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https://www.readbyqxmd.com/read/29346804/trabodenoson-an-adenosine-mimetic-with-a1-receptor-selectivity-lowers-intraocular-pressure-by-increasing-conventional-outflow-facility-in-mice
#1
Guorong Li, Karen Y Torrejon, Andrea M Unser, Feryan Ahmed, Iris D Navarro, Rudolf A Baumgartner, David S Albers, W Daniel Stamer
Purpose: To evaluate the relationship between the IOP-lowering effect of trabodenoson and the associated structural and functional changes in the trabecular meshwork (TM). Methods: Six independent cohorts of young and aged mice were exposed to three different topical once-a-day formulations of trabodenoson and eyes were compared to those treated with placebo drops. IOP was measured daily just before drug administration using rebound tonometry. Outflow facility was measured in enucleated eyes...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29345054/isoflurane-anesthesia-in-aged-mice-and-effects-of-a1-adenosine-receptors-on-cognitive-impairment
#2
Chun-Long Zuo, Chun-Man Wang, Jin Liu, Ting Shen, Jiang-Ping Zhou, Xin-Rui Hao, Yi-Zhao Pan, Hua-Cheng Liu, Qing-Quan Lian, Han Lin
AIMS: Isoflurane may not only accelerate the process of Alzheimer's disease (AD), but increase the risk of incidence of postoperative cognitive dysfunction (POCD). However, the underlying mechanisms remain unknown. This study was designed to investigate whether isoflurane contributed to the POCD occurrence through A1 adenosine receptor (A1AR) in aged mice. METHODS: We assessed cognitive function of mice with Morris water maze (MWM) and then measured expression level of two AD biomarkers (P-tau and Aβ) and a subtype of the NMDA receptor (NR2B) in aged wild-type (WT) and homozygous A1 adenosine receptor (A1AR) knockout (KO) mice at baseline and after they were exposed to isoflurane (1...
January 17, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29344645/targeted-disruption-of-adenosine-kinase-in-myeloid-monocyte-cells-increases-osteoclastogenesis-and-bone-resorption-in-mice
#3
Qiuying Ye, Ge Li, Shuhua Liu, Yalun Guan, Yunfeng Li, Jinling Li, Huanhuan Jia, Xuejiao Li, Qingnan Li, Ren Huang, Hui Wang, Yu Zhang
Adenosine kinase (ADK) serves an important role in intracellular adenosine clearance via phosphorylating adenosine to AMP. The role of adenosine and its receptors in the maintenance of bone homeostasis is well studied, particularly in osteoclastogenesis and bone resorption; however, the function of ADK in bone metabolism is still unclear. In the present study, utilizing the cre/floxp recombination system, mice with conditional loss of ADK function in myeloid monocyte cells were used to assess the effect of ADK deficiency on bone metabolism...
January 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29342124/the-root-of-atractylodes-macrocephala-koidzumi-prevents-obesity-and-glucose-intolerance-and-increases-energy-metabolism-in-mice
#4
Mi Young Song, Soo-Kyoung Lim, Jing-Hua Wang, Hojun Kim
Targeting energy expenditure offers a strategy for treating obesity more effectively and safely. In previous studies, we found that the root of Atractylodes macrocephala Koidzumi (Atractylodis Rhizoma Alba, ARA) increased energy metabolism in C2C12 cells. Here, we investigated the effects of ARA on obesity and glucose intolerance by examining energy metabolism in skeletal muscle and brown fat in high-fat diet (HFD) induced obese mice. ARA decreased body weight gain, hepatic lipid levels and serum total cholesterol levels, but did not modify food intake...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29340626/suppression-of-nlrp3-inflammasome-by-oral-treatment-with-sulforaphane-alleviates-acute-gouty-inflammation
#5
Gabsik Yang, Sang Hyeon Yeon, Hye Eun Lee, Han Chang Kang, Yong Yeon Cho, Hye Suk Lee, Joo Young Lee
Objective: The aetiology of gout is closely linked to the deposition of monosodium uric acid (MSU) crystals and the consequent activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we investigated whether oral administration of an NLRP3 inhibitor would be effective to attenuate the symptoms of gout. Methods: The effects of oral administration with sulforaphane (SFN) were examined in two mouse models of acute gout induced by injection of MSU crystals into footpads or air pouch...
