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https://www.readbyqxmd.com/read/28918591/platform-model-describing-pharmacokinetic-properties-of-vc-mmae-antibody-drug-conjugates
#1
Matts Kågedal, Leonid Gibiansky, Jian Xu, Xin Wang, Divya Samineni, Shang-Chiung Chen, Dan Lu, Priya Agarwal, Bei Wang, Ola Saad, Neelima Koppada, Bernard M Fine, Jin Y Jin, Sandhya Girish, Chunze Li
Antibody-drug conjugates (ADCs) developed using the valine-citrulline-MMAE (vc-MMAE) platform, consist of a monoclonal antibody (mAb) covalently bound with a potent anti-mitotic toxin (MMAE) through a protease-labile vc linker. Recently, clinical data for a variety of vc-MMAE ADCs has become available. The goal of this analysis was to develop a platform model that simultaneously described antibody-conjugated MMAE (acMMAE) pharmacokinetic (PK) data from eight vc-MMAE ADCs, against different targets and tumor indications; and to assess differences and similarities of model parameters and model predictions, between different compounds...
September 16, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28918508/metabolic-engineering-of-schizosaccharomyces-pombe-to-produce-punicic-acid-a-conjugated-fatty-acid-with-nutraceutic-properties
#2
Martina Garaiova, Elzbieta Mietkiewska, Randall J Weselake, Roman Holic
Punicic acid (PuA) is a conjugated linolenic acid (C18:3Δ(9c,11t,13c)) with a wide range of nutraceutic effects with the potential to reduce the incidence of a number of health disorders including diabetes, obesity, and cancer. It is the main component of seed oil from Punica granatum and Trichosanthes kirilowii. Previously, production of relatively high levels of this unusual fatty acid in the seed oil of transgenic Arabidopsis thaliana plant was accomplished by the use of A. thaliana fad3/fae1 mutant high in linoleic acid (18:2∆(9c,12c)) and by co-expression of P...
September 16, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28918472/a-reliable-protocol-for-colorimetric-determination-of-iron-oxide-nanoparticle-uptake-by-cells
#3
Daiana K Deda, Roberta M Cardoso, Mayara K Uchiyama, Christiane Pavani, Sergio H Toma, Mauricio S Baptista, Koiti Araki
Size, shape, and surface properties of superparamagnetic iron oxide nanoparticles (SPIONs) can influence their interaction with biological systems, particularly the incorporation by tumor cells and consequently the biological activity and efficiency in biomedical applications. Several strategies have been used to evaluate cellular uptake of SPIONs. While qualitative methods are generally based on microscopy techniques, quantitative assays are carried out by techniques such as inductively coupled plasma-mass spectrometry and flow cytometry...
September 16, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28918329/an-integrated-strategy-for-rapid-discovery-and-identification-of-the-sequential-piperine-metabolites-in-rats-using-ultra-high-performance-liquid-chromatography-high-resolution-mass-spectrometery
#4
Zhanpeng Shang, Wei Cai, Yanfeng Cao, Fei Wang, Zhibin Wang, Jianqiu Lu, Jiayu Zhang
Piperine, one of the major bioactive constituents isolated from natural flavorings and medicinal-culinary herbs, possesses various biological activities. In the present study, an integrated strategy based on ultra high-performance liquid chromatography/high resolution mass spectrometry was established to reveal piperine metabolism in rats. First of all, post-acquisition data-mining methods, including high resolution extracted ion chromatograms (HREICs) and multiple mass defect filtering (MMDF), were used to screen piperine metabolite candidates in a full-scan HRMS(1) level...
September 9, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28918150/short-communication-effects-of-lysolecithin-on-milk-fat-synthesis-and-milk-fatty-acid-profile-of-cows-fed-diets-differing-in-fiber-and-unsaturated-fatty-acid-concentration
#5
D E Rico, Y Ying, K J Harvatine
Thirteen multiparous Holstein cows were used in a crossover design that tested the effect of lysolecithin in diets differing in neutral detergent fiber (NDF) and unsaturated fatty acid (FA) concentrations. Experimental periods were 20 d in length and included two 10-d phases. A standard fiber and lower fat diet was fed the first 10 d (30.5% NDF, no added oil, lower-risk phase) and a lower NDF and higher oil diet was fed during the second 10 d (29.0% NDF and 2% oil from whole soybeans and soybean oil, high-risk phase)...
