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https://www.readbyqxmd.com/read/29048530/population-genomic-analysis-of-a-pitviper-reveals-microevolutionary-forces-underlying-venom-chemistry
#1
Steven D Aird, Jigyasa Arora, Agneesh Barua, Lijun Qiu, Kouki Terada, Alexander S Mikheyev
Venoms are among the most biologically active secretions known, and are commonly believed to evolve under extreme positive selection. Many venom gene families, however, have undergone duplication, and are often deployed in doses vastly exceeding the LD50 for most prey species, which should reduce the strength of positive selection. Here, we contrast these selective regimes using snake venoms, which consist of rapidly evolving protein formulations. Though decades of extensive studies have found that snake venom proteins are subject to strong positive selection, the greater action of drift has been hypothesized, but never tested...
October 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29047044/exosomes-for-the-enhanced-tissue-bioavailability-and-efficacy-of-curcumin
#2
Farrukh Aqil, Radha Munagala, Jeyaprakash Jeyabalan, Ashish Kumar Agrawal, Ramesh Gupta
Exosomes are extracellular microvesicles with a particle size of 30-100 nm and carry a cargo of proteins, lipids, RNA, and DNA. Their properties of shuttling in-and-out of the cells suggest that these particles can be exploited as a nano drug carrier. In this manuscript, we show that curcumin can be delivered effectively using milk-derived exosomes. Curcumin when mixed with exosomes in the presence of 10% ethanol:acetonitrile (1:1) provided a drug load of 18-24%, and the formulation stored at - 80°C was stable for 6 months as determined by particle size analysis, drug load, and antiproliferative activity...
October 18, 2017: AAPS Journal
https://www.readbyqxmd.com/read/29047017/effect-of-arginine-on-the-aggregation-of-protein-in-freeze-dried-formulations-containing-sugars-and-polyol-1-formulation-development
#3
Ellen Hackl, Joseph Darkwah, Geoff Smith, Irina Ermolina
L-arginine was introduced into protein-based freeze-dried formulations to study the ability of arginine to reduce/prevent from protein aggregation during manufacturing, storage and reconstitution of lyophilized protein-based pharmaceuticals. As L-arginine is known to be very hygroscopic, additional excipients which could provide a moisture buffering capacity need to be introduced into the formulation. In the first part of our study-excipient formulation development-the screening of a number of sugars/polyols has been done in order to select the best combination of excipients that, in a complex with L-arginine, can (i) produce freeze-dried cakes with elegant appearance, adequate mechanical properties and reconstitution times, and (ii) resist/minimise the moisture sorption...
October 18, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29046894/fatty-acid-mimetic-micelles-for-dual-delivery-of-antigens-and-imidazoquinoline-adjuvants
#4
Sema Sevimli, Frances C Knight, Pavlo Gilchuk, Sebastian Joyce, John T Wilson
Vaccine design has undergone a shift towards the use of purified protein subunit vaccines, which offer increased safety and greater control over antigen specificity, but at the expense of immunogenicity. Here we report the development of a new polymer-based vaccine delivery platform engineered to enhance immunity through the co-delivery of protein antigens and the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ). Owing to the preferential solubility of IMQ in fatty acids, a series of block copolymer micelles with a fatty acid-mimetic core comprising lauryl methacrylate (LMA) and methacrylic acid (MAA), and a poly(ethylene glycol) methyl ether methacrylate (PEGMA) corona decorated with pyridyl disulfide ethyl methacrylate (PDSM) moieties for antigen conjugation were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization...
February 13, 2017: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/29045884/effect-of-phosphate-ion-on-the-structure-of-lumazine-synthase-an-antigen-presentation-system-from-bacillus-anthracis
#5
Yangjie Wei, Newton Wahome, Prashant Kumar, Neal Whitaker, Wendy L Picking, C Russell Middaugh
Lumazine synthase (LS) is an oligomeric enzyme involved in the biosynthesis of riboflavin in microorganisms, fungi and plants. LS has become of significant interest to biomedical science because of its critical biological role and attractive structural properties for antigen presentation in vaccines. LS derived from Bacillus anthracis (BaLS) consists of 60 identical subunits forming an icosahedron. Its crystal structure has been solved, but its dynamic conformational properties have not yet been studied. We investigated the conformation of BaLS in response to different stress conditions (e...
