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https://www.readbyqxmd.com/read/28239939/combining-the-gpr40-agonist-fasiglifam-with-sitagliptin-improves-glycemic-control-in-patients-with-type-2-diabetes-with-or-without-metformin-a-randomized-12-week-trial
#1
Xuejun V Peng, John F Marcinak, Marsha G Raanan, Charlie Cao
AIMS: To evaluate the efficacy and safety of fasiglifam, an orally active G protein-coupled receptor 40 agonist, in combination with the dipeptidyl peptidase-4 inhibitor sitagliptin, in patients with type 2 diabetes inadequately controlled with diet/exercise (± metformin). METHODS: In this randomized, double-blind, phase II study, 368 patients received once-daily placebo, sitagliptin 100 mg, fasiglifam 25 or 50 mg, or the combination of sitagliptin 100 mg plus fasiglifam 25 or 50 mg...
February 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28239845/stimulation-of-na-k-pump-currents-by-epithelial-nicotinic-receptors-in-rat-colon
#2
Sandra Bader, Lena Lottig, Martin Diener
BACKGROUND AND PURPOSE: Acetylcholine-induced epithelial Cl(-) secretion is generally thought to be mediated by epithelial muscarinic receptors and nicotinic receptors on secretomotor neurons. However, recent data showed the expression of nicotinic receptors by intestinal epithelium and the stimulation of Cl(-) secretion by nicotine in the presence of the neurotoxin, tetrodotoxin. In the present study, we aimed to identify the transporters activated by epithelial nicotinic receptors and to clarify their role in cholinergic regulation of intestinal ion transport...
February 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28239807/adiponectin-partially-rescues-high-glucose-high-fat-induced-impairment-of-mitochondrial-biogenesis-and-function-in-a-pgc-1%C3%AE-dependent-manner
#3
H Wang, W-J Yan, J-L Zhang, F-Y Zhang, C Gao, Y-J Wang, W Bond Law, L Tao
OBJECTIVE: Plasma adiponectin (APN) levels are decreased in diabetic patients. Dysfunctional mitochondrial biogenesis is involved in type 2 diabetes (T2DM) pathogenesis, by unclear mechanisms. The present study determined (1) whether myocardial mitochondrial biogenesis was impaired in cardiomyocytes exposed to a high glucose/high fat (HGHF) medium (a T2DM in vitro model), (2) the effects of APN administration upon mitochondrial biogenesis in cardiomyocytes affected by HGHF incubation, and 3) the involved underlying mechanisms...
January 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28239803/nasal-hppsis-administration-enhances-ngf-and-tumor-suppressor-protein-p73-in-human-brain-cancer-tissues-preliminary-data
#4
L Aloe, M L Rocco, E Stigliano, F Angelini, M Iacoangeli, V Frari, F Salvinelli
OBJECTIVE: Nerve Growth Factor (NGF) is a neurotrophic factor known to play a critical role in growth, survival, differentiation and neuroprotection of peripheral sensory and sympathetic neurons, as well as brain neurons. We have recently reported that nasal administration of high-pressure isotonic physiological saline solution (HPpSIS) enhances the level of NGF and the expression of NGF receptors in neurons of the olfactory bulbs and forebrain cholinergic neurons of laboratory animals...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28239793/npy1-receptors-participate-in-the-regulation-of-myocardial-contractility-in-rats
#5
P M Masliuko, T A Anikina, A A Zverev, A V Krylova, K Yu Moiseev, T L Zefirov
Selective agonist (Leu(31)Pro(34)NPY) and blocker (BIBP-3226) of NPY1 receptors were used to determine the type of NPY receptors involved in myocardial contraction. Experiments with isometric contraction of myocardial strips from mature rats showed that the agonist produced the most potent effect in a concentration of 10(-7) M. In this concentration, Leu(31)Pro(34)NPY showed the greatest positive inotropic effect on the contraction of the atria and ventricles. In contrast, selective blocker BIBP-3226 reduced the force of myocardial contractions...
