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https://www.readbyqxmd.com/read/28107667/two-opposite-dose-dependent-effects-of-diazinon-on-the-motor-activity-of-the-rat-ileum
#1
Saša M Trailović, Djordje S Marjanović, Teodora Vidonja Uzelac, Mirjana Milovanović, Jelena Nedeljković Trailović
Acute poisoning with OPs may lead to a range of neurological effects, which cannot be explained by AChE inhibition alone. Several OPs interact directly with cholinergic receptors in mammals, but such data does not exist for invertebrates. The aim of current study was to investigate the direct and indirect effects of diazinon on the contractions of rat ileum and to compare those effects on the nervemuscle preparation of the Ascaris suum. In the presence of increasing concentrations of diazinon (3, 10 and 30nM), EFS-induced ileal contractions were increased significantly...
January 10, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28107369/impact-of-donor-activating-kir-genes-on-hsct-outcome-in-c1-ligand-negative-myeloid-disease-patients-transplanted-with-unrelated-donors-a-retrospective-study
#2
Christine Neuchel, Daniel Fürst, Dietger Niederwieser, Donald Bunjes, Chrysanthi Tsamadou, Gerald Wulf, Michael Pfreundschuh, Eva Wagner, Gernot Stuhler, Hermann Einsele, Hubert Schrezenmeier, Joannis Mytilineos
Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome...
2017: PloS One
https://www.readbyqxmd.com/read/28106828/bajijiasu-abrogates-osteoclast-differentiation-via-the-suppression-of-rankl-signaling-pathways-through-nf-%C3%AE%C2%BAb-and-nfat
#3
Guoju Hong, Lin Zhou, Xuguang Shi, Wei He, Haibin Wang, Qiushi Wei, Peng Chen, Longkai Qi, Jennifer Tickner, Li Lin, Jiake Xu
Pathological osteolysis is commonly associated with osteoporosis, bone tumors, osteonecrosis, and chronic inflammation. It involves excessive resorption of bone matrix by activated osteoclasts. Suppressing receptor activator of NF-κB ligand (RANKL) signaling pathways has been proposed to be a good target for inhibiting osteoclast differentiation and bone resorption. Bajijiasu-a natural compound derived from Morinda officinalis F. C. How-has previously been shown to have anti-oxidative stress property; however, its effect and molecular mechanism of action on osteoclastogenesis and bone resorption remains unclear...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106207/natural-sweetener-agave-inhibits-gastric-emptying-in-rats-by-a-cholecystokinin-2-and-glucagon-like-peptide-1-receptor-dependent-mechanism
#4
E Bihter Gürler, Dilek Özbeyli, Hülya Buzcu, Sezin Bayraktar, İrem Carus, Beyza Dağ, Yasemin Geriş, Seda Jeral, Berrak Ç Yeğen
Low-calorie sweeteners are considered to be beneficial in calorie control, but the impact of these sweeteners on gastric emptying is not well described. The purpose of this study was to compare the gastric emptying rate of agave nectar with those of glucose and fructose, and to evaluate the interaction of cholecystokinin (CCK)-1, CCK-2 and glucagon-like peptide-1 (GLP-1) receptors in agave-induced alterations in gastric emptying. Female Sprague-Dawley rats were fitted with gastric cannulas. Following the recovery, the gastric emptying rates of glucose, fructose and agave at 12...
January 20, 2017: Food & Function
https://www.readbyqxmd.com/read/28106152/cancer-immunotherapy-immune-checkpoint-blockade-and-associated-endocrinopathies
#5
REVIEW
David J Byun, Jedd D Wolchok, Lynne M Rosenberg, Monica Girotra
Advances in cancer therapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (IRAEs), which resemble autoimmune disease...