October 15, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29045407/bayesian-refinement-of-protein-structures-and-ensembles-against-saxs-data-using-molecular-dynamics
#6
Roman Shevchuk, Jochen S Hub
Small-angle X-ray scattering is an increasingly popular technique used to detect protein structures and ensembles in solution. However, the refinement of structures and ensembles against SAXS data is often ambiguous due to the low information content of SAXS data, unknown systematic errors, and unknown scattering contributions from the solvent. We offer a solution to such problems by combining Bayesian inference with all-atom molecular dynamics simulations and explicit-solvent SAXS calculations. The Bayesian formulation correctly weights the SAXS data versus prior physical knowledge, it quantifies the precision or ambiguity of fitted structures and ensembles, and it accounts for unknown systematic errors due to poor buffer matching...
October 18, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29045254/nutritional-interventions-in-sarcopenia-where-do-we-stand
#7
Jean Woo
PURPOSE OF REVIEW: To document recent evidence regarding the role of nutrition as an intervention for sarcopenia. RECENT FINDINGS: A review of seven randomized controlled trials (RCTs) on beta-hydroxy-beta-methylbutyrate (HMB) alone on muscle loss in 147 adults showed greater muscle mass gain in the intervention group, but no benefit in muscle strength and physical performance measures. Three other review articles examined nutrition and exercise as combined intervention, and suggest enhancement of benefits of exercise by nutrition supplements (energy, protein, vitamin D)...
October 17, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/29043794/dynamic-transition-from-%C3%AE-helices-to-%C3%AE-sheets-in-polypeptide-coiled-coil-motifs
#8
Kirill A Minin, Artem Zhmurov, Kenneth A Marx, Prashant K Purohit, Valeri Barsegov
We carried out dynamic force manipulations in silico on a variety of coiled-coil protein fragments from myosin, chemotaxis receptor, vimentin, fibrin, and phenylalanine zippers that vary in size and topology of their α-helical packing. When stretched along the superhelical axis, all superhelices show elastic, plastic, and inelastic elongation regimes, and undergo a dynamic transition from the α-helices to the β-sheets, which marks the onset of plastic deformation. Using Abeyaratne-Knowles formulation of phase transitions, we developed a new theoretical methodology to model mechanical and kinetic properties of protein coiled-coils under mechanical non-equilibrium conditions and to map out their energy landscapes...
October 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29043605/liquid-nanosize-emulsion-filled-enteric-coated-capsules-for-colon-delivery-of-immunosuppressant-peptide
#9
Sumit Sharma, Vivek Ranjan Sinha
Present study aims at solubilizing slightly water-soluble peptide into a nanosize emulsion which is filled into a hard gelatin capsule in the form of preconcentrate. Further, liquid-filled capsule was dip-coated with ethyl cellulose and Eudragit S100 for colon targeting. An in vitro release profile was studied for selected formulations, i.e., Formulation A (5 mg ethyl cellulose and 40 mg Eudragit S100), Formulation B (10 mg ethyl cellulose and 30 mg Eudragit S100), and Formulation C (10 mg ethyl cellulose and 20 mg Eudragit S100)...
October 17, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29039573/antitumor-effects-of-baicalin-on-ovarian-cancer-cells-through-induction-of-cell-apoptosis-and-inhibition-of-cell-migration-in%C3%A2-vitro
#10
Chen Gao, Yinglu Zhou, Huatao Li, Xia Cong, Zhongling Jiang, Xin Wang, Rongfeng Cao, Wenru Tian
Baicalin, an active flavone isolated from Scutellaria baicalensis Georgi, has been demonstrated to induce various beneficial biochemical effects such as anti‑inflammatory, anti‑viral, and antitumor effects. However, the antitumor mechanism of baicalin is not well understood. In the present study, baicalin was demonstrated to inhibit the viability and migration of a widely used ovarian cancer cell line, A2780, in a dose‑dependent manner. MTT assays revealed that cell viability significantly decreased in ovarian cancer cells treated with baicalin compared with untreated cells, without effect on normal ovarian cells...
