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https://www.readbyqxmd.com/read/28528363/caffeic-acid-phenethyl-ester-is-protective-in-experimental-ulcerative-colitis-via-reduction-in-levels-of-pro-inflammatory-mediators-and-enhancement-of-epithelial-barrier-function
#1
Mohammed N Khan, Majella E Lane, Paul A McCarron, Murtaza M Tambuwala
BACKGROUND: Inhibition of the nuclear factor kappa beta (NF-κβ) pathway has been proposed as a therapeutic target due to its key role in the expression of pro-inflammatory genes, including pro-inflammatory cytokines, chemokines, and adhesion molecules. Caffeic acid phenethyl ester (CAPE) is a naturally occurring anti-inflammatory agent, found in propolis, and has been reported as a specific inhibitor of NF-κβ. However, the impact of CAPE on levels of myeloperoxidases (MPO) and pro-inflammatory cytokines during inflammation is not clear...
May 20, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28528324/new-role-for-interleukin-13-receptor-%C3%AE-1-in-myocardial-homeostasis-and-heart-failure
#2
Uri Amit, David Kain, Allon Wagner, Avinash Sahu, Yael Nevo-Caspi, Nir Gonen, Natali Molotski, Tal Konfino, Natalie Landa, Nili Naftali-Shani, Galia Blum, Emmanuelle Merquiol, Danielle Karo-Atar, Yariv Kanfi, Gidi Paret, Ariel Munitz, Haim Y Cohen, Eytan Ruppin, Sridhar Hannenhalli, Jonathan Leor
BACKGROUND: The immune system plays a pivotal role in myocardial homeostasis and response to injury. Interleukins-4 and -13 are anti-inflammatory type-2 cytokines, signaling via the common interleukin-13 receptor α1 chain and the type-2 interleukin-4 receptor. The role of interleukin-13 receptor α1 in the heart is unknown. METHODS AND RESULTS: We analyzed myocardial samples from human donors (n=136) and patients with end-stage heart failure (n=177). We found that the interleukin-13 receptor α1 is present in the myocardium and, together with the complementary type-2 interleukin-4 receptor chain Il4ra, is significantly downregulated in the hearts of patients with heart failure...
May 20, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28528185/simvastatin-ameliorate-memory-deficits-and-inflammation-in-clinical-and-mouse-model-of-alzheimer-s-disease-via-modulating-the-expression-of-mir-106b
#3
Wenzhong Huang, Zhenyu Li, Liandong Zhao, Wei Zhao
BACKGROUND: Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, and several studies have shown that AD is closely related to the inflammation, so anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of simvastatin on inflammation was investigated and the underlying mechanisms were explored. METHODS: First, we tested the effect of simvastatin on AD in clinical research...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28527810/hif-1%C3%AE-stabilizing-agent-fg-4997-rescues-human-cd34-cell-mobilization-in-response-to-g-csf-in-immuno-deficient-mice
#4
Bianca Nowlan, Katarzyna Futrega, Marion E Brunck, Gail Walkinshaw, Lee E Flippin, Michael R Doran, Jean-Pierre Levesque
Granulocyte colony-stimulating factor (G-CSF) is routinely used in the clinic to mobilize hematopoietic stem progenitor cells (HSPC) into the patient's blood for collection and subsequent transplantation. However a significant proportion of patients who have previously received chemotherapy or radiotherapy and requiring autologous HSPC transplantation, cannot mobilize the minimal threshold of mobilized HSPC to achieve rapid and successful hematopoietic reconstitution. Although several alternatives to the G-CSF regime have been tested, few are in use in the clinic...
May 17, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28527698/non-diaphanous-formin-delphilin-acts-as-a-barbed-end-capping-protein
#5
Priyanka Dutta, Swagata Das, Sankar Maiti
Formins are multi domain protein present ubiquitously in all eukaryotes from lower fungi to higher vertebrates. Formins are characterized by the presence of formin homology domain-2 (FH2) and formin homology domain-1 (FH1). There are fifteen different formins present in mouse and human. Among these metazoan formins Delphilin is a unique formin having two PDZ domains at the N-terminal and FH1, FH2 domain at the C-terminus respectively. In this study we observed that Delphilin binds to actin filaments, and Delphilin inhibits actin filament elongation like barbed end capping protein CapZ...
