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https://www.readbyqxmd.com/read/28091410/molecular-mechanisms-of-increased-heart-rate-in-shenxianshengmai-treated-bradycardia-rabbits
#1
Zhou-Ying Liu, Jian Huang, Na-Na Liu, Min Zheng, Tao Zhao, Bu-Chang Zhao, Yi-Min Wang, Jie-Lin Pu
BACKGROUND: The molecular mechanisms of Shenxianshengmai (SXSM), a traditional Chinese medicine, on bradycardia have been incompletely understood. The study tried to investigate the gene expression profile and proteomics of bradycardia rabbits' hearts after SXSM treatment. METHODS: Twenty-four adult rabbits were randomly assigned in four groups: sham, model, model plus SXSM treatment, and sham plus SXSM treatment groups. Heart rate was recorded in all rabbits. Then, total RNA of atria and proteins of ventricle were isolated and quantified, respectively...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28089568/inhibition-of-intracellular-triglyceride-lipolysis-suppresses-cold-induced-brown-adipose-tissue-metabolism-and-increases-shivering-in-humans
#2
Denis P Blondin, Frédérique Frisch, Serge Phoenix, Brigitte Guérin, Éric E Turcotte, François Haman, Denis Richard, André C Carpentier
Indirect evidence from human studies suggests that brown adipose tissue (BAT) thermogenesis is fueled predominantly by fatty acids hydrolyzed from intracellular triglycerides (TGs). However, no direct experimental evidence to support this assumption currently exists in humans. The aim of this study was to determine the role of intracellular TG in BAT thermogenesis, in cold-exposed men. Using positron emission tomography with (11)C-acetate and (18)F-fluorodeoxyglucose, we showed that oral nicotinic acid (NiAc) administration, an inhibitor of intracellular TG lipolysis, suppressed the cold-induced increase in BAT oxidative metabolism and glucose uptake, despite no difference in BAT blood flow...
January 11, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28080034/the-mechanism-of-the-flavoprotein-6-hydroxy-l-nicotine-oxidase-ph-and-solvent-isotope-effects-and-identification-of-key-active-site-residues
#3
Paul F Fitzpatrick, Fatemeh Chadegani, Shengnan Zhang, Vi Dougherty
The flavoenzyme L-6-hydroxynicotine oxidase (LHNO) is a member of the monoamine oxidase family that catalyzes the oxidation of (S)-6-hydroxynicotine to 6-hydroxypseudooxynicotine during microbial catabolism of nicotine. While the enzyme has long been understood to catalyze oxidation of carbon-carbon bond, it has recently been shown to catalyze oxidation of a carbon-nitrogen bond (Fitzpatrick et al., Biochemistry 55, 697-703). The effects of pH and mutagenesis of active site residues have now been utilized to study the mechanism and the roles of active site residues...
January 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28074924/metabotyping-patients-journeys-reveals-early-predisposition-to-lung-injury-after-cardiac-surgery
#4
Raluca Georgiana Maltesen, Bodil Steen Rasmussen, Shona Pedersen, Munsoor Ali Hanifa, Sergey Kucheryavskiy, Søren Risom Kristensen, Reinhard Wimmer
Cardiovascular disease is the leading cause of death worldwide and patients with severe symptoms undergo cardiac surgery. Even after uncomplicated surgeries, some patients experience postoperative complications such as lung injury. We hypothesized that the procedure elicits metabolic activity that can be related to the disease progression, which is commonly observed two-three days postoperatively. More than 700 blood samples were collected from 50 patients at nine time points pre-, intra-, and postoperatively...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28069778/differential-contribution-of-subunit-interfaces-to-%C3%AE-9%C3%AE-10-nicotinic-acetylcholine-receptor-function
#5
Juan C Boffi, Irina Marcovich, JasKiran K Gill-Thind, Jeremias Corradi, Toby Collins, Maria M Lipovsek, Marcelo Moglie, Paola V Plazas, Patricio O Craig, Neil S Millar, Cecilia Bouzat, Ana Belen Elgoyhen
Nicotinic acetylcholine receptors can be assembled from either homomeric or heteromeric pentameric subunit combinations. At the interface of the extracellular domains of adjacent subunits lies the acetylcholine binding site, composed of a principal component provided by one subunit and a complementary component of the adjacent subunit. Compared to neuronal nAChRs assembled from α and β subunits, the α9α10 receptor is an atypical member of the family. It is a heteromeric receptor composed only of α subunits...
