adenocarcinoma. The predominant biomarker of EGFR TKI responsiveness is the presence of EGFR TKI-sensitizing mutations...
March 22, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28330616/systematic-analysis-of-human-protein-phosphatase-interactions-and-dynamics
#12
Leena Yadav, Fitsum Tamene, Helka Göös, Audrey van Drogen, Riku Katainen, Ruedi Aebersold, Matthias Gstaiger, Markku Varjosalo
Coordinated activities of protein kinases and phosphatases ensure phosphorylation homeostasis, which, when perturbed, can instigate diseases, including cancer. Yet, in contrast to kinases, much less is known about protein phosphatase functions and their interactions and complexes. Here, we used quantitative affinity proteomics to assay protein-protein interactions for 54 phosphatases distributed across the three major protein phosphatase families, with additional analysis of their 12 co-factors. We identified 838 high-confidence interactions, of which 631, to our knowledge, have not been reported before...
March 15, 2017: Cell Systems
https://www.readbyqxmd.com/read/28330481/diverse-characteristics-of-the-urinary-excretion-of-amino-acids-in-humans-and-the-use-of-amino-acid-supplementation-to-reduce-fatigue-and-sub-health-in-adults
#13
R H Dunstan, D L Sparkes, M M Macdonald, X Janse De Jonge, B J Dascombe, J Gottfries, C-G Gottfries, T K Roberts
BACKGROUND: The excretion of amino acids in urine represents an important avenue for the loss of key nutrients. Some amino acids such as glycine and histidine are lost in higher abundance than others. These two amino acids perform important physiological functions and are required for the synthesis of key proteins such as haemoglobin and collagen. METHODS: Stage 1 of this study involved healthy subjects (n = 151) who provided first of the morning urine samples and completed symptom questionnaires...
March 23, 2017: Nutrition Journal
https://www.readbyqxmd.com/read/28330073/cladosporium-cladosporioides-from-the-perspectives-of-medical-and-biotechnological-approaches
#14
REVIEW
Manaf AlMatar, Essam A Makky
Fungi are important natural product sources that have enormous potential for the production of novel compounds for use in pharmacology, agricultural applications and industry. Compared with other natural sources such as plants, fungi are highly diverse but understudied. However, research on Cladosporium cladosporioides revealed the existence of bioactive products such as p-methylbenzoic acid, ergosterol peroxide (EP) and calphostin C as well as enzymes including pectin methylesterase (PME), polygalacturonase (PG) and chlorpyrifos hydrolase...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329693/lanthanide-integrated-supramolecular-polymeric-nanoassembly-with-multiple-regulation-characteristics-for-multidrug-resistant-cancer-therapy
#15
Weihong Jin, Qiwen Wang, Min Wu, Yang Li, Guping Tang, Yuan Ping, Paul K Chu
Cancer treatment can in principle be enhanced by the synergistic effects of chemo- and nucleic acid-based combination therapies but the lack of efficient drug nanocarriers and occurrence of multidrug resistance (MDR) are major obstacles adversely affecting the effectiveness. Herein, a lanthanide-integrated supramolecular polymeric nanoassembly that delivers anticancer drugs and siRNA for more effective cancer therapy is described. This nanotherapeutic system is prepared by loading adamantane-modified doxorubicin (Dox) into polyethylenimine-crosslinked-γ-cyclodextrin (PC) through the supramolecular assembly to form the interior Dox-loaded PC (PCD) followed by electrostatically driven self-assembly of siRNA and PCD to produce the PCD/siRNA nanocomplexes...
March 16, 2017: Biomaterials
https://www.readbyqxmd.com/read/28328967/phenotypic-and-molecular-characterization-of-antimicrobial-resistance-in-enterobacter-spp-isolates-from-companion-animals-in-japan
#16
Kazuki Harada, Takae Shimizu, Yujiro Mukai, Ken Kuwajima, Tomomi Sato, Akari Kajino, Masaru Usui, Yutaka Tamura, Yui Kimura, Tadashi Miyamoto, Yuzo Tsuyuki, Asami Ohki, Yasushi Kataoka
The emergence of antimicrobial resistance among Enterobacter spp., including resistance to extended-spectrum cephalosporins (ESC), is of great concern in both human and veterinary medicine. In this study, we investigated the prevalence of antimicrobial resistance among 60 isolates of Enterobacter spp., including E. cloacae (n = 44), E. aerogenes (n = 10), and E. asburiae (n = 6), from clinical specimens of dogs and cats from 15 prefectures in Japan. Furthermore, we characterized the resistance mechanisms harbored by these isolates, including extended-spectrum β-lactamases (ESBLs) and plasmid-mediated quinolone resistance (PMQR); and assessed the genetic relatedness of ESC-resistant Enterobacter spp...
