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https://www.readbyqxmd.com/read/28098838/role-of-udp-glucuronosyltransferase-1a1-in-the-metabolism-and-pharmacokinetics-of-silymarin-flavonolignans-in-patients-with-hcv-and-nafld
#1
Ying Xie, Sonia R Miranda, Janelle M Hoskins, Roy L Hawke
Silymarin is the most commonly used herbal medicine by patients with chronic liver disease. Silymarin flavonolignans undergo rapid first-pass metabolism primarily by glucuronidation. The aims of this investigation were: (1) to determine the association of UGT1A1*28 polymorphism with the area under the plasma concentration-time curves (AUCs) for silybin A (SA) and silybin B (SB); (2) to evaluate the effect of UGT1A1*28 polymorphism on the profile of flavonolignan glucuronide conjugates found in the plasma; and (3) to investigate the role of UGT1A1 enzyme kinetics on the pharmacokinetics of SA and SB...
January 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28098746/marine-antibody-drug-conjugates-design-strategies-and-research-progress
#2
REVIEW
Yu-Jie Wang, Yu-Yan Li, Xiao-Yu Liu, Xiao-Ling Lu, Xin Cao, Bing-Hua Jiao
Antibody-drug conjugates (ADCs), constructed with monoclonal antibodies (mAbs), linkers, and natural cytotoxins, are innovative drugs developed for oncotherapy. Owing to the distinctive advantages of both chemotherapy drugs and antibody drugs, ADCs have obtained enormous success during the past several years. The development of highly specific antibodies, novel marine toxins' applications, and innovative linker technologies all accelerate the rapid R&D of ADCs. Meanwhile, some challenges remain to be solved for future ADCs...
January 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28098547/mcr-1-harboring-salmonella-enterica-serovar-typhimurium-sequence-type-34-in-pigs-china
#3
Linxian Yi, Jing Wang, Yanling Gao, Yiyun Liu, Yohei Doi, Renjie Wu, Zhenling Zeng, Zisen Liang, Jian-Hua Liu
We detected the mcr-1 gene in 21 (14.8%) Salmonella isolates from pigs at slaughter; 19 were serovar Typhimurium sequence type 34. The gene was located on IncHI2-like plasmids that also harbored IncF replicons and lacked a conjugative transfer region. These findings highlight the need to prevent further spread of colistin resistance in animals and humans.
February 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28098511/hemodynamic-effects-of-hpma-copolymer-based-doxorubicin-conjugate-a-randomized-controlled-and-comparative-spectral-study-in-conscious-rats
#4
Hoay Yan Cheah, Olivera Šarenac, Juan J Arroyo, Marko Vasić, Maja Lozić, Sofija Glumac, See Ziau Hoe, Charles Colin Thomas Hindmarch, David Murphy, Lik Voon Kiew, Hong Boon Lee, Marίa J Vicent, Lip Yong Chung, Nina Japundžić-Žigon
Conjugation of Doxorubicin (DOX) to N-(2-Hydroxypropyl) methylacrylamide copolymer (HPMA) has significantly reduced the DOX-associated cardiotoxicity. However, the reports on the impact of HPMA-DOX conjugates on the cardiovascular system such as blood pressure (BP) and heart rate (HR) were in restrained animals using tail cuff and/or other methods that lacked the resolution and sensitivity. Herein, we employed radiotelemetric-spectral-echocardiography approach to further understand the in vivo cardiovascular hemodynamics and variability post administration of free DOX and HPMA-DOX...
January 18, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28098453/surface-engineered-multifunctional-eu-gd2o3-nanoplates-for-targeted-and-ph-responsive-drug-delivery-and-imaging-applications
#5
Arindam Saha, Subas Chandra Mohanta, Kashmiri Deka, Pritam Deb, Parukuttyamma Sujatha Devi
In this paper, we report the synthesis of surface-engineered multifunctional Eu:Gd2O3 triangular nanoplates with small size and uniform shape via a high-temperature solvothermal technique. Surface engineering has been performed by a one-step polyacrylate coating, followed by controlled conjugation chemistry. This creates the desired number of surface functional groups that can be used to attach folic acid as a targeting ligand on the nanoparticle surface. To specifically deliver the drug molecules in the nucleus, the folate density on the nanoparticle surface has been kept low...