October 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29039295/effects-of-feeding-low-fishmeal-diets-with-increasing-soybean-meal-levels-on-growth-gut-histology-and-plasma-biochemistry-of-sea-bass
#11
E Bonvini, A Bonaldo, L Mandrioli, R Sirri, F Dondi, C Bianco, R Fontanillas, F Mongile, P P Gatta, L Parma
The aquaculture industry depends upon the development of sustainable protein sources to replace fishmeal (FM) in aquafeeds and the products derived from soybeans are some of the most studied plant feedstuffs. A key area of investigation for continuing to improve modern aquafeeds includes the evaluation of varying proportions and combinations of plant ingredients to identify mixtures that are more efficiently utilized by the fish. This study investigated the effects of increasing soybean meal (SBM) by replacing a mix of plant ingredients in low FM (20%) diets on growth, blood biochemistry profile and gut histology on European sea bass...
October 17, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/29039106/improved-ultrafiltration-method-to-measure-drug-release-from-nanomedicines-utilizing-a-stable-isotope-tracer
#12
Sarah L Skoczen, Stephan T Stern
An important step in the early development of a nanomedicine formulation is the evaluation of stability and drug release in biological matrices. Additionally, the measurement of encapsulated and unencapsulated nanomedicine drug fractions is important for the determination of bioequivalence (pharmacokinetic equivalence) of generic nanomedicines. Unfortunately, current methods to measure drug release in plasma are limited, and all have fundamental disadvantages including non-equilibrium conditions and process-induced artifacts...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29039100/analysis-of-complement-activation-by-nanoparticles
#13
Barry W Neun, Anna N Ilinskaya, Marina A Dobrovolskaia
The complement system is a group of proteins, which function in plasma to assist the innate immunity in rapid clearance of pathogens. The complement system also contributes to coordination of the adaptive immune response. Complement Activation Related Pseudo Allergy or CARPA is a life-threatening condition commonly reported with certain types of drugs and nanotechnology-based combination products. While CARPA symptoms are similar to that of anaphylaxis, the mechanism behind this pathology does not involve IgE and is mediated by the complement system...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29038510/lure-and-kill-yeast-interfering-rna-larvicides-targeting-neural-genes-in-the-human-disease-vector-mosquito-aedes-aegypti
#14
Limb K Hapairai, Keshava Mysore, Yingying Chen, Elizabeth I Harper, Max P Scheel, Alexandra M Lesnik, Longhua Sun, David W Severson, Na Wei, Molly Duman-Scheel
New mosquito control strategies are vitally needed to address established arthropod-borne infectious diseases such as dengue and yellow fever and emerging diseases such as Zika and chikungunya, all of which are transmitted by the disease vector mosquito Aedes aegypti. In this investigation, Saccharomyces cerevisiae (baker's yeast) was engineered to produce short hairpin RNAs (shRNAs) corresponding to the Aedes aegypti orthologs of fasciculation and elongation protein zeta 2 (fez2) and leukocyte receptor cluster (lrc) member, two genes identified in a recent screen for A...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038068/polymeric-microspheres-for-the-sustained-release-of-a-protein-based-drug-carrier-targeting-the-pdgf%C3%AE-receptor-in-the-fibrotic-kidney
#15
N Teekamp, F Van Dijk, A Broesder, M Evers, J Zuidema, R Steendam, E Post, J L Hillebrands, H W Frijlink, K Poelstra, L Beljaars, P Olinga, W L J Hinrichs
Injectable sustained release drug delivery systems are an attractive alternative for the intravenous delivery of therapeutic proteins. In particular, for chronic diseases such as fibrosis, this approach could improve therapy by reducing the administration frequency while avoiding large variations in plasma levels. In fibrotic tissues the platelet-derived growth factor receptor beta (PDGFβR) is highly upregulated, which provides a target for site-specific delivery of drugs. Our aim was to develop an injectable sustained release formulation for the subcutaneous delivery of the PDGFβR-targeted drug carrier protein pPB-HSA, which is composed of multiple PDGFβR-recognizing moieties (pPB) attached to human serum albumin (HSA)...
October 13, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29037872/preparation-and-characterization-of-microencapsulated-dwpt-trivalent-vaccine-using-water-soluble-chitosan-and-its-in-vitro-and-in-vivo-immunological-properties
#16
Shilratna Walke, Gopal Srivastava, Chinmayee Bar Routaray, Dilip Dhavale, Kalpana Pai, Jignesh Doshi, Rakesh Kumar, Pooja Doshi
The paper explained the microencapsulation of three different antigenic materials viz. Diphtheria toxoid (DT), whole cell pertussis antigens (PT and FHA) and tetanus toxoid (TT) by coacervation method using water soluble chitosan as a polymer crosslinked by vanillin/TPP co-crosslinkers for the development of oral trivalent DwPT vaccine. Instrumental characterization of chitosan microspheres suggested specific interaction with vanillin/TPP, higher thermal stability, amorphous nature, spherical morphology with size less than 2μm along with positive charge density offering mucoadhesive properties...
