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https://www.readbyqxmd.com/read/29223003/steroidogenic-factor-1-inverse-agonists-as-a-treatment-option-for-canine-hypercortisolism-in%C3%A2-vitro-study
#1
K Sanders, J A Mol, A Slob, H S Kooistra, S Galac
Hypercortisolism is one of the most commonly diagnosed endocrinopathies in dogs, and new targeted medical treatment options are desirable. Steroidogenic factor-1 (SF-1), an orphan nuclear hormone receptor, is a key regulator of adrenal steroidogenesis, development, and growth. In pituitary-dependent hypercortisolism (PDH), high plasma ACTH concentrations increase the transcriptional activity of SF-1. In adrenal-dependent hypercortisolism, SF-1 expression is significantly greater in dogs with recurrence after adrenalectomy than in those without recurrence...
November 21, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29222907/the-ameliorative-effect-of-fluoxetine-on-neuroinflammation-induced-by-sleep-deprivation
#2
Maosheng Xia, Xiaowei Li, Li Yang, Jiaan Ren, Guangfeng Sun, Shuang Qi, Alexei Verkhratsky, Baoman Li
It is well known that sleep disorders are harmful to people's health and performance, and growing evidence suggests that sleep deprivation (SD) can trigger neuroinflammation in the brain. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome is reported to be relevant to the neuroinflammation induced by SD, but the regulatory signaling that governs the NLRP3 inflammasome in SD is still unknown. Meanwhile, whether the regulatory action of antidepressants in astrocytes could affect the neuroinflammation induced by SD also remains obscure...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29222395/extracellular-adenosine-stimulates-vacuolar-atpase-dependent-proton-secretion-in-medullary-intercalated-cells
#3
Maria A Battistone, Anil V Nair, Claire R Barton, Rachel N Liberman, Maria A Peralta, Diane E Capen, Dennis Brown, Sylvie Breton
Acidosis is an important complication of AKI and CKD. Renal intercalated cells (ICs) express the proton pumping vacuolar H+-ATPase (V-ATPase) and are extensively involved in acid-base homeostasis. H+ secretion in type A intercalated cells (A-ICs) is regulated by apical vesicle recycling and stimulated by cAMP. In other cell types, cAMP is increased by extracellular agonists, including adenosine, through purinergic receptors. Adenosine is a Food and Drug Administration-approved drug, but very little is known about the effect of adenosine on IC function...
December 8, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29222249/thrombocytopenia-in-pregnancy
#4
REVIEW
Douglas B Cines, Lisa D Levine
Thrombocytopenia develops in 5% to 10% of women during pregnancy or in the immediate postpartum period. A low platelet count is often an incidental feature, but it might also provide a biomarker of a coexisting systemic or gestational disorder and a potential reason for a maternal intervention or treatment that might pose harm to the fetus. This chapter reflects our approach to these issues with an emphasis on advances made over the past 5 to 10 years in understanding and managing the more common causes of thrombocytopenia in pregnancy...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222242/treatment-of-inherited-bone-marrow-failure-syndromes-beyond-transplantation
#5
REVIEW
Rodrigo T Calado, Diego V Clé
Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure syndromes are still not eligible for a transplant. In addition, the availability of sequencing panels has significantly improved diagnosis by identifying cryptic inherited cases. Androgens are the main nontransplant therapy for bone marrow failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to 80% of cases. Danazol and oxymetholone are more commonly used, but virilization and liver toxicity are major adverse events...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222166/effect-of-il-7-therapy-on-phospho-ribosomal-protein-s6-and-traf1-expression-in-hiv-specific-cd8-t-cells-in-patients-receiving-antiretroviral-therapy
#6
Chao Wang, Maria I Edilova, Lisa E Wagar, Shariq Mujib, Meromit Singer, Nicole F Bernard, Thérèse Croughs, Michael M Lederman, Irini Sereti, Margaret A Fischl, Elisabeth Kremmer, Mario Ostrowski, Jean-Pierre Routy, Tania H Watts
IL-7 therapy has been evaluated in patients who do not regain normal CD4 T cell counts after virologically successful antiretroviral therapy. IL-7 increases total circulating CD4 and CD8 T cell counts; however, its effect on HIV-specific CD8 T cells has not been fully examined. TRAF1, a prosurvival signaling adaptor required for 4-1BB-mediated costimulation, is lost from chronically stimulated virus-specific CD8 T cells with progression of HIV infection in humans and during chronic lymphocytic choriomeningitis infection in mice...
