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https://www.readbyqxmd.com/read/29352769/resolvin-e1-resolvin-d1-and-resolvin-d2-inhibit-constriction-of-rat-thoracic-aorta-and-human-pulmonary-artery-induced-by-the-thromboxane-mimetic-u46619
#1
Melanie Jannaway, Christopher Torrens, Jane A Warner, Anthony P Sampson
BACKGROUND AND PURPOSE: Omega-6 fatty acid-derived lipid mediators such as prostanoids, thromboxane and leukotrienes have well-established roles in regulating both inflammation and smooth muscle contractility. Resolvins are derived from omega-3 fatty acids and have important roles in promoting the resolution of inflammation, but their activity on smooth muscle contractility is unknown. We investigated whether resolvin E1 (RvE1), resolvin D1 (RvD1) and resolvin D2 (RvD2) can modulate contractions of isolated segments of rat thoracic aorta (RTA) or human pulmonary artery (HPA) induced by the α1 -adrenoceptor agonist phenylephrine or the stable thromboxane A2 mimetic U46619...
January 20, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29352468/developmental-plasticity-of-gabaergic-neurotransmission-to-brainstem-motoneurons
#2
Lila Buls Wollman, Richard B Levine, Ralph F Fregosi
Nicotinic acetylcholine receptor (nAChR) signalling regulates neuronal differentiation and synaptogenesis. Here we test the hypothesis that developmental nicotine exposure (DNE) disrupts the development of GABAergic synaptic transmission to hypoglossal motoneurons (XIIMNs). GABAergic spontaneous and miniature inhibitory postsynaptic currents (sIPSC/mIPSC) were recorded from XIIMNs in brainstem slices from control and DNE rat pups of either sex, 1-5 days old, at baseline and following acute stimulation of nAChRs with nicotine...
January 20, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29352328/attenuation-of-serotonin-induced-itch-by-sumatriptan-possible-involvement-of-endogenous-opioids
#3
Nazgol-Sadat Haddadi, Arash Foroutan, Saeed Shakiba, Khashayar Afshari, Sattar Ostadhadi, Maryam Daneshpazhooh, Ahmad-Reza Dehpour
Serotonin (5-hydroxytryptamine or 5-HT) is a neurotransmitter in itch and impaired serotonin signaling has been linked to a variety of itch conditions. Intradermal injection of 5-HT induces scratching behavior in mice through stimulation of 5-HT receptors. Previous studies have demonstrated that selective 5-HT1B/1D receptors agonists, including sumatriptan, inhibits neurotransmission. We have also reported that sumatriptan suppresses chloroquine-induced itch. Therefore, we investigated if sumatriptan has inhibitory effects on serotonin-induced itch in mice...
January 19, 2018: Archives of Dermatological Research
https://www.readbyqxmd.com/read/29352320/high-level-production-and-purification-in-a-functional-state-of-an-extrasynaptic-gamma-aminobutyric-acid-type-a-receptor-containing-%C3%AE-4%C3%AE-3%C3%AE-subunits
#4
Xiaojuan Zhou, Rooma Desai, Yinghui Zhang, Wojciech J Stec, Keith W Miller, Youssef Jounaidi
The inhibitory γ-aminobutyric acid type A receptors are implicated in numerous physiological processes, including cognition and inhibition of neurotransmission, rendering them important molecular targets for many classes of drugs. Functionally, the entire GABAAR family of receptors can be subdivided into phasic, fast acting synaptic receptors, composed of α-, β- and γ-subunits, and tonic extrasynaptic receptors, many of which contain the δ-subunit in addition to α- and β-subunits. Whereas the subunit arrangement of the former group is agreed upon, that of the αβδ GABAARs remains unresolved by electrophysiological and pharmacological research...
