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https://www.readbyqxmd.com/read/30114704/pci29732-a-bruton-s-tyrosine-kinase-inhibitor-enhanced-the-efficacy-of-conventional-chemotherapeutic-agents-in-abcg2-overexpressing-cancer-cells
#1
Chunlei Ge, Fang Wang, Chaochu Cui, Xiaodong Su, Kenneth Kin Wah To, Xiaokun Wang, Hui Zhang, Xin Song, Liwu Fu
BACKGROUND/AIMS: Multidrug resistance (MDR) induced by the ABC transporter subfamily B member 1 (ABCB1) and subfamilyG member 2 (ABCG2) limits successful cancer chemotherapy and no commercially available MDR modulator is used in the clinic. In the current study, we aimed to investigate the effects of PCI29732 on the enhancement of chemotherapeutic agents. METHODS: Cell cytotoxicity and reversal effect were measured with MTT assay. Additionally, flow cytometry was employed to detect the accumulation and efflux of the drugs...
August 16, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30114562/the-effect-of-surface-poly-ethylene-glycol-length-on-in-vivo-drug-delivery-behaviors-of-polymeric-nanoparticles
#2
Ji-Long Wang, Xiao-Jiao Du, Jin-Xian Yang, Song Shen, Hong-Jun Li, Ying-Li Luo, Shoaib Iqbal, Cong-Fei Xu, Xiao-Dong Ye, Jie Cao, Jun Wang
Engineering nanoparticles of reasonable surface poly(ethylene glycol) (PEG) length is important for designing efficient drug delivery systems. Eliminating the disturbance by other nanoproperties, such as size, PEG density, etc., is crucial for systemically investigating the impact of surface PEG length on the biological behavior of nanoparticles. In the present study, nanoparticles with different surface PEG length but similar other nanoproperties were prepared by using poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) copolymers of different molecular weights and incorporating different contents of PCL3500 homopolymer...
August 7, 2018: Biomaterials
https://www.readbyqxmd.com/read/30114477/nqo1-regulates-mitotic-progression-and-response-to-mitotic-stress-through-modulating-sirt2-activity
#3
Hong-Jun Kang, Ha Yong Song, Yang Guo, Mohamed A Ahmed, Mingming Zhang, Chuyu Chen, Massimo Cristofanilli, Dai Horiuchi, Athanassios Vassilopoulos
Previous studies have shown that SIRT2 plays a role in mitosis through deacetylating specific downstream targets. However, the upstream regulation of SIRT2 activity has been relatively unexplored. In this study, we provide evidence that NAD(P)H:quinone oxidoreductase 1 (NQO1) interacts with and activates SIRT2 in an NAD-dependent manner. Strong protein-protein interaction and co-localization of the two proteins during mitosis is required to maintain an active NQO1-SIRT2 axis which is critical for successful completion of mitosis...
August 13, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/30114371/development-of-mithramycin-analogues-with-increased-selectivity-towards-ets-transcription-factor-expressing-cancers
#4
Prithiba Mitra, Joseph M Eckenrode, Abhisek Mandal, Amit K Jha, Shaimaa M Salem, Markos Leggas, Jurgen Rohr
Mithramycin A (1) was identified as the top potential inhibitor of the aberrant ETS transcription factor EWS-FLI1, which causes Ewing sarcoma. Unfortunately, 1 has a narrow therapeutic window compel-ling us to seek less toxic and more selective analogues. Here, we used MTMSA (2) to generate analogues via peptide coupling and fragment-based drug development strategies. Cytotoxicity assays in ETS and non-ETS dependent cell lines identified two dipeptide analogues, 60 and 61, with 19.1- and 15.6-fold selectivity, respectively, compared to 1...
August 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30114366/computational-approach-to-unravel-the-role-of-hydrogen-bonding-in-the-interaction-of-nami-a-with-dna-nucleobases-and-nucleotides
#5
Dharitri Das, Muntazir Saba Khan, Gayatree Barik, Vidya Avasare, Sourav Pal
Density functional theory method in combination with a continuum solvation model are used to understand the role of hydrogen bonding in interaction of tertiary nitrogen centres of guanine and adenine with monoaquated and diaquated NAMI-A. In case of adenine, interaction of N3 with monoaquated NAMI-A is preferred over N7 and N1 whereas N7 is preferred over N3 and N1 in diaquated ruthenium-adenine interaction. In monoaquate and diaquated NAMI-A-guanine interaction N7 site is preferred over N3 site. Here, strength and number of H-bonds play important role in stabilising intermediates and transition states involved in the interaction of NAMI-A and purine bases...