September 13, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28918148/mammalian-target-of-rapamycin-signaling-and-ubiquitin-proteasome-related-gene-expression-in-3-different-skeletal-muscles-of-colostrum-versus-formula-fed-calves
#6
H Sadri, J Steinhoff-Wagner, Harald M Hammon, R M Bruckmaier, S Görs, H Sauerwein
The rates of protein turnover are higher during the neonatal period than at any other time in postnatal life. The mammalian target of rapamycin (mTOR) and the ubiquitin-proteasome system are key pathways regulating cellular protein turnover. The objectives of this study were (1) to elucidate the effect of feeding colostrum versus milk-based formula on the mRNA abundance of key components of the mTOR pathway and of the ubiquitin-proteasome system in skeletal muscle of neonatal calves and (2) to compare different muscles...
September 13, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28918019/dual-tumor-targeting-nanocarrier-system-for-sirna-delivery-based-on-prna-and-modified-chitosan
#7
Lin Li, Xiaoqin Hu, Min Zhang, Siyu Ma, Fanglin Yu, Shiqing Zhao, Nan Liu, Zhiyuan Wang, Yu Wang, Hua Guan, Xiujie Pan, Yue Gao, Yue Zhang, Yan Liu, Yang Yang, Xuemei Tang, Mingyuan Li, Cheng Liu, Zhiping Li, Xingguo Mei
Highly specific and efficient delivery of siRNA is still unsatisfactory. Herein, a dual tumor-targeting siRNA delivery system combining pRNA dimers with chitosan nanoparticles (CNPPs) was designed to improve the specificity and efficiency of siRNA delivery. In this dual delivery system, folate-conjugated and PEGylated chitosan nanoparticles encapsulating pRNA dimers were used as the first class of delivery system and would selectively deliver intact pRNA dimers near or into target cells. pRNA dimers simultaneously carrying siRNA and targeting aptamer, the second class of delivery system, would specifically deliver siRNA into the target cells via aptamer-mediated endocytosis or proper particle size...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918018/locked-nucleic-acid-gapmers-and-conjugates-potently-silence-adam33-an-asthma-associated-metalloprotease-with-nuclear-localized-mrna
#8
Hannah M Pendergraff, Pranathi Meda Krishnamurthy, Alexandre J Debacker, Michael P Moazami, Vivek K Sharma, Liisa Niitsoo, Yong Yu, Yen Nee Tan, Hans Michael Haitchi, Jonathan K Watts
Two mechanisms dominate the clinical pipeline for oligonucleotide-based gene silencing, namely, the antisense approach that recruits RNase H to cleave target RNA and the RNAi approach that recruits the RISC complex to cleave target RNA. Multiple chemical designs can be used to elicit each pathway. We compare the silencing of the asthma susceptibility gene ADAM33 in MRC-5 lung fibroblasts using four classes of gene silencing agents, two that use each mechanism: traditional duplex small interfering RNAs (siRNAs), single-stranded small interfering RNAs (ss-siRNAs), locked nucleic acid (LNA) gapmer antisense oligonucleotides (ASOs), and novel hexadecyloxypropyl conjugates of the ASOs...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917924/synthesis-of-amphoteric-curdlan-derivatives-for-delivery-of-therapeutic-nucleic-acids
#9
Yao Tong, Tsogzolmaa Ganbold, Huricha Baigude
Cationic polymers are powerful carriers for intracellular delivery of therapeutic nucleic acids. However, the positively charged macromolecules have considerable cytotoxicity and often induce irreversible damages to the cells and tissues, which greatly negate the clinical application of such materials as drug delivery system. Herein, we report the synthesis of novel amphoteric polymers based on curdlan, and the evaluation of their cytotoxicity as well as the nucleic acid delivery efficiency. β-(1,3)-polyglucuronic acid, a TEMPO-oxidized derivative of curdlan, was chemically modified by conjugation of tetraethylenepentamine...
November 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28917910/cota-laccase-abts-hydrogen-peroxide-system-an-efficient-approach-to-produce-active-and-decolorized-chitosan-genipin-films
#10
Idalina Gonçalves, Cláudia Nunes, Sónia Mendes, Lígia O Martins, Paula Ferreira, Manuel A Coimbra
Chitosan-genipin films present a bluish-green color due to the conjugated double bonds formed when monomeric or dimeric genipin residues bridge chitosan. This phenomenon limits their use when colorless materials are required. In this work, a two-step oxidation strategy was developed aiming to remove color from chitosan-genipin films while preserving their functional properties. A combined system using the recombinant CotA laccase from Bacillus subtilis mediated by 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) followed by a H2O2 oxidation step was settled...
