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https://www.readbyqxmd.com/read/28345745/in-vitro-and-in-vivo-assessment-of-the-abuse-potential-of-pf614-a-novel-bio-md%C3%A2-prodrug-of-oxycodone
#1
D Lynn Kirkpatrick, William K Schmidt, Ricardo Morales, John Cremin, Julie Seroogy, Craig Husfeld, Thomas Jenkins
OBJECTIVE: The need for pain medication which will not lead to abuse is well recognized. Ensysce has designed prodrug analogs of the commonly used pain medications including hydromorphone, oxycodone (OC), hydrocodone, and morphine that limit their use to oral delivery, two of which are in clinical development. This study was undertaken to demonstrate that PF614, an extended-release prodrug of OC, allows the release of OC as designed when delivered orally, yet it resists ex vivo extraction with household chemicals and is pharmacologically inactive when administered by nonoral routes (nasal and parenteral), thereby substantially reducing its intravenous (IV) and intranasal abuse potential...
January 2017: Journal of Opioid Management
https://www.readbyqxmd.com/read/28345718/probing-the-binding-affinity-of-plasma-proteins-adsorbed-on-au-nanoparticles
#2
Xiaoning Zhang, Junting Zhang, Fan Zhang, Shaoning Yu
Nanoparticle (NP) surfaces are modified immediately by the adsorption of proteins when exposed to human blood, leading to the formation of a protein corona. The adsorption of serum proteins is the key process for exploring the bioapplication and biosafety of NPs. In this study, NP-protein binding affinity (Ka) was investigated. Some serum proteins, such as human serum albumin (HSA), trypsin (TRP), hemoglobin (Hb), myoglobin (MB), immunoglobulin G (IgG), carbonic anhydrase (CA), fibrinogen (FIB), chymotrypsin and r-globulin, were used with gold nanoparticles (AuNPs) to address binding affinity according to isothermal titration calorimetry (ITC) combined with dynamic light scattering (DLS) and fluorescence quenching...
March 27, 2017: Nanoscale
https://www.readbyqxmd.com/read/28345667/the-toxicity-of-angiotensin-converting-enzyme-inhibitors-to-larvae-of-the-disease-vectors-aedes-aegypti-and-anopheles-gambiae
#3
Zatul-'Iffah Abu Hasan, Helen Williams, Nur M Ismail, Hidayatulfathi Othman, Gyles E Cozier, K Ravi Acharya, R Elwyn Isaac
The control of mosquitoes is threatened by the appearance of insecticide resistance and therefore new control chemicals are urgently required. Here we show that inhibitors of mosquito peptidyl dipeptidase, a peptidase related to mammalian angiotensin-converting enzyme (ACE), are insecticidal to larvae of the mosquitoes, Aedes aegypti and Anopheles gambiae. ACE inhibitors (captopril, fosinopril and fosinoprilat) and two peptides (trypsin-modulating oostatic factor/TMOF and a bradykinin-potentiating peptide, BPP-12b) were all inhibitors of the larval ACE activity of both mosquitoes...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345637/rattusin-structure-reveals-a-novel-defensin-scaffold-formed-by-intermolecular-disulfide-exchanges
#4
Hye Jung Min, Hyosuk Yun, Sehyeon Ji, Ganesan Rajasekaran, Jae Il Kim, Jeong-Sun Kim, Song Yub Shin, Chul Won Lee
Defensin peptides are essential for innate immunity in humans and other living systems, as they provide protection against infectious pathogens and regulate the immune response. Here, we report the solution structure of rattusin (RTSN), an α-defensin-related peptide, which revealed a novel C2-symmetric disulfide-linked dimeric structure. RTSN was synthesized by solid-phase peptide synthesis (SPPS) and refolded by air oxidation in vitro. Dimerization of the refolded RTSN (r-RTSN) resulted from five intermolecular disulfide (SS) bond exchanges formed by ten cysteines within two protomer chains...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344516/ulinastatin-ameliorates-tissue-damage-of-severe-acute-pancreatitis-through-modulating-regulatory-t-cells
#5
Yu Pan, Haizong Fang, Fengchun Lu, Minggui Pan, Fei Chen, Ping Xiong, Yi Yao, Heguang Huang
BACKGROUND: Ulinastatin or urinary trypsin inhibitor (UTI) has been shown to ameliorate the inflammatory response induced by experimental severe acute pancreatitis (SAP) and hence reduce the mortality, however the mechanism of its action remains incompletely understood. We have investigated the effect of ulinastatin on regulatory T-cells (Tregs) in an established rat model of SAP. METHODS: We established a rat SAP model by injecting 5% Na-taurocholate into the pancreatic duct and treated the SAP rats with ulinastatin with different dose level (5000, 10000, 30000 U/kg) through intraperitoneal injection at 0, 6 and 12 h...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28344091/determination-of-structural-and-thermodynamic-parameters-of-bovine-%C3%AE-trypsin-isoform-in-aqueous-organic-media