2018: PloS One
https://www.readbyqxmd.com/read/29351998/detection-of-experimental-and-clinical-immune-complexes-by-measuring-ship-1-recruitment-to-the-inhibitory-fc%C3%AE-riib
#5
Richard J Stopforth, Robert J Oldham, Alison L Tutt, Patrick Duriez, H T Claude Chan, Brock F Binkowski, Chad Zimprich, Dun Li, Philip G Hargreaves, Mei Cong, Venkat Reddy, Maria J Leandro, Geraldine Cambridge, Anja Lux, Falk Nimmerjahn, Mark S Cragg
Fc γ receptors (FcγR) are involved in multiple aspects of immune cell regulation, are central to the success of mAb therapeutics, and underpin the pathology of several autoimmune diseases. However, reliable assays capable of accurately measuring FcγR interactions with their physiological ligands, IgG immune complexes (IC), are limited. A method to study and detect IC interactions with FcγRs was therefore developed. This method, designed to model the signaling pathway of the inhibitory FcγRIIB (CD32B), used NanoLuc Binary Interaction Technology to measure recruitment of the Src homology 2 domain-containing inositol phosphatase 1 to the ITIM of this receptor...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29351614/a-membrane-g-protein-coupled-estrogen-receptor-is-necessary-but-not-sufficient-for-sex-differences-in-zebra-finch-auditory-coding
#6
Amanda A Krentzel, Matheus Macedo-Lima, Maaya Z Ikeda, Luke Remage-Healey
Estradiol acts as a neuromodulator in brain regions important for cognition and sensory processing. Estradiol also shapes brain sex differences, but rarely have these concepts been considered simultaneously. In male and female songbirds, estradiol rapidly increases within the auditory forebrain during song exposure and enhances local auditory processing. We tested whether GPER1, a membrane bound estrogen receptor, is necessary and sufficient for neuroestrogen regulation of forebrain auditory processing in male and female zebra finches (Taeniopygia guttata)...
January 17, 2018: Endocrinology
https://www.readbyqxmd.com/read/29350907/excitatory-and-inhibitory-neuronal-circuits-in-the-spinal-cord-and-their-role-in-the-control-of-motor-neuron-function-and-degeneration
#7
Uri Nimrod Ramírez-Jarquín, Ricardo Tapia
The complex neuronal networks of the spinal cord coordinate a wide variety of motor functions, including walking, running and voluntary and involuntary movements. This is accomplished by different groups of neurons, called center pattern generators, which control left-right alternation and flexor-extensor patterns. These spinal circuits, located in the ventral horns, are formed by several neuronal types, and the specific function of most of them has been identified by means of studies in vivo and in the isolated spinal cord of mice harboring genetically induced ablation of specific neuronal populations...
January 19, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29350876/mechanism-of-mer-receptor-tyrosine-kinase-inhibition-of-glomerular-endothelial-cell-inflammation
#8
Yuxuan Zhen, Fred D Finkelman, Wen-Hai Shao
Endotoxin induces a variety of proinflammatory mediators and plays a crucial role in kidney inflammation. The receptor tyrosine kinase, Mer, diminishes renal inflammation by attenuating inflammatory responses. We previously reported that Mer is predominantly expressed on glomerular endothelial cells (GECs) and that Mer deficiency is associated with increased renal inflammation when mice are challenged with nephrotoxic serum. We consequently hypothesized that Mer signaling down-regulates LPS-driven inflammatory responses in GECs...
January 19, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29350874/diversification-of-human-nk-cells-lessons-from-deep-profiling
#9
REVIEW
Aaron J Wilk, Catherine A Blish
NK cells are innate lymphocytes with important roles in immunoregulation, immunosurveillance, and cytokine production. Originally defined on the functional basis of their "natural" ability to lyse tumor targets and thought to be a relatively homogeneous group of lymphocytes, NK cells possess a remarkable degree of phenotypic and functional diversity due to the combinatorial expression of an array of activating and inhibitory receptors. Diversification of NK cells is multifaceted: mechanisms of NK cell education that promote self-tolerance result in a heterogeneous repertoire that further diversifies upon encounters with viral pathogens...
January 19, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29349889/t-cell-immunoglobulin-and-itim-domain-contributes-to-cd8-t-cell-immunosenescence
#10
Yangzi Song, Beibei Wang, Rui Song, Yu Hao, Di Wang, Yuxin Li, Yu Jiang, Ling Xu, Yaluan Ma, Hong Zheng, Yaxian Kong, Hui Zeng
Aging is associated with immune dysfunction, especially T-cell defects, which result in increased susceptibility to various diseases. Previous studies showed that T cells from aged mice express multiple inhibitory receptors, providing evidence of the relationship between T-cell exhaustion and T-cell senescence. In this study, we showed that T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), a novel co-inhibitory receptor, was upregulated in CD8+ T cells of elderly adults...