November 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28917784/green-synthesis-of-graphitic-carbon-nitride-nanosheet-g-c3n4-and-using-it-as-a-label-free-fluorosensor-for-detection-of-metronidazole-via-quenching-of-the-fluorescence
#11
Amir Hatamie, Farzanh Marahel, Ali Sharifat
In this research, g-C3N4nanosheets were facilely fabricated by thermal polymerization and then exfoliated into ultrathin nanosheets through ultrasonication in water media. Low-cost C-N nanosheets prepared by melamine possessed a highly π-conjugated structure and fluorescence property. In the present study, the g-C3N4nanosheet was used as a switch-off fluorescence sensor for rapid and sensitive sensing of metronidazole in biological fluids. These nanosheets were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy...
January 1, 2018: Talanta
https://www.readbyqxmd.com/read/28917774/fret-on-lateral-flow-test-strip-to-enhance-sensitivity-for-detecting-cancer-biomarker
#12
Jidong Wang, Fengjing Cao, Songliang He, Yong Xia, Xinyu Liu, Wenxiao Jiang, Yangyang Yu, Huisheng Zhang, Wenwen Chen
Fluorescence resonance energy transfer (FRET) between fluorescein isothiocyanate (FITC) and gold nanoparticles (Au NPs) is introduced in the lateral flow strip to detect cancer biomarker CEA with the color and fluorescence dual-readout. Anti-CEA monoclonal antibody coated Au NPs were on the conjugate pad and FITC labelled antibody (FITC-Ab) for CEA was coated on the test line. All the reagents were general in the lateral flow strip or commercially available and no new materials or technique were involved, which make our proposal a more universal method and easier to operate...
January 1, 2018: Talanta
https://www.readbyqxmd.com/read/28917607/selection-of-reliable-reference-genes-for-gene-expression-studies-in-botrytis-cinerea
#13
He Ren, Xiaoqing Wu, Yuping Lyu, Hongzi Zhou, Xueying Xie, Xinjian Zhang, Hetong Yang
Botrytis cinerea is an important plant pathogen causing grey mold disease in a wide range of plant species. The aim of this study was to identify reliable reference genes that can be used for the analysis of relative gene expression in B. cinerea with quantitative real-time reverse transcription PCR (qRT-PCR). Six commonly used housekeeping genes including actin (ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ubiquitin (UBQ), ubiquitin-conjugating enzyme (UCE), α-tubulin (α-TUB) and β-tubulin (β-TUB) were selected to test their expression stabilities in B...
September 13, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28916826/in-vitro-and-in-vivo-biocompatibility-evaluation-of-polyallylamine-and-macromolecular-heparin-conjugates-modified-alginate-microbeads
#14
Vijayaganapathy Vaithilingam, Bjørg Steinkjer, Liv Ryan, Rolf Larsson, Bernard Edward Tuch, Jose Oberholzer, Anne Mari Rokstad
Host reactivity to biocompatible immunoisolation devices is a major challenge for cellular therapies, and a human screening model would be of great value. We designed new types of surface modified barium alginate microspheres, and evaluated their inflammatory properties using human whole blood, and the intraperitoneal response after three weeks in Wistar rats. Microspheres were modified using proprietary polyallylamine (PAV) and coupled with macromolecular heparin conjugates (Corline Heparin Conjugate, CHC)...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916621/-64-cu-labeled-repebody-molecules-for-imaging-of-epidermal-growth-factor-receptor-expressing-tumors
#15
Ayoung Pyo, Misun Yun, Hyeon-Sik Kim, Tae-Yoon Kim, Joong-Jae Lee, Jung Young Kim, Sunwoo Lee, Seong Young Kwon, Hee-Seung Bom, Hak-Sung Kim, Dong-Yeon Kim, Jung-Joon Min
The epidermal growth factor receptor (EGFR) is a member of the erbB family of receptors and is overexpressed in many tumor types. A repebody is a newly designed non-antibody protein scaffold for tumor targeting that contains leucine-rich repeat modules. In this study, three (64)Cu-labeled anti-EGFR repebodies with different chelators were synthesized, and their biological characteristics were assessed in cultured cells and tumor-bearing mice. Methods: Repebodies (rEgAs) were synthesized with the chelators p-SCN-Bn-NOTA, DOTA-NHS ester, or p-SCN-Bn-DTPA in 1...