December 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29222092/targeted-disruption-of-the-kcnj5-gene-in-the-female-mouse-lowers-aldosterone-levels
#7
Iris Hardege, Lu Long, Raya Al Maskari, Nicola Figg, Kevin M O'Shaughnessy
Aldosterone is released from adrenal zona glomerulosa cells and plays an important role in Na and K homeostasis. Mutations in the human KCNJ5 gene encoding the GIRK4 potassium channel cause abnormal aldosterone secretion and hypertension. To better understand the role of wild-type (WT) GIRK4 in regulating aldosterone release we have looked at aldosterone secretion in a Kcnj5 knock-out (KO) mouse.  We found that female, but not male, KO mice have reduced aldosterone levels compared to WT female controls, but higher levels of aldosterone after Ang-II stimulation...
December 8, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29221950/dha-supplementation-prevent-the-progression-of-nash-via-gpr120-signaling
#8
Kazuo Nakamoto, Koki Shimada, Shinichi Harada, Yasuko Morimoto, Akira Hirasawa, Shogo Tokuyama
Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases involving chronic accumulation of fat and inflammation, often leading to advanced fibrosis, cirrhosis and carcinoma. However, the pathological mechanism for this is unknown. GPR120/FFAR4 has been recognized as a functional fatty acid receptor and an attractive therapeutic target for metabolic diseases. In this study, we investigated the involvement of GPR120/FFAR4 in the pathogenesis of NASH. Mice fed with a 0.1% methionine and choline deficient high-fat (CDAHF) diet showed a significant increase in plasma aspartate transaminase and alanine transaminase levels, fatty deposition, inflammatory cell infiltration, and mild fibrosis...
December 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29221792/the-serotonin-hallucinogen-5-meo-dmt-alters-cortico-thalamic-activity-in-freely-moving-mice-regionally-selective-involvement-of-5-ht1a-and-5-ht2a-receptors
#9
REVIEW
Maurizio S Riga, Laia Lladó-Pelfort, Francesc Artigas, Pau Celada
5-MeO-DMT is a natural hallucinogen acting as serotonin 5-HT1A/5-HT2A receptor agonist. Its ability to evoke hallucinations could be used to study the neurobiology of psychotic symptoms and to identify new treatment targets. Moreover, recent studies revealed the therapeutic potential of serotonin hallucinogens in treating mood and anxiety disorders. Our previous results in anesthetized animals show that 5-MeO-DMT alters cortical activity via 5-HT1A and 5-HT2A receptors. Here, we examined 5-MeO-DMT effects on oscillatory activity in prefrontal (PFC) and visual (V1) cortices, and in mediodorsal thalamus (MD) of freely-moving wild-type (WT) and 5-HT2A-R knockout (KO2A) mice...
December 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29221778/long-term-treatment-with-dopamine-d3-receptor-agonists-induces-a-behavioral-switch-that-can-be-rescued-by-blocking-the-dopamine-d1-receptor
#10
Mai-Lynne Dinkins, Perrine Lallemand, Stefan Clemens
Restless legs syndrome (RLS) is commonly treated with the dopamine agonists pramipexole, and rotigotine, which target the inhibitory dopamine receptor subtype D3R. While initially highly effective, these compounds lose their efficacy in treating RLS over time, and long-term therapy regularly leads to a worsening of the symptoms (augmentation). This dopamine agonist-induced augmentation has become a prime concern in the treatment of RLS, and while alternate therapies are being proposed, the mechanisms leading to augmentation remain opaque...
