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https://www.readbyqxmd.com/read/28917803/atp-mediated-rolling-circle-amplification-and-opening-dna-gate-for-drug-delivery-to-cell
#1
Yujie Wang, Xinxin Shang, Jia Liu, Yingshu Guo
Here, we have developed a facile fluorometric system for the detection of adenosine triphosphate (ATP) by a rolling circle amplification (RCA) based on proximity ligation mediated amplification, and simultaneously achieved the release of the anticancer drug doxorubicin (DOX) through the mesoporous silicon system. Once the ATP molecule is present, the linker DNA will be released from the graphene oxide (GO) surface and hybridized to the template DNA of the GO surface joining with ligation enzyme. RCA reaction is followed by the addition of the phi29 DNA polymerase...
January 1, 2018: Talanta
https://www.readbyqxmd.com/read/28916378/clinical-pharmacology-of-anti-angiogenic-drugs-in-oncology
#2
REVIEW
P Gougis, J Wassermann, J P Spano, N Keynan, C Funck-Brentano, J E Salem
Abnormal vasculature proliferation is one of the so-called hallmarks of cancer. Angiogenesis inhibitor therapies are one of the major breakthroughs in cancer treatment in the last two decades. Two types of anti-angiogenics have been approved: monoclonal antibodies and derivatives, which are injected and target the extracellular part of a receptor, and protein kinase inhibitors, which are orally taken small molecules targeting the intra-cellular Adenosine Triphosphate -pocket of different kinases. They have become an important part of some tumors' treatment, both in monotherapy or in combination...
September 1, 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28912485/serial-millisecond-crystallography-for-routine-room-temperature-structure-determination-at-synchrotrons
#3
Tobias Weinert, Natacha Olieric, Robert Cheng, Steffen Brünle, Daniel James, Dmitry Ozerov, Dardan Gashi, Laura Vera, May Marsh, Kathrin Jaeger, Florian Dworkowski, Ezequiel Panepucci, Shibom Basu, Petr Skopintsev, Andrew S Doré, Tian Geng, Robert M Cooke, Mengning Liang, Andrea E Prota, Valerie Panneels, Przemyslaw Nogly, Ulrich Ermler, Gebhard Schertler, Michael Hennig, Michel O Steinmetz, Meitian Wang, Jörg Standfuss
Historically, room-temperature structure determination was succeeded by cryo-crystallography to mitigate radiation damage. Here, we demonstrate that serial millisecond crystallography at a synchrotron beamline equipped with high-viscosity injector and high frame-rate detector allows typical crystallographic experiments to be performed at room-temperature. Using a crystal scanning approach, we determine the high-resolution structure of the radiation sensitive molybdenum storage protein, demonstrate soaking of the drug colchicine into tubulin and native sulfur phasing of the human G protein-coupled adenosine receptor...
September 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28910154/activation-of-veratridine-sensitive-sodium-channels-but-not-electrical-field-stimulation-dilates-porcine-retinal-arterioles-with-preserved-perivascular-tissue
#4
Nils M Kratholm, Peter Skov Jensen, Sidse Kringelholt, Ulf Simonsen, Toke Bek
PURPOSE: Disturbances in retinal blood flow are a prominent feature of vision threatening retinal diseases. The regulation of tone in retinal resistance vessels involves the perivascular retinal tissue, but it is unknown to what extent neurons or glial cells contribute to the effect. Therefore, the purpose of the present study was to study the contribution of neurons in the perivascular retina to vascular tone during activation of voltage-gated sodium channels with veratridine and electrical field stimulation (EFS)...
September 14, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28905392/cryopreserved-platelets-demonstrate-reduced-activation-responses-and-impaired-signaling-after-agonist-stimulation
#5
Lauren Waters, Matthew P Padula, Denese C Marks, Lacey Johnson
BACKGROUND: Room temperature-stored (20-24°C) platelets (PLTs) have a shelf life of 5 days, making it logistically challenging to supply remote medical centers with PLT products. Cryopreservation of PLTs in dimethyl sulfoxide (DMSO) and storage at -80°C enables an extended shelf life up to 2 years. Although cryopreserved PLTs have been widely characterized under resting conditions, their ability to undergo agonist-induced activation is yet to be fully explored. STUDY DESIGN AND METHODS: Buffy coat PLTs were cryopreserved at -80°C with 5% to 6% DMSO and sampled before freezing and after thawing...