January 10, 2018: Rheumatology
https://www.readbyqxmd.com/read/29338068/single-and-combined-effects-of-plant-derived-thc-cbd-and-synthetic-win-55-212-cannabinoids-on-cognition-and-cannabinoid-associated-withdrawal-signs-in-mice
#6
Alyssa M Myers, Patrick B Siegele, Jeffrey D Foss, Ronald F Tuma, Sara Jane Ward
BACKGROUND AND PURPOSE: It has been suggested that the non-euphorogenic phytocannabinoid cannabidiol (CBD) can ameliorate adverse effects of delta-9-tetrahydrocannabinol (THC). We determined whether CBD ameliorates cognitive deficits and withdrawal signs induced by cannabinoid CB1/CB2 receptor agonists or produces these pharmacological effects on its own. EXPERIMENTAL APPROACH: The effects of THC or the CB1/CB2 receptor full agonist WIN55212 (WIN) alone, CBD alone, or their combination were tested across a range of doses...
January 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29337260/modelling-and-simulation-of-biased-agonism-dynamics-at-a-g%C3%A2-protein-coupled-receptor
#7
L J Bridge, J Mead, E Frattini, I Winfield, G Ladds
Theoretical models of G protein-coupled receptor (GPCR) concentration-response relationships often assume an agonist producing a single functional response via a single active state of the receptor. These models have largely been analysed assuming steady-state conditions. There is now much experimental evidence to suggest that many GPCRs can exist in multiple receptor conformations and elicit numerous functional responses, with ligands having the potential to activate different signalling pathways to varying extents - a concept referred to as biased agonism, functional selectivity or pluri-dimensional efficacy...
January 11, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29335859/arginine-vasopressin-aquaporin-2-pathway-mediated-dehydration-effects-of-electroacupuncture-in-guinea-pig-model-of-avp-induced-endolymphatic-hydrops
#8
Li-Yuan Jiang, Jiao-Jun He, Xi-Xi Chen, Xue-Jiao Sun, Xue-Zhong Wang, Shan Zhong, Hua-de Chen
OBJECTIVE: To investigate the effects of electroacupuncture (EA) on endolymphatic hydrops (EH) and the regulation of arginine vasopressin (AVP)-aquaporin-2 (AQP2) pathway in guinea pigs. METHODS: EH was induced in male guinea pigs by an intraperitoneal injection of AVP. For the treatment, EA was delivered to Baihui (GV 20) and Tinggong (SI 19) acupoints, once per day for 10 consecutive days. In histomorphological studies, cochlear hydrops degree was evaluated by hematoxylin-eosin (HE) staining, and then the ratio of scala media (SM) area to SM + scala vestibuli (SV) area (R value) was calculated...
January 15, 2018: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29335059/association-of-%C3%AE-2a-adrenergic-receptor-genetic-variants-with-platelet-reactivity-in-chinese-patients-on-dual-antiplatelet-therapy-undergoing-percutaneous-coronary-intervention
#9
Ying Song, Xiao Fang Tang, Yi Yao, Chen He, Jing Jing Xu, Huan Huan Wang, Zhan Gao, Mia Wang, Jin Qing Yuan
OBJECTIVE: The alpha 2A-adrenergic receptor gene (ADRA2A) polymorphism in individuals modifies the antiplatelet response to sympathetic stimulation. The aim of this study was to investigate the effect of ADRA2A variants on platelet reactivity in Chinese patients on dual antiplatelet therapy (DAPT) after undergoing percutaneous coronary intervention (PCI). METHODS: From March 2011 to March 2013, 1,024 patients were enrolled in this prospective, single-center, observational study in China...
December 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/29334795/progress-in-the-development-of-histamine-h3-receptor-antagonists-inverse-agonists-a-patent-review-2013-2017
#10
Dorota Łażewska, Katarzyna Kieć-Kononowicz
Since years, ligands blocking histamine H3 receptor (H3R) activity (antagonists/inverse agonists) are interesting targets in the search for new cures for CNS disorders. Intensive works done by academic and pharmaceutical company researchers have led to many potent and selective H3R antagonists/inverse agonists. Some of them have reached to clinical trials. Areas covered: Patent applications from January 2013 to September 2017 and the most important topics connected with H3R field are analysed. Espacenet, Patentscope, Pubmed, GoogleScholar or Cochrane Library online databases were principially used to collect all the materials...
