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https://www.readbyqxmd.com/read/28230861/ripk3-interactions-with-mlkl-and-camkii-mediate-oligodendrocytes-death-in-the-developing-brain
#1
Yi Qu, Jun Tang, Huiqing Wang, Shiping Li, Fengyan Zhao, Li Zhang, Q Richard Lu, Dezhi Mu
Oligodendrocyte progenitor cells (OPCs) death is a key contributor to cerebral white matter injury (WMI) in the developing brain. A previous study by our group indicated that receptor-interacting proteins (RIPs) are crucial in mediating necroptosis in developing neurons. However, whether this mechanism is involved in OPCs death is unclear. We aimed to explore the mechanisms of RIP-mediated oligodendrocytes (OLs) death in the developing brain. Oligodendrocytes necroptosis was induced by oxygen-glucose deprivation plus caspase inhibitor zVAD treatment (OGD/zVAD) in vitro...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28226339/current-concepts-of-phenylpiperidine-derivatives-use-in-the-treatment-of-acute-and-chronic-pain
#2
Nidal Elbaridi, Alan D Kaye, Stephanie Choi, Richard D Urman
Phenylpiperidines are a chemical class of drugs with a phenyl moiety directly attached to piperidine. These agents have an important role in many aspects of medicine including anesthesia and pain medicine. After the development of meperidine, fentanyl, which is a second generation synthetic phenylpiperidine series opioid, was synthesized and introduced into clinical anesthesia practice as fentanyl citrate in 1968. Fentanyl-mediated or modulated responses involve action at the mu-opioid receptor as an agonist at the dorsal horn inhibiting ascending pain pathways in the rostral ventral medulla, increasing pain threshold, and producing both analgesic and sedative effects...
February 2017: Pain Physician
https://www.readbyqxmd.com/read/28225824/caloric-restriction-reduces-the-systemic-progression-of-mouse-aapoaii-amyloidosis
#3
Lin Li, Jinko Sawashita, Xin Ding, Mu Yang, Zhe Xu, Hiroki Miyahara, Masayuki Mori, Keiichi Higuchi
In mouse senile amyloidosis, apolipoprotein (Apo) A-II is deposited extracellularly in many organs in the form of amyloid fibrils (AApoAII). Reduction of caloric intake, known as caloric restriction (CR), slows the progress of senescence and age-related disorders in mice. In this study, we intravenously injected 1 μg of isolated AApoAII fibrils into R1.P1-Apoa2c mice to induce experimental amyloidosis and investigated the effects of CR for the next 16 weeks. In the CR group, AApoAII amyloid deposits in the liver, tongue, small intestine and skin were significantly reduced compared to those of the ad libitum feeding group...
2017: PloS One
https://www.readbyqxmd.com/read/28216001/loperamide-inhibits-sodium-channels-to-alleviate-inflammatory-hyperalgesia
#4
Ying Wu, Beiyan Zou, Lingli Liang, Min Li, Yuan-Xiang Tao, Haibo Yu, Xiaoliang Wang, Min Li
Previous studies demonstrated that Loperamide, originally known as an anti-diarrheal drug, is a promising analgesic agent primarily targeting mu-opioid receptors. However some evidences suggested that non-opioid mechanisms may be contributing to its analgesic effect. In the present study, Loperamide was identified as a Nav1.7 blocker in a pilot screen. In HEK293 cells expressing Nav1.7 sodium channels, Loperamide blocked the resting state of Nav1.7 channels (IC50 = 1.86 ± 0.11 μM) dose-dependently and reversibly...
February 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28215164/innovative-opioid-peptides-and-biased-agonism-novel-avenues-for-more-effective-and-safer-analgesics-to-treat-chronic-pain
#5
Andrea Bedini, Santi Mario Spampinato
Chronic pain is a clinically relevant and yet unsolved conditions that is poorly treated with the currently available drugs, thus highlighting the urgent need of innovative analgesics. Although opiates are not very effective in the treatment of inflammatory and neuropathic pain, developing novel opioid receptor peptide agonists, as well as modulating the opioid receptor-mediated responses in a ligand-specific fashion, may represent an innovative and promising strategy to identify more efficacious and safer antalgic drugs...