September 14, 2017: Transfusion
https://www.readbyqxmd.com/read/28904003/preclinical-pharmacology-and-pharmacokinetics-of-inhaled-hexadecyl-treprostinil-c16tr-a-pulmonary-vasodilator-prodrug
#6
Michel R Corboz, Zhili Li, Vladimir Malinin, Adam J Plaunt, Donna M Konicek, Franziska G Leifer, Kuan-Ju Chen, Charles E Laurent, Han Yin, Marzena C Biernat, Dany Salvail, Jianguo Zhuang, Fadi Xu, Aidan Curran, Walter R Perkins, Richard W Chapman
This report describes the preclinical pharmacology and pharmacokinetics (PK) of hexadecyl-treprostinil (C16TR), a prodrug of treprostinil (TRE), formulated in a lipid nanoparticle (LNP) for inhalation as a pulmonary vasodilator. C16TR showed no activity (> 10 µM) in receptor binding and enzyme inhibition assays including binding to EP2, DP1, IP and EP4; TRE potently bound to each of these prostanoid receptors. C16TR had no effect (up to 200 nM) on platelet aggregation induced by adenosine diphosphate (ADP) in rat blood...
September 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28901521/adiponectin-receptor-agonist-adiporon-suppresses-adipogenesis-in-c3h10t1-2-cells-through-the-adenosine-monophosphate%C3%A2-activated-protein-kinase-signaling-pathway
#7
Shu-Juan Wang, Wen-Yi Lu, Kai-Yan Liu
The aim of the present study was to investigate the effects of AdipoRon, an adiponectin receptor agonist, on adipogenesis in C3H10T1/2 cells and to explore the underlying mechanisms. C3H10T1/2 cells were treated with increasing doses of AdipoRon for 8 days, and Oil Red O staining was used to assess lipid accumulation. The protein and mRNA expression levels of adipogenic transcription factors and adipocyte‑specific genes were examined by western blotting and reverse transcription quantitative polymerase chain reaction, respectively...
September 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28898282/p2x3-receptor-involvement-in-endometriosis-pain-via-erk-signaling-pathway
#8
Shaojie Ding, Libo Zhu, Yonghong Tian, Tianhong Zhu, Xiufeng Huang, Xinmei Zhang
The purinergic receptor P2X ligand-gated ion channel 3 (P2X3) is crucially involved in peripheral nociceptive processes of somatic and visceral pain. Endometriosis pain is considered as a kind of inflammatory and neuropathic pain. However, whether P2X3 is involved in endometriosis pain has not been reported up to date. Here, we aimed to determine whether P2X3 expression in endometriotic lesions is involved in endometriosis pain, which is regulated by inflammatory mediators through extracellular regulated protein kinases (ERK) signalling pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28895774/reduced-platelet-activation-and-platelet-aggregation-in-patients-with-alcoholic-liver-cirrhosis
#9
Pernille Just Vinholt, Anne-Mette Hvas, Christian Nielsen, Anna Cecilia Söderström, Ulrik Sprogøe, Annette Dam Fialla, Mads Nybo
Results from previous studies regarding platelet function in liver cirrhosis are discordant. The aim was to investigate platelet activation and platelet aggregation in patients with alcoholic liver cirrhosis. We included 27 patients with alcoholic liver cirrhosis and 22 healthy individuals. A recently established flow cytometric approach was used to measure platelet activation and platelet aggregation independent of sample platelet count. Platelet aggregation was further investigated using light transmission aggregometry (LTA) (for platelet count >100 × 10(9)/L)...
September 12, 2017: Platelets
https://www.readbyqxmd.com/read/28895043/effects-of-long-term-caffeine-consumption-on-the-adenosine-a1-receptor-in-the-rat-brain-an-in-vivo-pet-study-with-18-f-cpfpx
#10
Danje Nabbi-Schroeter, David Elmenhorst, Angela Oskamp, Stefanie Laskowski, Andreas Bauer, Tina Kroll
PURPOSE: Caffeine, a nonselective antagonist of adenosine receptors, is the most popular psychostimulant worldwide. Recently, a protective role of moderate chronic caffeine consumption against neurodegenerative diseases such as Alzheimer's and Parkinson's disease has been discussed. Thus, aim of the present study was an in vivo investigation of effects of long-term caffeine consumption on the adenosine A1 receptor (A1AR) in the rat brain. PROCEDURES: Sixteen adult, male rats underwent five positron emission tomography (PET) scans with the highly selective A1AR radioligand [(18)F]CPFPX in order to determine A1AR availability...
