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https://www.readbyqxmd.com/read/27936457/genetic-disruption-of-nrf2-promotes-the-development-of-necroinflammation-and-liver-fibrosis-in-a-mouse-model-of-hfe-hereditary-hemochromatosis
#1
Tiago L Duarte, Carolina Caldas, Ana G Santos, Sandro Silva-Gomes, Andreia Santos-Gonçalves, Maria João Martins, Graça Porto, José Manuel Lopes
BACKGROUND AND AIMS: In hereditary hemochromatosis, iron deposition in the liver parenchyma may lead to fibrosis, cirrhosis and hepatocellular carcinoma. Most cases are ascribed to a common mutation in the HFE gene, but the extent of clinical expression is greatly influenced by the combined action of yet unidentified genetic and/or environmental modifying factors. In mice, transcription factor NRF2 is a critical determinant of hepatocyte viability during exposure to acute dietary iron overload...
December 1, 2016: Redox Biology
https://www.readbyqxmd.com/read/27936239/a-broad-spectrum-chemokine-binding-protein-of-bovine-papular-stomatitis-virus-inhibits-neutrophil-and-monocyte-infiltration-in-inflammatory-and-wound-models-of-mouse-skin
#2
Saeed Sharif, Yoshio Nakatani, Lyn Wise, Michael Corbett, Nicola C Real, Gabriella S Stuart, Zabeen Lateef, Kurt Krause, Andrew A Mercer, Stephen B Fleming
Bovine papular stomatitis virus (BPSV) is a Parapoxvirus that induces acute pustular skin lesions in cattle and is transmissible to humans. Previous studies have shown that BPSV encodes a distinctive chemokine-binding protein (CBP). Chemokines are critically involved in the trafficking of immune cells to sites of inflammation and infected tissue, suggesting that the CBP plays a role in immune evasion by preventing immune cells reaching sites of infection. We hypothesised that the BPSV-CBP binds a wide range of inflammatory chemokines particularly those involved in BPSV skin infection, and inhibits the recruitment of immune cells from the blood into inflamed skin...
2016: PloS One
https://www.readbyqxmd.com/read/27936173/insights-into-basal-signaling-regulation-oligomerization-and-structural-organization-of-the-human-g-protein-coupled-receptor-83
#3
Anne Müller, Julia Catherine Berkmann, Patrick Scheerer, Heike Biebermann, Gunnar Kleinau
The murine G-protein coupled receptor 83 (mGPR83) is expressed in the hypothalamus and was previously suggested to be involved in the regulation of metabolism. The neuropeptide PEN has been recently identified as a potent GPR83 ligand. Moreover, GPR83 constitutes functionally relevant hetero-oligomers with other G-protein coupled receptors (GPCR) such as the ghrelin receptor (GHSR) or GPR171. Previous deletion studies also revealed that the long N-terminal extracellular receptor domain (eNDo) of mGPR83 may act as an intra-molecular ligand, which participates in the regulation of basal signaling activity, which is a key feature of GPCR function...
2016: PloS One
https://www.readbyqxmd.com/read/27935481/structure-of-the-transporter-associated-with-antigen-processing-trapped-by-herpes-simplex-virus
#4
Michael L Oldham, Nikolaus Grigorieff, Jue Chen
The transporter associated with antigen processing (TAP) is an ATP-binding cassette (ABC) transporter essential to cellular immunity against viral infection. Some persistent viruses have evolved strategies to inhibit TAP so that they may go undetected by the immune system. The herpes simplex virus for example evades immune surveillance by blocking peptide transport with a small viral protein ICP47. In this study, we determined the structure of human TAP bound to ICP47 by electron cryo-microscopy (cryo-EM) to 4...
December 9, 2016: ELife
https://www.readbyqxmd.com/read/27935260/in-vitro-studies-on-flubromazolam-metabolism-and-detection-of-its-metabolites-in-authentic-forensic-samples
#5
Carolina Noble, Marie Mardal, Niels Bjerre Holm, Sys Stybe Johansen, Kristian Linnet
Flubromazolam is a triazole benzodiazepine with high potency and long-lasting central nervous system depressant effects; however, limited data about its pharmacokinetics are available. Here, we report in vitro studies of the human flubromazolam metabolism analyzed by liquid chromatography high-resolution mass spectrometry (LC-HRMS). In vitro investigations were carried out in pooled human liver microsomes (pHLM) and recombinant cytochrome P450 (CYP)-enzymes. To confirm those metabolites detected in vitro, authentic samples obtained from two forensic cases were also analyzed by LC-HRMS...