February 15, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28204957/insights-into-the-role-of-opioid-receptors-in-the-gi-tract-experimental-evidence-and-therapeutic-relevance
#6
James J Galligan, Catia Sternini
Opioid drugs are prescribed extensively for pain treatment but when used chronically they induce constipation that can progress to opioid-induced bowel dysfunction. Opioid drugs interact with three classes of opioid receptors: mu opioid receptors (MORs), delta opioid receptors (DOR), and kappa opioid receptors (KORs), but opioid drugs mostly target the MORs. Upon stimulation, opioid receptors couple to inhibitory Gi/Go proteins that activate or inhibit downstream effector proteins. MOR and DOR couple to inhibition of adenylate cyclase and voltage-gated Ca(2+) channels and to activation of K(+) channels resulting in reduced neuronal activity and neurotransmitter release...
February 16, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28202635/short-term-subclinical-zinc-deficiency-in-weaned-piglets-affects-cardiac-redox-metabolism-and-zinc-concentration
#7
Daniel Brugger, Wilhelm M Windisch
Background: Subclinical zinc deficiency (SZD) represents the common zinc malnutrition phenotype. However, its association with oxidative stress is not well understood. The heart muscle may be a promising target for studying early changes in redox metabolism.Objective: We investigated the effects of short-term SZD on cardiac redox metabolism in weaned piglets.Methods: Forty-eight weaned German Large White × Landrace × Piétrain piglets (50% castrated males and 50% females; body weight of 8.5 kg) were fed diets with different zinc concentrations for 8 d...
February 15, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28199982/n-acetyl-cysteine-attenuates-remifentanil-induced-postoperative-hyperalgesia-via-inhibiting-matrix-metalloproteinase-9-in-dorsal-root-ganglia
#8
Yue Liu, Yuan Ni, Wei Zhang, Yu-E Sun, Zhengliang Ma, Xiaoping Gu
Treatment of remifentanil-induced postoperative hyperalgesia (RIH) remains a clinical challenge because the mechanisms are not fully understood. Matrix metalloproteinase-9 (MMP-9) is a key component in neuroinflammation because of its facilitation of pro-inflammatory cytokine maturation. Therefore, inhibition of MMP-9 may represent a novel therapeutic approach to the treatment of RIH. Sprague-Dawley rats were randomly divided into three groups: Control, Incision and Remifentanil. A right plantar surgical incision was performed in Group Incision, and intraoperative remifentanil (0...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197194/cortical-regulation-of-striatal-projection-neurons-and-interneurons-in-a-parkinson-s-disease-rat-model
#9
Jia-Jia Wu, Si Chen, Li-Si Ouyang, Yu Jia, Bing-Bing Liu, Shu-Hua Mu, Yu-Xin Ma, Wei-Ping Wang, Jia-You Wei, You-Lan Li, Zhi Chen, Wan-Long Lei
Striatal neurons can be either projection neurons or interneurons, with each type exhibiting distinct susceptibility to various types of brain damage. In this study, 6-hydroxydopamine was injected into the right medial forebrain bundle to induce dopamine depletion, and/or ibotenic acid was injected into the M1 cortex to induce motor cortex lesions. Immunohistochemistry and western blot assay showed that dopaminergic depletion results in significant loss of striatal projection neurons marked by dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein, molecular weight 32 kDa, calbindin, and μ-opioid receptor, while cortical lesions reversed these pathological changes...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28192273/gabaa-receptor-subtypes-in-the-mouse-brain-regional-mapping-and-diazepam-receptor-occupancy-by-in-vivo-18-f-flumazenil-pet
#10
Adrienne Müller Herde, Dietmar Benke, William T Ralvenius, Linjing Mu, Roger Schibli, Hanns Ulrich Zeilhofer, Stefanie D Krämer
Classical benzodiazepines, which are widely used as sedatives, anxiolytics and anticonvulsants, exert their therapeutic effects through interactions with heteropentameric GABAA receptors composed of two α, two β and one γ2 subunit. Their high affinity binding site is located at the interface between the γ2 and the adjacent α subunit. The α-subunit gene family consists of six members and receptors can be homomeric or mixed with respect to the α-subunits. Previous work has suggested that benzodiazepine binding site ligands with selectivity for individual GABAA receptor subtypes, as defined by the benzodiazepine-binding α subunit, may have fewer side effects and may even be effective in diseases, such as schizophrenia, autism or chronic pain, that do not respond well to classical benzodiazepines...