May 17, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28527664/a-new-hdv-mouse-model-identifies-mitochondrial-antiviral-signaling-protein-mavs-as-a-key-player-in-ifn-%C3%AE-induction
#6
Lester Suárez-Amarán, Carla Usai, Marianna Di Scala, Cristina Godoy, Yi Ni, Mirja Hommel, Laura Palomo, Víctor Segura, Cristina Olagüe, Africa Vales, Alicia Ruiz-Ripa, Maria Buti, Eduardo Salido, Jesús Prieto, Stephan Urban, Francisco Rodríguez-Frias, Rafael Aldabe, Gloria González-Aseguinolaza
BACKGROUND & AIMS: Studying hepatitis delta virus (HDV) and developing new treatments is hampered by the limited availability of small animal models. Here a description of a robust mouse model of HDV infection that mimics several important characteristics of the human disease is presented. METHODS: HDV- and HBV-replication competent genomes were delivered to the mouse liver using adeno-associated viruses (AAV) (AAV-HDV and AAV-HBV). Viral load, antigen expression and genomes were quantified at different time points after AAV injection...
May 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28527575/coup-tf-genes-human-diseases-and-the-development-of-the-central-nervous-system-in-murine-models
#7
Xiong Yang, Su Feng, Ke Tang
COUP-TFI and -TFII are members of the steroid/thyroid nuclear receptor superfamily. Recent clinical studies reveal that COUP-TFI gene mutations are associated with Bosch-Boonstra-Schaaf optic atrophy syndrome displaying symptoms of optic atrophy, intellectual disability, hypotonia, seizure, autism spectrum disorders, oromotor dysfunction, thin corpus callosum, or hearing defects, and COUP-TFII gene mutations lead to congenital heart defects and/or congenital diaphragmatic hernia with developmental delay and mental defects...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28527569/estrogen-hormone-biology
#8
Katherine J Hamilton, Sylvia C Hewitt, Yukitomo Arao, Kenneth S Korach
The hormone estrogen is involved in both female and male reproduction, as well as numerous other biological systems including the neuroendocrine, vascular, skeletal, and immune systems. Therefore, it is also implicated in many different diseases and conditions such as infertility, obesity, osteoporosis, endometriosis, and a variety of cancers. Estrogen works through its two distinct nuclear receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). Various transcriptional regulation mechanisms have been identified as the mode of action for estrogen, mainly the classical mechanism with direct DNA binding but also a nongenomic mode of action and one using tethered or indirect binding...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28527208/neuronal-expression-of-truncated-tau-efficiently-promotes-neurodegeneration-in-animal-models-pitfalls-of-toxic-oligomer-analysis
#9
Rostislav Skrabana, Branislav Kovacech, Peter Filipcik, Norbert Zilka, Santosh Jadhav, Tomas Smolek, Eva Kontsekova, Michal Novak
Animal models of neurodegeneration induced by neuronal expression of truncated tau protein emerge as an important tool for understanding the pathogenesis of human tauopathies and for therapy development. Here we highlight common features of truncated tau models and make a critical assessment of possible pitfalls in their analysis. Particularly, the amount of soluble tau oligomers, which are suspected to be neurotoxic agents participating on the spreading of pathology inside the brain, may be overestimated due to a post-lysis oxidative tau oligomerization...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28527154/structure-based-classification-for-bile-salt-export-pump-bsep-inhibitors-using-comparative-structural-modeling-of-human-bsep
#10
Sankalp Jain, Melanie Grandits, Lars Richter, Gerhard F Ecker
The bile salt export pump (BSEP) actively transports conjugated monovalent bile acids from the hepatocytes into the bile. This facilitates the formation of micelles and promotes digestion and absorption of dietary fat. Inhibition of BSEP leads to decreased bile flow and accumulation of cytotoxic bile salts in the liver. A number of compounds have been identified to interact with BSEP, which results in drug-induced cholestasis or liver injury. Therefore, in silico approaches for flagging compounds as potential BSEP inhibitors would be of high value in the early stage of the drug discovery pipeline...