January 20, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28105535/the-neuropeptide-orexin-a-inhibits-the-gabaa-receptor-by-pkc-and-ca-2-camkii-dependent-phosphorylation-of-its-%C3%AE-1-subunit
#6
Divya Sachidanandan, Haritha P Reddy, Anitha Mani, Geoffrey J Hyde, Amal Kanti Bera
Orexin-A and orexin-B (Ox-A, Ox-B) are neuropeptides produced by a small number of neurons that originate in the hypothalamus and project widely in the brain. Only discovered in 1998, the orexins are already known to regulate several behaviours. Most prominently, they help to stabilise the waking state, a role with demonstrated significance in the clinical management of narcolepsy and insomnia. Orexins bind to G-protein-coupled receptors (predominantly postsynaptic) of two subtypes, OX1R and OX2R. The primary effect of Ox-OXR binding is a direct depolarising influence mediated by cell membrane cation channels, but a wide variety of secondary effects, both pre- and postsynaptic, are also emerging...
January 19, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28105120/effects-of-curcumin-on-the-apoptosis-of-cardiomyocytes-and-the-expression-of-nf-%C3%AE%C2%BAb-ppar-%C3%AE-and-bcl-2-in-rats-with-myocardial-infarction-injury
#7
Feng-Hua Lv, Hong-Lei Yin, Yi-Qun He, Hui-Min Wu, Juan Kong, Xiao-Yan Chai, Su-Rong Zhang
Curcumin is a natural polyphenol with powerful antioxidant and anti-inflammatory properties. The present study evaluated the protective effect of curcumin on myocardial injury in rats as well as the mechanisms underlying these effects, and examined the expression of nuclear factor-κB (NF-κB), peroxisome proliferator-activated receptor-γ (PPAR-γ) and B-cell leukemia/lymphoma-2 (Bcl-2) following myocardial infarction. A rat model of myocardial infarction was successfully established. Hematoxylin and eosin staining showed cellular atrophy and hyperchromatic cytoplasm in the myocardial infarction area...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28104434/effects-of-human-opiorphin-on-food-intake-and-water-intake-in-mice-following-central-administration
#8
Yong Chen, Xiao-Zhu Tian, Lu Bai, Ze-Qi Liu, Xing-Peng Xiao, Pu Liu, Xiang-Kai Li
Human opiorphin, plays important pharmacological functions in rats or mice. The present study was performed to investigate effects and underlying mechanism of central injected opiorphin on food intake and water intake in mice. Intracerebroventricularly (i.c.v.) administered opiorphin (5-20μg/kg) dose-dependently suppressed food intake in fasted mice, but had no influence on food intake in freely feeding mice. The cumulative food intake was significantly decreased at 60min after injection of 10 and 20μg/kg opiorphin and the food intake was significantly reduced during the 20-60min period after treatment...
January 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28104430/regional-and-subcellular-distribution-of-gabac-%C3%AF-3-receptor-in-brain-of-r6-2-mouse-model-of-huntington-s-disease
#9
Ujendra Kumar, Michael Heer, Rishi K Somvanshi
In the present study, we describe the distribution of GABAC ρ3 receptor immunoreactivity in the cortex, striatum and hippocampus of wild type (wt) and 11 weeks old HD transgenic (tg) R6/2 mouse brain. In the brain of wt mice, GABAC ρ3 immunoreactivity is well expressed in neuronal cells, nerve fibers and axonal processes. In comparison to wt, GABAC ρ3 receptor like immunoreactivity decreases significantly in all three brain regions of R6/2 mice. The altered distributional pattern and significant changes in GABAC ρ3 receptor immunoreactivity as seen in the R6/2 mouse brain might be a plausible molecular mechanism for excitotoxicity in HD pathogenesis due to the loss of inhibitory input...
January 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28104285/resisting-the-urge-to-act-dreadds-modifying-habits
#10
Mark A G Eldridge, Barry J Richmond
Recently, Meyer and Bucci used chemogenetic technology - artificial excitatory and inhibitory receptors - to modulate neuronal activity in two connected brain regions in opposite directions simultaneously. This innovative manipulation revealed that the two regions studied, orbitofrontal cortex and nucleus accumbens, are not sequentially dependent during contextual decision-making.