January 15, 2018: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29333376/anti-inflammatory-and-anti-obesity-properties-of-food-bioactive-components-effects-on-adipose-tissue
#11
REVIEW
Shasika Jayarathne, Iurii Koboziev, Oak-Hee Park, Wilna Oldewage-Theron, Chwan-Li Shen, Naima Moustaid-Moussa
Obesity is an epidemic and costly disease affecting 13% of the adult population worldwide. Obesity is associated with adipose tissue hypertrophy and hyperplasia, as well as pathologic endocrine alterations of adipose tissue including local and chronic systemic low-grade inflammation. Moreover, this inflammation is a risk factor for both metabolic syndrome (MetS) and insulin resistance. Basic and clinical studies demonstrate that foods containing bioactive compounds are capable of preventing both obesity and adipose tissue inflammation, improving obesity-associated MetS in human subjects and animal models of obesity...
December 2017: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/29332604/the-effect-of-an-adenosine-a2a-agonist-on-intra-tumoral-concentrations-of-temozolomide-in-patients-with-recurrent-glioblastoma
#12
Sadhana Jackson, Jon Weingart, Edjah K Nduom, Thura T Harfi, Richard T George, Dorothea McAreavey, Xiaobu Ye, Nicole M Anders, Cody Peer, William D Figg, Mark Gilbert, Michelle A Rudek, Stuart A Grossman
BACKGROUND: The blood-brain barrier (BBB) severely limits the entry of systemically administered drugs including chemotherapy to the brain. In rodents, regadenoson activation of adenosine A2A receptors causes transient BBB disruption and increased drug concentrations in normal brain. This study was conducted to evaluate if activation of A2A receptors would increase intra-tumoral temozolomide concentrations in patients with glioblastoma. METHODS: Patients scheduled for a clinically indicated surgery for recurrent glioblastoma were eligible...
January 15, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29332488/role-of-the-hippocampal-5-ht1a-receptor-mediated-camp-pka-signalling-pathway-in-sevoflurane-induced-cognitivedysfunction-in-aged-rats
#13
Yi Qiu, Ying Wang, Xiaodong Wang, Caixia Wang, Zhong-Yuan Xia
Objective This study aimed to evaluate the role of the hippocampal 5-hydroxytryptamine-1A (5-HT1A)-mediated cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signalling pathway in sevoflurane-induced cognitive dysfunction in aged rats. Methods Sixty 18-month-old Sprague-Dawley rats were divided into the control (n = 30) and experimental (Sev, n = 30) groups. The experimental group inhaled 50% air/oxygen mixture (2 L/min) and 2% sevoflurane for 4 hours. The control group inhaled 50% air/oxygen mixture (2 L/min) for 4 hours...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29332180/cd39-adenosinergic-axis-in-renal-pathophysiology-and-therapeutics
#14
REVIEW
Bellamkonda K Kishore, Simon C Robson, Karen M Dwyer
Extracellular ATP interacts with purinergic type 2 (P2) receptors and elicits many crucial biological functions. Extracellular ATP is sequentially hydrolyzed to ADP and AMP by the actions of defined nucleotidases, such as CD39, and AMP is converted to adenosine, largely by CD73, an ecto-5'-nucleotidase. Extracellular adenosine interacts with P1 receptors and often opposes the effects of P2 receptor activation. The balance between extracellular ATP and adenosine in the blood and extracellular fluid is regulated chiefly by the activities of CD39 and CD73, which constitute the CD39-adenosinergic axis...
