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https://www.readbyqxmd.com/read/28647364/crystal-structures-of-the-isochorismatase-domains-from-vibrio-anguillarum
#1
Jiansen Du, Tian Deng, Qingjun Ma
Antibiotic resistance is becoming a global threat and overuse of antibiotics in aquaculture disease control worsens the situation. To reduce the risk of drug resistance developed in aquaculture, safer biocontrol programs are needed. Antivirulence therapy, with less chance for developing drug resistance, is a promising approach. To facilitate antivirulence inhibitor design against Vibrio anguillarum, a serious aquaculture pathogen, we present crystal structures for isochorismatase domains of AngB and VabB, which are required to synthesize siderophore, a critical virulence factor...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28637659/enduring-effects-of-perinatal-nicotine-exposure-on-murine-sleep-in-adulthood
#2
Jeremy Charles Borniger, Reuben F Don, Ning Zhang, Robert Thomas Boyd, Randy J Nelson
The long-term consequences of early life nicotine exposure are poorly defined. Approximately 8-10% of women report smoking during pregnancy, and this may promote aberrant development in the offspring. To this end, we investigated potential enduring effects of perinatal nicotine exposure on murine sleep and affective behaviors in adulthood (~13-15 weeks of age) in C57Bl6j mice. Mothers received a water bottle containing 200 µg/ml nicotine bitartrate dihydrate in 2% w/v saccharin or pH-matched 2% saccharin with 0...
June 21, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28633997/nicotinamide-inhibits-the-growth-of-p-falciparum-and-enhances-the-antimalarial-effect-of-artemisinin-chloroquine-and-pyrimethamine
#3
Sergey O Tcherniuk, Olga Chesnokova, Irina V Oleinikov, Andrew V Oleinikov
Nicotinamide (vitamin B3) - is a water soluble amide derivative of nicotinic acid, which has been used at high doses for a variety of therapeutic applications. However, its antimalarial effect has not been intensively explored. In this work we analysed the effect of nicotinamide alone and in combination with artemisinin, chloroquine andpyrimethamine on the growth of blood stages of P. falciparum. Our results demonstrate that nicotinamide effectively inhibits the growth of blood stage parasites with IC50 of 6...
June 17, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28624424/fusaric-acid-fa-protects-heart-failure-induced-by-isoproterenol-isp-in-mice-through-fibrosis-prevention-via-tgf-%C3%AE-1-smads-and-pi3k-akt-signaling-pathways
#4
Xin Li, Zhou-Long Zhang, Hui-Fen Wang
Fusaric acid (FA) is a novel compound derived from a class of nicotinic acid derivatives, exhibiting activity against cancers. However, its role in regulating cardiac injury is limited. Our study was aimed to investigate the role and the underlying molecular mechanism of FA in heart fibrosis and hypertrophy. Isoproterenol (ISP) was used to induce cardiac fibrosis and hypertrophy in vitro and in vivo. FA administration ameliorated hypertrophy by reducing atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β -myosin heavy chain (β-MHC) in vitro and in vivo...
June 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28621793/kinetics-and-mechanism-of-oxidation-of-the-anti-tubercular-prodrug-isoniazid-and-its-analog-by-iridium-iv-as-models-for-biological-redox-systems
#5
Jingran Dong, Yanli Ren, Sufang Sun, Jiao Yang, Chunxia Nan, Hongmei Shi, Jianzhong Xu, Jie Duan, Tiesheng Shi, Lars I Elding
A complex reaction mechanism of oxidation of the anti-tubercular prodrug isoniazid (isonicotinic hydrazide, INH) by [IrCl6](2-) as a model for redox processes of such drugs in biological systems has been studied in aqueous solution as a function of pH between 0 and 8.5. Similar experiments have been performed with its isomer nicotinic hydrazide (NH). All reactions are overall second-order, first-order in [IrCl6](2-) and hydrazide, and the observed second-order rate constants k' have been determined as a function of pH...
June 16, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28618990/biological-roles-of-the-eclectic-chromogranin-a-derived-peptide-catestatin
#6
Teresa Pasqua, Tommaso Angelone, Angela Spena, Maria Carmela Cerra
Research on Chromogranin A (CGA) and its derived fragments convincingly demonstrated the multifunctional activity of the 21 amino acid peptide named Catestatin (CST: human CGA352-372, bovine CGA344-364, rat CGA367-387). It is mainly known as an inhibitor of the nicotinic-dependent Catecholamine (CA) release, and an anti-hypertensive peptide, but its role includes a modulation of antioxidant and immune defense, epidermal function, and adipose tissue homeostasis. CST influences the cardiocirculatory system acting both indirectly, via the autonomic nervous system, and directly by influencing the basal cardiac function, and the stretch-dependent myocardial performance...