#6
Dayanne Pinho Rosa, Evaldo Vitor Pereira, Antonio Victor Baioco Vasconcelos, Maria Aparecida Cicilini, André Romero da Silva, Caroline Dutra Lacerda, Jamil Silvano de Oliveira, Marcelo Matos Santoro, Juliana Barbosa Coitinho, Alexandre Martins Costa Santos
The α-trypsin isoform is a globular protein that belongs to serine-protease family and has a polypeptide chain of 223 amino acid residues, six disulfide bridges and two domains with similar structures. The effects of aqueous-organic solvent (ethanol) in different concentration on the α-trypsin structure have been investigated by spectroscopic techniques and thermodynamic data analysis. The results from spectroscopic measurements, including far-UV Circular Dichroism, UV-vis absorption spectroscopy, intrinsic tryptophan fluorescence and dynamic light scattering (DLS) suggest the formation of partially folded states, instead of aggregate states, at high ethanol concentration (>60% v/v ethanol), with little loss of secondary structure, but with significant tertiary structure changes...
March 23, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28340705/towards-automation-in-protein-digestion-development-of-a-monolithic-trypsin-immobilized-reactor-for-highly-efficient-on-line-digestion-and-analysis
#7
Marina Naldi, Urh Černigoj, Ales Štrancar, Manuela Bartolini
Reducing experimental variability, limiting contamination and increasing automation are essential goals in the development of reliable analytical platforms for mass spectrometry (MS)-based proteomics. In this work novel trypsin-based monolithic immobilized enzyme reactors (tryp-IMERs), obtained by covalent immobilization on convective interaction media (CIMac™) analytical columns (5mm×5.2mm I.D.), were developed. Notwithstanding the small dimensions, column format allowed the insertion in common high performance liquid chromatography (HPLC) systems, thus avoiding the use of expensive micro- or nano-platforms...
May 15, 2017: Talanta
https://www.readbyqxmd.com/read/28338078/the-transmembrane-serine-protease-hat-like-4-is-important-for-epidermal-barrier-function-to-prevent-body-fluid-loss
#8
Zhiwei Zhang, Yae Hu, Ruhong Yan, Liang Dong, Yizhi Jiang, Zhichao Zhou, Meng Liu, Tiantian Zhou, Ningzheng Dong, Qingyu Wu
Membrane-bound proteases are essential for epidermal integrity. Human airway trypsin-like protease 4 (HAT-L4) is a type II transmembrane serine protease. Currently, its biochemical property, cellular distribution and physiological function remain unknown. Here we examined HAT-L4 expression and function in vitro and in vivo. In Western analysis, HAT-L4 expressed in transfected CHO cells appeared as a 48-kDa protein. Flow cytometry confirmed HAT-L4 expression on the cell surface with the expected membrane topology...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336547/glycans-in-the-intestinal-peptide-transporter-pept1-contribute-to-function-and-protect-from-proteolysis
#9
Tamara Stelzl, Kerstin Elisabeth Geillinger-Kästle, Jürgen Stolz, Hannelore Daniel
Despite the fact that many membrane proteins carry extracellular glycans, little is known about whether the glycan chains also affect protein function. We recently demonstrated that the proton-coupled oligopeptide transporter 1 (PEPT1) in the intestine is glycosylated at six asparagine residues (N50, N406, N439, N510, N515, N532). Mutagenesis-induced disruption of the individual N-glycosylation site N50, which is highly conserved among mammals, was detected to significantly enhance the PEPT1 mediated inward transport of peptides...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28336271/helminth-secretomes-reflect-different-lifestyles-and-parasitized-hosts
#10
Yesid Cuesta-Astroz, Francislon Silva de Oliveira, Laila Alves Nahum, Guilherme Oliveira
Helminths cause a number of medical and agricultural problems and are a major cause of parasitic infections in humans, animals and plants. Comparative analysis of helminth genes and genomes are important to understand the genomic biodiversity and evolution of parasites and their hosts in terms of different selective pressures in their habitats. The interactions between the infective organisms and their hosts are mediated in large part by secreted proteins, known collectively as the "secretome". Proteins secreted by parasites are able to modify a host's environment and modulate their immune system...