August 16, 2018: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/30114322/the-use-of-variable-temperature-13-c-solid-state-mas-nmr-and-gipaw-dft-calculations-to-explore-the-dynamics-of-diethylcarbamazine-citrate
#6
Tiago Venâncio, Lyege Magalhaes Oliveira, Tomasz Pawlak, Javier Ellena, Nubia Boechat, Steven P Brown
Experimental 13 C solid-state magic-angle spinning (MAS) NMR as well as DFT (gauge-including projector augmented wave) GIPAW calculations were used to probe disorder and local mobility in diethylcarbamazine citrate, (DEC)+ (citrate)- . This compound has been used as the first option drug for the treatment of filariasis, a disease endemic in tropical countries and caused by adult worms of Wuchereria bancrofti, which is transmitted by mosquitoes. We firstly present 2D 13 C-1 H dipolar-coupling mediated heteronuclear correlation spectra recorded at moderate spinning frequency, to explore the intermolecular interaction between DEC and citrate molecules...
August 16, 2018: Magnetic Resonance in Chemistry: MRC
https://www.readbyqxmd.com/read/30114293/efavirenz-reduces-renal-excretion-of-lamivudine-in-rats-by-inhibiting-organic-cation-transporters-oct-oct-and-multidrug-and-toxin-extrusion-proteins-mate-mate
#7
Martina Ceckova, Josef Reznicek, Birgit Deutsch, Martin F Fromm, Frantisek Staud
Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor used in first-line combination antiretroviral therapy (cART). It is usually administered with nucleoside reverse transcriptase inhibitors (NRTI), many of which are substrates of OCT uptake solute carriers (SLC22A) and MATE (SLC47A), P-gp (MDR1, ABCB1), BCRP (ABCG2), or MRP2 (ABCC2) efflux transporters. The aim of this study was to evaluate the inhibitory potential of efavirenz towards these transporters and investigate its effects on the pharmacokinetics and tissue distribution of a known Oct/Mate substrate, lamivudine, in rats...
2018: PloS One
https://www.readbyqxmd.com/read/30114258/in-vitro-assessment-of-the-influence-of-intravenous-extension-set-materials-on-insulin-aspart-drug-delivery
#8
Morgane Masse, Mickael Maton, Stéphanie Genay, Nicolas Blanchemain, Christine Barthélémy, Bertrand Décaudin, Pascal Odou
Insulin is a frequently prescribed drug in hospitals and is usually administered by syringe pumps with an extension line which can be made of various materials. Two insulin solutions were studied: an insulin analogue, Novorapid® which contains insulin aspart and two phenolic preservatives (e.g. phenol and metacresol) and Umuline rapide® with human insulin and metacresol as preservative. Some studies have indicated interactions between insulin, polyvinyl chloride (PVC) and polyethylene (PE). The aim of this work was to study such interactions between Novorapid® or Umuline rapide® and infusion extension line materials (PVC, PE and coextruded (PE/PVC))...
2018: PloS One
https://www.readbyqxmd.com/read/30113831/come-together-molecular-details-into-the-synergistic-effects-of-polymer-surfactant-adsorption-at-the-oil-water-interface
#9
Brandon Kurt Schabes, Rebecca Marie Altman, Geraldine L Richmond
The synergistic adsorption of polymers with surfactants at the oil/water interface has applications that range from oil remediation to targeted drug delivery. However, the inherent inaccessibility of the buried oil/water interface has challenged the development of a molecular-level understanding of these systems' structure-function relationship. This study uses vibrational sum frequency spectroscopy to examine molecular structure, orientation and electrostatic effects of synergistic adsorption of the surfactant cetrimonium bromide (CTAB) and polymer poly(acrylic acid) (PAA) at a planar oil/water interface...
August 16, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/30113793/-strategies-of-using-the-new-antiepileptic-drugs-for-epilepsy-in-adults
#10
REVIEW
János Nikl
The new antiepileptic drugs have not changed the basic pharmacological treatment principles of epilepsy, but they have given greater choice in focal and in generalized epilepsies as well. The new drugs are not necessarily more effective than traditional drugs, but they have favourable pharmacokinetic characteristics, fewer interactions and better adverse effect profile in the acute and chronic phase of the treatment. They generally show a lower teratogenicity risk than the standard antiepileptics, although carbamazepine, one of the standard drugs can be used and zonisamide, a new one must be avoid in pregnancy...