December 2017: Sleep Medicine
https://www.readbyqxmd.com/read/29221659/cardiovascular-outcomes-with-glucagon-like-peptide-1-receptor-agonists-in-patients-with-type-2-diabetes-a-meta-analysis
#11
M Angelyn Bethel, Rishi A Patel, Peter Merrill, Yuliya Lokhnygina, John B Buse, Robert J Mentz, Neha J Pagidipati, Juliana C Chan, Stephanie M Gustavson, Nayyar Iqbal, Aldo P Maggioni, Peter Öhman, Neil R Poulter, Ambady Ramachandran, Bernard Zinman, Adrian F Hernandez, Rury R Holman
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs. Findings from cardiovascular outcome trials showed cardiovascular safety of GLP-1 receptor agonists, but results for cardiovascular efficacy were varied. We aimed to examine overall cardiovascular efficacy for lixisenatide, liraglutide, semaglutide, and extended-release exenatide. METHODS: In this systematic review and meta-analysis, we analysed data from eligible trials that assessed the safety and efficacy of GLP-1 receptor agonists compared with placebo in adult patients (aged 18 years or older) with type 2 diabetes and had a primary outcome including, but not limited to, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke...
December 5, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29221658/glp-1-receptor-agonists-differentiation-within-the-class
#12
Simeon I Taylor
No abstract text is available yet for this article.
December 5, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29221189/novel-direct-ampk-activator-suppresses-non-small-cell-lung-cancer-through-inhibition-of-lipid-metabolism
#13
Xi Chen, Chun Xie, Xing-Xing Fan, Ze-Bo Jiang, Vincent Kam-Wai Wong, Jia-Hui Xu, Xiao-Jun Yao, Liang Liu, Elaine Lai-Han Leung
Drug resistance is becoming an obstacle in anti-cancer therapies. For target-based therapy of lung cancer, gefitinib, as the first generation of tyrosine kinase inhibitors (TKIs), demonstrated good initial response to the non-small cell lung cancer (NSCLC) patients whom harbors epidermal growth factor receptor (EGFR) mutation. However, within one year, additional EGFR mutation occurred, leading to eventual gefitinib-resistance. Therefore, it is urgently to discover novel effective small molecule inhibitors for those patients...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221188/overexpression-of-agt-promotes-bronchopulmonary-dysplasis-via-the-jak-stat-signal-pathway
#14
Lili Shen, Tiancheng Zhang, Hongyan Lu
Angiotensinogen (AGT) is involved in the production of angiotensin II which is the main mediator of action of the rennin-angiotensin system (RAS), whereas the RAS mediates the regulation of sodium homeostasis, blood pressure, and inflammation. The present study aimed to investigate the roles of the AGT in the progression of broncopulmonary dysplasia in premature newborns. By bioinformatics analysis, AGT was found to be the major node in molecular interaction networks of BPD mouse model. Quantitative PCR and western blot analyses were applied to examine AGT expression in A549 cells which were treated with the hyperoxic condition...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221176/alpha-tocopherol-prevents-esophageal-squamous-cell-carcinoma-by-modulating-ppar%C3%AE-akt-signaling-pathway-at-the-early-stage-of-carcinogenesis
#15
Miao Xu, Hui Yang, Qiannan Zhang, Ping Lu, Yongquan Feng, Xue Geng, Lishi Zhang, Xudong Jia
The poor prognosis of esophageal squamous cell carcinoma (ESCC) emphasizes the urgent need to better understand the carcinogenesis and develop prevention strategies. Previous studies have highlighted the potential of using Vitamin E (tocopherols) for cancer chemoprevention, but the preventive activity of α-Tocopherol against ESCC remains to be elucidated. Our data showed that early-stage supplementation with α-Tocopherol significantly prevented esophageal carcinogenesis induced by N-nitrosomethylbenzylamine (NMBA) in ESCC rat model...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220863/a-small-dose-of-apomorphine-counteracts-the-deleterious-effects-of-middle-cerebral-artery-occlusion-in-different-models
#16
F Mastroiacovo, A Gaglione, C L Busceti, L Ryskalin, G Bozza, F Nicoletti, F Orzi, F Fornai
The present manuscript investigates in two animal species by using two different experimental models of middle cerebral artery occlusion (permanent and transient), the neuroprotective effects of the dopamine receptor agonist apomorphine. These effects were evaluated by measuring the infarct volume and by counting muscle strength at different time points following the ischemic insult. Apomorphine at the dose of 3 mg/Kg when adminsitered at two hours following the occlusion of the middle cerebral artery was able to reduce significantly the infarct volume in the cortex of mice and the ischemic volume of the basal ganglia perfused by the perforant branches of the middle cerebral artery in the rat...
