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https://www.readbyqxmd.com/read/29036906/from-2-alkylsulfanylimidazoles-to-2-alkylimidazoles-an-approach-towards-metabolically-more-stable-p38%C3%AE-map-kinase-inhibitors
#1
Fabian Heider, Urs Haun, Eva Döring, Mark Kudolo, Catharina Sessler, Wolfgang Albrecht, Stefan Laufer, Pierre Koch
In vitro and in vivo metabolism studies revealed that 2-alkylsulfanylimidazole ML3403 (4-(5-(4-fluorophenyl)-2-(methylthio)-1H-imidazol-4-yl)-N-(1-phenylethyl)pyridin-2-amine) undergoes rapid oxidation to the sulfoxide. Replacing the sulfur atom present in the two potent p38α mitogen-activated protein (MAP) kinase inhibitors ML3403 and LN950 (2-((5-(4-fluorophenyl)-4-(2-((3-methylbutan-2-yl)amino)pyridin-4-yl)-1H-imidazol-2-yl)thio)ethan-1-ol) by a methylene group resulted in 2-alkylimidazole derivatives 1 and 2, respectively, having a remarkably improved metabolic stability...
October 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29036882/biomineralization-of-fucoidan-peptide-blends-and-their-potential-applications-in-bone-tissue-regeneration
#2
Harrison T Pajovich, Ipsita A Banerjee
Fucoidan (Fuc), a natural polysaccharide derived from brown seaweed algae, and gelatin (Gel) were conjugated to form a template for preparation of biomimetic scaffolds for potential applications in bone tissue regeneration. To the Fuc-Gel we then incorporated the peptide sequence MTNYDEAAMAIASLN (MTN) derived from the E-F hand domain, known for its calcium binding properties. To mimic the components of the extracellular matrix of bone tissue, the Fuc-Gel-MTN assemblies were incubated in simulated body fluid (SBF) to induce biomineralization, resulting in the formation of β-tricalcium phosphate, and hydroxyapatite (HAp)...
September 20, 2017: Journal of Functional Biomaterials
https://www.readbyqxmd.com/read/29036474/casanova-a-multiclass-support-vector-machine-model-for-the-classification-of-human-sperm-motility-patterns
#3
Summer G Goodson, Sarah White, Alicia M Stevans, Sanjana Bhat, Chia-Yu Kao, Scott Jaworski, Tamara R Marlowe, Martin Kohlmeier, Leonard McMillan, Steven H Zeisel, Deborah A O'Brien
The ability to accurately monitor alterations in sperm motility is paramount to understanding multiple genetic and biochemical perturbations impacting normal fertilization. Computer-aided sperm analysis (CASA) of human sperm typically reports motile percentage and kinematic parameters at the population level, and uses kinematic gating methods to identify subpopulations such as progressive or hyperactivated sperm. The goal of this study was to develop an automated method that classifies all patterns of human sperm motility during in vitro capacitation following the removal of seminal plasma...
October 4, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29036196/understanding-the-antimicrobial-activity-of-selected-disinfectants-against-methicillin-resistant-staphylococcus-aureus-mrsa
#4
Ebrahim Aboualizadeh, Violet V Bumah, Daniela S Masson-Meyers, Janis T Eells, Carol J Hirschmugl, Chukuka S Enwemeka
Disinfectants and biocidal products have been widely used to combat Methicillin-resistant Staphylococcus aureus (MRSA) infections in homes and healthcare environments. Although disruption of cytoplasmic membrane integrity has been documented as the main bactericidal effect of biocides, little is known about the biochemical alterations induced by these chemical agents. In this study, we used Fourier transform infrared (FT-IR) spectroscopy and chemometric tools as an alternative non-destructive technique to determine the bactericidal effects of commonly used disinfectants against MRSA USA-300...
