keyword
MENU ▼
Read by QxMD icon Read
search

Inhibitory receptors

keyword
https://www.readbyqxmd.com/read/28647281/serotonergic-modulation-of-nicotine-induced-kinetic-tremor-in-mice
#1
Naofumi Kunisawa, Higor A Iha, Yuji Nomura, Misaki Onishi, Nami Matsubara, Saki Shimizu, Yukihiro Ohno
We previously demonstrated that nicotine elicited kinetic tremor by elevating the neural activity of the inferior olive via α7 nicotinic acetylcholine (nACh) receptors. Since α7 nACh receptors reportedly facilitate synaptic monoamine release, we explored the role of 5-HT receptors in induction and/or modulation of nicotine tremor. Treatment of mice with nicotine induced kinetic tremor that normally appeared during movement. The 5-HT1A agonist, 8-hydroxydipropylaminotetraline (8-OH-DPAT), significantly enhanced nicotine-induced tremor and the action of 8-OH-DPAT was antagonized by WAY-100135 (5-HT1A antagonist)...
June 9, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28646884/the-increased-concentration-of-macrophage-migration-inhibitory-factor-in-serum-and-cerebrospinal-fluid-of-patients-with-tick-borne-encephalitis
#2
Sambor Grygorczuk, Miłosz Parczewski, Renata Świerzbińska, Piotr Czupryna, Anna Moniuszko, Justyna Dunaj, Maciej Kondrusik, Sławomir Pancewicz
BACKGROUND: Host factors determining the clinical presentation of tick-borne encephalitis (TBE) are not fully elucidated. The peripheral inflammatory response to TBE virus is hypothesized to facilitate its entry into central nervous system by disrupting the blood-brain barrier with the involvement of a signaling route including Toll-like receptor 3 (TLR3) and pro-inflammatory cytokines macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNFα), and interleukin-1 beta (IL-1β)...
June 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28646117/cyclin-dependent-kinase-9-is-a-novel-specific-molecular-target-in-adult-t-cell-leukemia-lymphoma
#3
Tomoko Narita, Takashi Ishida, Asahi Ito, Ayako Masaki, Shiori Kinoshita, Susumu Suzuki, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Kazunori Imada, Yuetsu Tanaka, Takaori-Kondo Akifumi, Hiroshi Inagaki, Arne Scholz, Philip Lienau, Taruho Kuroda, Ryuzo Ueda, Shinsuke Iida
Cyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII).  The deregulation of CDK9/P-TEFb has important implications for many cancer types.  BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase I studies. We evaluated the therapeutic potential of BAY 1143572 in adult T-cell leukemia/lymphoma (ATL)...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28646041/concurrent-ox40-and-cd30-ligand-blockade-abrogates-the-cd4-driven-autoimmunity-associated-with-ctla4-and-pd1-blockade-while-preserving-excellent-anti-cd8-tumor-immunity
#4
Maher G Nawaf, Maria H Ulvmar, David R Withers, Fiona M McConnell, Fabrina M Gaspal, Gwilym J Webb, Nick D Jones, Hideo Yagita, James P Allison, Peter J L Lane
Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28646020/mcam-mediates-chemoresistance-in-small-cell-lung-cancer-via-the-pi3k-akt-sox2-signaling-pathway
#5
Satyendra C Tripathi, Johannes F Fahrmann, Muge Celiktas, Mitzi Aguilar, Kieren D Marini, Mohit Kumar Jolly, Hiroyuki Katayama, Hong Wang, Eunice N Murage, Jennifer B Dennison, D Neil Watkins, Herbert Levine, Edwin J Ostrin, Ayumu Taguchi, Samir M Hanash
Despite favorable responses to initial therapy, small cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Due to limited accessibility of patient tissues for research purposes, SCLC-patient derived xenografts (PDX) have provided the best opportunity to address this limitation. Here we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared to matched treatment-naïve tumors...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28646017/ror%C3%AE-modulates-semaphorin-3e-transcription-and-neurovascular-interaction-in-pathological-retinal-angiogenesis
#6
Ye Sun, Chi-Hsiu Liu, Zhongxiao Wang, Steven S Meng, Samuel B Burnim, John Paul SanGiovanni, Theodore M Kamenecka, Laura A Solt, Jing Chen
Pathological proliferation of retinal blood vessels commonly causes vision impairment in proliferative retinopathies, including retinopathy of prematurity. Dysregulated crosstalk between the vasculature and retinal neurons is increasingly recognized as a major factor contributing to the pathogenesis of vascular diseases. Class 3 semaphorins (SEMA3s), a group of neuron-secreted axonal and vascular guidance factors, suppress pathological vascular growth in retinopathy. However, the upstream transcriptional regulators that mediate the function of SEMA3s in vascular growth are poorly understood...