2017: PloS One
https://www.readbyqxmd.com/read/28327797/bacterial-immunostat-mycobacterium-tuberculosis-lipids-and-their-role-in-the-host-immune-response
#17
Adriano Queiroz, Lee W Riley
The lipid-rich cell wall of Mycobacterium tuberculosis is a dynamic structure that is involved in the regulation of the transport of nutrients, toxic host-cell effector molecules, and anti-tuberculosis drugs. It is therefore postulated to contribute to the long-term bacterial survival in an infected human host. Accumulating evidence suggests that M. tuberculosis remodels the lipid composition of the cell wall as an adaptive mechanism against host-imposed stress. Some of these lipid species (trehalose dimycolate, diacylated sulphoglycolipid, and mannan-based lipoglycans) trigger an immunopathologic response, whereas others (phthiocerol dimycocerosate, mycolic acids, sulpholipid-1, and di-and polyacyltrehalose) appear to dampen the immune responses...
January 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28327659/the-immunosuppressant-mycophenolic-acid-alters-nucleotide-and-lipid-metabolism-in-an-intestinal-cell-model
#18
Svenja Heischmann, Monika Dzieciatkowska, Kirk Hansen, Dieter Leibfritz, Uwe Christians
The study objective was to elucidate the molecular mechanisms underlying the negative effects of mycophenolic acid (MPA) on human intestinal cells. Effects of MPA exposure and guanosine supplementation on nucleotide concentrations in LS180 cells were assessed using liquid chromatography-mass spectrometry. Proteomics analysis was carried out using stable isotope labeling by amino acids in cell culture combined with gel-based liquid chromatography-mass spectrometry and lipidome analysis using (1)H nuclear magnetic resonance spectroscopy...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327532/a-combination-of-soybean-and-haematococcus-extract-alleviates-ultraviolet-b-induced-photoaging
#19
Jieun Shin, Jong-Eun Kim, Kum-Ju Pak, Jung Il Kang, Tae-Seok Kim, Sang-Yoon Lee, Ik-Hyun Yeo, Jung Han Yoon Park, Jong Hun Kim, Nam Joo Kang, Ki Won Lee
Soybean-derived isoflavones have been investigated for their preventative effects against UV-induced symptoms of skin damage including wrinkle formation and inflammation. Haematococcus pluvialis is a freshwater species of Chlorophyta that contains high concentrations of the natural carotenoid pigment astaxanthin. Astaxanthin is known to be involved in retinoic acid receptor (RAR) signaling and previously been associated with the inhibition of activator protein (AP)-1 dependent transcription. Based on previous studies, we hypothesized that a combination of soy extract (SE) and Haematococcus extract (HE) may prevent UVB-induced photoaging through specific signaling pathways, as measured by UVB-induced wrinkling on hairless mice skin and expression changes in human dermal fibroblasts (HDFs)...
March 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28327196/primary-hepatic-angiomyolipoma-immunohistochemistry-and-electron-microscopic-observations-a-case-report
#20
Hidefumi Kubo, Hitoshi Yamazaki, Takemichi Okada, Yoshihito Takahashi, Yatsushi Nishi, Hiroaki Yokomori
BACKGROUND: Hepatic angiomyolipomas are a rare, benign group of mesenchymal tumors in the liver. Hepatic angiomyolipoma is sometimes misdiagnosed as hepatocellular carcinoma, and there is the possibility of a malignant transformation. Hence, the accurate diagnosis of this disorder is necessary. CASE PRESENTATION: A 64-year-old Japanese man was observed to have a space-occupying lesion of 15-mm diameter in the liver during a follow-up examination for a previously resected cecal carcinoma...
March 22, 2017: Journal of Medical Case Reports
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