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https://www.readbyqxmd.com/read/29783197/quantification-of-21-antihypertensive-drugs-in-serum-using-uhplc-ms-ms
#1
Per Ole M Gundersen, Arne Helland, Olav Spigset, Solfrid Hegstad
BACKGROUND: Poor drug adherence in hypertensive patients can lead to treatment failure and increased cardiovascular morbidity, as well as increased costs to society. An analytical method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MSMS) was developed and validated for use in routine therapeutic drug monitoring (TDM). The method includes 21 antihypertensive drugs or active metabolites from the groups beta blockers (n=5), calcium antagonists (n=5), angiotensin II receptor antagonists (n=4), angiotensin converting enzyme (ACE) inhibitors (n=3) and diuretics (n = 3), in addition to one α1-selective alpha blocker...
April 28, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29783151/formation-and-characterization-of-chitosan-protein-particles-with-fractal-whey-protein-aggregates
#2
Khouloud Fekih Ahmed, Adel Aschi, Taco Nicolai
Hybrid protein-polysaccharide particles were formed by complexation of fractal whey protein aggregates and the cationic polysaccharide chitosan. The fractal aggregates were preformed by heating native whey protein isolate at pH 7 and subsequently mixed with chitosan at pH 3 where these proteins and polysaccharides don't interact with each other. Stable dispersions of protein-polysaccharide particles were formed spontaneously when the pH was gradually increased between 4.1 and 6.8, whereas in the absence of chitosan the fractal aggregates precipitated between pH 4...
May 15, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29783089/self-stabilized-silk-sericin-based-nanoparticles-in-vivo-biocompatibility-and-reduced-doxorubicin-induced-toxicity
#3
Doudou Hu, Ting Li, Zongpu Xu, Di Liu, Mingying Yang, Liangjun Zhu
A variety of colloid stabilizers and cryoprotectants confer improved nanoparticle (NP) colloidal stability and redisperability. However, the discounted tumor targetability, delivery efficacy and possible side effects limit the application in the vascular delivery of NPs. Here we present the water-soluble silk sericin (SS) not only as a material for the preparation of NPs, but also both a dispersion stabilizer and a cryoprotectant. In the absence of any stabilizers, SS-based NPs (SSC@NPs) could resist to the serum protein adsorption, preventing the formation of particle agglomerates...
May 18, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29782948/dendritic-peg-outer-shells-enhance-serum-stability-of-polymeric-micelles
#4
Hao-Jui Hsu, Yanxiao Han, Michael Cheong, Petr Král, Seungpyo Hong
A higher surface density of poly(ethylene glycol) (PEG) on polymeric micelles enhances their stability in serum, leading to improved plasma circulation. To obtain fundamental, mechanistic understanding of the PEG effect associated with polymeric architecture/configuration, we have synthesized PEGylated dendron-based copolymers (PDCs) and linear block copolymers (LBCs) with similar molecular weights. These copolymers formed dendron (hyperbranched) and linear micelles, respectively, which were compared in terms of their stabilities in serum, micelle-serum protein interactions, and in vivo biodistributions...
May 18, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29782833/insights-into-stabilizing-forces-in-amyloid-fibrils-of-differing-sizes-from-polarizable-molecular-dynamics-simulations
#5
Darcy S Davidson, Anne M Brown, Justin A Lemkul
Pathological aggregation of amyloid-forming proteins is a hallmark of a number of human diseases, including Alzheimer's, type 2 diabetes, Parkinson's, and more. Despite having very different primary amino acid sequences, these amyloid proteins form similar supramolecular, fibril structures that are highly resilient to physical and chemical denaturation. To better understand the structural stability of disease-related amyloids and to gain a greater understanding of factors that stabilize functional amyloid assemblies, insights into tertiary and quaternary interactions are needed...