January 19, 2018: Aging Cell
https://www.readbyqxmd.com/read/29349763/immune-checkpoint-blockade-for-breast-cancer
#11
April Swoboda, Rita Nanda
An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29349630/developmental-changes-in-serotonergic-modulation-of-gabaergic-synaptic-transmission-and-postsynaptic-gabaa-receptor-composition-in-the-cerebellar-nuclei
#12
Fumihito Saitow, Masatoshi Nagano, Hidenori Suzuki
Outputs from the cerebellar nuclei (CN) are important for generating and controlling movement. The activity of CN neurons is controlled not only by excitatory inputs from mossy and climbing fibers and by γ-aminobutyric acid (GABA)-based inhibitory transmission from Purkinje cells in the cerebellar cortex but is also modulated by inputs from other brain regions, including serotonergic fibers that originate in the dorsal raphe nuclei. We examined the modulatory effects of serotonin (5-HT) on GABAergic synapses during development, using rat cerebellar slices...
January 19, 2018: Cerebellum
https://www.readbyqxmd.com/read/29348811/disconnecting-the-estrogen-receptor-binding-properties-and-antimicrobial-properties-of-parabens-through-3-5-substitution
#13
Bridget L Bergquist, Kaelyn G Jefferson, Hailey N Kintz, Amorette E Barber, Andrew A Yeagley
Commercially utilized parabens are employed for their antimicrobial properties, but a weak binding to the estrogen receptor alpha (ERα) may lead to breast cancer in some applications. Modification of the paraben scaffold should allow for a disconnection of these observed properties. Toward this goal, various 3,5-substituted parabens were synthesized and assessed for antimicrobial properties against S. aureus as well as competitive binding to the ERα. The minimum inhibitory concentration assay confirmed retention of antimicrobial activity in many of these derivatives, while all compounds exhibited decreased xenoestrogen activity as determined by a combination of competitive enzyme linked immunosorbent assay (ELISA), proliferation, and estrogen receptor binding assay...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29348629/the-suppressive-role-of-calcium-sensing-receptor-in-endometrial-cancer
#14
Xiaoyan Xin, Xianqin Zeng, Dilu Feng, Teng Hua, Shuangge Liu, Shuqi Chi, Qinghua Hu, Hongbo Wang
Studies have shown that calcium sensing receptor (CaSR) is involved in the progressions of several human cancers. However, the role of CaSR in endometrial cancer remains unknown. This study provides a preliminary analysis of the CaSR effect on endometrial cancer development. Ectopic CaSR expression by lentiviral transfection (CaSR-OV) in Ishikawa cells significantly increased intracellular calcium ([Ca2+]i) levels and cell apoptosis. E-cadherin and β-catenin expression and complex formation at the membrane were increased in CaSR-OV Ishikawa cells relative to control Ishikawa cells (vector)...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348488/interferon-alpha-enhances-the-antitumour-activity-of-egfr-targeted-therapies-by-upregulating-rig-i-in-head-and-neck-squamous-cell-carcinoma
#15
Hailong Ma, Shufang Jin, Wenyi Yang, Ge Zhou, Mei Zhao, Sijie Fang, Zhiyuan Zhang, Jingzhou Hu
BACKGROUND: The epidermal growth factor receptor (EGFR)-targeted therapies have been tested in the clinic as treatments for head and neck squamous cell carcinoma (HNSCC). Owing to intrinsic or acquired resistance, EGFR-targeted therapies often lead to a low response rate and treatment failure. Interferon-alpha (IFNα) is a chemosensitising agent and multi-functional cytokine with a tumour inhibitory effect. However, the synergic effect of IFNα and EGFR-targeted therapies (erlotinib and nimotuzumab) and their mechanisms in HNSCC remain unclear...