January 9, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28056803/de-novo-transcriptome-and-expression-profile-analyses-of-the-asian-corn-borer-ostrinia-furnacalis-reveals-relevant-flubendiamide-response-genes
#6
Li Cui, Changhui Rui, Daibin Yang, Zhenying Wang, Huizhu Yuan
BACKGROUND: The Asian corn borer (ACB), Ostrinia furnacalis (Guenée), has become the most damaging insect pest of corn in Asia. However, the lack of genome or transcriptome information heavily hinders our further understanding of ACB in every aspect at a molecular level and on a genome-wide scale. Here, we used the Ion Torrent Personal Genome Machine (PGM) Sequencer to explore the ACB transcriptome and to identify relevant genes in response to flubendiamide, showing high selective activity against ACB...
January 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28055974/glutamate-induces-autophagy-via-the-two-pore-channels-in-neural-cells
#7
Gustavo J S Pereira, Manuela Antonioli, Hanako Hirata, Rodrigo P Ureshino, Aline R Nascimento, Claudia Bincoletto, Tiziana Vescovo, Mauro Piacentini, Gian Maria Fimia, Soraya S Smaili
NAADP (nicotinic acid adenine dinucleotide phosphate) has been proposed as a second messenger for glutamate in neuronal and glial cells via the activation of the lysosomal Ca2+ channels TPC1 and TPC2. However, the activities of glutamate that are mediated by NAADP remain unclear. In this study, we evaluated the effect of glutamate on autophagy in astrocytes at physiological, non-toxic concentration. We found that glutamate induces autophagy at similar extent as NAADP. By contrast, the NAADP antagonist NED-19 or SiRNA-mediated inhibition of TPC1/2 decreases autophagy induced by glutamate, confirming a role for NAADP in this pathway...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28044208/hepatic-vagus-nerve-regulates-kupffer-cell-activation-via-%C3%AE-7-nicotinic-acetylcholine-receptor-in-nonalcoholic-steatohepatitis
#8
Takahiro Nishio, Kojiro Taura, Keiko Iwaisako, Yukinori Koyama, Kazutaka Tanabe, Gen Yamamoto, Yukihiro Okuda, Yoshinobu Ikeno, Kenji Yoshino, Yosuke Kasai, Masayuki Okuno, Satoru Seo, Takaki Sakurai, Masataka Asagiri, Etsuro Hatano, Shinji Uemoto
BACKGROUND: Nonalcoholic fatty liver disease ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Kupffer cells play a central role in promoting hepatic inflammation, which leads to the development of NASH. We investigated the anti-inflammatory effect of hepatic vagus-mediated stimulation of the α7 nicotinic acetylcholine receptor (α7nAChR) on Kupffer cells in NASH pathogenesis. METHODS: Wild-type (WT) mice undergoing hepatic vagotomy (HV) were fed a methionine- and choline-deficient (MCD) diet for 1 week...
January 2, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28042540/melissa-officinalis-acidic-fraction-protects-cultured-cerebellar-granule-neurons-against-beta-amyloid-induced-apoptosis-and-oxidative-stress
#9
Maliheh Soodi, Abolfazl Dashti, Homa Hajimehdipoor, Shole Akbari, Nasim Ataei
OBJECTIVE: Extracellular deposition of the beta-amyloid (Aβ) peptide, which is the main finding in the pathophysiology of Alzheimer's disease (AD), leads to oxidative damage and apoptosis in neurons. Melissa officinalis (M. officinalis) is a medicinal plant from the Lamiaceae family that has neuroprotective activity. In the present study we have investigated the protective effect of the acidic fraction of M. officinalis on Aβ-induced oxidative stress and apoptosis in cultured cerebellar granule neurons (CGN)...
2017: Cell Journal
https://www.readbyqxmd.com/read/28018295/combined-whole-cell-high-throughput-functional-screening-for-identification-of-new-nicotinamidases-pyrazinamidases-in-metagenomic-polygenomic-libraries
#10
Rubén Zapata-Pérez, Antonio G García-Saura, Mohamed Jebbar, Peter N Golyshin, Álvaro Sánchez-Ferrer
Nicotinamidases catalyze the hydrolysis of the amide bond in nicotinamide (NAM) to produce ammonia and nicotinic acid (NA). These enzymes are an essential component of the NAD(+) salvage pathway and are implicated in the viability of several pathogenic organisms. Its absence in humans makes them a promising drug target. In addition, although they are key analytical biocatalysts for screening modulators in relevant biomedical enzymes, such as sirtuins and poly-ADP-ribosyltransferases, no commercial sources are available...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28018117/single-drop-electroanalysis-and-interfacial-interactions-sensitivity-versus-limit-of-detection-%C3%A2
#11
Charuksha Walgama, Matthew Gallman, Sadagopan Krishnan
We report single drop electroanalytical measurements of pharmaceutically and biologically relevant compounds using screen printed electrodes (SPEs) modified with carboxylated multiwalled carbon nanotubes (MWCNT-COOH) as the sensor surface. Acetaminophen, nicotine, ascorbic acid, and nicotinamide adenine dinucleotide reduced form (NADH) were detected in a single drop of solution. We show that combined polar and nonpolar interactions of analytes with -COOH functional groups and large surface area of MWCNT, respectively, allow highly sensitive analyte detection with wide dynamic range...