September 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/29220747/effects-of-group-ii-metabotropic-glutamate-receptor-modulation-on-ethanol-and-sucrose-seeking-and-consumption-in-the-rat
#17
Kyle A Windisch, Cristine L Czachowski
Previous studies suggest that group II metabotropic glutamate receptors (mGluR2/3) are involved in regulating ethanol-seeking and consumption. The mGluR2/3 agonist LY379268 (LY37) and selective mGluR2 positive allosteric modulator biphenyl‑indanone A (BINA) were used to investigate the relative contribution of mGlu2 and mGlu3 receptors on ethanol- and sucrose-seeking and consumption. A microinjection study was then performed to examine the role of nucleus accumbens (NAc) core mGluR2/3 on ethanol-seeking. For the systemic experiments, separate groups of male Wistar rats [LY37 (0-2...
September 23, 2017: Alcohol
https://www.readbyqxmd.com/read/29220642/substance-use-patterns-associated-with-recent-exposure-to-fentanyl-among-people-who-inject-drugs-in-vancouver-canada-a-cross-sectional-urine-toxicology-screening-study
#18
Kanna Hayashi, M-J Milloy, Mark Lysyshyn, Kora DeBeck, Ekaterina Nosova, Evan Wood, Thomas Kerr
INTRODUCTION: Vancouver, Canada is experiencing an opioid overdose crisis where fentanyl, a potent, synthetic opioid contaminating the illicit drug supply, has been detected in the majority of fatal overdose cases. Despite its growing presence throughout North America, few studies have characterized exposure to fentanyl among people who use illicit drugs (PWUD). We sought to identify the prevalence and correlates of fentanyl exposure among PWUD in Vancouver. METHODS: Data were derived from cohort studies of PWUD in Vancouver...
December 5, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29220177/-methyl-1r-2s-2-4-4-chlorophenyl-4-hydroxypiperidin-1-yl-methyl-1-phenylcyclopropanecarboxylate-mr200-derivatives-as-potent-and-selective-sigma-receptor-ligands-stereochemistry-and-pharmacological-properties
#19
Emanuele Amata, Antonio Rescifina, Orazio Prezzavento, Emanuela Arena, Maria Dichiara, Valeria Pittalà, Ángeles Montilla-García, Francesco Punzo, Pedro Merino, Enrique J Cobos, Agostino Marrazzo
Methoxycarbonyl-1-phenyl-2-cyclopropylmethyl based derivatives cis-(+)-1a [cis-(+)-MR200], cis-(-)-1a [cis-(-)-MR201], and trans-(±)-1a [trans-(±)-MR204], have been identified as new potent sigma (σ) receptor ligands. In the present paper, novel enantiomerically pure analogues were synthesized and optimized for their σ receptor affinity and selectivity. Docking studies rationalized the results obtained in the radioligand binding assay. Absolute stereochemistry was unequivocally established by X-ray analysis of precursor trans-(+)-5a as camphorsulfonyl derivative 9...
December 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29219183/mechanical-unloading-reduces-microtubule-actin-crosslinking-factor-1-expression-to-inhibit-%C3%AE-catenin-signaling-and-osteoblast-proliferation
#20
Chong Yin, Yan Zhang, Lifang Hu, Ye Tian, Zhihao Chen, Dijie Li, Fan Zhao, Peihong Su, Xiaoli Ma, Ge Zhang, Zhiping Miao, Liping Wang, Airong Qian, Cory J Xian
Mechanical unloading was considered a major threat to bone homeostasis, and has been shown to decrease osteoblast proliferation although the underlying mechanism is unclear. Microtubule actin crosslinking factor 1 (MACF1) is a cytoskeletal protein that regulates cellular processes and Wnt/β-catenin pathway, an essential signaling pathway for osteoblasts. However, the relationship between MACF1 expression and mechanical unloading, and the function and the associated mechanisms of MACF1 in regulating osteoblast proliferation are unclear...
December 8, 2017: Journal of Cellular Physiology
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