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https://www.readbyqxmd.com/read/29236288/disaster-preparedness-biological-threats-and-treatment-options
#1
Navaneeth Narayanan, Clifton R Lacy, Joseph E Cruz, Meghan Nahass, Jonathan Karp, Joseph A Barone, Evelyn Hermes-DeSantis
Biological disasters can be natural, accidental, or intentional. Biological threats have made a lasting impact on civilization. This review will focus on agents of clinical significance, bioterrorism, and national security; specifically Category A agents (anthrax, botulism, plague, tularemia, and smallpox), as well as briefly discuss other naturally-emerging infections of public health significance including Ebola virus (also a Category A agent) and Zika virus. The role of the pharmacist in disaster preparedness and disaster response is multifaceted and important...
December 13, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29235598/the-stimulation-of-glp-1-secretion-and-delivery-of-glp-1-agonists-via-nanostructured-lipid-carriers
#2
Neha Shrestha, Oriane Bouttefeux, Kevin Vanvarenberg, Patrik Lundquist, Juan Cunarro, Sulay Tovar, Georgiy Khodus, Ellen Andersson, Åsa V Keita, Carlos Gonzalez Dieguez, Per Artursson, Véronique Préat, Ana Beloqui
Nanoparticulate based drug delivery systems have been extensively studied to efficiently encapsulate and deliver peptides orally. However, most of the existing data mainly focus on the nanoparticles as a drug carrier, but the ability of nanoparticles having a biological effect has not been exploited. Herein, we hypothesize that nanostructured lipid carriers (NLCs) could activate the endogenous glucagon-like peptide-1 (GLP-1) secretion and also act as oral delivery systems for GLP-1 analogs (exenatide and liraglutide)...
December 13, 2017: Nanoscale
https://www.readbyqxmd.com/read/29235360/halo-109-301-a-phase-iii-trial-of-pegph20-with-gemcitabine-and-nab-paclitaxel-in-hyaluronic-acid-high-stage-iv-pancreatic-cancer
#3
Gary J Doherty, Margaret Tempero, Pippa G Corrie
The outlook for patients with advanced pancreatic cancer remains poor, despite significant advances in our understanding of pancreatic tumor biology. One emerging theme highlights the distinct composition of the pancreatic tumor microenvironment. Hyaluronic acid is a hydrophilic glycosaminoglycan whose production within the tumor leads to increased interstitial tumor pressure, thereby limiting the access of potentially effective circulating anticancer drugs via reduced tumor perfusion. PEGylated rHuPH20 is a multiply PEGylated recombinant human hyaluronidase that has shown promising efficacy in preclinical models and early phase clinical trials in pancreatic cancer patients...
October 23, 2017: Future Oncology
https://www.readbyqxmd.com/read/29234984/bober-web-interface-to-the-base-of-bioisosterically-exchangeable-replacements
#4
Samo Lešnik, Blaž Škrlj, Nika Eržen, Urban Bren, Stanislav Gobec, Janez Konc, Dušanka Janežič
We describe a novel freely available web server Base of Bioisosterically Exchangeable Replacements (BoBER), which implements an interface to a database of bioisosteric and scaffold hopping replacements. Bioisosterism and scaffold hopping are key concepts in drug design and optimization, and can be defined as replacements of biologically active compound's fragments with other fragments to improve activity, reduce toxicity, change bioavailability or to diversify the scaffold space. Our web server enables fast and user-friendly searches for bioisosteric and scaffold replacements which were obtained by mining the whole Protein Data Bank...
December 12, 2017: Journal of Cheminformatics
https://www.readbyqxmd.com/read/29234892/how-accurate-is-the-description-of-ligand-protein-interactions-by-a-hybrid-qm-mm-approach
#5
Jakub Kollar, Vladimir Frecer
During the last decades, the application of hybrid quantum mechanical/molecular mechanical (QM/MM) methods has been extended to the field of drug design. In principle, the approximate QM/MM approach offers a more complete description of drug-receptor non-covalent interactions. This is especially true when charge or proton transfer, chelation of metal ions or strong polarization of ligand and protein or surface chemical groups are involved. The aim of this work was to assess the accuracy of calculated non-covalent ligand-protein interaction energies ([Formula: see text]) obtained by the hybrid QM/MM approach employed in QSite/Jaguar of Schrödinger's Small-Molecule Drug Discovery Suite on a set of small-molecule model systems when compared to rigorous QM calculations...