January 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28098320/versatile-tissue-lasers-based-on-high-q-fabry-p%C3%A3-rot-microcavities
#6
Yu-Cheng Chen, Qiushu Chen, Tingting Zhang, Wenjie Wang, Xudong Fan
Biolasers are an emerging technology for next generation biochemical detection and clinical applications. Progress has recently been made to achieve lasing from biomolecules and single living cells. Tissues, which consist of cells embedded in an extracellular matrix, mimic more closely the actual complex biological environment in a living body and therefore are of more practical significance. Here, we developed a highly versatile tissue laser platform, in which tissues stained with fluorophores are sandwiched in a high-Q Fabry-Pérot microcavity...
January 18, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28098257/a-comprehensive-platform-for-the-analysis-of-ubiquitin-like-protein-modifications-using-in-vivo-biotinylation
#7
Lucia Pirone, Wendy Xolalpa, Jón Otti Sigurðsson, Juanma Ramirez, Coralia Pérez, Monika González, Ainara Ruiz de Sabando, Félix Elortza, Manuel S Rodriguez, Ugo Mayor, Jesper V Olsen, Rosa Barrio, James D Sutherland
Post-translational modification by ubiquitin and ubiquitin-like proteins (UbLs) is fundamental for maintaining protein homeostasis. Efficient isolation of UbL conjugates is hampered by multiple factors, including cost and specificity of reagents, removal of UbLs by proteases, distinguishing UbL conjugates from interactors, and low quantities of modified substrates. Here we describe bioUbLs, a comprehensive set of tools for studying modifications in Drosophila and mammals, based on multicistronic expression and in vivo biotinylation using the E...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098245/natural-cytotoxicity-receptor-1-in-mouse-unk-cell-maturation-and-function
#8
A M Felker, B A Croy
Early and midgestational decidua of mice genetically ablated for expression of the natural killer (NK) cell natural cytotoxicity receptor (NCR; Ncr1(Gfp/Gfp) mice) shows restricted angiogenesis and atypically small uterine (u)NK cells . We hypothesized that NCR1 inactivation disturbs maturation and angiokine production by uterine natural killer (uNK) cells. Using histological and morphometric approaches, we observed that Ncr1(Gfp/Gfp) but not control C57BL/6 (B6) implantation sites sustain immature, non-granulated uNK cells into midpregnancy...
January 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28097916/exploring-the-first-rimonabant-analog-opioid-peptide-hybrid-compound-as-bivalent-ligand-for-cb1-and-opioid-receptors
#9
Adriano Mollica, Sveva Pelliccia, Valeria Famiglini, Azzurra Stefanucci, Giorgia Macedonio, Annalisa Chiavaroli, Giustino Orlando, Luigi Brunetti, Claudio Ferrante, Stefano Pieretti, Ettore Novellino, Sandor Benyhe, Ferenc Zador, Anna Erdei, Edina Szucs, Reza Samavati, Szalbolch Dvrorasko, Csaba Tomboly, Rino Ragno, Alexandros Patsilinakos, Romano Silvestri
Cannabinoid (CB) and opioid systems are both involved in analgesia, food intake, mood and behavior. Due to the co-localization of µ-opioid (MOR) and CB1 receptors in various regions of the central nervous system (CNS) and their ability to form heterodimers, bivalent ligands targeting to both these systems may be good candidates to investigate the existence of possible cross-talking or synergistic effects, also at sub-effective doses. In this work, we selected from a small series of new Rimonabant analogs one CB1R reverse agonist to be conjugated to the opioid fragment Tyr-D-Ala-Gly-Phe-NH2...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28097898/two-approaches-to-the-use-of-benzo-c-1-2-oxaboroles-as-active-fragments-for-synthetic-transformation-of-clarithromycin
#10
Gennady B Lapa, Elena P Mirchink, Elena B Isakova, Maria N Preobrazhenskaya
Clarithromycin (active against Gram positive infections) and 1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole derivatives (effective for Gram negative microbes) are the ligands of bacterial RNA. The antimicrobial activities of these benzoxaboroles linked with clarithromycin at 9 or 4″ position were compared. Two synthetic pathways for these conjugates were elaborated. First pathway explored the substitution of the C-9 carbonyl group of macrolactone's cycle via oxime linker, the second direction used the modification of the 4″-O-group of cladinose via the formation of carbamates of benzoxaboroles...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28097756/aazta-an-ideal-chelating-agent-for-the-development-of-44-sc-pet-imaging-agents
#11
Gábor Nagy, Dezső Szikra, György Trencsényi, Anikó Fekete, Ildikó Garai, Arianna M Giani, Roberto Negri, Norberto Masciocchi, Alessandro Maiocchi, Fulvio Uggeri, Imre Tóth, Silvio Aime, Giovanni B Giovenzana, Zsolt Baranyai
Unprecedented fast and efficient complexation of Sc(III) was demonstrated with the chelating agent AAZTA (AAZTA=1,4-bis(carboxymethyl)-6-[bis(carboxymethyl)]amino-6-methylperhydro-1,4-diazepine) under mild experimental conditions. The robustness of the (44) Sc(AAZTA)(-) chelate and conjugated biomolecules thereof is further shown by in vivo PET imaging in healthy and tumor mice models. The new results pave the way towards development of efficient Sc-based radiopharmaceuticals using the AAZTA chelator.