January 16, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28103770/integrating-multiple-receptor-conformation-docking-and-multi-dimensional-qsar-for-enhancing-accuracy-of-binding-affinity-prediction
#11
Vangala Radhika, Hassan Araimsh Jaraf, Sivan Sree Kanth, Manga Vijjulatha
BACKGROUND: The accuracy of molecular conformation for Quantitative Structure Activity Relationship (QSAR) studies is an important criteria, and the most favourable bioactive conformer selection is a tough task. Correct ligand alignment as input for 3D-QSAR is an important step that is prone to human biases. Multiple-dimensional QSAR (mQSAR) approach provides a promising alternative to classic 3D-QSAR for drug discovery purposes. OBJECTIVE: Obtaining ligand conformations from multiple receptor conformation docking (MRCD) will reduce the margin of error by incorporating the receptor based alignment of ligand conformations...
January 19, 2017: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/28103263/splenic-cd4-t-cells-in-progressive-visceral-leishmaniasis-show-a-mixed-effector-regulatory-phenotype-and-impair-macrophage-effector-function-through-inhibitory-receptor-expression
#12
Audrie A Medina-Colorado, Elvia Y Osorio, Omar A Saldarriaga, Bruno L Travi, Fanping Kong, Heidi Spratt, Lynn Soong, Peter C Melby
Visceral leishmaniasis (VL), caused by infection with the intracellular protozoan Leishmania donovani, is a chronic progressive disease with a relentlessly increasing parasite burden in the spleen, liver and bone marrow. The disease is characterized by fever, splenomegaly, cachexia, and pancytopenia, and progresses to death if not treated. Control of Leishmania infection is mediated by Th1 (IFNγ-producing) CD4+ T cells, which activate macrophages to produce nitric oxide and kill intracellular parasites. However, despite expansion of CD4+ T cells and increased IFNγ expression in the spleen, humans with active VL do not control the infection...
2017: PloS One
https://www.readbyqxmd.com/read/28103235/real-time-multiplicative-memory-amplification-mediated-by-whole-cell-scaling-of-synaptic-response-in-key-neurons
#13
Iris Reuveni, Sourav Ghosh, Edi Barkai
Intense spiking response of a memory-pattern is believed to play a crucial role both in normal learning and pathology, where it can create biased behavior. We recently proposed a novel model for memory amplification where the simultaneous two-fold increase of all excitatory (AMPAR-mediated) and inhibitory (GABAAR-mediated) synapses in a sub-group of cells that constitutes a memory-pattern selectively amplifies this memory. Here we confirm the cellular basis of this model by validating its major predictions in four sets of experiments, and demonstrate its induction via a whole-cell transduction mechanism...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28103033/design-synthesis-and-biological-evaluation-of-small-high-affinity-siglec-7-ligands-toward-novel-inhibitors-of-cancer-immune-evasion
#14
Horst Prescher, Martin Frank, Stephan Gütgemann, Elena Kuhfeldt, Astrid Schweizer, Lars Nitschke, Carsten Watzl, Reinhard Brossmer
Natural killer cells are able to directly lyse tumor cells, thereby participating in the immune surveillance against cancer. Unfortunately, many cancer cells use immune evasion strategies to avoid their eradication by the immune system. A prominent escape strategy of malignant cells is to camouflage themselves with Siglec-7 ligands, thereby recruiting the inhibitory receptor Siglec-7 expressed on the NK cell surface which subsequently inhibits NK-cell-mediated lysis. Here we describe the synthesis and evaluation of the first, high-affinity low molecular weight Siglec-7 ligands to interfere with cancer cell immune evasion...
January 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28102227/singular-location-and-signaling-profile-of-adenosine-a2a-cannabinoid-cb1-receptor-heteromers-in-the-dorsal-striatum
#15
Estefanía Moreno, Anna Chiarlone, Mireia Medrano, Mar Puigdellívol, Lucka Bibic, Lesley A Howell, Eva Resel, Nagore Puente, María J Casarejos, Juan Perucho, Joaquín Botta, Nuria Suelves, Francisco Ciruela, Silvia Ginés, Ismael Galve-Roperh, Vicent Casadó, Pedro Grandes, Beat Lutz, Krisztina Monory, Enric I Canela, Carmen Lluís, Peter J McCormick, Manuel Guzmán
The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A2A receptor (A2AR) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A2AR and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A2AR-CB1R heteromeric complexes...