January 13, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29331420/dacomitinib-antagonizes-multidrug-resistance-mdr-in-cancer-cells-by-inhibiting-the-efflux-activity-of-abcb1-and-abcg2-transporters
#15
Ying-Fang Fan, Wei Zhang, Leli Zeng, Zi-Ning Lei, Chao-Yun Cai, Pranav Gupta, Dong-Hua Yang, Qingbin Cui, Zuo-Dong Qin, Zhe-Sheng Chen, Louis D Trombetta
The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Numerous mechanisms have been recognized that cause MDR, but one of the most important mechanisms is overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters, through which the efflux of various anticancer drugs against their concentration gradients is powered by ATP. In recent years, small molecular tyrosine kinase inhibitors (TKIs) have been developed for treatment in various human cancers overexpressing epidermal growth factor receptor (EGFR)...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29330344/parathyroid-hormone-related-protein-exhibits-antioxidant-features-in-osteoblastic-cells-through-its-n-terminal-and-osteostatin-domains
#16
S Portal-Núñez, J A Ardura, D Lozano, I Martínez de Toda, M De la Fuente, G Herrero-Beaumont, R Largo, P Esbrit
OBJECTIVES: Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain...
January 2018: Bone & Joint Research
https://www.readbyqxmd.com/read/29329032/targeting-expression-of-adenosine-receptors-during-hypoxia-induced-angiogenesis-a-study-using-zebrafish-model
#17
Navina Panneerselvan, Malathi Ragunathan
Hypoxia is known to be a major player during pathological angiogenesis and adenosine as a negative feedback signaling to maintain oxygen delivery in pathological ischemic condition. We mimicked hypoxic condition and studied angiogenesis by inducing adenosine receptors using forskolin, a plant compound and NECA analogue of adenosine using zebrafish model. Vascular endothelial growth factor (VEGF) is known to play a key role during pathological angiogenesis and regulated by the factors HIF1a under hypoxic condition and recently Notch is proposed to play a negative feedback loop mechanism along with VEGF signaling but the role of adenosine receptor during the process is not known...
January 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29328405/liraglutide-repairs-the-infarcted-heart-the-role-of-the-sirt1-parkin-mitophagy-pathway
#18
Huiying Qiao, Haiyan Ren, He Du, Minfang Zhang, Xiaofang Xiong, Rong Lv
Liraglutide is glucagon‑like peptide‑1 receptor agonist used for treating patients with type 2 diabetes mellitus. The present study aimed to investigate the role and mechanism of liraglutide in repairing the infarcted heart following myocardial infarction. The results of the present study demonstrated that amplification of the dose of liraglutide for ~28 days was able to reduce cardiac fibrosis, inflammatory responses and myocardial death in the post‑infarcted heart. In vitro, liraglutide protected cardiomyocyte mitochondria against the chronic hypoxic damage, inhibiting the mitochondrial apoptosis pathways...
January 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29327202/transient-disruption-of-adenosine-signaling-during-embryogenesis-triggers-a-pro-epileptic-phenotype-in-adult-zebrafish
#19
Fabiano Peres Menezes, Felipe Machado Torresini, Laura Roesler Nery, Rosane Souza da Silva
Adenosinergic signaling has important effects on brain function, anatomy, and physiology in both late and early stages of development. Exposure to caffeine, a non-specific blocker of adenosine receptor, has been indicated as a developmental risk factor. Disruption of adenosinergic signaling during early stages of development can change the normal neural network formation and possibly lead to an increase in susceptibility to seizures. In this work, morpholinos (MO) temporarily blocked the translation of adenosine receptor transcripts, adora1, adora2aa, and adora2ab, during the embryonic phase of zebrafish...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29326489/ondansetron-ameliorates-depression-associated-with-obesity-in-high-fat-diet-fed-experimental-mice-an-investigation-based-on-the-behavioral-biochemical-and-molecular-approach
#20
Yeshwant Kurhe, Radhakrishnan Mahesh
INTRODUCTION: Obesity is an important risk factor for depression as more than half of the obese population is susceptible for depression at double rate. Our earlier studies reported the antidepressant potential of 5-HT3 receptor antagonist, ondansetron (OND) in depression associated obesity using behavioral tasks. The present research work is aimed to evaluate the effect of OND on depression associated with obesity with special emphasis on biochemical and molecular mechanisms such as hippocampal brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate (cAMP), 5-hydroxytryptamine (5-HT), hippocampal histological examination and immunohistochemical expression of p53 proteins...
July 2017: Indian Journal of Pharmacology
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