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https://www.readbyqxmd.com/read/29449373/tyrosine-hydroxylase-down-regulation-after-loss-of-abelson-helper-integration-site-1-ahi1-promotes-depression-via-the-circadian-clock-pathway-in-mice
#1
Dongkai Guo, Shun Zhang, Hongyang Sun, Xingyun Xu, Zongbing Hao, Chenchen Mu, Xingshun Xu, Guanghui Wang, Haigang Ren
Abelson helper integration site 1 (AHI1) is associated with several neuropsychiatric and brain developmental disorders such as schizophrenia, depression, autism, and Joubert syndrome. Ahi1 deficiency in mice leads to behaviors typical of depression. However, the mechanisms by which AHI1 regulates behavior remain to be elucidated. Here, we found that down-regulation of expression of the rate-limiting enzyme in dopamine biosynthesis, tyrosine hydroxylase (TH), in the midbrains of Ahi1 -knockout (KO) mice is responsible for Ahi1 -deficiency-mediated depressive symptoms...
February 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29447132/role-of-gpcr-mu-opioid-receptor-tyrosine-kinase-epidermal-growth-factor-crosstalk-in-opioid-induced-hyperalgesic-priming-type-ii
#2
Dionéia Araldi, Luiz F Ferrari, Jon D Levine
Repeated stimulation of mu-opioid receptors (MORs), by an MOR-selective agonist DAMGO induces type II priming, a form of nociceptor neuroplasticity, which has 2 components: opioid-induced hyperalgesia (OIH) and prolongation of prostaglandin-E2 (PGE2)-induced hyperalgesia. We report that intrathecal antisense knockdown of the MOR in nociceptors, prevented the induction of both components of type II priming. Type II priming was also eliminated by SSP-saporin, which destroys the peptidergic class of nociceptors...
January 11, 2018: Pain
https://www.readbyqxmd.com/read/29441714/time-dependent-regional-brain-distribution-of-methadone-and-naltrexone-in-the-treatment-of-opioid-addiction
#3
Belin G Teklezgi, Annapurna Pamreddy, Sooraj Baijnath, Hendrik G Kruger, Tricia Naicker, Nirmala D Gopal, Thavendran Govender
Opioid addiction is a serious public health concern with severe health and social implications; therefore, extensive therapeutic efforts are required to keep users drug free. The two main pharmacological interventions, in the treatment of addiction, involve management with methadone an mu (μ)-opioid agonist and treatment with naltrexone, μ-opioid, kappa (κ)-opioid and delta (δ)-opioid antagonist. MET and NAL are believed to help individuals to derive maximum benefit from treatment and undergo a full recovery...
February 14, 2018: Addiction Biology
https://www.readbyqxmd.com/read/29440403/suppression-of-rgsz1-function-optimizes-the-actions-of-opioid-analgesics-by-mechanisms-that-involve-the-wnt-%C3%AE-catenin-pathway
#4
Sevasti Gaspari, Immanuel Purushothaman, Valeria Cogliani, Farhana Sakloth, Rachael L Neve, David Howland, Robert H Ring, Elliott M Ross, Li Shen, Venetia Zachariou
Regulator of G protein signaling z1 (RGSz1), a member of the RGS family of proteins, is present in several networks expressing mu opioid receptors (MOPRs). By using genetic mouse models for global or brain region-targeted manipulations of RGSz1 expression, we demonstrated that the suppression of RGSz1 function increases the analgesic efficacy of MOPR agonists in male and female mice and delays the development of morphine tolerance while decreasing the sensitivity to rewarding and locomotor activating effects...
February 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29439730/resolvin-d2-protects-against-cerebral-ischemia-reperfusion-injury-in-rats
#5
Gang Zuo, Dongping Zhang, Rutao Mu, Haitao Shen, Xiang Li, Zhong Wang, Haiying Li, Gang Chen
Cerebral ischemia/reperfusion (I/R) injury is a critical factor leading to a poor prognosis for ischemic stroke patients. ω-3 fatty acid supplements taken as part of a daily diet have been shown to improve the prognosis of patients with ischemic stroke. In this study, we aimed to investigate the potential effects of resolvin D2 (RvD2), a derivative of ω-3 fatty acids, and its possible advantage on cerebral I/R injury in rats. Cerebral I/R caused by middle cerebral artery occlusion and reperfusion (MCAO/R) was established in Sprague-Dawley rats...