March 20, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28335458/in-vitro-antioxidant-activity-and-in-vivo-anti-fatigue-effect-of-sea-horse-hippocampus-peptides
#11
Zebin Guo, Duanquan Lin, Juanjuan Guo, Yi Zhang, Baodong Zheng
This study investigated changes the in vitro antioxidant activity of Hippocampus polypeptides during enzymatic hydrolysis, including the effects of enzyme species, enzyme concentration, material-liquid ratio, hydrolysis time, pH, and temperature of the reaction system. Its in vivo anti-fatigue activity was also studied. Hippocampus peptide prepared by papain digestion exhibited the highest 1,1-diphenyl-2-picryl-hydrazyl free radical scavenging rate (71.89% ± 1.50%) and strong hydroxyl radical scavenging rate (75...
March 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28335094/growth-and-physiological-responses-of-broiler-chickens-to-diets-containing-raw-full-fat-soybean-meal-and-supplemented-with-a-high-impact-microbial-protease
#12
Mammo Mengesha Erdaw, Shubiao Wu, Paul A Iji, Rider A Perez-Maldonado
Objective: This study was to evaluate the change and function of the pancreas, and small intestine in relation to growth performance of broilers on diets supplemented with raw soybean meal (RSBM) and protease. Samples of test ingredients and diets, after mixing and prior to being used were also assessed on contents of anti-nutritional factors. Methods: A 3 x 3 factorial study was used, with three levels of RSBM (commercial SBM was replaced by RSBM at 0, 10 or 20%) and protease (0...
March 21, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28328201/double-fueled-janus-swimmers-with-magnetotactic-behaviour
#13
Philipp Sebastian Schattling, Miguel Alexandre Ramos-Docampo, Veronica Salgueiriño, Brigitte Städler
Self-propelled particles attract a great deal of attention due to the auspicious range of application nanobots can be used for. In a biomedical context, self-propelled swimmers hold promise to autonomously navigate to a desired location in an attempt to counteract cell/tissue defects either by releasing drugs or performing surgical tasks. The vast majority of prior reports deal with single engine assemblies, often utilizing fuel molecules which are considered as highly cytotoxic. Herein, we introduce two engines: 1) a motor which couples enzymes i...
March 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/28325335/an-advance-for-removing-antinutritional-protease-inhibitors-soybean-whey-purification-of-bowman-birk-chymotrypsin-inhibitor-by-combination-of-two-oppositely-charged-polysaccharides
#14
Xingfei Li, Yufei Hua, Yeming Chen, Xiangzhen Kong, Caimeng Zhang, Xiaobin Yu
Two successive and selective coacervations induced by chitosan (Ch) and carrageenan (CG) were applied to remove antinutritional protease inhibitors and purify Bowman-Birk protease inhibitor (BBI) from soybean whey. At the first coacervation induced by Ch (66.7, 200, and 510kDa), only Kunitz trypsin inhibitor (KTI) and BBI complexed with Ch were extracted, while β-amylase and soybean agglutinin remained in supernatant. The binding constants for the interaction increased on the order Ch-66.7<Ch-200<Ch-510...
May 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28323908/effects-of-protease-and-non-starch-polysaccharide-enzyme-on-performance-digestive-function-activity-and-gene-expression-of-endogenous-enzyme-of-broilers
#15
Lin Yuan, Mingfa Wang, Xiaotu Zhang, Zhixiang Wang
Three hundred one-day-old male broiler chickens (Ross-308) were fed corn-soybean basal diets containing non-starch polysaccharide (NSP) enzyme and different levels of acid protease from 1 to 42 days of age to investigate the effects of exogenous enzymes on growth performance, digestive function, activity of endogenous digestive enzymes in the pancreas and mRNA expression of pancreatic digestive enzymes. For days 1-42, compared to the control chickens, average daily feed intake (ADFI) and average daily gain (ADG) were significantly enhanced by the addition of NSP enzyme in combination with protease supplementation at 40 or 80 mg/kg (p<0...