November 2016: Electroanalysis
https://www.readbyqxmd.com/read/28008281/nicoboxil-nonivamide-cream-effectively-and-safely-reduces-acute-nonspecific-low-back-pain-a-randomized-placebo-controlled-trial
#12
Zuzana Blahova, Janina Claudia Holm, Thomas Weiser, Erika Richter, Matthias Trampisch, Elena Akarachkova
BACKGROUND/OBJECTIVE: Low back pain affects many patients and has a high socioeconomic impact. Topical capsaicinoids have been used for decades to treat musculoskeletal pain. This study investigated the effects of the fixed dose combination (FDC) of nonivamide (a capsaicinoid) and nicoboxil (a nicotinic acid ester) cream in the treatment of acute nonspecific low back pain. MATERIALS AND METHODS: This phase III randomized, double-blind, placebo-controlled, multinational, multi-center trial investigated efficacy, safety, and tolerability of topical nicoboxil 1...
2016: Journal of Pain Research
https://www.readbyqxmd.com/read/27997162/carbohydrate-neuroactive-hybrid-strategy-for-metabolic-glycan-engineering-of-the-central-nervous-system-in-vivo
#13
Asif Shajahan, Shubham Parashar, Surbhi Goswami, Syed Meheboob Ahmed, Perumal Nagarajan, Srinivasa-Gopalan Sampathkumar
Sialic acids are abundant in the central nervous system (CNS) and are essential for brain development, learning, and memory. Dysregulation in biosynthesis of sialo-glycoconjugates is known to be associated with neurological disorders, CNS injury, and brain cancer. Metabolic glycan engineering (MGE) and bioorthogonal ligation have enabled study of biological roles of glycans in vivo; however, direct investigations of sialoglycans in brain have been intractable. We report a simple strategy utilizing carbohydrate-neuroactive hybrid (CNH) molecules, which exploit carrier-mediated transport systems available at the blood-brain barrier, to access brain via tail vein injection in mice...
January 5, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27987880/structural-elucidation-and-immunostimulating-property-of-a-novel-polysaccharide-extracted-from-an-edible-mushroom-lentinus-fusipes
#14
Dilip K Manna, Prasenjit Maity, Ashis K Nandi, Manabendra Pattanayak, Bibhash C Panda, Amit K Mandal, Satyajit Tripathy, Krishnendu Acharya, Atish K Sahoo, Nibha Gupta, Somnath Roy, Syed S Islam
A water soluble heteroglycan (PS-II) with an average molecular weight∼60kDa was isolated from the hot aqueous extract of an edible mushroom Lentinus fusipes. The structural characterization of PS-II was carried out using total acid hydrolysis, methylation analyses, periodate oxidation, Smith degradation and 1D/2D NMR experiments. Total acid hydrolysis indicated the presence of D-galactose and D-glucose in a molar ratio of approximately 1:1. The chemical and NMR analyses revealed that the proposed repeating unit of the PS-II had a backbone chain consisting of three (1→6)-linked α-d-galactopyranosyl residue and two (1→6)-linked β-d-glucopyranosyl residues, one of the β-d-glucopyranosyl residue was branched at O-3 position with a terminal β-d-glucopyranosyl...
February 10, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/27984041/structural-and-functional-characterization-of-plasmodium-falciparum-nicotinic-acid-mononucleotide-adenylyltransferase
#15
Jochen Bathke, Karin Fritz-Wolf, Christina Brandstädter, Anja Burkhardt, Esther Jortzik, Stefan Rahlfs, Katja Becker
Nicotinic acid mononucleotide adenylyltransferase (NaMNAT) is an indispensable enzyme for the synthesis of NAD and NADP. It catalyzes the adenylylation of nicotinic acid mononucleotide (NaMN) to yield nicotinic acid adenine dinucleotide (NaAD). Since NAD(H) and NADP(H) are essentially involved in metabolic and redox regulatory reactions, NaMNAT is an attractive drug target in the fight against bacterial and parasitic infections. Notably, NaMNAT of the malaria parasite Plasmodium falciparum possesses only 20% sequence identity with the homologous human enzyme...