February 13, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29438224/erlotinib-protects-lps-induced-acute-lung-injury-in-mice-by-inhibiting-egfr-tlr4-signaling-pathway
#6
Huan Tao, Na Li, Zhao Zhang, Honglan Mu, Chen Meng, Huimin Xia, Lisha Fu, Younian Xu, Shihai Zhang
Epidermal growth factor receptor (EGFR) has been reported to initiate the inflammatory response, but its activation in lipopolysaccharide (LPS)-induced murine model of acute lung injury (ALI) remains unclear. In this study, we investigated the role of EGFR in the LPS-induced murine model of ALI and explored whether its inhibitor erlotinib could affect the progression of lung injury. We first detected the phosphorylated EGFR (p-EGFR)/EGFR ratio at different time points after LPS stimulation, and then different concentrations of erlotinib were used to treat mice at 1 h before LPS stimulation and collected samples at the time point of the highest p-EGFR/EGFR ratio...
February 12, 2018: Shock
https://www.readbyqxmd.com/read/29436576/the-effects-of-traf6-on-proliferation-apoptosis-and-invasion-in-osteosarcoma-are-regulated-by-mir-124
#7
Qingbing Meng, Wensheng Zhang, Xingli Xu, Jian Li, Hongxin Mu, Xiaolan Liu, Ling Qin, Xiaoqi Zhu, Minqian Zheng
The present study aimed to verify tumor necrosis factor receptor‑associated factor 6 (TRAF6) as the target gene of microRNA-124 (miR-124). In addition, the expression of miR‑124 was investigated in osteosarcoma tissues and cells, and its effects on the biological characteristics of osteosarcoma cells were determined, in order to provide an experimental and theoretical basis for the application of TRAF6 in the treatment of osteosarcoma. A fluorescence reporter enzyme system was used to verify TRAF6 as a target gene of miR‑124, and western blotting was used to detect the effects of miR‑124 on the protein expression levels of TRAF6 in cells...
February 5, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29431655/fentanyl-induces-rapid-onset-hyperalgesic-priming-type-i-at-peripheral-and-type-ii-at-central-nociceptor-terminals
#8
Dioneia Araldi, Eugen V Khomula, Luiz F Ferrari, Jon D Levine
Systemic fentanyl induces hyperalgesic priming, long-lasting neuroplasticity in nociceptor function characterized by prolongation of inflammatory mediator hyperalgesia. To evaluate priming at both nociceptor terminals, we studied, in male Sprague--Dawley rats, the effect of local administration of agents that reverse Type I (protein translation) or Type II (combination of Src and mitogen-activated protein kinase [MAPK]) priming. While at the central terminal, priming induced by systemic, intradermal or intrathecal fentanyl was reversed by the combination of Src and MAPK inhibitors, at the peripheral terminal it was reversed by the protein translation inhibitor...
February 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29422390/novel-naftopidil-derivatives-containing-methyl-phenylacetate-and-their-blocking-effects-on-%C3%AE-1d-1a-adrenoreceptor-subtypes
#9
Jun-Jun Huang, Zhi-Han Zhang, Fei He, Xia-Wen Liu, Xing-Jie Xu, Li-Jun Dai, Qi-Meng Liu, Mu Yuan
α1-Adrenoceptor (α1-AR) antagonists are considered to be the most effective monotherapy agents for lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). In this study, we synthesized compounds 2-17, which are novel piperazine derivatives that contain methyl phenylacetate. We then evaluated the vasodilatory activities of these compounds. Among them, we found that compounds 2, 7, 12, which contain 2-OCH3, 2-CH3 or 2, 5-CH3, respectively, exhibited potent α1-blocking activity similar to protype drug naftopidil (1)...
February 5, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29413524/mu-opioid-pharmacology-40-years-to-the-promised-land
#10
Gavril W Pasternak
Opioids continue to play a major role in medicine, but not without problems. Side effects limit their utility medically, while the potential of addiction has had a major societal impact. Pharmacologists have been trying to develop opioids lacking side effects since the first derivative, heroin, was synthesized in the 1870s. The identification of opioid receptors about 40 years ago opened up new insights into our understanding of opioid action, fueled by the molecular biology revolution of the 1980s and 1990s...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29405492/effects-of-naloxegol-on-whole-gut-transit-in-opioid-na%C3%A3-ve-healthy-subjects-receiving-codeine-a-randomized-controlled-trial
#11
H Halawi, P Vijayvargiya, I Busciglio, I Oduyebo, D Khemani, M Ryks, D Rhoten, D Burton, L A Szarka, A Acosta, M Camilleri
BACKGROUND: Nausea, vomiting, and constipation (OIC) are common adverse effects of acute or chronic opioid use. Naloxegol (25 mg) is an approved peripherally active mu-opiate opioid receptor antagonist. AIM: To compare the effects on pan-gut transit of treatment with codeine, naloxegol, or combination in healthy volunteers. METHODS: We conducted a randomized, double-blind, placebo-controlled, single-center, parallel-group study in 72 healthy opioid-naïve adults, randomized to: codeine (30 mg q...
