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https://www.readbyqxmd.com/read/29782982/process-optimization-purification-and-characterization-of-a-novel-acidic-thermostable-chitinase-from-humicola-grisea
#1
Manish Kumar, Amandeep Brar, V Vivekanand, Nidhi Pareek
An extracellular acidic and thermostable chitinase (HgChi) from thermophilic Humicola grisea was purified and characterized. Enhancement in chitinase production (Qp  = 2.9662 Ul-1  h-1 ) was achieved through derivation of optimum fermentation conditions via central composite design. H. grisea observed to produce various isoforms of chitinase, among which the major expressed form has molecular mass of about 50 kDa. Purified chitinases exhibited optimal activity at pH 3.0 and 70 °C. Chitinase showed notable stability at increasing temperatures...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29782948/dendritic-peg-outer-shells-enhance-serum-stability-of-polymeric-micelles
#2
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/29781759/development-of-simultaneous-quantification-method-of-loteprednol-etabonate-le-and-its-acidic-metabolites-and-analysis-of-le-metabolism-in-rat
#3
Ahmed Samir, Ayano Kage, Ohura Kayoko, Teruko Imai
1. Loteprednol etabonate (LE) is a soft corticosteroid with two labile ester bonds at 17α- and 17β-positions. Its corticosteroidal activity disappears upon hydrolysis of either ester bond. Hydrolysis of both ester bonds produces the inactive metabolite, Δ1 -cortienic acid (Δ1 -CA). 2. The simple high performance liquid chromatography method using acetic acid gradient was developed for the simultaneous determination of LE and its acidic metabolites. 3. LE was hydrolyzed in rat plasma with a half-life of 9 minutes...
May 21, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29780562/kinetic-studies-on-strand-displacement-in-de-novo-designed-parallel-heterodimeric-coiled-coils
#4
Mike C Groth, W Mathis Rink, Nils F Meyer, Franziska Thomas
Among the protein folding motifs, which are accessible by de novo design, the parallel heterodimeric coiled coil is most frequently used in bioinspired applications and chemical biology in general. This is due to the straightforward sequence-to-structure relationships, which it has in common with all coiled-coil motifs, and the heterospecificity, which allows control of association. Whereas much focus was laid on designing orthogonal coiled coils, systematic studies on controlling association, for instance by strand displacement, are rare...
May 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780379/point-mutation-of-a-non-elastase-binding-site-in-human-%C3%AE-1-antitrypsin-alters-its-anti-inflammatory-properties
#5
Yotam Lior, Mariana Zaretsky, David E Ochayon, Diana Lotysh, Boris M Baranovski, Ronen Schuster, Ofer Guttman, Amir Aharoni, Eli C Lewis
Introduction: Human α1-antitrypsin (hAAT) is a 394-amino acid long anti-inflammatory, neutrophil elastase inhibitor, which binds elastase via a sequence-specific molecular protrusion (reactive center loop, RCL; positions 357-366). hAAT formulations that lack protease inhibition were shown to maintain their anti-inflammatory activities, suggesting that some attributes of the molecule may reside in extra-RCL segments. Here, we compare the protease-inhibitory and anti-inflammatory profiles of an extra-RCL mutation (cys232pro) and two intra-RCL mutations (pro357cys, pro357ala), to naïve [wild-type (WT)] recombinant hAAT, in vitro , and in vivo ...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29779406/inhalation-delivery-of-topotecan-is-superior-to-intravenous-exposure-for-suppressing-lung-cancer-in-a-preclinical-model
#6
Philip J Kuehl, Marcie J Grimes, Devon Dubose, Michael Burke, David A Revelli, Andrew P Gigliotti, Steven A Belinsky, Mathewos Tessema
Intravenous (IV) topotecan is approved for the treatment of various malignancies including lung cancer but its clinical use is greatly undermined by severe hematopoietic toxicity. We hypothesized that inhalation delivery of topotecan would increase local exposure and efficacy against lung cancer while reducing systemic exposure and toxicity. These hypotheses were tested in a preclinical setting using a novel inhalable formulation of topotecan against the standard IV dose. Respirable dry-powder of topotecan was manufactured through spray-drying technology and the pharmacokinetics of 0...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29778897/measurement-of-ambient-dose-equivalent-rates-by-walk-survey-around-fukushima-dai-ichi-nuclear-power-plant-using-kurama-ii-until-2016
#7
Masaki Andoh, Hideaki Yamamoto, Takashi Kanno, Kimiaki Saito
Ambient dose equivalent rates in various environments related to human lives were measured by walk surveys using the KURAMA-II systems from 2013 to 2016 within an 80-km radius of the Fukushima Dai-ichi Nuclear Power Plant. The dose rate of the locations where the walk survey was performed decreased to about 38% of its initial value in the 42 months from June 2013 to the December 2016, which was beyond that attributable to the physical decay of radiocaesium. The ecological half-life of the slow decreasing component was evaluated to be 4...