June 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28645943/the-structure-of-the-tetanus-toxin-reveals-ph-mediated-domain-dynamics
#7
Geoffrey Masuyer, Julian Conrad, Pål Stenmark
The tetanus neurotoxin (TeNT) is a highly potent toxin produced by Clostridium tetani that inhibits neurotransmission of inhibitory interneurons, causing spastic paralysis in the tetanus disease. TeNT differs from the other clostridial neurotoxins by its unique ability to target the central nervous system by retrograde axonal transport. The crystal structure of the tetanus toxin reveals a "closed" domain arrangement stabilised by two disulphide bridges, and the molecular details of the toxin's interaction with its polysaccharide receptor...
June 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28645623/identification-of-a-coumarin-based-antihistamine-as-an-anti-filoviral-entry-inhibitor
#8
Han Cheng, Adam Schafer, Veronica Soloveva, Dima Gharaibeh, Tara Kenny, Cary Retterer, Rouzbeh Zamani, Sina Bavari, Norton P Peet, Lijun Rong
Filoviruses, consisting of Ebola virus, Marburg virus and Cuevavirus, cause severe hemorrhagic fevers in humans with high mortality rates up to 90%. Currently, there is no approved vaccine or therapy available for the prevention and treatment of filovirus infection in humans. The recent 2013-2015 West African Ebola epidemic underscores the urgency to develop antiviral therapeutics against these infectious diseases. Our previous study showed that GPCR antagonists, particularly histamine receptor antagonists (antihistamines) inhibit Ebola and Marburg virus entry...
June 20, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28645613/regulation-of-testicular-steroidogenesis-by-foxa3-via-transcriptional-modulation-of-er%C3%AE-signaling-in-type-2-diabetes-mellitus-t2dm
#9
Yong Zhao, Hong-Xin Li, Ke Wang, Bin-Yuan Yan, Wei Li
Although both insulin and estrogen receptor α (ERα) are known to exert inhibitory effects on testicular steroidogenesis, it remains unknown whether these pathways regulate testosterone (T) production under certain pathological conditions [e.g., type 2 diabetes mellitus (T2DM)] in a coordinated manner. Here, we found that the expression of forkhead box protein A3 (Foxa3), an essential transcriptional regulator engaged in adipogenesis and energy metabolism, was significantly down-regulated in the Leydig cells (LCs) from T-deficient T2DM mice...
June 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28645554/monocrotophos-an-organophosphorus-insecticide-disrupts-the-expression-of-hpnetrin-and-its-receptor-neogenin-during-early-development-in-the-sea-urchin-hemicentrotus-pulcherrimus
#10
Xiaona Zhang, Lei Xu, Hua Tian, Cuicui Wang, Wei Wang, Shaoguo Ru
Netrins, chemotropic guidance cues, can guide the extension of serotonergic axons by binding to netrin receptors during neural development. However, little is known about whether disruption of netrin signaling is involved in the mechanisms by which organophosphorus pesticides affect serotonergic nervous system (SNS) development. In this study, we evaluated the effects of the pesticide monocrotophos (MCP) on the expression patterns of HpNetrin and its receptor neogenin as well as on the intracellular calcium ion (Ca(2+)) levels in Hemicentrotus pulcherrimus (sea urchin) by exposing fertilized embryos to 0, 0...