February 27, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28239785/pharmacological-analysis-of-the-therapeutic-effect-of-radioprotectors-cystamine-and-indralin-in-the-capacity-of-radiomitigators
#6
M V Vasin, I B Ushakov, V Yu Kovtun, S N Komarova, L A Semenova, A A Galkin, R V Afanas'ev, I V Bukhtiyarov
The therapeutic radiomitigating effect of cystamine and indralin was studied in experiments on mice and rats and pharmacological analysis of these drugs was carried out. The animals were subjected to whole-body (60)Co γ-irradiation. The mice were exposed to single (9-10 Gy) or double (8 Gy) irradiation with an interval of 1 month. The rats were exposed to 10 Gy with partial shielding of the upper quarter of the abdomen. In experiments on mice, pretreatment with reserpine abolished the therapeutic effect of cystamine administered repeatedly every 15 min over 1 h after irradiation...
February 27, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28239768/prostaglandin-e2-ep4-receptor-activation-attenuates-neuroinflammation-and-early-brain-injury-induced-by-subarachnoid-hemorrhage-in-rats
#7
Jie Xu, Zhen Xu, Ai Yan
Activation of E prostanoid 4 receptor (EP4) shows neuroprotective effects in multiple central nervous system (CNS) lesions, but the roles of EP4 receptor in subarachnoid hemorrhage (SAH) are not explored. This study was designed to research the effects of EP4 modulation on early brain injury (EBI) after experimental SAH in rats. We found that the administration of EP4 selective agonist AE1-329 significantly improved neurological dysfunction, blood brain barrier (BBB) damage and brain edema at 24 h after SAH...
February 27, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28239767/down-regulation-of-pin1-in-temporal-lobe-epilepsy-patients-and-mouse-model
#8
Lan Tang, Yanke Zhang, Guojun Chen, Yan Xiong, Xuefeng Wang, Binglin Zhu
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) is a unique PPIase belonging to the parvulin family, and it isomerizes peptide bond between phospho-(Ser/Thr) and Pro. Pin1 has been linked to the pathogenesis of various human diseases; however, its exact biological functions remain unclear. The aim of the present study is to explore the expression pattern of Pin1 in patients with refractory epilepsy and in a chronic pilocarpine-induced epileptic mouse model. Using Western blot, immunofluorescence and immunoprecipitation analysis, we found that Pin1 protein was mainly distributed in neurons, demonstrated by colocalization with the dendritic marker, MAP2...
February 27, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28239762/-1-h-13-c-and-15-n-backbone-chemical-shift-assignments-of-camelid-single-domain-antibodies-against-active-state-%C3%A2%C2%B5-opioid-receptor
#9
Remy Sounier, Yinshan Yang, Joanna Hagelberger, Sébastien Granier, Hélène Déméné
Nanobodies are single chain antibodies that have become a highly valuable and versatile tool for biomolecular and therapeutic research. One application field is the stabilization of active states of flexible proteins, among which G-protein coupled receptors represent a very important class of membrane proteins. Here we present the backbone and side-chain assignment of the (1)H, (13)C and (15)N resonances of Nb33 and Nb39, two nanobodies that recognize and stabilize the µ-opioid receptor to opioids in its active agonist-bound conformation...
February 26, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28239754/neprilysin-facilitates-adipogenesis-through-potentiation-of-the-phosphatidylinositol-3-kinase-pi3k-signaling-pathway
#10
Juwan Kim, Dasol Han, Sung-Hyun Byun, Mookwang Kwon, Sun-Jung Cho, Young Ho Koh, Keejung Yoon
Neprilysin (NEP) is a zinc metallopeptidase that cleaves a number of small peptides into inactive forms. Despite the recent evidence of a significant correlation between the levels of NEP in plasma and the severity of obesity in humans, a cause-and-effect relationship or a functional role of NEP in obesity has remained uncertain. In this study, we show that NEP has a positive regulatory effect on fat cell formation from precursor cells. NEP increases the accumulation of cytoplasmic triglycerides in 3T3-L1 preadipocytes or the C3H10T1/2 mesenchymal stem cell line in differentiation conditions...