October 27, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27983781/one-shot-in-vitro-evolution-generated-an-antibody-fragment-for-testing-urinary-cotinine-with-more-than-40-fold-enhanced-affinity
#16
Hiroyuki Oyama, Izumi Morita, Yuki Kiguchi, Erika Banzono, Kasumi Ishii, Satoshi Kubo, Yoshiro Watanabe, Anna Hirai, Chiaki Kaede, Mitsuhiro Ohta, Norihiro Kobayashi
Immunoassays for cotinine, a major nicotine metabolite, in the urine are useful for monitoring the degree of tobacco smoke exposure. However, hybridoma-based anti-cotinine antibodies lack sufficient binding affinity to perform practically sensitive measurements, and thus most cotinine assays still rely on polyclonal antibodies. Here, we describe the generation of a mutant single-chain Fv fragment (scFv) that was used in an enzyme-linked immunosorbent assay (ELISA) to determine urinary cotinine levels in passive smokers...
December 16, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27966953/scalable-one-pot-microwave-accelerated-tandem-synthesis-of-unsymmetrical-urea-derivatives
#17
Abhijit R Kulkarni, Sumanta Garai, Ganesh A Thakur
We report a facile, microwave-accelerated, one-pot tandem synthesis of unsymmetrical ureas via a Curtius rearrangement. In this method, one-pot microwave irradiation of commercially available (hetero)aromatic acids and amines in the presence of diphenylphosphoryl azide enabled extremely rapid (1-5 min) construction of an array of unsymmetrical ureas in good to excellent yields. We demonstrate the utility of our method in the efficient, gram-scale synthesis of key biologically active compounds targeting the cannabinoid 1 and α7 nicotinic acetylcholine receptors...
December 30, 2016: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/27941121/a-novel-copolymer-based-functional-spect-mr-imaging-agent-for-asialoglycoprotein-receptor-targeting
#18
Pu Zhang, Zhide Guo, Deliang Zhang, Chang Liu, Guibing Chen, Rongqiang Zhuang, Manli Song, Hua Wu, Xianzhong Zhang
The aim of this study is to develop a copolymer-based single-photon emission computed tomography/magnetic resonance (SPECT/MR) dual-modality imaging agent that can be labeled with both technetium-99m ((99m)Tc) and gadolinium (Gd) and target asialoglycoprotein receptor (ASGPR) via galactose. Monomers of N-p-vinylbenzyl-6-(2-(4-dimethylamino)benzaldehydehydrazono) nicotinate (VNI) for labeling of (99m)Tc, 5,8-bis(carboxymethyl)-3-oxo-11-(2-oxo-2-((4-vinylbenzyl)amino)ethyl)-1-(4-vinylphenzyl)-2,5,8,11-tetraazatridecan-13-oic acid (V2DTPA) for labeling of Gd, and vinylbenzyl-O-β-d-galactopyranosyl-d-gluconamide (VLA) for targeting ASGPR were synthesized, respectively...
2016: Molecular Imaging
https://www.readbyqxmd.com/read/27940344/melatonin-influences-no-nos-pathway-and-reduces-oxidative-and-nitrosative-stress-in-a-model-of-hypoxic-ischemic-brain-damage
#19
Santos Blanco, Raquel Hernández, Gustavo Franchelli, Manuel Miguel Ramos-Álvarez, María Ángeles Peinado
In this work, using a rat model combining ischemia and hypobaric hypoxia (IH), we evaluate the relationships between the antioxidant melatonin and the cerebral nitric oxide/nitric oxide synthase (NO/NOS) system seeking to ascertain whether melatonin exerts its antioxidant protective action by balancing this key pathway, which is highly involved in the cerebral oxidative and nitrosative damage underlying these pathologies. The application of the IH model increases the expression of the three nitric oxide synthase (NOS) isoforms, as well as nitrogen oxide (NOx) levels and nitrotyrosine (n-Tyr) impacts on the cerebral cortex...
January 30, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/27939939/cd38-in-the-pathogenesis-of-allergic-airway-disease-potential-therapeutic-targets
#20
REVIEW
Deepak A Deshpande, Alonso G P Guedes, Frances E Lund, Subbaya Subramanian, Timothy F Walseth, Mathur S Kannan
CD38 is an ectoenzyme that catalyzes the conversion of β-nicotinamide adenine dinucleotide (β-NAD) to cyclic adenosine diphosphoribose (cADPR) and adenosine diphosphoribose (ADPR) and NADP to nicotinic acid adenine dinucleotide phosphate (NAADP) and adenosine diphosphoribose-2'-phosphate (ADPR-P). The metabolites of NAD and NADP have roles in calcium signaling in different cell types including airway smooth muscle (ASM) cells. In ASM cells, inflammatory cytokines augment CD38 expression and to a greater magnitude in cells from asthmatics, indicating a greater capacity for the generation of cADPR and ADPR in ASM from asthmatics...
December 7, 2016: Pharmacology & Therapeutics
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