May 19, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28527011/the-prdm9-krab-domain-is-required-for-meiosis-and-involved-in-protein-interactions
#11
Yukiko Imai, Frédéric Baudat, Miguel Taillepierre, Marcello Stanzione, Attila Toth, Bernard de Massy
PR domain-containing protein 9 (PRDM9) is a major regulator of the localization of meiotic recombination hotspots in the human and mouse genomes. This role involves its DNA-binding domain, which is composed of a tandem array of zinc fingers, and PRDM9-dependent trimethylation of histone H3 at lysine 4. PRDM9 is a member of the PRDM family of transcription regulators, but unlike other family members, it contains a Krüppel-associated box (KRAB)-related domain that is predicted to be a potential protein interaction domain...
May 19, 2017: Chromosoma
https://www.readbyqxmd.com/read/28526807/dihydroartemisinin-induces-autophagy-dependent-death-in-human-tongue-squamous-cell-carcinoma-cells-through-dna-double-strand-break-mediated-oxidative-stress
#12
Xinli Shi, Li Wang, Xiaoming Li, Jing Bai, Jianchun Li, Shenghao Li, Zeming Wang, Mingrui Zhou
Dihydroartemisinin is an effective antimalarial agent with multiple biological activities. In the present investigation, we elucidated its therapeutic potential and working mechanism on human tongue squamous cell carcinoma (TSCC). It was demonstrated that dihydroartemisinin could significantly inhibit cell growth in a dose- and time-dependent manner by the Cell Counting Kit-8 and colony formation assay in vitro. Meanwhile, autophagy was promoted in the Cal-27 cells treated by dihydroartemisinin, evidenced by increased LC3B-II level, increased autophagosome formation, and increased Beclin-1 level compared to dihydroartemisinin-untreated cells...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28526770/therapeutic-ige-antibodies-harnessing-a-macrophage-mediated-immune-surveillance-mechanism-against-cancer
#13
REVIEW
Sophia N Karagiannis, Debra H Josephs, Heather J Bax, James F Spicer
IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surveillance and superior effector cell potency against cancer cells. In our recent article, we elaborate our proof-of-concept studies of a mouse/human chimeric IgE antibody (MOv18 IgE), which is specific for the cancer-associated antigen folate receptor alpha...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28526768/direct-comparison-of-the-enzymatic-characteristics-and-superoxide-production-of-the-four-aldehyde-oxidase-enzymes-present-in-mouse
#14
Gokhan Kucukgoze, Mineko Terao, Enrico Garattini, Silke Leimkuhler
Aldehyde oxidases (AOXs) are molybdoflavoenzymes with an important role in the metabolism and detoxification of heterocyclic compounds and aliphatic as well as aromatic aldehydes. The enzymes use oxygen as the terminal electron acceptor and produce reduced oxygen species during turnover. Four different enzymes, mAOX1, mAOX3, mAOX4 and mAOX2, which are the products of distinct genes, are present in the mouse. A direct and simultaneous comparison of the enzymatic properties and characteristics of the four enzymes has never been performed...
May 19, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28526683/autoreactivity-to-sulfatide-by-human-invariant-nkt-cells
#15
Annelein M Stax, Jessica Tuengel, Enrico Girardi, Naoki Kitano, Lenka L Allan, Victor Liu, Dongjun Zheng, William J Panenka, Joren Guillaume, Chi-Huey Wong, Serge van Calenbergh, Dirk M Zajonc, Peter van den Elzen
Invariant NKT (iNKT) cells are innate-like lymphocytes that recognize lipid Ags presented by CD1d. The prototypical Ag, α-galactosylceramide, strongly activates human and mouse iNKT cells, leading to the assumption that iNKT cell physiology in human and mouse is similar. In this article, we report the surprising finding that human, but not mouse, iNKT cells directly recognize myelin-derived sulfatide presented by CD1d. We propose that sulfatide is recognized only by human iNKT cells because of the unique positioning of the 3-O-sulfated β-galactose headgroup...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28526606/identification-of-emsox2-a-member-of-the-sox-family-of-transcription-factors-as-a-potential-regulator-of-echinococcus-multilocularis-germinative-cells
#16
Zhe Cheng, Fan Liu, Mengya Dai, Jianjian Wu, Xiu Li, Xinrui Guo, Huimin Tian, Zhijie Heng, Ying Lu, Xiaoli Chai, Yanhai Wang
Larvae of the tapeworm Echinococcus multilocularis cause alveolar echinococcosis (AE), one of the most lethal helminthic infections in humans. The germinative cells, a population of stem cell-like cells, are considered to drive the continuous growth of the metacestodes within the host. The mechanisms and relative molecules controlling the behavior of germinative cells are poorly understood. Sox transcription factors play important roles in maintenance and regulation of stem/progenitor cells. We here describe the identification of a Sox family member in E...