December 9, 2016: Drug Testing and Analysis
https://www.readbyqxmd.com/read/27934969/quantitative-hdl-proteomics-identifies-peroxiredoxin-6-as-a-biomarker-of-human-abdominal-aortic-aneurysm
#6
Elena Burillo, Inmaculada Jorge, Diego Martínez-López, Emilio Camafeita, Luis Miguel Blanco-Colio, Marco Trevisan-Herraz, Iakes Ezkurdia, Jesús Egido, Jean-Baptiste Michel, Olivier Meilhac, Jesús Vázquez, Jose Luis Martin-Ventura
High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma)...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27934311/a-switch-on-nir-probe-for-specific-detection-of-hg-2-ion-in-aqueous-medium-and-in-mitochondria
#7
Hridesh Agarwalla, Pankaj S Mahajan, Debashis Sahu, Nandaraj Taye, Bishwajit Ganguly, Santosh B Mhaske, Samit Chattopadhyay, Amitava Das
A new 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based probe molecule (L) is synthesized for specific binding to Hg(2+) ion in physiological condition with an associated luminescence ON response in the near-IR region of the spectrum. Appropriate functionalization in the 5-position of each of two pyrrole moieties with styryl functionality in a BODIPY core helped us in achieving the extended conjugation and a facile intramolecular charge transfer transition with a narrow energy gap for frontier orbitals...
November 21, 2016: Inorganic Chemistry
https://www.readbyqxmd.com/read/27934299/interaction-of-the-hiv-ncp7-protein-with-platinum-ii-and-gold-iii-complexes-containing-tridentate-ligands
#8
Victor H F Bernardes, Yun Qu, Zhifeng Du, James Beaton, Maria D Vargas, Nicholas P Farrell
The human immunodeficiency virus (HIV) nucleocapsid protein (NCp7) plays significant roles in the virus life cycle and has been targeted by compounds that could lead to its denaturation or block its interaction with viral RNA. Herein, we describe the interactions of platinum(II) and gold(III) complexes with NCp7 and how the reactivity/affinity of potential inhibitors can be modulated by judicious choice of ligands. The interactions of [MCl(N3)](n+) (M = Pt(2+) (n = 1) and Au(3+) (n = 2); N3 = tridentate chelate ligands: bis(2-pyridylmethyl)methylamine (Mebpma, L(1)) and bis(2-pyridylmethyl)amine (bpma, L(2)) with the C-terminal zinc finger of NCp7 (ZF2) were investigated by electrospray ionization-mass spectroscopy (ESI-MS)...
November 7, 2016: Inorganic Chemistry
https://www.readbyqxmd.com/read/27934222/probing-the-local-secondary-structure-of-human-vimentin-with-electron-spin-echo-envelope-modulation-eseem-spectroscopy
#9
Lishan Liu, John Hess, Indra D Sahu, Paul G FitzGerald, Robert M McCarrick, Gary A Lorigan
Previously, an electron spin echo envelope modulation (ESEEM) spectroscopic approach was established to probe the local secondary structure of membrane proteins and peptides utilizing site-directed spin-labeling (SDSL). In this method, the side chain of one amino acid residue is selectively (2)H-labeled and a nitroxide spin label is strategically placed 1, 2, 3, or 4 amino acids away from the (2)H-labeled amino acid (denoted as i ± 1 to i ± 4, i represents the (2)H-labeled amino acid). ESEEM can detect the dipolar coupling between the nitroxide spin label and (2)H atoms on the amino acid side chain...
December 8, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27933948/discovery-of-the-3-imino-1-2-4-thiadiazinane-1-1-dioxide-derivative-verubecestat-mk-8931-a-%C3%AE-site-amyloid-precursor-protein-cleaving-enzyme-1-inhibitor-for-the-treatment-of-alzheimer-s-disease
#10
Jack D Scott, Sarah W Li, Andrew P J Brunskill, Xia Chen, Kathleen Cox, Jared N Cumming, Mark Forman, Eric J Gilbert, Robert A Hodgson, Lynn A Hyde, Qin Jiang, Ulrich Iserloh, Irina Kazakevich, Reshma Kuvelkar, Hong Mei, John Meredith, Jeffrey Misiaszek, Peter Orth, Lana M Rossiter, Meagan Slater, Julie Stone, Corey O Strickland, Johannes H Voigt, Ganfeng Wang, Hongwu Wang, Yusheng Wu, William J Greenlee, Eric M Parker, Matthew E Kennedy, Andrew W Stamford
Verubecestat 3 (MK-8931), a diaryl amide-substituted 3-imino-1,2,4-thiadiazinane 1,1-dioxide derivative, is a high-affinity β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor currently undergoing Phase 3 clinical evaluation for the treatment of mild to moderate and prodromal Alzheimer's disease. Although not selective over the closely related aspartyl protease BACE2, verubecestat has high selectivity for BACE1 over other key aspartyl proteases, notably cathepsin D, and profoundly lowers CSF and brain Aβ levels in rats and nonhuman primates and CSF Aβ levels in humans...