February 6, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29401539/associations-of-tnfrsf1a-polymorphisms-with-autoimmune-thyroid-diseases-a-case-control-study
#12
Xiao-Qing Shao, Xiao-Lian Ding, Kaida Mu, Xuan Wang, Xiao-Fei An, Qiu-Ming Yao, Ling Li, Qian Li, Rong-Hua Song, Shuang-Tao He, Jian Xu, Jin-An Zhang
Previous studies have shown associations of polymorphisms in the tumor necrosis factor (TNF) receptor super family member 1A (TNFRSF1A) gene with several groups of inflammatory and autoimmune related diseases, but associations of TNFRSF1A polymorphisms with autoimmune thyroid diseases (AITD), mainly including two sub-types of Hashimoto's thyroiditis (HT) and Graves' disease (GD), in the Chinese Han population is unclear. A case-control study of 1812 subjects (965 AITD patients and 847 unrelated healthy controls) was conducted to assess AITD associations with five single nucleotide polymorphisms (SNPs), including rs4149576, rs4149577, rs4149570, rs1800693, and rs767455 in the TNFRSF1A gene locus...
February 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29396617/resistance-exercise-decreases-heroin-self-administration-and-alters-gene-expression-in-the-nucleus-accumbens-of-heroin-exposed-rats
#13
Mark A Smith, Gaylen E Fronk, Jean M Abel, Ryan T Lacy, Sarah E Bills, Wendy J Lynch
RATIONALE: Preclinical studies consistently report that aerobic exercise decreases drug self-administration and other forms of drug-seeking behavior; however, relatively few studies have examined other types of physical activity. OBJECTIVES: The purpose of the present study was to examine the effects of resistance exercise (i.e., strength training) on heroin self-administration and mRNA expression of genes known to mediate opioid reinforcement and addictive behavior in the nucleus accumbens (NAc) of heroin-exposed rats...
February 2, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29396147/focusing-on-the-opioid-system-for-addiction-biomarker-discovery
#14
REVIEW
Raoul Belzeaux, Laurence Lalanne, Brigitte L Kieffer, Pierre-Eric Lutz
Substance use disorders (SUD) and behavioral addictions are devastating conditions that impose a severe burden on all societies, and represent difficult challenges for clinicians. Therefore, biomarkers are urgently needed to help predict vulnerability, clinical course, and response to treatment. Here, we elaborate on the potential for addiction biomarker discovery of the opioid system, particularly within the emerging framework aiming to probe opioid function in peripheral tissues. Mu, delta, and kappa opioid receptors all critically regulate neurobiological and behavioral processes that define addiction, and are also targeted by major pharmacotherapies used in the management of patients with SUD...
January 27, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29395326/breaching-self-tolerance-to-alu-duplex-rna-underlies-mda5-mediated-inflammation
#15
Sadeem Ahmad, Xin Mu, Fei Yang, Emily Greenwald, Ji Woo Park, Etai Jacob, Cheng-Zhong Zhang, Sun Hur
Aberrant activation of innate immune receptors can cause a spectrum of immune disorders, such as Aicardi-Goutières syndrome (AGS). One such receptor is MDA5, a viral dsRNA sensor that induces antiviral immune response. Using a newly developed RNase-protection/RNA-seq approach, we demonstrate here that constitutive activation of MDA5 in AGS results from the loss of tolerance to cellular dsRNAs formed by Alu retroelements. While wild-type MDA5 cannot efficiently recognize Alu-dsRNAs because of its limited filament formation on imperfect duplexes, AGS variants of MDA5 display reduced sensitivity to duplex structural irregularities, assembling signaling-competent filaments on Alu-dsRNAs...