2017: PloS One
https://www.readbyqxmd.com/read/28323389/atomic-force-microscopy-in-the-production-of-a-biovital-skin-graft-based-on-human-acellular-dermal-matrix-produced-in-house-and-in-vitro-cultured-human-fibroblasts
#16
Wojciech Łabuś, Justyna Glik, Agnieszka Klama-Baryła, Diana Kitala, Małgorzata Kraut, Mariusz Maj, Mariusz Nowak, Marcelina Misiuga, Andrzej Marcinkowski, Barbara Trzebicka, Ryszard Poloczek, Marek Kawecki
The most efficient method in III° burn treatment is the use of the autologous split thickness skin grafts that were donated from undamaged body area. The main limitation of this method is lack of suitable donor sites. Tissue engineering is a useful tool to solve this problem. The goal of this study was to find the most efficient way of producing biovital skin substitute based on in house produced acellular dermal matrix ADM and in vitro cultured fibroblasts. Sixty samples of sterilized human allogeneic skin (that came from 10 different donors) were used to examine the influence of decellularizing substances on extracellular matrix and clinical usefulness of the test samples of allogeneic human dermis...
March 21, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28321527/effects-of-site-mutations-within-the-22%C3%A2-kda-no-core-fragment-of-the-vip3aa11-insecticidal-toxin-of-bacillus-thuringiensis
#17
Ming Liu, Rongmei Liu, Guoxing Luo, Haitao Li, Jiguo Gao
Bacillus thuringiensis vegetative insecticidal proteins (VIPs) are not homologous to other known Cry proteins, and they act against lepidopteran larvae via a unique process. All reported studies on the mode of action of Vip3 proteins have been performed on the Vip3A family, mostly on the Vip3Aa subfamily. Vip3Aa proteins are activated by midgut proteases, and they cross the peritrophic membrane and bind specific proteins in apical membrane epithelial midgut cells, which results in pore formation and, eventually, death to the insects...
March 20, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28319020/in%C3%A2-vitro-preparation-and-assessment-of-radical-reducing-peptide-from-octopus-aegina-using-digestive-proteases
#18
Sekar Sudhakar, Rasool Abdul Nazeer
Antioxidant peptides protect biological macromolecules against radical damages. The use of these peptides was evaluated using free radicals scavenging assays [2,2-diphenyl-1 picrylhydrazyl (DPPH) and hydroxyl] with the help of UV-visible and electron spin resonance (ESR) spectroscopy methods. The Octopus aegina mantle protein were tested upon hydrolysis using gastrointestinal enzymes up to 12 h, where pepsin hydrolysate exhibited superior properties (DPPH: 44.39±0.67% and hydroxyl: 38.84±1.07%) compared with trypsin and α-chymotrypsin...
March 16, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28317757/antihypertensive-peptides-from-animal-products-marine-organisms-and-plants
#19
REVIEW
Seung Yun Lee, Sun Jun Hur
Bioactive peptides from food proteins exert beneficial effects on human health, such as angiotensin-converting enzyme (ACE) inhibition and antihypertensive activity. Several studies have reported that ACE-inhibitory peptides can come from animal products, marine organisms, and plants-derived by hydrolyzing enzymes such as pepsin, chymotrypsin, and trypsin-and microbial enzymes such as alcalase, thermolysin, flavourzyme, and proteinase K. Different ACE-inhibitory effects are closely related with different peptide sequences and molecular weights...
August 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28317701/interaction-of-phenolic-acids-with-trypsin-experimental-and-molecular-modeling-studies
#20
Benguo Liu, Huizhi Xiao, Jiaqi Li, Sheng Geng, Hanjun Ma, Guizhao Liang
Trypsin is a kind of protease for digestion and food processing, whose activity can be inhibited by phenolic acids in plant foods. However, most reports explained the inhibitory difference of phenolic acids based on the number and position of substituent groups, which failed to reveal the comprehensive inhibitory mechanism. In this work, the inhibitory effects of 11 common phenolic acids on trypsin were investigated. Amongst the tested cinnamic and benzoic acid derivatives, caffeic acid and gallic acid showed the strongest anti-trypsin activity with a noncompetitive inhibition pattern, respectively...
August 1, 2017: Food Chemistry
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