December 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27933947/in-silico-discovery-and-validation-of-amide-based-small-molecule-targeting-the-enzymatic-site-of-shiga-toxin
#11
Vinita Chauhan, Dilip Chaudhary, Uma Pathak, Nandita Saxena, Ram Kumar Dhaked
Shiga toxin (Stx), a category B biothreat agent, is a ribosome inactivating protein and toxic to human and animals. Here, we designed and synthesized small molecules that block the active site of the Stx A subunit. On the basis of binding energy, 20 molecules were selected for synthesis and evaluation. These molecules were primarily screened using fluorescence-based thermal shift assay and in vitro in Vero cells. Among 32 molecules (including 12 reported), six molecules offered protection with IC50 of 2.60-23...
December 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27933797/nuclear-magnetic-resonance-and-molecular-dynamics-simulation-of-the-interaction-between-recognition-protein-h7-of-the-novel-influenza-virus-h7n9-and-glycan-cell-surface-receptors
#12
Eleonora Macchi, Timothy R Rudd, Rahul Raman, Ram Sasisekharan, Edwin A Yates, Annamaria Naggi, Marco Guerrini, Stefano Elli
Avian influenza A viruses, which can also propagate between humans, present serious pandemic threats, particularly in Asia. The specificity (selectivity) of interactions between the recognition protein hemagglutinin (HA) of the virus capsid and the glycoconjugates of host cells also contributes to the efficient spread of the virus by aerosol between humans. Some avian origin viruses, such as H1N1 (South Carolina 1918), have improved their selectivity for human receptors by mutation in the HA receptor binding site, to generate pandemic viruses...
December 6, 2016: Biochemistry
https://www.readbyqxmd.com/read/27933733/mannich-bases-of-1-2-4-triazole-3-thione-containing-adamantane-moiety-synthesis-preliminary-anticancer-evaluation-and-molecular-modeling-studies
#13
Milorad Z Milošev, Katarina Jakovljević, Milan D Joksović, Tatjana Stanojković, Ivana Z Matić, Milka Perović, Vesna Tešić, Selma Kanazir, Milan Mladenović, Marko V Rodić, Vukadin M Leovac, Snežana Trifunović, Violeta Marković
A series of 18 novel N-Mannich bases derived from 5-adamantyl-1,2,4-triazole-3-thione was synthesized and characterized using NMR spectroscopy and X-ray diffraction technique. All derivatives were evaluated for their anticancer potential against four human cancer cell lines. Several tested compounds exerted good cytotoxic activities on K562 and HL-60 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal fibroblasts MRC-5 compared to cancer cells. The effects of compounds 5b, 5e and 5j on the cell cycle were investigated by flow cytometric analysis...
December 9, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27933510/anti-fibrotic-effects-of-salvia-miltiorrhiza-and-ligustrazine-injection-on-lx-2-cells-involved-with-increased-n-myc-downstream-regulated-gene-2-expression
#14
Jin Zheng, Li-Tian Ma, Qin-You Ren, Yue Hu, Yang Bai, Huan Bian, Yi Zhang, Yong-Chun Zhou, Ming-Hui Yang
OBJECTIVE: To investigate the effects of Salvia miltiorrhiza and Ligustrazine Injection (SML) on proliferation and apoptosis of human hepatic stellate cell LX-2 and the expression of N-myc downstream-regulated gene 2 (NDRG2, a tumor suppressor gene). METHODS: HSCs from the LX-2 cell line were cultured in vitro. The proliferative state of different initial LX-2 cell numbers was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay...
December 8, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27933445/correlation-of-crevicular-fluid-and-serum-levels-of-retinol-binding-protein-4-and-leptin-in-chronic-periodontitis-and-obesity
#15
Dharmendra Kanoriya, A R Pradeep, A Mallika, Sandeep Singhal, Vibhuti Garg
OBJECTIVE: Retinol-binding protein 4 (RBP4) and leptin are both adipokines and involved in the pathophysiology of different vascular and inflammatory diseases and selectively elevated in patients with obesity. The aim of the present study was to determine and correlate the levels of RBP4 and leptin in gingival crevicular fluid (GCF) and serum in patients with chronic periodontitis (CP) and obesity. MATERIALS AND METHODS: A total of 70 patients with age group 25 to 45 years were divided into four groups based on gingival index (GI), probing depth (PD), clinical attachment level (CAL), body mass index (BMI) and radiographic evidence of bone loss...