May 18, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29782652/adenosine-methylation-as-a-molecular-imprint-defining-the-fate-of-rna
#6
REVIEW
Philip Knuckles, Marc Bühler
Multiple lines of evidence suggest the RNA modification N6 -methyladonsine (m6 A), which is installed in the nucleus co-transcriptionally and, thereafter, serves as a reversible chemical imprint that influences several steps of mRNA metabolism. This includes but is not limited to RNA folding, splicing, stability, transport, and translation. In this Review we focus on the current view of the nuclear installation of m6 A as well the molecular players involved, the so called m6 A writers. We also explore the effector proteins, or m6 A readers, that decode the imprint in different cellular contexts and compartments, and ultimately, the way the modification influences the lifecycle of an RNA molecule...
May 21, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29782551/structural-insights-on-the-efficient-catalysis-of-hydroperoxide-reduction-by-ohr-crystallographic-and-molecular-dynamics-approaches
#7
Erika Piccirillo, Thiago G P Alegria, Karen F Discola, José R R Cussiol, Renato M Domingos, Marcos A de Oliveira, Leandro de Rezende, Luis E S Netto, Antonia T-do Amaral
Organic hydroperoxide resistance (Ohr) enzymes are highly efficient Cys-based peroxidases that play central roles in bacterial response to fatty acid hydroperoxides and peroxynitrite, two oxidants that are generated during host-pathogen interactions. In the active site of Ohr proteins, the conserved Arg (Arg19 in Ohr from Xylella fastidiosa) and Glu (Glu51 in Ohr from Xylella fastidiosa) residues, among other factors, are involved in the extremely high reactivity of the peroxidatic Cys (Cp) toward hydroperoxides...
2018: PloS One
https://www.readbyqxmd.com/read/29782520/polymorphic-sites-preferentially-avoid-co-evolving-residues-in-mhc-class-i-proteins
#8
Linda Dib, Nicolas Salamin, David Gfeller
Major histocompatibility complex class I (MHC-I) molecules are critical to adaptive immune defence mechanisms in vertebrate species and are encoded by highly polymorphic genes. Polymorphic sites are located close to the ligand-binding groove and entail MHC-I alleles with distinct binding specificities. Some efforts have been made to investigate the relationship between polymorphism and protein stability. However, less is known about the relationship between polymorphism and MHC-I co-evolutionary constraints...
May 21, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29782227/cdk5-mediated-acn-acinus-phosphorylation-regulates-basal-autophagy-independently-of-metabolic-stress
#9
Nilay Nandi, Helmut Krämer
In neurons, autophagy counteracts consequences of aging. It is therefore of interest how basal rates of macroautophagy/autophagy can be controlled independently of metabolic stress. We recently investigated the regulation of basal, starvation-independent autophagy by Acn/Acinus, a multifunctional nuclear protein with proposed roles in apoptosis, alternative RNA splicing, and basal autophagy. We found that Acn is stabilized by phosphorylation of the conserved serine 437. The phosphomimetic AcnS437D mutation causes no overt developmental phenotypes, but significantly elevates levels of basal autophagy and extends life spans...
May 21, 2018: Autophagy
https://www.readbyqxmd.com/read/29782191/lipid-protein-and-microrna-composition-within-mesenchymal-stem-cell-derived-exosomes
#10
Hao Deng, Chun Sun, Yingxin Sun, Huhu Li, Lin Yang, Danbin Wu, Qing Gao, Xijuan Jiang
Mesenchymal stem cells (MSCs) were regarded as one of the most promising type of seed cells in tissue engineering due to its easy accessibility and multipotent feature of being able to differentiate into adipocyte, osteoblast, cardiomyocytes, and neurons. For years, MSCs have been applied in treating cardiovascular disease, reconstructing kidney injury, and remodeling immune system with remarkable achievements. Basic researches revealed that its clinic effects are not only due to their pluripotent ability but also through their paracrine function that they synthesize and secrete a broad spectrum of growth factors and cytokines...