July 30, 2018: Ideggyógyászati Szemle
https://www.readbyqxmd.com/read/30113724/safety-pharmacokinetics-and-pharmacodynamics-of-multiple-rising-doses-of-bi-655064-an-antagonistic-anti-cd40-antibody-in-healthy-subjects-a-potential-novel-treatment-for-autoimmune-diseases
#11
Christian Schwabe, Bernd Rosenstock, Thi Doan, Paul Hamilton, P Rod Dunbar, Anastasia G Eleftheraki, David Joseph, James Hilbert, Corinna Schoelch, Steven J Padula, Jürgen Steffgen
BI 655064 is a humanized antagonistic anti-cluster of differentiation (CD) 40 monoclonal antibody that selectively blocks the CD40-CD40L interaction. The CD40-CD40L pathway is a promising treatment target for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and lupus nephritis. The safety, tolerability, pharmacokinetics, and pharmacodynamics of repeated once-weekly BI 655064 subcutaneous dosing over 4 weeks were evaluated in a multiple-dose study in healthy subjects. Subjects (N = 40) were randomized 4:1 to four sequential BI 655064 dose groups (80, 120, 180, 240 mg) or to placebo...
August 16, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/30113694/aminoglycoside-ribosome-interactions-reveal-novel-conformational-states-at-ambient-temperature
#12
Mary E O'Sullivan, Frédéric Poitevin, Raymond G Sierra, Cornelius Gati, E Han Dao, Yashas Rao, Fulya Aksit, Halilibrahim Ciftci, Nicholas Corsepius, Robert Greenhouse, Brandon Hayes, Mark S Hunter, Mengling Liang, Alex McGurk, Paul Mbgam, Trevor Obrinsky, Fátima Pardo-Avila, Matthew H Seaberg, Alan G Cheng, Anthony J Ricci, Hasan DeMirci
The bacterial 30S ribosomal subunit is a primary antibiotic target. Despite decades of discovery, the mechanisms by which antibiotic binding induces ribosomal dysfunction are not fully understood. Ambient temperature crystallographic techniques allow more biologically relevant investigation of how local antibiotic binding site interactions trigger global subunit rearrangements that perturb protein synthesis. Here, the structural effects of 2-deoxystreptamine (paromomycin and sisomicin), a novel sisomicin derivative, N1-methyl sulfonyl sisomicin (N1MS) and the non-deoxystreptamine (streptomycin) aminoglycosides on the ribosome at ambient and cryogenic temperatures were examined...
August 3, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/30113218/interactions-of-helminths-with-macrophages-therapeutic-potential-for-inflammatory-intestinal-disease
#13
Hannah Smith, Ruth Forman, Iris Mair, Kathryn J Else
Macrophages represent a highly heterogeneous and plastic cell type found in most tissues of the body; the intestine is home to enormous numbers of these cells. Considerable interest surrounds the 'M2 macrophage,' as it is able to control and regulate inflammation, while promoting tissue repair. Areas covered: As potent inducers of M2 macrophages, intestinal helminths and helminth-derived products are ideal candidates for small molecule drug design to drive M2 macrophage polarization. Several gastrointestinal helminths have been found to cause M2 macrophage-inducing infections...
August 16, 2018: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/30113216/pentamidine-inhibits-the-growth-of-sporothrix-schenckii-complex-and-exhibits-synergism-with-antifungal-agents
#14
Raimunda Sn Brilhante, Vandbergue S Pereira, Jonathas S Oliveira, Raissa Gp Lopes, Anderson M Rodrigues, Zoilo P Camargo, Waldemiro A Pereira-Neto, Débora Scm Castelo-Branco, Rossana A Cordeiro, José Jc Sidrim, Marcos Fg Rocha
AIM: The purpose of this study was to evaluate the effects of the antileishmanials meglumine antimoniate and pentamidine against Sporothrix schenckii complex. MATERIALS & METHODS: The antifungal activity of the two antileishmanials was assessed by broth microdilution. The interaction between the antileishmanials and antifungal drugs (amphotericin B, itraconazole and terbinafine) was evaluated by the checkerboard assay. The effect of prior exposure of Sporothrix spp...
August 16, 2018: Future Microbiology
https://www.readbyqxmd.com/read/30113075/is-this-the-time-to-reconsider-the-names-for-xenobiotic-nuclear-receptors
#15
EDITORIAL
Bo Kong, Grace L Guo
Pregnane X receptor (PXR) has been known as a xenobiotic nuclear receptor and transcriptional factor that is important for inducing the expression of genes involved in drug disposition (1, 2). Recently, PXR has emerged to critically regulate endobiotic metabolism, including the homeostasis of glucose, lipids, steroids, bile acids, bilirubin, retinoids and bone minerals, and maybe implicated in the treatment of cholestasis, inflammatory bowel disease, and nonalcoholic fatty liver diseases (3). PXR activation is also well known to increase liver size and cause liver hypertrophy...