December 12, 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29234086/n-acetylcysteine-functionalized-coating-avoids-bacterial-adhesion-and-biofilm-formation
#6
Fabíola Costa, Daniela M Sousa, Paula Parreira, Meriem Lamghari, Paula Gomes, M Cristina L Martins
N-acetyl cysteine (NAC) is an FDA-approved drug clinically applied on a broad range of pathologies. Further research has been conducted with this drug to benefit from its antimicrobial activity potential. However, NAC has a very short half-life and therefore strategies that accomplish high local concentrations would be beneficial. In this study, covalent immobilization of NAC was performed, in order to obtain long-lasting high local concentration of the drug onto a chitosan(Ch)-derived implant-related coating...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29234067/the-human-blood-nerve-barrier-transcriptome
#7
Steven P Palladino, E Scott Helton, Preti Jain, Chaoling Dong, Michael R Crowley, David K Crossman, Eroboghene E Ubogu
The blood-nerve barrier (BNB), formed by tight junction-forming microvessels within peripheral nerve endoneurium, exists to regulate its internal microenvironment essential for effective axonal signal transduction. Relatively little is known about the unique human BNB molecular composition. Such knowledge is crucial to comprehend the relationships between the systemic circulation and peripheral nerves in health, adaptations to intrinsic or extrinsic perturbations and alterations that may result in disease. We performed RNA-sequencing on cultured early- and late-passage adult primary human endoneurial endothelial cells and laser-capture microdissected endoneurial microvessels from four cryopreserved normal adult human sural nerves referenced to the Genome Reference Consortium Human Reference 37 genome browser, using predefined criteria guided by known transcript or protein expression in vitro and in situ...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233710/magnetic-field-driven-drug-release-from-modified-iron-oxide-integrated-polysaccharide-hydrogel
#8
Xinyu Hu, Yongmei Wang, Liangliang Zhang, Man Xu, Jianfa Zhang, Wei Dong
Salecan is a novel water-soluble extracellular β-glucan and suitable for the hydrogel preparation due to its excellent physicochemical and biological properties. The present article describes the fabrication and characterization of a pH/magnetic field-driven hydrogel based on salecan-g-poly(vinylacetic acid-co-2-hydroxyethyl acrylate) [poly(VA-co-HEA)] copolymer and Fe3O4@Agarose nanoparticles for drug release testing. Vibrating sample magnetometer characterization verified that integration of Fe3O4@Agarose nanoparticles in the copolymer provided the sensitivity to magnetic fields...
December 9, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29233521/the-elements-of-translational-chemical-biology
#9
REVIEW
Robert A Copeland, P Ann Boriack-Sjodin
A causal relationship between target activity modulation by small molecules and phenotypic consequence is the cornerstone of chemical biology and drug discovery. Here we articulate elements of translational chemical biology, as guideposts to ensure the appropriate use of chemical probes and the conclusions drawn from cellular studies with these molecules.
November 27, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29233500/tumor-budding-is-a-prognostic-factor-linked-to-epithelial-mesenchymal-transition-in-pancreatic-ductal-adenocarcinoma-study-report-and-literature-review
#10
Ezzeddine Chouat, Alia Zehani, Ines Chelly, Manel Njima, Houcine Maghrebi, Mohammed Amine Bani, Leila Njim, Abdelfatteh Zakhama, Slim Haouet, Nidhameddine Kchir
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a devastatingly poor prognosis. Surgical resection is undertaken in only 20% of patients. Most of well-known prognostic factors reflect tumor stage more than its biology. So it is important to identify new biological indicators related to survival in order to develop new therapies. OBJECTIVE: To determine the relation between tumor budding and Epithelial Mesenchymal Transition (EMT) and to evaluate their impact on survival for patients after resection of PDAC...