January 18, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29348190/pronounced-hyperactivity-cognitive-dysfunctions-and-bdnf-dysregulation-in-dopamine-transporter-knockout-rats
#16
Damiana Leo, Ilya Sukhanov, Francesca Zoratto, Placido Illiano, Lucia Caffino, Fabrizio Sanna, Giulia Messa, Marco Emanuele, Alessandro Esposito, Maria Dorofeikova, Evgeny A Budygin, Liudmila Mus, Evgenia E Efimova, Marco Niello, Stefano Espinoza, Tatyana D Sotnikova, Marius C Hoener, Gianni Laviola, Fabio Fumagalli, Walter Adriani, Raul R Gainetdinov
Dopamine (DA) controls many vital physiological functions and is critically involved in several neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder (ADHD). The major function of the plasma membrane dopamine transporter (DAT) is the rapid uptake of released DA into presynaptic nerve terminals leading to control of both the extracellular levels of DA and the intracellular stores of DA. Here, we present a newly developed strain of rats (DAT-knockout, DAT-KO rats) in which the gene encoding the DAT has been disrupted by using zinc finger nuclease technology (ZFN)...
January 18, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29347844/docking-analysis-targeted-to-the-whole-enzyme-an-application-to-the-prediction-of-inhibition-of-ptp1b-by-thiomorpholine-and-thiazolyl-derivatives
#17
C A Ganou, P Th Eleftheriou, P Theodosis-Nobelos, M Fesatidou, A A Geronikaki, T Lialiaris, E A Rekka
PTP1b is a protein tyrosine phosphatase involved in the inactivation of insulin receptor. Since inhibition of PTP1b may prolong the action of the receptor, PTP1b has become a drug target for the treatment of type II diabetes. In the present study, prediction of inhibition using docking analysis targeted specifically to the active or allosteric site was performed on 87 compounds structurally belonging to 10 different groups. Two groups, consisting of 15 thiomorpholine and 10 thiazolyl derivatives exhibiting the best prediction results, were selected for in vitro evaluation...
February 2018: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/29346833/phase-1b-trial-of-ficlatuzumab-a-humanized-hepatocyte-growth-factor-inhibitory-monoclonal-antibody-in-combination-with-gefitinib-in-asian-patients-with-nsclc
#18
Eng-Huat Tan, Wan-Teck Lim, Myung-Ju Ahn, Quan-Sing Ng, Jin Seok Ahn, Daniel Shao-Weng Tan, Jong-Mu Sun, May Han, Francis C Payumo, Krista McKee, Wei Yin, Marc Credi, Shefali Agarwal, Jaroslaw Jac, Keunchil Park
Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 κ HGF inhibitory monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC)...
January 18, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29346767/functional-principles-of-posterior-septal-inputs-to-the-medial-habenula
#19
Yo Otsu, Salvatore Lecca, Katarzyna Pietrajtis, Charly Vincent Rousseau, Païkan Marcaggi, Guillaume Pierre Dugué, Caroline Mailhes-Hamon, Manuel Mameli, Marco Alberto Diana
The medial habenula (MHb) is an epithalamic hub contributing to expression and extinction of aversive states by bridging forebrain areas and midbrain monoaminergic centers. Although contradictory information exists regarding their synaptic properties, the physiology of the excitatory inputs to the MHb from the posterior septum remains elusive. Here, combining optogenetics-based mapping with ex vivo and in vivo physiology, we examine the synaptic properties of posterior septal afferents to the MHb and how they influence behavior...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346754/input-specific-nmdar-dependent-potentiation-of-dendritic-gabaergic-inhibition
#20
Chiayu Q Chiu, James S Martenson, Maya Yamazaki, Rie Natsume, Kenji Sakimura, Susumu Tomita, Steven J Tavalin, Michael J Higley
Preservation of a balance between synaptic excitation and inhibition is critical for normal brain function. A number of homeostatic cellular mechanisms have been suggested to play a role in maintaining this balance, including long-term plasticity of GABAergic inhibitory synapses. Many previous studies have demonstrated a coupling of postsynaptic spiking with modification of perisomatic inhibition. Here, we demonstrate that activation of NMDA-type glutamate receptors leads to input-specific long-term potentiation of dendritic inhibition mediated by somatostatin-expressing interneurons...
January 17, 2018: Neuron
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