May 17, 2018: Journal of Environmental Radioactivity
https://www.readbyqxmd.com/read/29778181/live-attenuated-duck-hepatitis-virus-vaccine-in-breeder-ducks-protective-efficacy-and-kinetics-of-maternally-derived-antibodies
#8
Jae-Hee Roh, Min Kang
Duck viral hepatitis type I is a rapidly spreading infection lethal in young ducklings, caused by the duck hepatitis A virus (DHAV). Vaccination of breeder ducks is a common practice to control DHAV. However, maintaining proper maternal antibody levels in large flocks is difficult. Therefore, a simple vaccination strategy that can induces stable high antibody levels through mass vaccination is desirable. We evaluated a DHAV vaccination strategy for breeder ducks involving oral administration under field conditions, and examined the kinetics of antibody response in the ducks and their progeny...
June 2018: Veterinary Microbiology
https://www.readbyqxmd.com/read/29778058/plasma-polymer-facilitated-magnetic-technology-for-removal-of-oils-from-contaminated-waters
#9
Satriyo Krido Wahono, Alex Cavallaro, Krasimir Vasilev, Agnieszka Mierczynska
Oil pollution of waters is one of the most serious environmental problems globally. The long half-life and persistence within the environment makes oil particularly toxic and difficult to remediate. There is a significant need for efficient and cost-effective oil recovery technologies to be brought in to practice. In this study, we developed a facile and efficient magnetic separation method. The surface of 316L stainless steel nanoparticles was modified by plasma deposition of 1,7-octadiene and perfluorooctane, producing relatively hydrophobic coatings having water contact angles of 86 and 100°, respectively...
May 16, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29777569/improving-metabolic-stability-with-deuterium-the-discovery-of-hwl-066-a-potent-and-long-acting-free-fatty-acid-receptor-1-agonists
#10
Chunxia Liu, Zheng Li, Wei Shi, Huilan Li, Nasi Wang, Yuxuan Dai, Chen Liao, Wenlong Huang, Hai Qian
The free fatty acid receptor 1 (FFA1) is a potential target due to its function in enhancing of glucose-stimulated insulin secretion. The FFA1 agonist GW9508 has great potential for the treatment of type 2 diabetes mellitus, but it has been suffering from high plasma clearance probably because the phenylpropanoic acid is vulnerable to β-oxidation. To identify orally available analog without influence on the unique pharmacological mechanism of GW9508, we tried to interdict the metabolically labile group by incorporating two deuterium atoms at the α-position of phenylpropionic acid affording compound 4 (HWL-066)...
May 18, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29777164/mrna-treatment-produces-sustained-expression-of-enzymatically-active-human-adamts13-in-mice
#11
Susan Liu-Chen, Brendan Connolly, Lei Cheng, Romesh R Subramanian, Zhaozhong Han
Thrombotic thrombocytopenic purpura (TTP) is primarily caused by deficiency of ADAMTS13 within the blood stream due to either genetic defects or presence of inhibitory autoantibodies. Preclinical and clinical studies suggest that enzyme replacement therapy with recombinant human ADAMTS13 protein (rhADAMTS13) is effective and safe in treatment of TTP. However, frequent dosing would be required due to the relatively short half-life of rhADAMTS13 in circulation as well as the presence of inhibitory autoantibodies that collectively result in the poor pharmacological profile of rhADAMTS13...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29776930/modifying-the-lantibiotic-mutacin-1140-for-increased-yield-activity-and-stability
#12
Mengxin Geng, Leif Smith
Mutacin 1140 belongs to the epidermin family of type AI lantibiotics. This family has a broad spectrum of activity against Gram-positive bacteria. The binding of mutacin 1140 to lipid II leads to the inhibition of cell wall synthesis. Pharmacokinetic experiments on type AI lantibiotics are generally discouraging for clinical applications due to their short half-life. The unprotected dehydrated and protease susceptible residues outside of the lanthionine rings may play a role in their short half-life in physiological settings...
May 18, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29775953/effect-of-adjuvant-on-pendimethalin-and-dimethenamid-p-behaviour-in-soil
#13
Martin Kočárek, Radka Kodešová, Umrbek Sharipov, Miroslav Jursík
Adjuvants are used to improve pesticides' performance. It is expected that adjuvants should increase sorption and persistence, as well as decrease mobility of pesticides in soils. Impact of the "Grounded" brand adjuvant on the behaviour of two herbicides, pendimethalin and dimethenamid-P, was investigated in a Haplic Chernozem. Both herbicides were tested in a laboratory batch sorption experiment with and without adjuvant. The sorption experiment showed that adjuvant negligibly increased dimethenamid-P sorption (KF  = 2...
April 30, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29775827/responses-of-atrazine-degradation-and-native-bacterial-community-in-soil-to-arthrobacter-sp-strain-hb-5
#14
Jianpeng Gao, Peipei Song, Guanying Wang, Jinhua Wang, Lusheng Zhu, Jun Wang
The bioremediation of soil contaminated with organic pesticides is a safe and effective approach to remove pollutants from the soil. However, whether the invasion of foreign aid organisms affects the local organisms has received increasing attention in recent years. Therefore, the purpose of this study was to examine the degradation ability of atrazine by the strain HB-5 and evaluate its effects on natural bacterial communities in a miniature pot experiment. Results showed that HB-5 accelerated the degradation of atrazine and the degradation half-life of atrazine was 3...