2017: PloS One
https://www.readbyqxmd.com/read/29035884/protective-effects-of-pretreatment-with-quercetin-against-lipopolysaccharide-induced-apoptosis-and-the-inhibition-of-osteoblast-differentiation-via-the-mapk-and-wnt-%C3%AE-catenin-pathways-in-mc3t3-e1-cells
#5
Chun Guo, Rui-Juan Yang, Ke Jang, Xiao-Ling Zhou, Yu-Zhen Liu
BACKGROUND/AIMS: Quercetin, a flavonoid found in onions and other vegetables, has potential inhibitory effects on bone resorption in vivo and in vitro. In our previous study, we found that quercetin treatment reversed lipopolysaccharide (LPS)-induced inhibition of osteoblast differentiation through the mitogen-activated protein kinase (MAPK) pathway in MC3T3-E1 cells. In this study, we investigated the underlying mechanisms of pretreatment with quercetin on apoptosis and the inhibition of osteoblast differentiation in MC3T3-E1 cells induced by LPS...
October 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29035881/activation-of-signaling-cascades-by-weak-extremely-low-frequency-electromagnetic-fields
#6
Einat Kapri-Pardes, Tamar Hanoch, Galia Maik-Rachline, Manuel Murbach, Patricia L Bounds, Niels Kuster, Rony Seger
BACKGROUND/AIMS: Results from recent studies suggest that extremely low frequency magnetic fields (ELF-MF) interfere with intracellular signaling pathways related to proliferative control. The mitogen-activated protein kinases (MAPKs), central signaling components that regulate essentially all stimulated cellular processes, include the extracellular signal-regulated kinases 1/2 (ERK1/2) that are extremely sensitive to extracellular cues. Anti-phospho-ERK antibodies serve as a readout for ERK1/2 activation and are able to detect minute changes in ERK stimulation...
October 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29035820/real-time-monitoring-of-amyloid-fibrillation-by-electrical-impedance-spectroscopy
#7
Rafael R da Silva, Sandro V de Lima, Helinando P de Oliveira, Celso P de Melo, Isaac A M Frías, Maria D L Oliveira, César A S Andrade
Electrical impedance spectroscopy (EIS) appears a promising label-free methodology for the investigation of processes related to the aggregation of macromolecules in solution. Here, we explore the EIS technique as a convenient tool for studying the irreversible aggregation of human insulin and describing its corresponding fibrillation kinetics. The in situ measurement of the electrical response of pure insulin solutions at 60°C allows for the real-time monitoring of the protein fibrillation as a function of the incubation time...
October 7, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29035746/the-exploration-of-endocytic-mechanisms-of-pla-peg-nanoparticles-prepared-by-coaxialtri-capillary-electrospray-template-removal-method
#8
Jiaming Chen, Lihua Cao, Yuecheng Cui, Kehua Tu, Hongjun Wang, Li-Qun Wang
The nano-sized poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) particles with core-shell structure were efficiently prepared by using coaxial tri-capillary electrospray-template removal method. The cellular uptake mechanism, intracellular distribution and exocytosis in A549 cell model of electrosprayed PLA-PEG nanoparticles were systemically studied. The drug release behavior of electrosprayed PLA-PEG nanoparticles were also investigated. Our results showed that PLA-PEG nanoparticles can be endocytosed quickly by A549 cells...
October 2, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29035726/nonionic-surfactants-enhanced-enzymatic-hydrolysis-of-cellulose-by-reducing-cellulase-deactivation-caused-by-shear-force-and-air-liquid-interface
#9
Hongming Lou, Meijun Zeng, Qiaoyan Hu, Cheng Cai, Xuliang Lin, Xueqing Qiu, Dongjie Yang, Yuxia Pang
Effects of nonionic surfactants on enzymatic hydrolysis of Avicel at different agitation rates and solid loadings and the mechanism were studied. Nonionic surfactants couldn't improve the enzymatic hydrolysis efficiency at 0 and 100rpm but could enhance the enzymatic hydrolysis significantly at high agitation rate (200 and 250rpm). Cellulase was easily deactivated at high agitation rate and the addition of nonionic surfactants can protect against the shear-induced deactivation, especially when the cellulase concentration was low...