November 21, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29233266/inflammation-and-dna-damage-probing-pathways-to-cancer-and-neurodegeneration
#11
REVIEW
Mehran Makvandi, Mark A Sellmyer, Robert H Mach
Cancer and neurodegeneration represent two opposite ends of the biological spectrum but contain many common biological mechanisms. Two such mechanisms include the elevated levels of oxidative stress and DNA damage. In this brief review, we describe current approaches for imaging these biological pathways with the molecular imaging technique, Positron Emission Tomography (PET), and the potential of PET imaging studies to measure the efficacy of anticancer drugs and strategies for delaying the progression of neurodegenerative disorders...
November 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/29232886/the-diverse-range-of-possible-cell-membrane-interactions-with-substrates-drug-delivery-interfaces-and-mobility
#12
REVIEW
Hyun-Sook Jang
The cell membrane has gained significant attention as a platform for the development of bio-inspired nanodevices due to its immune-evasive functionalities and copious bio-analogs. This review will examine several uses of cell membranes such as (i) therapeutic delivery carriers with or without substrates (i.e., nanoparticles and artificial polymers) that have enhanced efficiency regarding copious cargo loading and controlled release, (ii) exploiting nano-bio interfaces in membrane-coated particles from the macro- to the nanoscales, which would help resolve the biomedical issues involved in biological interfacing in the body, and (iii) its effects on the mobility of bio-moieties such as lipids and/or proteins in cell membranes, as discussed from a biophysical perspective...
December 11, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29232689/a-computational-model-for-regulation-of-nanoscale-glucan-exposure-in-candida-albicans
#13
Michael J Wester, Jia Lin, Aaron K Neumann
Candida albicans is a virulent human opportunistic pathogen. It evades innate immune surveillance by masking an immunogenic cell wall polysaccharide, β-glucan, from recognition by the immunoreceptor Dectin-1. Glucan unmasking by the antifungal drug caspofungin leads to changes in the nanostructure of glucan exposure accessible to Dectin-1. The physical mechanism that regulates glucan exposure is poorly understood, but it controls the nanobiology of fungal pathogen recognition. We created computational models to simulate hypothetical physical processes of unmasking glucan in a biologically realistic distribution of cell wall glucan fibrils...
2017: PloS One
https://www.readbyqxmd.com/read/29232586/synthesis-and-biological-evaluation-of-coumarin-derivatives-containing-imidazole-skeleton-as-potential-antibacterial-agents
#14
Yang Hu, Yufeng Shen, Xiaohu Wu, Xiao Tu, Gao-Xue Wang
Emergence of multidrug-resistant bacteria causes an urgent need for new generation of antibiotics, which may have a different mechanism of inhibition or killing action from the existing. Here, we report on the design, synthesis, and biological evaluation of thirty-nine coumarin derivatives in order to solve the antibacterial resistance by targeting at the inhibition of biosynthesis pathway of fatty acids. Their antibacterial activities against Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae, and Flavobacterium cloumnare are tested and action mechanism against the key enzyme in bacterial fatty acid synthesis pathway are studied...
December 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232322/incidence-of-antidrug-antibodies-in-rheumatoid-arthritis-patients-from-argentina-treated-with-adalimumab-etanercept-or-infliximab-in-a-real-world-setting
#15
Pablo J Maid, Ricardo Xavier, Rosa M Real, Ron Pedersen, Qi Shen, Lisa Marshall, Gaston Solano, Cecilia Elena Borlenghi, Rodolfo Pardo Hidalgo
BACKGROUND: Biologic agents may induce immune responses that could impact drug action. OBJECTIVES: The aims of this study were to assess antidrug antibodies (ADAs) in patients with rheumatoid arthritis (RA) from Argentina treated with etanercept, adalimumab, or infliximab at a single visit and correlate it with efficacy outcomes. METHODS: In this subset analysis of a noninterventional, multinational, cross-sectional study (NCT01981473), adult patients with RA treated continuously for 6 to 24 months with etanercept, adalimumab, or infliximab were evaluated for ADAs and trough drug concentrations of 2 days or less prior to the next scheduled dose...