January 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28102026/piperine-a-pungent-alkaloid-from-black-pepper-inhibits-b-lymphocyte-activation-and-effector-functions
#16
David A Soutar, Carolyn D Doucette, Robert S Liwski, David W Hoskin
Piperine has several well-documented anti-inflammatory properties; however, little is known regarding its effect on humoral immunity. In this study, we describe the immunosuppressive effect of piperine on B lymphocytes, which are integral to the humoral immune response. Mouse B cells were cultured in the absence or presence of non-cytotoxic concentrations (25, 50, and 100 μM) of piperine during T-dependent or T-independent stimulation. Piperine inhibited B cell proliferation by causing G0/G1 phase cell cycle arrest in association with reduced expression of cyclin D2 and D3...
January 19, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28101847/off-target-anti-inflammatory-activity-of-the-p2x7-receptor-antagonist-az11645373
#17
Olga V Oskolkova, Viktoria Godschachner, Valery N Bochkov
We have found that a well-characterized P2X7 receptor antagonist AZ11645373 blocked production of pro-inflammatory chemokine IL-8 in endothelial cells treated with OxPAPC. The effect was not due to toxicity of AZ11645373 as documented by cellular metabolic activity assay. The mechanism of inhibition by AZ11645373 was apparently independent of the P2X7 receptor because this receptor was not involved in induction of IL-8 under our experimental conditions. In support of this notion, two P2X7 agonists ATP and BzATP did not upregulate IL-8...
January 19, 2017: Inflammation
https://www.readbyqxmd.com/read/28101679/inhibitory-effect-of-saliva-on-osteoclastogenesis-in-vitro-requires-toll-like-receptor-4-signaling
#18
Heinz-Dieter Müller, Jordi Caballé-Serrano, Adrian Lussi, Reinhard Gruber
OBJECTIVES: Saliva can suppress osteoclastogenesis, but the underlying mechanism has not been discovered yet. Considering that endotoxins suppress osteoclastogenesis in bone marrow cultures and that saliva contains endotoxins, it was reasonable to hypothesize that the impact of saliva on osteoclastogenesis requires toll-like receptor 4 signaling. MATERIAL AND METHODS: To test this hypothesis, we blocked toll-like receptor 4 signaling with TAK-242 in the presence of saliva in murine bone marrow cultures...
January 18, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28101246/detection-of-microrna-200b-may-predict-the-inhibitory-effect-of-gefitinib-on-non-small-cell-lung-cancer-and-its-potential-mechanism
#19
Zhiwu Liu, Liqiong Yao, Bangyun Tan, Li Li, Baojin Chen
The present study aimed to investigate the association and underlying mechanisms between microRNA-200b level and the inhibitory effect of gefitinib on non-small cell lung cancer. In total, 100 patients (43 males and 57 females; median age, 63 years) with advanced non-small cell lung cancer (NSCLC) were selected. All patients were administered with gefitinib orally (250 mg/day) and the effect of gefitinib was evaluated according to the Response Evaluation Criteria in Solid Tumors guidelines. Tumor tissue and plasma samples were collected prior to and subsequent to therapy...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101216/epidermal-growth-factor-receptor-mutation-enhances-expression-of-vascular-endothelial-growth-factor-in-lung-cancer
#20
Ming-Szu Hung, I-Chuan Chen, Paul-Yann Lin, Jr-Hau Lung, Ya-Chin Li, Yu-Ching Lin, Cheng-Ta Yang, Ying-Huang Tsai
Epidermal growth factor receptor (EGFR) activation has been demonstrated to have a critical role in tumor angiogenesis. In the present study, the correlation between EGFR mutations and vascular endothelial growth factor (VEGF) was investigated in lung cancer cell lines and non-small-cell lung cancer (NSCLC) tumor tissues. VEGF levels were significantly increased in culture medium of lung cancer cells and NSCLC tissues with EGFR mutations (H1650 vs. A549, P=0.0399; H1975 vs. A549, P<0.0001). Stable lung cancer cell lines expressing mutant (exon 19 deletion, E746-A750; exon 21 missense mutation, L858R) and wild-type EGFR genes were established...
December 2016: Oncology Letters
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