June 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28616955/niacin-for-primary-and-secondary-prevention-of-cardiovascular-events
#7
REVIEW
Stefan Schandelmaier, Matthias Briel, Ramon Saccilotto, Kelechi K Olu, Armon Arpagaus, Lars G Hemkens, Alain J Nordmann
BACKGROUND: Nicotinic acid (niacin) is known to decrease LDL-cholesterol, and triglycerides, and increase HDL-cholesterol levels. The evidence of benefits with niacin monotherapy or add-on to statin-based therapy is controversial. OBJECTIVES: To assess the effectiveness of niacin therapy versus placebo, administered as monotherapy or add-on to statin-based therapy in people with or at risk of cardiovascular disease (CVD) in terms of mortality, CVD events, and side effects...
June 14, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28616862/loops-d-e-and-g-in-the-drosophila-d%C3%AE-1-subunit-contribute-to-high-neonicotinoid-sensitivity-of-d%C3%AE-1-chicken-%C3%AE-2-nicotinic-acetylcholine-receptor
#8
Makoto Ihara, Mai Hikida, Hiroyuki Matsushita, Kyosuke Yamanaka, Yuya Kishimoto, Kazuki Kubo, Shun Watanabe, Mifumi Sakamoto, Koutaro Matsui, Akihiro Yamaguchi, Daiki Okuhara, Shogo Furutani, David B Sattelle, Kazuhiko Matsuda
BACKGROUND AND PURPOSE: Neonicotinoid insecticides interact with the orthosteric site formed at subunit interfaces of insect nicotinic acetylcholine receptors (insect nACh receptors). However, their interactions with the orthosteric sites at α-non α and α-α subunit interfaces remain poorly understood. The aim of this study was to elucidate the mechanism of neonicotinoid actions using the Drosophila Dα1-chicken β2 hybrid nACh receptor. EXPERIMENTAL APPROACH: Computer models of the (Dα1)3 (β2)2 nACh receptor in complex with imidacloprid and thiacloprid were generated...
June 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28611586/the-distribution-of-charged-amino-acid-residues-and-the-ca-2-permeability-of-nicotinic-acetylcholine-receptors-a-predictive-model
#9
Sergio Fucile
Nicotinic acetylcholine receptors (nAChRs) are cation-selective ligand-gated ion channels exhibiting variable Ca(2+) permeability depending on their subunit composition. The Ca(2+) permeability is a crucial functional parameter to understand the physiological role of nAChRs, in particular considering their ability to modulate Ca(2+)-dependent processes such as neurotransmitter release. The rings of extracellular and intracellular charged amino acid residues adjacent to the pore-lining TM2 transmembrane segment have been shown to play a key role in the cation selectivity of these receptor channels, but to date a quantitative relationship between these structural determinants and the Ca(2+) permeability of nAChRs is lacking...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28608863/nicotine-affects-hydrogen-sulfide-concentrations-in-mouse-kidney-and-heart-but-not-in-brain-and-liver-tissues
#10
Jerzy Wiliński, Bogdan Wiliński, Eugeniusz Somogyi, Joanna Piotrowska, Tomasz Kameczura, Małgorzata Zygmunt
Nicotine, a potent parasympathomimetic alkaloid with stimulant effects, is contributing to addictive properties of tobacco smoking and is though used in the smoking cessation therapy. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology of various systems in mammals. The interactions between nicotine and H2S are not fully recognized. The aim of the study is to assess the influence of nicotine on the H2S tissue concentrations in different mouse organs. Adult CBA male mice were administered intraperitoneally 1...
2017: Folia Medica Cracoviensia
https://www.readbyqxmd.com/read/28606760/progress-in-the-discovery-of-small-molecule-modulators-of-the-cys-loop-superfamily-receptors
#11
REVIEW
Brian A Sparling, Erin F DiMauro
The vertebrate Cys-loop family of ligand-gated ion channels (LGICs) are comprised of nicotinic acetylcholine (nAChR), serotonin type 3 (5-HT3R), γ-aminobutyric acid (GABAAR), and glycine (GlyR) receptors. Here, we review efforts to discover selective small molecules targeting one or more Cys-loop receptors, with a focus on state-of-the-art modulators that have been reported over the past five years. Several highlighted compounds offer robust oral bioavailability and central exposure and have thus been useful in delineating pharmacokinetic/pharmacodynamic relationships in pre-clinical disease models...