May 15, 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29775713/enhancement-of-catalytic-activity-and-thermostability-of-a-thermostable-cellobiohydrolase-from-chaetomium-thermophilum-by-site-directed-mutagenesis
#15
Chao Han, Weiguang Li, Chengyao Hua, Fengqing Sun, Pengsheng Bi, Qunqing Wang
Enzymatic saccharification of lignocellulosic biomass is increasingly applied in agricultural and industrial applications. Nevertheless, low performance in the extreme environment severely prevents the utilization of commercial enzyme preparations. To obtain cellobiohydrolases with improved catalytic activity and thermostability, structure-based rational design was performed based on a thermostable cellobiohydrolase CtCel6 from Chaetomium thermophilum. In the present study, four conserved and noncatalytic residue substitutions were generated via site-directed mutagenesis...
May 15, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29775704/alkaline-active-cyanide-dihydratase-of-flavobacterium-indicum-mtcc-6936-growth-optimization-purification-characterization-and-in-silico-analysis
#16
Virender Kumar, Vijay Kumar, Tek Chand Bhalla
The present work explores a rare cyanide dihydratase of Flavobacterium indicum MTCC 6936 for its potential of cyanide degradation. The enzyme is purified to 12 fold with a yield of 76%. SDS and native-PAGE analysis revealed that enzyme was monomer of 40 kDa size. The enzyme works well in mesophilic range at wide array of pH. The thermostability profile of cyanide dihydratase revealed that the enzyme is quite stable at 30 °C and 35 °C with half-life of 6 h 30 min and 5 h respectively. Km and Vmax for cyanide dihydratase of F...
May 15, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29775664/auto-induction-for-high-level-production-of-biologically-active-reteplase-in-escherichia-coli
#17
Mehrnoosh Fathi-Roudsari, Nader Maghsoudi, Amirhossein Maghsoudi, Sepideh Niazi, Morvarid Soleiman
Reteplase is a third generation tissue plasminogen activator (tPA) with a modified structure and prolonged half-life in comparison to native tPA. As a non-glycosylated protein, reteplase is expressed in Escherichia coli. Due to presence of several disulfide bonds, high level production of reteplase is complicated and needs extra steps for conversion to biologically active form. Auto-induction represents a method for high-yield growth of bacterial cells and higher expression of recombinant proteins. Here we have tried to optimize the auto-induction procedure for soluble and active expression of reteplase in E...
May 15, 2018: Protein Expression and Purification
https://www.readbyqxmd.com/read/29775284/multifunctional-tumor-targeting-cathepsin-b-sensitive-gemcitabine-prodrug-covalently-targets-albumin-in-situ-and-improves-cancer-therapy
#18
Huicong Zhang, Zhisu Sun, Kuanglei Wang, Na Li, Hongxiang Chen, Xiao Tan, Lingxiao Li, Zhonggui He, Jin Sun
We report a new type of amide bond-bearing cathepsin B-sensitive gemcitabine (GEM) prodrugs, capable of in situ covalently targeting circulating albumin and then making a hitchhike to the tumor. Specially, less plasma-enzyme deactivation, long plasma half-life, independence on nucleoside transporters, outstanding tumor targeting and site-specific drug release are achieved and such these multifunctional advantages contribute to the dramatically increased in vivo antitumor efficacy.
May 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29773199/health-risk-assessment-of-arsenic-in-realgar-and-niuhuangjiedu-tablets-based-on-pharmacokinetic-study
#19
Xiao Wu, Shanhu Wu, Yuexin Liu, Rong Guan, Fangmei Liang, Min Song, Taijun Hang
NiuHuangJieDu Tablets (NHJDT), a popular realgar (As4 S4 ) containing patented traditional Chinese medicine (TCM), is widely used in the treatment of acute tonsillitis, pharyngitis, periodontitis and mouth ulcer. However, arsenic is considered as one of the most toxic elements, leading to growing concerns about the quality and safety of realgar-containing TCMs recently. In this study, health risk assessment of arsenic in realgar and NHJDT was conducted through oral administration of both substances to rats with single and multiple doses, respectively...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29773063/conversion-of-protein-active-regions-into-peptidomimetic-therapeutic-leads-using-backbone-cyclization-and-cycloscan-how-to-do-it-yourself
#20
Samuel J S Rubin, Yftah Tal-Gan, Chaim Gilon, Nir Qvit
Protein-protein interactions (PPIs) are particularly important for controlling both physiologic and pathologic biological processes but are difficult to target due to their large and/or shallow interaction surfaces unsuitable for small molecules. Linear peptides found in nature interact with some PPIs, and protein active regions can be used to design synthetic peptide compounds for inhibition of PPIs. However, linear peptides are limited therapeutically by poor metabolic and conformational stability, which can compromise their bioactivity and half-life...
May 17, 2018: Current Topics in Medicinal Chemistry
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