January 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28097755/a-solution-processable-liquid-crystalline-semiconductor-for-low-temperature-annealed-air-stable-n-channel-field-effect-transistors
#12
Resul Ozdemir, Donghee Choi, Mehmet Ozdemir, Hyekyoung Kim, Sinem Tuncel Kostakoğlu, Mustafa Erkartal, Hyungsug Kim, Choongik Kim, Hakan Usta
A new solution-processable and air-stable liquid-crystalline n-channel organic semiconductor (α,ω-2OD-TIFDMT) employing a donor-acceptor-donor (D-A-D) type of π-conjugation has been designed, synthesized, and fully characterized. The new semiconductor exhibits a low LUMO energy (-4.19 eV) and a narrow optical band gap (1.35 eV). Typical pseudo focal-conic fan-shaped texture of a hexagonal columnar liquid crystalline (LC) phase was observed over a wide temperature range. The spin-coated semiconductor thin-films shows the formation of large (~0...
January 17, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/28097751/bifunctional-br%C3%A3-nsted-base-catalyst-enables-regio-diastereo-and-enantioselective-c%C3%AE-alkylation-of-%C3%AE-tetralones-and-related-aromatic-ring-fused-cycloalkanones
#13
Iñaki Urruzuno, Odei Mugica, Mikel Oiarbide, Claudio Palomo
The catalytic asymmetric synthesis of both α-substituted and α,α-disubstituted (quaternary) β-tetralones through direct α-functionalization of the corresponding β-tetralone precursor remains elusive. A designed Brønsted base-squaramide bifunctional catalyst promotes the conjugate addition of either unsubstituted or α-monosubstituted β-tetralones to nitroalkenes. Under these reaction conditions, not only enolization, and thus functionalization, occurs at the α-carbon atom of the β-tetralone exclusively, but adducts including all-carbon quaternary centers are also formed in highly diastereo- and enantioselective manner...
January 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28097733/optimized-amplitude-modulated-multiband-rf-pulse-design
#14
Samy Abo Seada, Anthony N Price, Joseph V Hajnal, Shaihan J Malik
PURPOSE: Multiband pulses are characterized by highly temporally modulated waveforms. Rapid phase or frequency modulation can be extremely demanding on the performance of radiofrequency (RF) pulse generation, which can lead to errors that can be avoided if pulses are restricted to amplitude modulation (AM) only. In this work, three existing multiband pulse design techniques are modified to produce AM waveforms. THEORY AND METHODS: Multiband refocusing pulses were designed using phase optimization, time shifting, and root flipping...
January 17, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28097690/an-overview-of-structural-features-of-antibacterial-glycoconjugate-vaccines-that-influence-their-immunogenicity
#15
REVIEW
Farjana Khatun, Rachel J Stephenson, Istvan Toth
Bacterial cell-surface-derived or mimicked carbohydrate moieties that act as protective antigens are used in the development of antibacterial glycoconjugate vaccines. The carbohydrate antigen must have a minimum length or size to maintain the conformational structure of the antigenic epitope(s). The presence or absence of O-acetate, phosphate, glycerol phosphate and pyruvate ketal plays a vital role in defining the immunogenicity of the carbohydrate antigen. The nature of the carrier protein, spacer and conjugation pattern used to develop the glycoconjugate vaccine also defines its overall spatial orientation which in turn affects its avidity and selectivity of interaction with the desired target(s)...