June 20, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28644433/ctla-4-mediated-posttranslational-modifications-direct-cytotoxic-t-lymphocyte-differentiation
#11
Holger Lingel, Josef Wissing, Aditya Arra, Denny Schanze, Stefan Lienenklaus, Frank Klawonn, Mandy Pierau, Martin Zenker, Lothar Jänsch, Monika C Brunner-Weinzierl
The blockade of inhibitory receptors such as CTLA-4 (CD152) is being used as immune-checkpoint therapy, offering a powerful strategy to restore effective immune responses against tumors. To determine signal components that are induced under the control of CTLA-4 we analyzed activated murine CD8(+) T cells by quantitative proteomics. Accurate mass spectrometry revealed that CTLA-4 engagement led to central changes in the phosphorylation of proteins involved in T-cell differentiation. Beside other targets, we discovered a CTLA-4-mediated induction of the translational inhibitor programmed cell death-4 (PDCD4) as a result of FoxO1 nuclear re-localization...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28643478/critical-role-of-tnf-inhibition-in-combination-therapy-for-elderly-mice-with-atherosclerosis
#12
Kyung-Yeon Park, Tae-Hwe Heo
We have previously shown that the combination of pravastatin and sarpogrelate is synergistically beneficial for atherosclerosis. In this study, we investigated whether the pravastatin-sarpogrelate combination was sufficient for treatment in an old mouse model of atherosclerosis or if additional intervention would be needed to address the newly included aging factor and its complex pathophysiological impact on the atherosclerogenic state. We added an anti-TNF biologic to the combination treatment cocktail because of the known pathologic roles of TNF in the aging process...
June 23, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28643288/inhibitory-effect-of-fsllry-nh2-on-inflammatory-responses-induced-by-hydrogen-peroxide-in-hepg2-cells
#13
Yeon Joo Lee, Su Jin Kim, Kyoung Wan Kwon, Won Mo Lee, Wi Joon Im, Uy Dong Sohn
Proteinase activated receptor 2 (PAR2), which is localized in the GI tract, the respiratory system, and the kidney tubules is a G protein-coupled receptor associated with inflammation, metabolism, and disease. The aim of this study was to explore the role of PAR2 in hydrogen peroxide (H2O2)-induced HepG2 cells by using FSLLRY-NH2 a PAR2 antagonist. H2O2 treatment resulted in induction of PAR2 in esophageal, gastric, and liver cells, with the most robust response being in HepG2 cells. Furthermore, this effect was dose-dependent in HepG2 cells...
June 22, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28642997/pd-1-and-cancer-molecular-mechanisms-and-polymorphisms
#14
REVIEW
Arash Salmaninejad, Vahid Khoramshahi, Alireza Azani, Ehsan Soltaninejad, Saeed Aslani, Mohammad Reza Zamani, Masoud Zal, Abolfazl Nesaei, Sayed Mostafa Hosseini
The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers...
June 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28642706/toll-like-receptor-4-modulates-small-intestine-neuromuscular-function-through-nitrergic-and-purinergic-pathways
#15
Valentina Caputi, Ilaria Marsilio, Silvia Cerantola, Mona Roozfarakh, Isabella Lante, Francesca Galuppini, Massimo Rugge, Eleonora Napoli, Cecilia Giulivi, Genny Orso, Maria Cecilia Giron
Objective: Toll-like receptors (TLRs) play a pivotal role in the homeostatic microflora-host crosstalk. TLR4-mediated modulation of both motility and enteric neuronal survival has been reported mainly for colon with limited information on the role of TLR4 in tuning structural and functional integrity of enteric nervous system (ENS) and in controlling small bowel motility. Methods: Male TLR4 knockout (TLR4(-/-), 9 ± 1 weeks old) and sex- and age-matched wild-type (WT) C57BL/6J mice were used for the experiments...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642681/%C3%AE-1-containing-gaba-a-receptors-cluster-at-synapses-where-they-mediate-slower-synaptic-currents-than-%C3%AE-2-containing-gaba-a-receptors
#16
Christine L Dixon, Pankaj Sah, Angelo Keramidas, Joseph W Lynch, Nela Durisic