May 21, 2018: Cellular Reprogramming
https://www.readbyqxmd.com/read/29781756/development-and-in-vivo-evaluation-of-chitosan-nanoparticles-for-the-oral-delivery-of-albumin
#11
Dalia Nashaat, Mahmoud Elsabahy, Tahra El-Sherif, Mostafa A Hamad, Gamal A El-Gindy, Ehsan H Ibrahim
Albumin is used as a plasma expander in critically ill patients and for several other clinical applications mainly via intravenous infusion. Oral administration of albumin can improve patient compliance although limited oral bioavailability of proteins is still a major challenge. Although nanomaterials have been extensively utilized for improving oral delivery of proteins, albumin has been utilized only as either a model drug or as a carrier for drug delivery. In the current study, for the first time, chitosan nanoparticles have been developed and extensively optimized to improve oral bioavailability of albumin as a therapeutic protein...
May 21, 2018: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29781745/using-dextran-of-different-molecular-weights-to-achieve-faster-freeze-drying-and-improved-storage-stability-of-lactate-dehydrogenase
#12
Bjarke Strøm Larsen, Jeppe Skytte, Anna J Svagan, Helena Meng-Lund, Holger Grohganz, Korbinian Löbmann
Freeze-drying of protein formulations is frequently used to maintain protein activity during storage. The freeze-drying process usually requires long primary drying times because the highest acceptable drying temperature to obtain acceptable products is dependent on the glass transition temperature of the maximally freeze-concentrated solution (Tg '). On the other hand, retaining protein activity during storage is related to the glass transition temperature (Tg ) of the final freeze-dried product. In this study, dextrans with different molecular weight (1 kDa and 40 kDa) and mixtures thereof at the ratio 3:1, 1:1 and 1:3 (w/w) were used as cryo-/lyoprotectant and their impact on the stability of the model protein lactate dehydrogenase (LDH) was investigated at elevated temperatures (40 and 60°C)...
May 21, 2018: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29781190/in-situ-study-of-the-functions-of-bacterioruberin-in-the-dual-chromophore-photoreceptor-archaerhodopsin-4
#13
Chao Sun, Xiaoyan Ding, Haolin Cui, Yanan Yang, Sijin Chen, Anthony Watts, Xin Zhao
While certain archaeal ion pumps have been shown to contain two chromophores, retinal and carotenoid bacterioruberin, the functions of the bacterioruberin have not been well explored. To address this research gap, the recombinant archaerhodopsin-4 (aR4), either with retinal chromophore only or with both retinal and bacterioruberin chromophores, was successfully expressed together with endogenous lipids in H. salinarum L33 and MPK409 respectively. In situ solid-state NMR, supported by molecular spectroscopy and functional assays, revealed for the first time that the retinal thermal equilibrium in the dark-adapted state is modulated by bacterioruberin binding via a cluster of aromatic residues on helix E...
May 20, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29780898/sumoylation-and-phosphorylation-cross-talk-in-hepatocellular-carcinoma
#14
REVIEW
Maria Lauda Tomasi, Komal Ramani
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. The large spectrum of protein post-translational modification (PTM) includes numerous critical signaling events that occur during neoplastic transformation. PTMs occur to nearly all proteins and increase the functional diversity of proteins. We have reviewed the role of two major PTMs, SUMOylation and phosphorylation, in the altered signaling of key players in HCC...
2018: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29780554/mechanistic-perspective-and-functional-activity-of-insulin-in-amylin-aggregation
#15
Michal Baram, Sharon Gilead, Ehud Gazit, Yifat Miller
Insulin is a key regulatory polypeptide that is secreted from pancreatic β-cells and has several important effects on the synthesis of lipids, regulation of enzymatic activities, blood glucose levels and the prevention of hyperglycemia. Insulin was demonstrated to self-assemble into ordered amyloid fibrils upon repeated injections, although the possible biological significance of the supramolecular structures is enigmatic. Amylin is also an amyloidogenic polypeptide that is secreted from pancreatic β-cells and plays an important role in glycemic regulation preventing post-prandial spikes in blood glucose levels...