August 16, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30112986/preclinical-pharmacokinetics-of-triptolide-a-potential-antitumor-drug
#16
Wei Song, Meilin Liu, Junjun Wu, Hong Zhai, Yong Chen, Zhihong Peng
Triptolide, a bioactive component in Tripterygium wilfordii extracts, possess strong anti-proliferative activity on all 60-national cancer institute (NCI) cancer cell lines. The antitumor property of triptolide has made it become a promising anti-cancer drug. However, the widespread use of triptolide in the clinical practice is greatly limited for its multi-organ toxicity and narrow therapeutic window. All the toxic characteristics of triptolide are associated with the pharmacokinetics especially its distribution and accumulation in the target organ...
August 16, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/30112863/rate-and-appropriateness-of-polypharmacy-in-older-patients-with-hemophilia-compared-with-age-matched-controls
#17
Pier Mannuccio Mannucci, Alessandro Nobili, Emanuela Marchesini, Emily Oliovecchio, Laura Cortesi, Antonio Coppola, Elena Santagostino, Paolo Radossi, Giancarlo Castaman, Lelia Valdrè, Cristina Santoro, Annarita Tagliaferri, Cosimo Ettorre, Ezio Zanon, Giovanni Barillari, Isabella Cantori, Teresa Maria Caimi, Gianluca Sottilotta, Flora Peyvandi, Alfonso Iorio
BACKGROUND: In older people, multiple chronic ailments lead to the intake of multiple medications (polypharmacy) that carry a number of negative consequences (adverse events, prescription and intake errors, poor adherence, higher mortality). Because ageing patients with haemophilia (PWHs) may be particularly at risk due to their pre-existing multiple comorbidities (arthropathy, liver disease), we chose to analyse the pattern of chronic drug intake in a cohort of PWHs aged 60 years or more...
August 16, 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/30112775/monocytes-are-involved-in-the-balance-between-regulatory-t-cells-and-th17-cells-in-severe-drug-eruptions
#18
Y Ushigome, Y Mizukawa, M Kimishima, Y Yamazaki, R Takahashi, Y Kano, T Shiohara
BACKGROUND: Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DiHS/DRESS) is a distinct phenotype of severe drug eruptions characterized by sequential reactivations of herpesviruses. Although a progressive loss of suppressive function in regulatory T cells (Tregs) occurred during the course of DIHS/DRESS, but not in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), no previous studies investigated the mechanism. Given the recent finding that Treg development could be differentially regulated by CD16+ patrolling monocytes (pMOs) and CD14+ classical monocytes (cMOs), we can hypothesize that a differential fine-tuned interaction between Tregs and monocytes is the driving force behind the possible shift from Tregs to Th17 cells over a prolonged period of time in DiHS/DRESS...
August 15, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/30112660/a-luciferase-complementation-assay-system-using-transferable-mouse-artificial-chromosomes-to-monitor-protein-protein-interactions-mediated-by-g-protein-coupled-receptors
#19
Narumi Uno, Tomohito Fujimoto, Shinya Komoto, Gene Kurosawa, Masaaki Sawa, Teruhiko Suzuki, Yasuhiro Kazuki, Mitsuo Oshimura
G protein-coupled receptors (GPCRs) are seven-transmembrane domain receptors that interact with the β-arrestin family, particularly β-arrestin 1 (ARRB1). GPCRs interact with 33% of small molecule drugs. Ligand screening is promising for drug discovery concerning GPCR-related diseases. Luciferase complementation assay (LCA) enables detection of protein-protein complementation via bioluminescence following complementation of N- and C-terminal luciferase fragments (NEluc and CEluc) fused to target proteins, but it is necessary to co-express the two genes...
July 31, 2018: Cytotechnology
https://www.readbyqxmd.com/read/30112645/encapsulation-of-cinnamon-essential-oil-in-whey-protein-enhances-the-protective-effect-against-single-or-combined-sub-chronic-toxicity-of-fumonisin-b-1-and-or-aflatoxin-b-1-in-rats
#20
Mosaad A Abdel-Wahhab, Aziza A El-Nekeety, Nabila S Hassan, Abdullah A Y Gibriel, Khaled G Abdel-Wahhab
Fumonisin B1 (FB1 ) and aflatoxin B1 (AFB1 ) are fungal metabolites that frequently co-occur in foodstuffs and are responsible for mycotoxicosis and several primary cancers. Cinnamon essential oil (CEO) has a spacious range of benefit effects but also has some limitations owing to its strong taste or its interaction with some drugs. This study aimed to use the cinnamon oil emulsion droplets (COED) for the protection against oxidative stress, cytotoxicity, and reproductive toxicity in male Sprague-Dawley rats sub-chronically exposed to FB1 and/or AFB1 ...
August 15, 2018: Environmental Science and Pollution Research International
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