July 14, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/29035351/rebalancing-%C3%AE-amyloid-induced-decrease-of-atp-level-by-amorphous-nano-micro-polyphosphate-suppression-of-the-neurotoxic-effect-of-amyloid-%C3%AE-protein-fragment-25-35
#10
Werner E G Müller, Shunfeng Wang, Maximilian Ackermann, Meik Neufurth, Renate Steffen, Egherta Mecja, Rafael Muñoz-Espí, Qingling Feng, Heinz C Schröder, Xiaohong Wang
Morbus Alzheimer neuropathology is characterized by an impaired energy homeostasis of brain tissue. We present an approach towards a potential therapy of Alzheimer disease based on the high-energy polymer inorganic polyphosphate (polyP), which physiologically occurs both in the extracellular and in the intracellular space. Rat pheochromocytoma (PC) 12 cells, as well as rat primary cortical neurons were exposed to the Alzheimer peptide Aβ25-35. They were incubated in vitro with polyphosphate (polyP); ortho-phosphate was used as a control...
October 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29035245/in-vivo-and-in-vitro-models-for-scanning-drug-substances-in-malaria-prestudy
#11
Ahmet Özbilgin, İbrahim Çavuş, Alicem Nuraydın, Tuğba Kaya
OBJECTIVE: The Wolrd Health Organization (WHO) encourages all countries to investigate antimalarial drug substances derived from herbal sources with the slogan "Hunt of the Next Artemisinin" due to the emergence of resistant strains of Plasmodium species to artemisinin. In the broad and simple sense, it was planned to help guide the young researchers set in-vitro and in-vivo models of malaria in order to be used in drug research and active ingredient studies. METHODS: In-vitro study, young Plasmodium berghei trophozoites were removed from the liquid nitrogen tank and resuspended in appropriate conditions, followed by incubation with chloroquine and tetracycline at concentrations of 0...
September 2017: Türkiye Parazitolojii Dergisi
https://www.readbyqxmd.com/read/29035140/cytoskeleton-genes-expression-and-survival-rate-comparison-between-immature-and-mature-yak-oocyte-after-ops-vitrification
#12
Xia Wei, Ye Sijie, Zeng Weibin, Xu Qing, Zheng Jie, Zi Xiangdong
This study was conducted to investigate the effect of vitrification on survival rate and cytoskeleton gene expression during yak oocyte maturation. The yak oocytes were incubated for 0 h [germinal vesicle (GV) stage] and in vitro matured for 24 h [metaphase II (MII) stage] to obtain immature and mature oocytes. Survival rate after vitrification were compared between immature and mature yak oocytes and cytoskeleton-related genes [cytokeratin 8 (CK8), β-actin (ACTB), and gap junction protein, alpha 1 (GJA1)] were tested by real-time PCR...
October 16, 2017: Animal Biotechnology
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
#13
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
https://www.readbyqxmd.com/read/29034469/effect-of-mono-2-ethylhexyl-phthalate-mehp-on-proliferation-of-and-steroid-hormone-synthesis-in-rat-ovarian-granulosa-cells-in-vitro
#14
Na Li, Te Liu, Kun Guo, Jian Zhu, Guangyan Yu, Shuyue Wang, Lin Ye
This study aimed to examine the proliferation of and secretion by rat ovarian granulosa cells (GCs) treated with mono-(2-ethylhexyl) phthalate (MEHP). Ovarian GCs were incubated with MEHP at concentration of 0, 25, 50, 100, and 200µM for 24 hours. Cell viability was determined using the MTT Cell Proliferation Assay. Progesterone and estradiol production was evaluated by radioimmunoassay (RIA) and the expression of FSHR, PR, and ER was measured by immunocytochemistry. StAR, P450scc, 3β-HSD, 17β-HSD, and P450 arom mRNA levels were determined by RT-PCR...