GABA-A receptors (GABAARs) are pentameric ligand-gated ion channels that are assembled mainly from α (α1-6), β (β1-3) and γ (γ1-3) subunits. Although GABAARs containing γ2L subunits mediate most of the inhibitory neurotransmission in the brain, significant expression of γ1 subunits is seen in the amygdala, pallidum and substantia nigra. However, the location and function of γ1-containing GABAARs in these regions remains unclear. In "artificial" synapses, where the subunit composition of postsynaptic receptors is specifically controlled, γ1 incorporation slows the synaptic current decay rate without affecting channel deactivation, suggesting that γ1-containing receptors are not clustered and therefore activated by diffuse neurotransmitter...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28642283/selective-inhibition-of-trigeminovascular-neurons-by-fremanezumab-a-humanized-monoclonal-anti-cgrp-antibody
#17
Agustin Melo-Carrillo, Rodrigo Noseda, Rony Nir, Aaron Schain, Jennifer Stratton, Andrew M Strassman, Rami Burstein
A large body of evidence supports an important role for CGRP in migraine pathophysiology. This evidence gave rise to a global effort to develop a new generation of therapeutics that inhibit the interaction of CGRP with its receptor in migraineurs. Recently, a new class of such drugs, humanized monoclonal anti-CGRP antibodies (CGRP-mAb) were found to be effective in reducing the frequency of migraine. The purpose of this study was to better understand how the CGRP-mAb fremanezumab (TEV-48125) modulates meningeal sensory pathways...
June 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28642282/kappa-opioid-receptors-mediate-heterosynaptic-suppression-of-hippocampal-inputs-in-the-rat-ventral-striatum
#18
Julie Brooks, Patricio O'Donnell
Kappa opioid receptors (KOR) are highly enriched within the ventral striatum (VS) and are thought to modulate striatal neurotransmission. This includes presynaptic inhibition of local glutamatergic release from excitatory inputs to the VS. However, it is not known which inputs drive this modulation and what impact they have on the local circuit dynamics within the VS. Individual medium spiny neurons (MSNs) within the VS serve as a site of convergence for glutamatergic inputs arising from the prefrontal cortex (PFC) and limbic regions, such as the hippocampus (HP)...
June 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28642037/testosterone-regulates-3t3-l1pre-adipocyte-differentiation-and-epididymal-fat-accumulation-in-mice-through-modulating-macrophage-polarization
#19
Xiaojiao Ren, Xiaojian Fu, Xinhua Zhang, Shiqiang Chen, Shuguang Huang, Lun Yao, Guoquan Liu
Low testosterone levels are strongly related to obesity in males. The balance between the classically M1 and alternatively M2 polarized macrophages also plays a critical role in obesity. It is not clear whether testosterone regulates macrophage polarization and then affects adipocyte differentiation. In this report, we demonstrate that testosterone strengthens interleukin (IL) -4-induced M2 polarization and inhibits lipopolysaccharide (LPS) -induced M1 polarization, but has no direct effect on adipocyte differentiation...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28642028/discovery-of-novel-5-oxa-2-6-diazaspiro-3-4-oct-6-ene-derivatives-as-potent-selective-and-orally-available-somatostatin-receptor-subtype-5-sstr5-antagonists-for-treatment-of-type-2-diabetes-mellitus
#20
Hideki Hirose, Takeshi Yamasaki, Masaki Ogino, Ryo Mizojiri, Yumiko Tamura-Okano, Hiroaki Yashiro, Yo Muraki, Yoshihide Nakano, Jun Sugama, Akito Hata, Shinji Iwasaki, Masanori Watanabe, Tsuyoshi Maekawa, Shizuo Kasai
Somatostatin receptor subtype 5 (SSTR5) has emerged as a novel attractive drug target for type 2 diabetes mellitus. Starting from N-benzyl azetidine derivatives 1 and 2 as in-house hit compounds, we explored the introduction of a carboxyl group into the terminal benzene of 1 to enhance SSTR5 antagonistic activity by the combination of the substituents at the 3-position of the isoxazoline. Incorporation of a carboxyl group at the 4-position of the benzene ring resulted in a significant enhancement in potency, however, the 4-benzoic acid derivative 10c exhibited moderate human ether-a-go-go related gene (hERG) inhibitory activity...
June 9, 2017: Bioorganic & Medicinal Chemistry
keyword
keyword
18219
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"