December 8, 2016: Clinical Oral Investigations
https://www.readbyqxmd.com/read/27933331/characterization-of-arsenic-biotransformation-by-a-typical-bryophyte-physcomitrella-patens
#16
Xixiang Yin, Lihong Wang, Yifei Liu, Tenglong Jiang, Jianwei Gao
Arsenic (As) is a ubiquitous environmental toxin that has created catastrophic human health and environmental problems around world. Physcomitrella patens is a potential model plant for the study of environmental monitoring, which exists in all kinds of ecosystems. In this study, arsenic metabolism was investigated by this moss. When supplied with different levels of arsenate (50, 100, 200 µmol/L) for a 4-week period, the total arsenic concentrations were up to 231.4-565.4 mg/kg DW in this moss. Arsenite concentration increased with increasing external arsenate concentrations, the proportion was up to 25...
December 8, 2016: Bulletin of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/27933184/coxsackie-adenovirus-receptor-expression-is-enhanced-in-pancreas-from-patients-with-type-1-diabetes
#17
M Hodik, M Anagandula, J Fuxe, L Krogvold, K Dahl-Jørgensen, H Hyöty, L Sarmiento, G Frisk
OBJECTIVES: One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie-adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. DESIGN: Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals...
2016: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/27933092/effects-of-purified-anthocyanin-supplementation-on-platelet-chemokines-in-hypocholesterolemic-individuals-a-randomized-controlled-trial
#18
Xiandan Zhang, Yanna Zhu, Fenglin Song, Yanling Yao, Fuli Ya, Dan Li, Wenhua Ling, Yan Yang
BACKGROUND: It is becoming increasingly evident that platelet chemokines are involved in distinct aspects of atherosclerosis. The aim of this study was to examine the effects of long-term supplementation with purified anthocyanins on platelet chemokines in hypercholesterolemic individuals and to identify correlations of decreased platelet chemokine levels with serum lipid and inflammatory marker levels. METHODS: A total of 146 hypercholesterolemic individuals were recruited and treated with 320 mg of purified anthocyanins (n = 73) or a placebo (n = 73) daily for 24 weeks in this randomized, double-blind, placebo-controlled trial...
2016: Nutrition & Metabolism
https://www.readbyqxmd.com/read/27932980/tnf-%C3%AE-induced-cpla2-expression-via-nadph-oxidase-reactive-oxygen-species-dependent-nf-%C3%AE%C2%BAb-cascade-on-human-pulmonary-alveolar-epithelial-cells
#19
Chih-Chung Lin, Wei-Ning Lin, Rou-Ling Cho, Chen-Yu Wang, Li-Der Hsiao, Chuen-Mao Yang
Tumor necrosis factor-α (TNF-α) triggers activation of cytosolic phospholipase A2 (cPLA2) and then enhancing the synthesis of prostaglandin (PG) in inflammatory diseases. However, the detailed mechanisms of TNF-α induced cPLA2 expression were not fully defined in human pulmonary alveolar epithelial cells (HPAEpiCs). We found that TNF-α-stimulated increases in cPLA2 mRNA (5.2 folds) and protein (3.9 folds) expression, promoter activity (4.3 folds), and PGE2 secretion (4.7 folds) in HPAEpiCs, determined by Western blot, real-time PCR, promoter activity assay and PGE2 ELISA kit...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27932973/decline-in-proliferation-and-immature-neuron-markers-in-the-human-subependymal-zone-during-aging-relationship-to-egf-and-fgf-related-transcripts
#20
Christin Weissleder, Samantha J Fung, Matthew W Wong, Guy Barry, Kay L Double, Glenda M Halliday, Maree J Webster, Cynthia Shannon Weickert
Neuroblasts exist within the human subependymal zone (SEZ); however, it is debated to what extent neurogenesis changes during normal aging. It is also unknown how precursor proliferation may correlate with the generation of neuronal and glial cells or how expression of growth factors and receptors may change throughout the adult lifespan. We found evidence of dividing cells in the human SEZ (n D 50) in conjunction with a dramatic age-related decline (21-103 years) of mRNAs indicative of proliferating cells (Ki67) and immature neurons (doublecortin)...
2016: Frontiers in Aging Neuroscience
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