May 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780538/competition-between-li-and-na-in-sodium-transporters-and-receptors-which-na-binding-sites-are-therapeutic-li-targets
#16
Todor Dudev, Karine Mazmanian, Carmay Lim
Sodium (Na+ ) acts as an indispensable allosteric regulator of the activities of biologically important neurotransmitter transporters and G-protein coupled receptors (GPCRs), which comprise well-known drug targets for psychiatric disorders and addictive behavior. How selective these allosteric Na+ -binding sites are for the cognate cation over abiogenic Li+ , a first-line drug to treat bipolar disorder, is unclear. Here, we reveal how properties of the host protein and its binding cavity affect the outcome of the competition between Li+ and Na+ for allosteric binding sites in sodium transporters and receptors...
May 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780502/the-impact-of-o-glycan-chemistry-on-the-stability-of-intrinsically-disordered-proteins
#17
Erica T Prates, Xiaoyang Guan, Yaohao Li, Xinfeng Wang, Patrick K Chaffey, Munir S Skaf, Michael F Crowley, Zhongping Tan, Gregg T Beckham
Protein glycosylation is a diverse post-translational modification that serves myriad biological functions. O -linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O -mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions. However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs)...
April 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780480/on-chip-measurements-of-protein-unfolding-from-direct-observations-of-micron-scale-diffusion
#18
Yuewen Zhang, Emma V Yates, Liu Hong, Kadi L Saar, Georg Meisl, Christopher M Dobson, Tuomas P J Knowles
Investigations of protein folding, unfolding and stability are critical for the understanding of the molecular basis of biological structure and function. We describe here a microfluidic approach to probe the unfolding of unlabelled protein molecules in microliter volumes. We achieve this objective through the use of a microfluidic platform, which allows the changes in molecular diffusivity upon folding and unfolding to be detected directly. We illustrate this approach by monitoring the unfolding of bovine serum albumin in solution as a function of pH...
April 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780459/folding-mechanisms-steer-the-amyloid-fibril-formation-propensity-of-highly-homologous-proteins
#19
Gaetano Malgieri, Gianluca D'Abrosca, Luciano Pirone, Angelo Toto, Maddalena Palmieri, Luigi Russo, Michele Francesco Maria Sciacca, Rosarita Tatè, Valeria Sivo, Ilaria Baglivo, Roksana Majewska, Massimo Coletta, Paolo Vincenzo Pedone, Carla Isernia, Mario De Stefano, Stefano Gianni, Emilia Maria Pedone, Danilo Milardi, Roberto Fattorusso
Significant advances in the understanding of the molecular determinants of fibrillogenesis can be expected from comparative studies of the aggregation propensities of proteins with highly homologous structures but different folding pathways. Here, we fully characterize, by means of stopped-flow, T-jump, CD and DSC experiments, the unfolding mechanisms of three highly homologous proteins, zinc binding Ros87 and Ml153-149 and zinc-lacking Ml452-151 . The results indicate that the three proteins significantly differ in terms of stability and (un)folding mechanisms...
April 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780245/protein-delivery-nanosystem-of-six-arm-copolymer-poly-%C3%AE%C2%B5-caprolactone-poly-ethylene-glycol-for-long-term-sustained-release
#20
Jianwei Duan, Chao Liu, Xiaoyu Liang, Xuanling Li, Youlu Chen, Zuoguan Chen, Xiaoli Wang, Deling Kong, Yongjun Li, Jing Yang
Background: To address the issue of delivery of proteins, a six-arm copolymer, six-arm poly (ε-caprolactone)-poly(ethylene glycol) (6S-PCL-PEG), was synthesized by a simple two-step reaction. Thereafter, the application of 6S-PCL-PEG as a protein carrier was evaluated. Materials and methods: A six-arm copolymer, six-arm poly(ε-caprolactone) (6S-PCL), was synthesized by ring-opening polymerization, with stannous octoate as a catalyst and inositol as an initiator...
2018: International Journal of Nanomedicine
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