October 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29034364/microenvironmental-agonists-generate-de-novo-phenotypic-resistance-to-combined-ibrutinib-plus-venetoclax-in-cll-and-mcl
#15
Kallesh D Jayappa, Craig A Portell, Vicki L Gordon, Brian J Capaldo, Stefan Bekiranov, Mark J Axelrod, L Kyle Brett, Julia D Wulfkuhle, Rosa I Gallagher, Emanuel F Petricoin, Timothy P Bender, Michael E Williams, Michael J Weber
De novo resistance and rapid recurrence often characterize responses of B-cell malignancies to ibrutinib (IBR), indicating a need to develop drug combinations that block compensatory survival signaling and give deeper, more durable responses. To identify such combinations, we previously performed a combinatorial drug screen and identified the Bcl-2 inhibitor venetoclax (VEN) as a promising partner for combination with IBR in Mantle Cell Lymphoma (MCL). We have opened a multi-institutional clinical trial to test this combination...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29034051/on-chip-cell-labelling-and-washing-by-capture-and-release-using-microfluidic-trap-arrays
#16
Yu Chen, Robert H Austin, James C Sturm
Flow cytometry analysis requires a large amount of isolated, labelled, and purified cells for accurate results. To address the demand for a large quantity of cells prepared in a timely manner, we describe a novel microfluidic trap structure array for on-chip cell labelling, such as intracellular and extracellular labelling, and subsequent washing and release of cells. Each device contains [Formula: see text] trap structures, which made the preparation of large numbers of cells [Formula: see text] possible. The structure has a streamlined shape, which minimizes clogging of cells in capture and release steps...
September 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/29033917/newly-isolated-bacteriophages-from-the-podoviridae-siphoviridae-and-myoviridae-families-have-variable-effects-on-putative-novel-dickeya-spp
#17
Špela Alič, Tina Naglič, Magda Tušek-Žnidarič, Maja Ravnikar, Nejc Rački, Matjaž Peterka, Tanja Dreo
Soft rot pathogenic bacteria from the genus Dickeya cause severe economic losses in orchid nurseries worldwide, and there is no effective control currently available. In the last decade, the genus Dickeya has undergone multiple changes as multiple new taxa have been described, and just recently a new putative Dickeya species was reported. This study reports the isolation of three bacteriophages active against putative novel Dickeya spp. isolates from commercially produced infected orchids that show variable host-range profiles...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29033916/contribution-of-ruminal-fungi-archaea-protozoa-and-bacteria-to-the-methane-suppression-caused-by-oilseed-supplemented-diets
#18
Shaopu Wang, Katrin Giller, Michael Kreuzer, Susanne E Ulbrich, Ueli Braun, Angela Schwarm
Dietary lipids can suppress methane emission from ruminants, but effects are variable. Especially the role of bacteria, archaea, fungi and protozoa in mediating the lipid effects is unclear. In the present in vitro study, archaea, fungi and protozoa were selectively inhibited by specific agents. This was fully or almost fully successful for fungi and protozoa as well as archaeal activity as determined by the methyl-coenzyme M reductase alpha subunit gene. Five different microbial treatments were generated: rumen fluid being intact (I), without archaea (-A), without fungi (-F), without protozoa (-P) and with bacteria only (-AFP)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29033853/proinflammatory-effect-of-high-glucose-concentrations-on-hmrsv5-cells-via-the-autocrine-effect-of-hmgb1
#19
Yuening Chu, Yi Wang, Zhihuang Zheng, Yuli Lin, Rui He, Jun Liu, Xuguang Yang
Background: Peritoneal fibrosis, in which inflammation and apoptosis play crucial pathogenic roles, is a severe complication associated with the treatment of kidney failure with peritoneal dialysis (PD) using a glucose-based dialysate. Mesothelial cells (MCs) take part in the inflammatory processes by producing various cytokines and chemokines, such as monocyte chemoattractant protein 1 (MCP-1) and interleukin 8 (IL-8). The apoptosis of MCs induced by high glucose levels also contributes to complications of PD...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29033838/the-target-residence-time-of-antihistamines-determines-their-antagonism-of-the-g-protein-coupled-histamine-h1-receptor
#20
Reggie Bosma, Gesa Witt, Lea A I Vaas, Ivana Josimovic, Philip Gribbon, Henry F Vischer, Sheraz Gul, Rob Leurs
The pharmacodynamics of drug-candidates is often optimized by metrics that describe target binding (Kd or Ki value) or target modulation (IC50). However, these metrics are determined at equilibrium conditions, and consequently information regarding the onset and offset of target engagement and modulation is lost. Drug-target residence time is a measure for the lifetime of the drug-target complex, which has recently been receiving considerable interest, as target residence time is shown to have prognostic value for the in vivo efficacy of several drugs...
2017: Frontiers in Pharmacology
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