May 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28603600/synthesis-and-pharmacological-evaluation-of-novel-selective-mor-agonist-6%C3%AE-pyridinyl-amidomorphines-exhibiting-long-lasting-antinociception
#12
Ákos Urai, András Váradi, Levente Szőcs, Balázs Komjáti, Valerie Le Rouzic, Amanda Hunkele, Gavril W Pasternak, Susruta Majumdar, Sándor Hosztafi
It was previously reported that 6β-aminomorphinan derivatives show high affinity for opiate receptors. Novel 6β-heteroarylamidomorphinanes were designed based on the MOR selective antagonist NAP. The 6β-aminomorphinanes were prepared with stereoselective Mitsunobu reaction and subsequently acylated with nicotinic acid and isonicotinic acid chloride hydrochlorides. The receptor binding and efficacy were determined in vitro and the analgesic activity was studied in vivo. The in vitro studies revealed moderate selectivity for MOR...
January 1, 2017: MedChemComm
https://www.readbyqxmd.com/read/28587964/nicotinic-acetylcholine-receptor-alpha-1-nachr%C3%AE-1-subunit-peptides-as-potential-antiviral-agents-against-rabies-virus
#13
Basavaraj Sajjanar, Kalyani Dhusia, Shikha Saxena, Vinay Joshi, Deepika Bisht, Dimpal Thakuria, Gundallahalli B Manjunathareddy, Pramod W Ramteke, Satish Kumar
Rabies virus (RABV) is neurotropic and infects all warm-blooded animals. The binding of the virus with host cell receptor components is critical for infection. The present study reports the interaction of nicotinic acetylcholine receptor alpha 1 (nAChRα1) peptides with the rabies virus glycoprotein (RABVG) to design potential anti-rabies agents. The nAChRα1peptide sequences from different species (bovine, human and electric fish/torpedo) were synthesized and their secondary structures were characterized using CD spectroscopy...
June 3, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28585068/a-novel-nitrilase-from-ralstonia-eutropha-h16-and-its-application-to-nicotinic-acid-production
#14
Haiyang Fan, Lifeng Chen, Huihui Sun, Hualei Wang, Yuhong Ren, Dongzhi Wei
A novel aliphatic nitrilase, REH16, was found in Ralstonia eutropha H16 and overexpressed in Escherichia coli BL21(DE3), and its enzymatic properties were studied. The temperature and pH optima were 37 °C and 6.6, respectively, and the best thermostability of the nitrilase was observed at 25 °C, which preserved 95% of activity after 120 h of incubation. REH16 has a broad hydrolytic activity toward aliphatic and heterocyclic nitriles and showed high tolerance of 3-cyanopyridine; this enzyme could hydrolyze as high as 100 mM 3-cyanopyridine completely...
June 5, 2017: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/28578873/mechanism-informed-refinement-reveals-altered-substrate-binding-mode-for-catalytically-competent-nitroreductase
#15
Warintra Pitsawong, Chad A Haynes, Ronald L Koder, David W Rodgers, Anne-Frances Miller
Nitroreductase (NR) from Enterobacter cloacae reduces diverse nitroaromatics including herbicides, explosives, and prodrugs, and holds promise for bioremediation, prodrug activation, and enzyme-assisted synthesis. We solved crystal structures of NR complexes with bound substrate or analog for each of its two half-reactions. We complemented these with kinetic isotope effect (KIE) measurements elucidating H-transfer steps essential to each half-reaction. KIEs indicate hydride transfer from NADH to the flavin consistent with our structure of NR with the NADH analog nicotinic acid adenine dinucleotide (NAAD)...