February 27, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28239742/the-role-of-the-sdf-1-cxcr7-axis-on-the-growth-and-invasion-ability-of-endometrial-cancer-cells
#11
Hong-Qin Gu, Zhen-Bo Zhang, Jia-Wen Zhang, Qian-Qian Wang, Xiao-Wei Xi, Yin-Yan He
PURPOSE: Stroma-derived factor-1 (SDF-1) and its receptor C-X-C chemokine receptor-4 (CXCR4) are involved in human endometrial carcinoma (EC) progression. CXCR7 is another important receptor of SDF-1 and has a higher affinity with SDF-1 compared with that of CXCR4. This paper aims to study the effects of the SDF-1/CXCR7 axis on the growth and invasion ability of EC cells. METHODS: CXCR7 expression was evaluated by quantitative RT-PCR, immunohistochemistry, immunocytochemistry and Western blotting in EC cell lines and 30 cases of primary EC tissue from patients...
February 27, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28239665/myeloid-12-15-lox-regulates-b-cell-numbers-and-innate-immune-antibody-levels-in-vivo
#12
Sarah N Lauder, Victoria J Tyrrell, Keith Allen-Redpath, Maceler Aldrovandi, David Gray, Peter Collins, Simon A Jones, Philip R Taylor, Valerie O'Donnell
Background. The myeloid enzyme 12/15-lipoxygenase (LOX), which generates bioactive oxidized lipids, has been implicated in numerous inflammatory diseases, with several studies demonstrating an improvement in pathology in mice lacking the enzyme. However, the ability of 12/15-LOX to directly regulate B cell function has not been studied. Methods. The influence of 12/15-LOX on B cell phenotype and function, and IgM generation, was compared using wildtype (WT) and 12/15-LOX (Alox15(-/-)) deficient mice. The proliferative and functional capacity of splenic CD19(+) B cells was measured in vitro in response to various toll-like receptor agonists...
January 4, 2017: Wellcome Open Res
https://www.readbyqxmd.com/read/28239660/%C3%AE-2-adrenergic-blockade-rescues-hypoglossal-motor-defense-against-obstructive-sleep-apnea
#13
Gang Song, Chi-Sang Poon
Decreased noradrenergic excitation of hypoglossal motoneurons during sleep causing hypotonia of pharyngeal dilator muscles is a major contributor to the pathogenesis of obstructive sleep apnea (OSA), a widespread disease for which treatment options are limited. Previous OSA drug candidates targeting various excitatory/inhibitory receptors on hypoglossal motoneurons have proved unviable in reactivating these neurons, particularly during rapid-eye-movement (REM) sleep. To identify a viable drug target, we show that the repurposed α2-adrenergic antagonist yohimbine potently reversed the depressant effect of REM sleep on baseline hypoglossal motoneuron activity (a first-line motor defense against OSA) in rats...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28239648/liver-x-receptor-%C3%AE-mediates-hepatic-triglyceride-accumulation-through-upregulation-of-g0-g1-switch-gene-2-expression
#14
Bradlee L Heckmann, Xiaodong Zhang, Alicia M Saarinen, Gabriele Schoiswohl, Erin E Kershaw, Rudolf Zechner, Jun Liu
Liver X receptors (LXRs) are transcription factors essential for cholesterol homeostasis and lipogenesis. LXRα has been implicated in regulating hepatic triglyceride (TG) accumulation upon both influx of adipose-derived fatty acids (FAs) during fasting and stimulation of de novo FA synthesis by chemical agonism of LXR. However, whether or not a convergent mechanism is employed to drive deposition of FAs from these 2 different sources in TGs is undetermined. Here, we report that the G0/G1 Switch Gene 2 (G0S2), a selective inhibitor of intracellular TG hydrolysis/lipolysis, is a direct target gene of LXRα...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28239647/enhanced-fcgr2a-and-fcgr3a-signaling-by-hiv-viremic-controller-igg
#15
Raymond A Alvarez, Ana M Maestre, Kenneth Law, Natasha D Durham, Maria Ines Barria, Akiko Ishii-Watabe, Minoru Tada, Manav Kapoor, Mathew T Hotta, Gabriela Rodriguez-Caprio, Daniel S Fierer, Ana Fernandez-Sesma, Viviana Simon, Benjamin K Chen
HIV-1 viremic controllers (VC) spontaneously control infection without antiretroviral treatment. Several studies indicate that IgG Abs from VCs induce enhanced responses from immune effector cells. Since signaling through Fc-γ receptors (FCGRs) modulate these Ab-driven responses, here we examine if enhanced FCGR activation is a common feature of IgG from VCs. Using an infected cell-based system, we observed that VC IgG stimulated greater FCGR2A and FCGR3A activation as compared with noncontrollers, independent of the magnitude of HIV-specific Ab binding or virus neutralization activities...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28239633/dataset-of-proinflammatory-cytokine-and-cytokine-receptor-gene-expression-in-rainbow-trout-oncorhynchus-mykiss-measured-using-a-novel-gexp-multiplex-rt-pcr-assay
#16
Ivan Kutyrev, Beth Cleveland, Timothy Leeds, Gregory D Wiens
A GeXP multiplex, RT-PCR assay was developed and optimized that simultaneously measures expression of a suite of immune-relevant genes in rainbow trout (Oncorhynchus mykiss), concentrating on tumor necrosis factor and interleukin-1 ligand/receptor systems and acute phase response genes. The dataset includes expression values for drpt, il11a, il1b1, il1b2, il1b3, il1r-like-1(e3-5), il1r-like-1(e9-11), il1r1-like-a, il1r1-like-b, il1r2, saa, tnfa1, tnfa2, tnfa3, tnfrsf1a, tnfrsf1a-like-a, tnfrsf1a-like-b, tnfrsf5, and tnfrsf9...