October 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29037466/the-use-of-a-groel-bli-biosensor-to-rapidly-assess-pre-aggregate-populations-for-antibody-solutions-exhibiting-different-stability-profiles
#17
Samantha E Pace, Sangeeta B Joshi, Reza Esfandiary, Robert Stadelman, Steven M Bishop, C R Middaugh, Mark Fisher, David B Volkin
An automated method using biotinylated GroEL-streptavidin biosensors with Bio-Layer Interferometry (GroEL-BLI) was evaluated to detect the formation of transiently formed, pre-aggregate species in various pharmaceutically relevant monoclonal antibody (mAb) samples. The relative aggregation propensity of various IgG1 and IgG4 mAbs was rank-ordered using the GroEL-BLI biosensor method, and the least stable IgG4 mAb was subjected to different stresses including elevated temperatures, acidic pH, and addition of guanidine-HCl...
October 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29035747/studies-on-the-adsorption-and-desorption-of-mitoxantrone-to-lauric-acid-albumin-coated-iron-oxide-nanoparticles
#18
Jan Zaloga, Artem Feoktystov, Vasil M Garamus, Weronika Karawacka, Alexander Ioffe, Thomas Brückel, Rainer Tietze, Christoph Alexiou, Stefan Lyer
A rational use of superparamagnetic iron oxide nanoparticles (SPIONs) in drug delivery, diagnostics, and other biomedical applications requires deep understanding of the molecular drug adsorption/desorption mechanisms for proper design of new pharmaceutical formulations. The adsorption and desorption of the cytostatic Mitoxantrone (MTO) to lauric acid-albumin hybrid coated particles SPIONs (SEON(LA-HSA)) was studied by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), surface titration, release experiments and small-angle neutron and X-ray scattering...
September 28, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29035637/design-and-characterization-of-mp0250-a-tri-specific-anti-hgf-anti-vegf-darpin%C3%A2-drug-candidate
#19
H Kaspar Binz, Talitha R Bakker, Douglas J Phillips, Andreas Cornelius, Christof Zitt, Thomas Göttler, Gabriel Sigrist, Ulrike Fiedler, Savira Ekawardhani, Ignacio Dolado, Johan Abram Saliba, Gaby Tresch, Karl Proba, Michael T Stumpp
MP0250 is a multi-domain drug candidate currently being tested in clinical trials for the treatment of cancer. It comprises one anti-vascular endothelial growth factor-A (VEGF-A), one anti-hepatocyte growth factor (HGF), and two anti-human serum albumin (HSA) DARPin® domains within a single polypeptide chain. While there is first clinical validation of a single-domain DARPin® drug candidate, little is known about DARPin® drug candidates comprising multiple domains. Here, we show that MP0250 can be expressed at 15 g/L in soluble form in E...
October 16, 2017: MAbs
https://www.readbyqxmd.com/read/29035132/hybrid-lipid-polymer-nanoparticles-for-pulmonary-delivery-of-sirna-development-and-fate-upon-in-vitro-deposition-on-the-human-epithelial-airway-barrier
#20
Ivana d'Angelo, Gabriella Costabile, Estelle Durantie, Paola Brocca, Valeria Rondelli, Annapina Russo, Giulia Russo, Agnese Miro, Fabiana Quaglia, Alke Petri-Fink, Barbara Rothen-Rutishauser, Francesca Ungaro
BACKGROUND: Nowadays, the downregulation of genes involved in the pathogenesis of severe lung diseases through local siRNA delivery appears an interesting therapeutic approach. In this study, we propose novel hybrid lipid-polymer nanoparticles (hNPs) consisting of poly(lactic-co-glycolic) acid (PLGA) and dipalmitoyl phosphatidylcholine (DPPC) as siRNA inhalation system. METHODS: A panel of DPPC/PLGA hNPs was prepared by emulsion/solvent diffusion and fully characterized...
October 16, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
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