May 30, 2017: Structure
https://www.readbyqxmd.com/read/28561771/characterization-and-genome-analysis-of-a-nicotine-and-nicotinic-acid-degrading-strain-pseudomonas-putida-jq581-isolated-from-marine
#16
Aiwen Li, Jiguo Qiu, Dongzhi Chen, Jiexu Ye, Yuhong Wang, Lu Tong, Jiandong Jiang, Jianmeng Chen
The presence of nicotine and nicotinic acid (NA) in the marine environment has caused great harm to human health and the natural environment. Therefore, there is an urgent need to use efficient and economical methods to remove such pollutants from the environment. In this study, a nicotine and NA-degrading bacterium-strain JQ581-was isolated from sediment from the East China Sea and identified as a member of Pseudomonas putida based on morphology, physio-biochemical characteristics, and 16S rDNA gene analysis...
May 31, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28556459/does-coffee-consumption-impact-on-heaviness-of-smoking
#17
Jennifer J Ware, Julie-Anne Tanner, Amy E Taylor, Zhao Bin, Philip Haycock, Jack Bowden, Peter J Rogers, George Davey Smith, Rachel F Tyndale, Marcus R Munafo
BACKGROUND AND AIMS: Coffee consumption and cigarette smoking are strongly associated, but whether this association is causal remains unclear. We sought to: 1) determine whether coffee consumption causally influences cigarette smoking, 2) estimate the magnitude of any association, and 3) explore potential mechanisms. DESIGN: We used Mendelian randomization (MR) analyses of observational data, using publicly available summarised data from the Tobacco and Genetics (TAG) consortium, individual level data from the UK Biobank, and in vitro experiments of candidate compounds...
May 27, 2017: Addiction
https://www.readbyqxmd.com/read/28555334/prenatal-nicotine-exposure-induces-hpa-axis-hypersensitivity-in-offspring-rats-via-the-intrauterine-programming-of-up-regulation-of-hippocampal-gad67
#18
Xia He, Juan Lu, Wanting Dong, Zhexiao Jiao, Chong Zhang, Ying Yu, Zhaohui Zhang, Hui Wang, Dan Xu
The intrauterine programming of hypothalamic-pituitary-adrenal (HPA) axis hypersensitivity is associated with chronic adult diseases. Our previous studies demonstrated the HPA-axis hypersensitivity in offspring rats induced by prenatal nicotine exposure. The goal of the present study is to further investigate the intrauterine programming mechanism. Pregnant Wistar rats were subcutaneously administered with 2.0 mg/kg day of nicotine from gestational day (GD) 9-20. A group of the pregnant rats was euthanized at GD20, and the fetal rats were extracted...
May 29, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28551702/alpha-7-nicotinic-receptor-signaling-pathway-participates-in-the-neurogenesis-induced-by-chat-positive-neurons-in-the-subventricular-zone
#19
Jianping Wang, Zhengfang Lu, Xiaojie Fu, Di Zhang, Lie Yu, Nan Li, Yufeng Gao, Xianliang Liu, Chunmao Yin, Junji Ke, Liyuan Li, Mengmeng Zhai, Shiwen Wu, Jiahong Fan, Liang Lv, Junchao Liu, Xuemei Chen, Qingwu Yang, Jian Wang
Choline acetyltransferase-positive (ChAT(+)) neurons within the subventricular zone (SVZ) have been shown to promote neurogenesis after stroke in mice by secreting acetylcholine (ACh); however, the mechanisms remain unclear. Receptors known to bind ACh include the nicotinic ACh receptors (nAChRs), which are present in the SVZ and have been shown to be important for cell proliferation, differentiation, and survival. In this study, we investigated the neurogenic role of the alpha-7 nAChR (α7 nAChR) in a mouse model of middle cerebral artery occlusion (MCAO) by using α7 nAChR inhibitor methyllycaconitine...
May 27, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28549680/thiomers-impact-of-in-situ-cross-linkers-on-mucoadhesive-properties
#20
Hung Thanh Lam, Gintare Leonaviciute, Ožbej Zupančič, Andreas Bernkop-Schnürch
The aim of this study was to evaluate the impact of in situ cross-linkers on the gelling and mucoadhesive properties of thiomers. Polycarbophil-cysteine conjugate (PCP-cys) was synthesized by covalent attachment of l-cysteine to polycarbophil via amide bond formation mediated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) and N-hydroxysuccinimide (NHS) whereas in situ cross-linkers (PAA-cys-MNA) were synthesized by the same bond formation between poly(acrylic acid) (PAA) of 2.1-, 6-, and 15kDa and 2-((2-amino-2-carboxyethyl)disulfanyl)nicotinic acid (cys-MNA) used as ligand...
May 23, 2017: European Journal of Pharmaceutical Sciences
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