December 12, 2017: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/29232104/the-effects-of-biological-fluids-on-colloidal-stability-and-sirna-delivery-of-a-ph-responsive-micellar-nanoparticle-delivery-system
#16
Dominic W Malcolm, Jomy J Varghese, Janet E Sorrells, Catherine E Ovitt, Danielle S W Benoit
Nanoparticles (NP) interact with complex protein milieus in biological fluids, and these interactions have profound effects on NP physicochemical properties and function. Surprisingly, most studies neglect the impact of these interactions, especially with respect to NP-mediated siRNA delivery. Here, the effects of serum on colloidal stability and siRNA delivery of a pH-responsive micellar NP delivery system were characterized. Results show cationic NP-siRNA complexes aggregate in  2% serum in buffer, but are stable in serum-free media...
December 12, 2017: ACS Nano
https://www.readbyqxmd.com/read/29231944/stability-of-plant-virus-based-nanocarriers-in-gastrointestinal-fluids
#17
Alberto Berardi, David J Evans, Francesca Baldelli Bombelli, George P Lomonossoff
Cowpea mosaic virus (CPMV) is a plant virus which is being extensively investigated as a drug delivery and vaccine nanocarrier for parenteral administration. However, to date little is known about the suitability of plant-based nanocarriers for oral delivery. In this study, the colloidal (i.e. aggregation), physical (i.e. denaturation) and chemical (i.e. digestion of the polypeptides) stability of CPMV and its empty virus-like particles (eVLPs) in conditions resembling the gastrointestinal fluids were evaluated...
December 12, 2017: Nanoscale
https://www.readbyqxmd.com/read/29231880/facile-chemical-access-to-biologically-active-norcantharidin-derivatives-from-biomass
#18
Konstantin I Galkin, Fedor A Kucherov, Oleg N Markov, Ksenia S Egorova, Alexandra V Posvyatenko, Valentine P Ananikov
Reductive amination of 2,5-diformylfuran (DFF) was used to implement the transition from bio-derived 5-hydroxymethylfurfural (HMF) to pharmaceuticals. The synthesized bis(aminomethyl)furans were utilized as building blocks for the construction of new derivatives with structural cores of naturally occurring biologically active compounds. Using the one-pot procedure, which included the Diels-Alder reaction followed by hydrogenation of the double bond, bio-derived analogues of the anticancer drug norcantharidin were obtained...
December 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29231282/new-insight-into-the-synthesis-and-biological-activity-of-the-polymeric-materials-consisting-of-folic-acid-and-%C3%AE-cyclodextrin
#19
Artur Kasprzak, Ireneusz P Grudzinski, Magdalena Bamburowicz-Klimkowska, Andrzej Parzonko, Maciej Gawlak, Magdalena Poplawska
This work presents a very new look at folate targeting and is focused on synthesizing and assessing the biological activity of folic acid-targeted drug delivery materials based on β-cyclodextrin. Both folic acid and β-cyclodextrin have been covalently conjugated to branched polyethylenimine as the polymeric vector. Host-guest inclusion of folic acid into a β-cyclodextrin cavity, demonstrated by means of the spectroscopic methods (2-D NMR, IR, UV-Vis), is found to be of crucial importance for biological activity of nanotherapeutics...
December 12, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/29231235/the-perioperative-use-of-synthetic-and-biological-disease-modifying-antirheumatic-drugs-in-patients-with-rheumatoid-arthritis
#20
Gregory Fleury, Silvano Mania, Didier Hannouche, Cem Gabay
Disease-modifying antirheumatic drugs (DMARDs) have become essential treatments in the management of patients with inflammatory rheumatic diseases. Their use has resulted in a marked improvement of disease control and a limitation of joint damage, although some patients still require subsequent corrective or joint replacement surgery. Due to their immunosuppressive effects, some DMARDs are associated with an increased risk of infection. The aim of this review is to discuss the available literature on the management of DMARDs during the perioperative period, particularly in the case of orthopaedic surgery...
December 12, 2017: Swiss Medical Weekly
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