May 16, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28526448/the-catechol-o-methyltransferase-inhibitors-tolcapone-and-entacapone-uncouple-and-inhibit-the-mitochondrial-respiratory-chain-in-heparg-cells
#17
David Grünig, Andrea Felser, Jamal Bouitbir, Stephan Krähenbühl
The catechol-O-methyltransferase inhibitor tolcapone causes hepatotoxicity and mitochondrial damage in animal models. We studied the interaction of tolcapone with mitochondrial respiration in comparison to entacapone in different experimental models. In HepaRG cells (human cell-line), tolcapone decreased the ATP content (estimated IC50 100±15μM) and was cytotoxic (estimated IC50 333±45μM), whereas entacapone caused no cytotoxicity and no ATP depletion up to 200μM. Cytochrome P450 induction did not increase the toxicity of the compounds...
May 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28526353/stretch-activated-two-pore-domain-k2p-potassium-channels-in-the-heart-focus-on-atrial-fibrillation-and-heart-failure
#18
REVIEW
Constanze Schmidt, Felix Wiedmann, Stefan M Kallenberger, Antonius Ratte, Jan S Schulte, Beatrix Scholz, Frank Ulrich Müller, Niels Voigt, Maria-Patapia Zafeiriou, Joachim R Ehrlich, Ursula Tochtermann, Gábor Veres, Arjang Ruhparwar, Matthias Karck, Hugo A Katus, Dierk Thomas
Two-pore-domain potassium (K2P) channels modulate cellular excitability. The significance of stretch-activated cardiac K2P channels (K2P2.1, TREK-1, KCNK2; K2P4.1, TRAAK, KCNK4; K2P10.1, TREK-2, KCNK10) in heart disease has not been elucidated in detail. The aim of this work was to assess expression and remodeling of mechanosensitive K2P channels in atrial fibrillation (AF) and heart failure (HF) patients in comparison to murine models. Cardiac K2P channel levels were quantified in atrial (A) and ventricular (V) tissue obtained from patients undergoing open heart surgery...
May 16, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28526351/docosahexaenoyl-serotonin-emerges-as-most-potent-inhibitor-of-il-17-and-ccl-20-released-by-blood-mononuclear-cells-from-a-series-of-n-acyl-serotonins-identified-in-human-intestinal-tissue
#19
Ya Wang, Michiel G J Balvers, Henk F J Hendriks, Tessa Wilpshaar, Tjarda van Heek, Renger F Witkamp, Jocelijn Meijerink
Fatty acid amides (FAAs), conjugates of fatty acids with ethanolamine, mono-amine neurotransmitters or amino acids are a class of molecules that display diverse functional roles in different cells and tissues. Recently we reported that one of the serotonin-fatty acid conjugates, docosahexaenoyl serotonin (DHA-5-HT), previously found in gut tissue of mouse and pig, attenuates the IL-23-IL-17 signaling axis in LPS-stimulated mice macrophages. However, its presence and effects in humans remained to be elucidated...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28526333/systemic-manifestations-of-primary-sj%C3%A3-gren-s-syndrome-in-the-nod-b10sn-h2-b-j-mouse-model
#20
Jeremy Kiripolsky, Long Shen, Yichen Liang, Alisa Li, Lakshmanan Suresh, Yun Lian, Quan-Zhen Li, Daniel P Gaile, Jill M Kramer
Animal models that recapitulate human disease are crucial for the study of Sjögren's Syndrome (SS). While several SS mouse models exist, there are few primary SS (pSS) models that mimic systemic disease manifestations seen in humans. Similar to pSS patients, NOD.B10Sn-H2(b)/J (NOD.B10) mice develop exocrine gland disease and anti-nuclear autoantibodies. However, the disease kinetics and spectrum of extra-glandular disease remain poorly characterized in this model. Our objective was to characterize local and systemic SS manifestations in depth in NOD...
May 16, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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