February 10, 2017: NeuroImage
https://www.readbyqxmd.com/read/28192197/characterization-of-3-h-oxymorphone-binding-sites-in-mouse-brain-quantitative-autoradiography-in-opioid-receptor-knockout-mice
#11
Ji Hoon Yoo, Anna Borsodi, Géza Tóth, Sándor Benyhe, Robert Gaspar, Audrey Matifas, Brigitte L Kieffer, Athanasios Metaxas, Ian Kitchen, Alexis Bailey
Oxymorphone, one of oxycodone's metabolic products, is a potent opioid receptor agonist which is thought to contribute to the analgesic effect of its parent compound and may have high potential abuse liability. Nonetheless, the in vivo pharmacological binding profile of this drug is still unclear. This study uses mice lacking mu (MOP), kappa (KOP) or delta (DOP) opioid receptors as well as mice lacking all three opioid receptors to provide full characterisation of oxymorphone binding sites in the brain. Saturation binding studies using [(3)H]oxymorphone revealed high affinity binding sites in mouse brain displaying Kd of 1...
February 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28188737/genetic-variation-in-the-behavioral-effects-of-buprenorphine-in-female-mice-derived-from-a-murine-model-of-the-oprm1-a118g-polymorphism
#12
Caroline A Browne, Rebecca L Erickson, Julie A Blendy, Irwin Lucki
Pharmacogenetic studies have identified the non-synonymous single nucleotide polymorphism (A118G) in the human mu opioid receptor (MOR) gene (OPRM1) as a critical genetic variant capable of altering the efficacy of opioid therapeutics. To date few studies have explored the potential impact of the OPRM1 A118G polymorphism on the pharmacological effects of buprenorphine (BPN), a potent MOR partial agonist and kappa opioid receptor antagonist, which is approved by the FDA for the treatment of opioid addiction and chronic pain...
February 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28185645/mu-opioid-receptors-in-gamma-aminobutyric-acidergic-forebrain-neurons-moderate-motivation-for-heroin-and-palatable-food
#13
Pauline Charbogne, Olivier Gardon, Elena Martín-García, Helen L Keyworth, Aya Matsui, Anna E Mechling, Thomas Bienert, Taufiq Nasseef, Anne Robé, Luc Moquin, Emmanuel Darcq, Sami Ben Hamida, Patricia Robledo, Audrey Matifas, Katia Befort, Claire Gavériaux-Ruff, Laura-Adela Harsan, Dominik von Elverfeldt, Jurgen Hennig, Alain Gratton, Ian Kitchen, Alexis Bailey, Veronica A Alvarez, Rafael Maldonado, Brigitte L Kieffer
BACKGROUND: Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward. METHODS: We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons...
December 26, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28184196/ag36-inhibits-human-breast-cancer-cells-proliferation-by-promotion-of-apoptosis-in-vitro-and-in-vivo
#14
Li-Hua Mu, Yu-Ning Wang, Dong-Xiao Wang, Jing Zhang, Li Liu, Xian-Zhe Dong, Yuan Hu, Ping Liu
AG36 is the biotransformation product of triterpenoid saponin from Ardisia gigantifolia stapf. In this study, the antitumor activity and underlying molecular mechanisms of AG36 against human breast MCF-7, MDA-MB-231, and SK-BR-3 cancer cells were investigated. AG36 inhibited the viability of MCF-7, MDA-MB-231, and SK-BR-3 cells in a dose and time-dependent manner, with an IC50 of approximately 0.73, 18.1, and 23.4 μM at 48 h, respectively. AG36 obviously induced apoptosis and G2/M arrest of all the three breast cancer cells...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28178768/distribution-of-endomorphin-like-immunoreactive-neurones-in-the-brain-of-the-cichlid-fish-oreochromis-mossambicus
#15
Vijayalaxmi, C B Ganesh
Endomorphins are tetrapeptides involved in pain and neuroendocrine responses with high affinity for mu opioid receptors in mammals. In the present investigation, we studied the distribution of endomorphin-like-immunoreactive (EM-L-ir) neurones in the brain of the cichlid fish Oreochromis mossambicus. Application of antisera against endomorphin 1 and 2 (EM-1-2) revealed the presence of EM-L-ir somata and fibres throughout the different subdivisions of the olfactory bulb such as the olfactory nerve layer and the granule cell layer...