November 7, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28097276/hydrophobicity-determines-the-fate-of-self-assembled-fluorescent-nanoparticles-in-cells
#16
Arthur H A M van Onzen, Lorenzo Albertazzi, Albertus P H J Schenning, Lech-Gustav Milroy, Luc Brunsveld
The fate of small molecule nanoparticles (SMNPs) composed of self-assembling intrinsically fluorescent π-conjugated oligomers was studied in cells as a function of side-chain hydrophobicity. While the hydrophobic SMNPs remained intact upon cellular uptake, the more hydrophilic SMNPs disassembled and dispersed throughout the cytosol.
January 18, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28097238/quantitative-measurement-of-lymphatic-function-in-mice-by-noninvasive-near-infrared-imaging-of-a-peripheral-vein
#17
Steven T Proulx, Qiaoli Ma, Diana Andina, Jean-Christophe Leroux, Michael Detmar
Optical imaging methods have been developed to measure lymphatic function in skin; however, the lymphatic system of many organs is not accessible to this technology. Since lymphatic transport of macromolecules from any organ proceeds to the blood circulation, we aimed to develop a method that can measure lymphatic function by monitoring the fluorescence in a superficial vein of an interstitially injected tracer. We selected a 40-kDa PEGylated near-infrared dye conjugate, as it showed lymphatic system-specific uptake and extended circulation in blood...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28096941/transport-of-biomolecules-to-binding-partners-displayed-on-the-surface-of-microbeads-arrayed-in-traps-in-a-microfluidic-cell
#18
Xiaoxiao Chen, Thomas F Leary, Charles Maldarelli
Arrays of probe molecules integrated into a microfluidic cell are utilized as analytical tools to screen the binding interactions of the displayed probes against a target molecule. These assay platforms are useful in enzyme or antibody discovery, clinical diagnostics, and biosensing, as their ultraminiaturized design allows for high sensitivity and reduced consumption of reagents and target. We study here a platform in which the probes are first grafted to microbeads which are then arrayed in the microfluidic cell by capture in a trapping course...
January 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28096463/deneddylase1-counters-automodification-of-neddylating-enzymes-to-maintain-nedd8-homeostasis-in-arabidopsis
#19
Julia Mergner, Bernhard Kuster, Claus Schwechheimer
In eukaryotes, the conjugation of the ubiquitin-like protein NEDD8 onto protein targets is an important post-translational modification. The best understood neddylation targets are the cullins, scaffold subunits of E3 ubiquitin ligases, where neddylation as well as deneddylation, facilitated by the protease activity of the CSN (COP9 signalosome), are required to control ubiquitin ligase assembly, function and ultimately substrate degradation. Little is known about the role of other deneddylating enzymes besides CSN and the role of neddylation and deneddylation of their substrates...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096456/antibody-conjugated-dna-based-nanocarriers-intercalated-with-doxorubicin-eliminate-myofibroblasts-in-explants-of-human-lens-tissue
#20
Jacquelyn Gerhart, Marvin Greenbaum, Lou Casta, Anthony Clemente, Keith Mathers, Robert Getts, Mindy George-Weinstein
Posterior capsule opacification (PCO) occurs in some adults and most children following cataract surgery. The fibrotic form of PCO arises, in part, from migratory, contractile myofibroblasts that deform the lens capsule and impair vision. In short-term cultures of human anterior lens tissue, myofibroblasts emerge from Myo/Nog cells that are identified with the G8 monoclonal antibody and by their expression of the MyoD transcription factor and bone morphogenetic protein inhibitor noggin. In this study, we tested the hypothesis that targeted depletion of Myo/Nog cells with the G8 mAb conjugated to three-dimensional DNA nanocarriers intercalated with Doxorubicin (G8:3DNA:Dox) would prevent the accumulation of myofibroblasts in long-term, serum and growth factor free cultures of human lens tissue obtained by capsulorhexis...
January 17, 2017: Journal of Pharmacology and Experimental Therapeutics
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