September 15, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28916497/two-step-polymer-and-liposome-enzyme-prodrug-therapies-for-cancer-pdept-and-pelt-concepts-and-future-perspectives
#16
Anna Scomparin, Helena F Florindo, Galia Tiram, Elaine L Ferguson, Ronit Satchi-Fainaro
Polymer-directed enzyme prodrug therapy (PDEPT) and polymer enzyme liposome therapy (PELT) are two-step therapies developed to provide anticancer drugs site-selective intratumoral accumulation and release. Nanomedicines, such as polymer-drug conjugates and liposomal drugs, accumulate in the tumor site due to extravasation-dependent mechanism (enhanced permeability and retention - EPR - effect), and further need to cross the cellular membrane and release their payload in the intracellular compartment. The subsequent administration of a polymer-enzyme conjugate able to accumulate in the tumor tissue and to trigger the extracellular release of the active drug showed promising preclinical results...
September 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28916119/safety-and-efficacy-of-glycerol-phenylbutyrate-for-management-of-urea-cycle-disorders-in-patients-aged-2months-to-2years
#17
Susan A Berry, Nicola Longo, George A Diaz, Shawn E McCandless, Wendy E Smith, Cary O Harding, Roberto Zori, Can Ficicioglu, Uta Lichter-Konecki, Beth Robinson, Jerry Vockley
INTRODUCTION: Glycerol phenylbutyrate (GPB) is approved in the US for the management of patients 2months of age and older with urea cycle disorders (UCDs) that cannot be managed with protein restriction and/or amino acid supplementation alone. Limited data exist on the use of nitrogen conjugation agents in very young patients. METHODS: Seventeen patients (15 previously on other nitrogen scavengers) with all types of UCDs aged 2months to 2years were switched to, or started, GPB...
September 8, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28916108/a-eu-iii-doped-metal-organic-framework-conjugated-with-fluorescein-labeled-single-stranded-dna-for-detection-of-cu-ii-and-sulfide
#18
Han Weng, Bing Yan
In this paper, Bio-MOF-1 is prepared as reported and then Eu(3+) is introduced into it via cation exchange method. A FAM-labeled ssDNA is chosen to fabricate with the obtained Eu(3+)@Bio-MOF-1. A luminescent hybrid material is assembled, which can exhibit the fluorescence of Eu(3+) and FAM simultaneously by adjusting the ratio of FAM-ssDNA and Eu(3+)@Bio-MOF-1. The sample is then used for the detecting of metal ions, results shows which has good selectively for Cu(2+) (LOD = 0.14 μM, 0-250 μM). The introduction of Cu(2+) can quench the fluorescence of FAM while the luminescent intensity of Eu(3+) enhancing...
October 2, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28916107/genetically-functionalized-ferritin-nanoparticles-with-a-high-affinity-protein-binder-for-immunoassay-and-imaging
#19
Jong-Won Kim, Woosung Heu, Sukyo Jeong, Hak-Sung Kim
Molecular detection of target molecules with high sensitivity and specificity is of great significance in bio and medical sciences. Here, we present genetically functionalized ferritin nanoparticles with a high-affinity protein binder, and their utility as a signal generator in a variety of immunoassays and imaging. As a high-affinity protein binder, human IgG-specific repebody, which is composed of LRR (Leucine-rich repeat) modules, was used. The repebody was genetically fused to the N-terminal heavy-chain ferritin, and the resulting subunits were self-assembled to the repebody-ferritin nanoparticles composed of 24 subunits...
October 2, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28915940/accurate-and-reliable-quantification-of-the-protein-surface-coverage-on-protein-functionalized-nanoparticles
#20
Siyao Liu, Jeannie Horak, Markus Höldrich, Michael Lämmerhofer
The ability to accurately quantify the protein coverage on nanoparticles is critical for assessing the quality of the surface chemistry and the success of the functionalization process of protein-nanoparticle conjugates. Surface coverage determination is therefore an integral part in the quality control of protein-modified nanoparticles in industrial nanotechnology. In this work, a novel and conventional method was established for direct quantification of the protein surface coverage on metallic nanoparticles...
October 9, 2017: Analytica Chimica Acta
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