February 8, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28178640/a-phase-i-ii-study-of-the-investigational-drug-alisertib-in-combination-with-abiraterone-and-prednisone-for-patients-with-metastatic-castration-resistant-prostate-cancer-progressing-on-abiraterone
#16
Jianqing Lin, Sheel A Patel, Ashwin R Sama, Jean H Hoffman-Censits, Brooke Kennedy, Deborah Kilpatrick, Zhong Ye, Hushan Yang, Zhaomei Mu, Benjamin Leiby, Nancy Lewis, Massimo Cristofanilli, William Kevin Kelly
LESSONS LEARNED: Patients with metastatic castration-resistant prostate cancer did not tolerate the combination of alisertib with abiraterone and prednisone.There was no clear signal indicating that adding alisertib might be beneficial for those patients progressing on abiraterone. BACKGROUND: We hypothesized that Aurora A kinase (AK) contributes to castrate resistance in prostate cancer (PCa) and that inhibiting AK with alisertib can resensitize PCa cells to androgen receptor (AR) inhibitor abiraterone...
November 2016: Oncologist
https://www.readbyqxmd.com/read/28174489/alk-gene-expression-status-in-pleural-effusion-predicts-tumor-responsiveness-to-crizotinib-in-chinese-patients-with-lung-adenocarcinoma
#17
Zheng Wang, Xiaonan Wu, Xiaohong Han, Gang Cheng, Xinlin Mu, Yuhui Zhang, Di Cui, Chang Liu, Dongge Liu, Yuankai Shi
OBJECTIVE: The relationship between anaplastic lymphoma kinase (ALK) expression in malignant pleural effusion (MPE) samples detected only by Ventana immunohistochemistry (IHC) ALK (D5F3) and the efficacy of ALK-tyrosine kinase inhibitor therapy is uncertain. METHODS: Ventana anti-ALK (D5F3) rabbit monoclonal primary antibody testing was performed on 313 cell blocks of MPE samples from Chinese patients with advanced lung adenocarcinoma, and fluorescence in situ hybridization (FISH) was used to verify the ALK gene status in Ventana IHC ALK (D5F3)-positive samples...
December 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28166603/electroacupuncture-attenuates-hyperalgesia-in-rats-withdrawn-from-chronic-alcohol-drinking-via-habenular-mu-opioid-receptors
#18
Jing Li, Caihong Fu, Hongwei Liu, Rao Fu, Wanhong Zuo, Seungwoo Kang, Pei Chen, Danielle Gregor, Rose Paulose, Alex Bekker, Jiang-Hong Ye
BACKGROUND: Hyperalgesia or increased sensitivity to pain is often found in alcoholics during alcohol withdrawal and may contribute to relapse drinking. Alternative therapies such as acupuncture and electroacupuncture (EA), through mechanisms involving opioid receptors, may reduce pain and substance dependence and withdrawal syndromes. The lateral habenula (LHb), an epithalamic structure rich in mu opioid receptors (MORs), is a critical target for both drugs of abuse and pain. We previously observed hyperalgesia in rats withdrawn from chronic ethanol (EtOH) drinking and found that EA at the acupoint Zusanli (ST36) reduced EtOH intake...
February 6, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28162521/-285-phosphatidylethanolamine-binding-protein-regulates-mu-opioid-receptor-induced-%C3%AE-arrestin2-recruitment-and-downstream-signaling
#19
K Edwards, J Bogusz, J LaVigne, K Pangilinan, J Streicher
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28158929/the-analgesic-and-anti-inflammatory-effects-of-salvinorin-a-analogue-%C3%AE-tetrahydropyran-salvinorin-b-in-mice
#20
K F Paton, N Kumar, R S Crowley, J L Harper, T E Prisinzano, B M Kivell
BACKGROUND: Drugs activating the mu opioid receptor are routinely used to treat severe acute and chronic pain. Unfortunately, side effects including nausea, constipation, respiratory depression, addiction and tolerance can limit clinical utility. In contrast, kappa opioid receptor (KOPr) agonists, such as Salvinorin A (SalA), have analgesic properties with little potential for abuse. METHODS: We evaluated SalA and the novel analogue β-tetrahydropyran Salvinorin B (β-THP SalB) for the ability to modulate pain and inflammation in vivo...
February 3, 2017: European Journal of Pain: EJP
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