April 2017: Data in Brief
https://www.readbyqxmd.com/read/28239564/cancer-stem-cells-and-early-stage-basal-like-breast-cancer
#17
Pang-Kuo Lo, Benjamin Wolfson, Qun Zhou
Ductal carcinoma in situ (DCIS) is a category of early stage, non-invasive breast tumor defined by the intraductal proliferation of malignant breast epithelial cells. DCIS is a heterogeneous disease composed of multiple molecular subtypes including luminal, HER2 and basal-like types, which are characterized by immunohistochemical analyses and gene expression profiling. Following surgical and radiation therapies, patients with luminal-type, estrogen receptor-positive DCIS breast tumors can benefit from adjuvant endocrine-based treatment...
May 10, 2016: World Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28239558/role-of-androgen-receptor-splice-variants-in-prostate-cancer-metastasis
#18
Jin Xu, Yun Qiu
Prostate cancer (PCa) is one of the most lethal cancers in western countries. Androgen receptor (AR) signaling pathway plays a key role in PCa progression. Despite the initial effectiveness of androgen deprivation therapy (ADT) for treatment of patients with advanced PCa, most of them will develop resistance to ADT and progress to metastatic castration resistant prostate cancer (mCRPC). Constitutively transcriptional activated AR splice variants (AR-Vs) have emerged as critical players in the development and progression of mCRPC...
October 2016: Asian J Urol
https://www.readbyqxmd.com/read/28239502/immunooncology-can-the-right-chimeric-antigen-receptors-t-cell-design-be-made-to-cure-all-types-of-cancers-and-will-it-be-covered
#19
REVIEW
Regina Au
Immunooncology (IO) is the buzz word today and it has everyone doing IO research. If we look back at the history of cancer treatment, the survival rate was measured in months which, according to oncologists, was a lot back then because the mortality rate in most cancers was 100%. However, most traditional chemotherapies were not well tolerated because they would kill both cancerous and healthy cells, which lead to major side effects such as loss of hair, nausea and vomiting, and risk of infection. Survival was better but not much better depending on the type of cancer and the patient's own genetic and physiological make-up...
2017: Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28239467/ccr7-selected-gene-modified-t-cells-maintain-a-central-memory-phenotype-and-display-enhanced-persistence-in-peripheral-blood-in-vivo
#20
Gray Kueberuwa, Hannah Gornall, Erik Marcelo Alcantar-Orozco, Deborah Bouvier, Zainul Abedin Kapacee, Robert Edward Hawkins, David Edward Gilham
BACKGROUND: Adoptive T cell immunotherapy (ATCT) for cancer entails infusing patients with T cells that recognise and destroy tumour cells. Efficient engraftment of T cells and persistence in the circulation correlate with favourable clinical outcomes. T cells of early differentiation possess an increased capacity for proliferation and therefore persistence, using these cells for ATCT could therefore lead to improved clinical outcomes. METHOD: We describe a method to enrich T cells of early differentiation status using paramagnetic beads and antibodies targeting cells expressing C-C motif chemokine receptor 7 (CCR7)...
2017: Journal for Immunotherapy of Cancer
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