January 8, 2018: Cell
https://www.readbyqxmd.com/read/29385578/factors-influencing-the-impact-of-pharmacogenomic-prescribing-on-adherence-to-nicotine-replacement-therapy-a-qualitative-study-of-participants-from-a-randomized-controlled-trial
#16
Alison J Wright, Stephen Sutton, David Armstrong, Paul Aveyard, Ann Louise Kinmonth, Theresa M Marteau
Pharmacogenomics may improve health outcomes in two ways: by more precise and therefore more effective prescribing, tailored to genotype, and by increasing perceived effectiveness of treatments and so motivation for adherence. Little is known about patients' experiences of, and reactions to, receiving pharmacogenomically tailored treatments. The aim of this study was to explore the impact of pharmacogenomic prescribing of nicotine replacement therapy (NRT) on smokers' initial expectations of quit success, adherence, and perceived important differences from previous quit attempts...
January 29, 2018: Translational Behavioral Medicine
https://www.readbyqxmd.com/read/29377758/levorphanol-for-treatment-of-intractable-neuropathic-pain-in-cancer-patients
#17
Akhila Reddy, Amy Ng, Tarun Mallipeddi, Eduardo Bruera
Neuropathic pain in cancer patients is often difficult to treat, requiring a combination of several different pharmacological therapies. We describe two patients with complex neuropathic pain syndromes in the form of phantom limb pain and Brown-Sequard syndrome who did not respond to conventional treatments but responded dramatically to the addition of levorphanol. Levorphanol is a synthetic strong opioid that is a potent N-methyl-d-aspartate receptor antagonist, mu, kappa, and delta opioid receptor agonist, and reuptake inhibitor of serotonin and norepinephrine...
January 29, 2018: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/29377216/the-safety-and-efficacy-of-low-dose-naltrexone-in-the-management-of-chronic-pain-and-inflammation-in-multiple-sclerosis-fibromyalgia-crohn-s-disease-and-other-chronic-pain-disorders
#18
Denise K Patten, Bob G Schultz, Daniel J Berlau
Chronic inflammatory diseases are complex to treat and have an impact on a large number of patients. Due to the difficulty of treating these diseases and the great impact on quality of life, patients often seek off-label, complimentary, or alternative medicines to gain relief from symptoms. Low-dose naltrexone has been used off-label for treatment of pain and inflammation in multiple sclerosis, Crohn's disease, fibromyalgia, and other diseases. Naltrexone is a mu-opioid receptor antagonist indicated by the Food and Drug Administration for opioid and alcohol dependence...
January 27, 2018: Pharmacotherapy
https://www.readbyqxmd.com/read/29371114/a-kappa-opioid-receptor-agonist-blocks-bone-cancer-pain-without-altering-bone-loss-tumor-size-or-cancer-cell-proliferation-in-a-mouse-model-of-cancer-induced-bone-pain
#19
Katie A Edwards, Joshua J Havelin, Mary I Mcintosh, Haley A Ciccone, Kathlene Pangilinan, Ian Imbert, Tally M Largent-Milnes, Tamara King, Todd W Vanderah, John M Streicher
Breast cancer metastasizes to bone, diminishing quality of life of patients due to pain, fracture, and limited mobility. Cancer-induced bone pain (CIBP) is characterized as moderate to severe ongoing pain, primarily managed by Mu opioid agonists such as fentanyl. However, opioids are limited by escalating doses and serious side effects. One alternative may be kappa opioid receptor (KOR) agonists. There are few studies examining KOR efficacy on CIBP, while KOR agonists are efficacious in peripheral and inflammatory pain...
January 22, 2018: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29367176/the-morphological-changes-and-molecular-biomarker-responses-in-the-liver-of-fluoride-exposed-bufo-gargarizans-larvae
#20
Xiaoxue Bo, Danyang Mu, Minyao Wu, Hui Xiao, Hongyuan Wang
The goal of the current study was to evaluate the negative influences of fluoride on liver of Bufo gargarizans larvae. B. gargarizans larvae were treated with 42.4mgF-/L for 0, 24, 48 and 72h at Gosner stage 37. The morphological changes and responses of molecular biomarkers involved in lipid metabolism, oxidative stress and apoptosis were examined in liver. Disappearance of cell boundaries, degeneration of hepatic parenchyma cells and significant increase in the number of melanomacrophage centres and the quantity of lipid droplets were found in the liver treated with 42...
January 20, 2018: Ecotoxicology and Environmental Safety
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