September 11, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28893911/molecular-and-functional-characterization-of-the-endothelial-atp-sensitive-potassium-channel
#11
Qadeer Aziz, Yiwen Li, Naomi Anderson, Leona Ojake, Elena Tsisanova, Andrew Tinker
ATP-sensitive potassium (KATP) channels are widely expressed in the cardiovascular system where they regulate a range of biological activities by linking cellular metabolism with membrane excitability. KATP channels in vascular smooth muscle have a well-defined role in regulating vascular tone. KATP channels are also thought to be expressed in vascular endothelial cells (ECs), but their presence and function in this context is less clear. As a result, we aimed to investigate the molecular composition and physiological role of endothelial KATP channels...
September 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28893553/caffeine-has-no-effect-on-eyeblink-conditioning-in-mice
#12
Anders Rasmussen, Anna C H G Ijpelaar, Chris I De Zeeuw, Henk-Jan Boele
Caffeine is one of the most widely used drugs in the world. In the brain, caffeine acts as an antagonist for the adenosine A1 and A2B receptors. Since A1 receptors are highly concentrated in the cortex of the cerebellum, we hypothesized that caffeine could potentially affect learning tasks that require the cerebellar cortex, such as eyeblink conditioning. To test this hypothesis, we examined the effect of low (5mg/kg) and high (50mg/kg) doses of caffeine, injected intraperitoneally before training, on eyeblink conditioning in mice...
September 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28893353/the-cholangiocyte-adenosine-il6-axis-regulates-survival-during-biliary-cirrhosis
#13
Elise Lavoie, Michel Fausther, Jessica Goree, Jonathan Dranoff
BACKGROUND AND AIMSEpithelial response to injury is critical to the pathogenesis of biliary cirrhosis, and IL6 has been suggested as a mediator of this phenomenon. Several liver cell types can secrete IL6 following activation by various signaling molecules including circulating adenosine. The aims of this study are to assess whether adenosine can induce IL6 secretion by cholangiocytes via the A2b adenosine receptor (A2bAR) and determine the effect of A2bAR-sensitive IL6 release on injury response in biliary cirrhosis...
September 11, 2017: Gene Expression
https://www.readbyqxmd.com/read/28892884/effect-of-metaboreflex-on-cardiovascular-system-in-subjects-of-metabolic-syndrome
#14
Pramita Dubey, Sunita Tiwari, Manish Bajpai, Kalpana Singh, Praveen Jha
INTRODUCTION: Metaboreflex is a reflex in which muscle receptors send signals regarding metabolic (metabolites accumulation like lactic acid, potassium, adenosine) conditions of the muscles to nucleus tractus solitarius via afferent III and IV fibres to cause haemodynamic adjustments in order to regulate blood flow on the basis of the status of contracting muscle. Dysregulation in its mechanism in metabolic syndrome is demonstrated. AIM: To study the effect of metaboreflex by both isometric and rhythmic handgrip exercise on CVS parameters {Blood Pressure (BP), Cardiac Output (CO) and Systemic Vascular Resistance (SVR)} in subjects of metabolic syndrome...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28891341/small-molecule-therapy-for-managing-moderate-to-severe-psoriatic-arthritis
#15
Luisa Costa, Antonio Del Puente, Rosario Peluso, Marco Tasso, Paolo Caso, Maria Sole Chimenti, Vincenzo Sabbatino, Nicolò Girolimetto, Carolina Benigno, Nicoletta Bertolini, Aurora Del Puente, Roberto Perricone, Raffaele Scarpa, Francesco Caso
The majority of psoriatic arthritis (PsA) patients experience a good clinical response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologic therapies (bDMARDs). However, treatment failure with these drugs can represent a relevant clinical problem. Moreover, in daily clinical practice, the appropriate identification of patients eligible for these agents can be conditioned by numerous aspects, mainly represented by comorbidities, such as history of malignancies, chronic and recurrent infectious diseases...
September 11, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28890385/reduced-coronary-reactive-hyperemia-in-mice-was-reversed-by-the-soluble-epoxide-hydrolase-inhibitor-t-aucb-role-of-adenosine-a2a-receptor-and-plasma-oxylipins
#16
Ahmad Hanif, Matthew L Edin, Darryl C Zeldin, Christophe Morisseau, John R Falck, Catherine Ledent, Stephen L Tilley, Mohammed A Nayeem
Coronary reactive hyperemia (CRH) protects the heart against ischemia. Adenosine A2AAR-deficient (A2AAR(-/-)) mice have increased expression of soluble epoxide hydrolase (sEH); the enzyme responsible for breaking down the cardioprotective epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs). sEH-inhibition enhances CRH, increases EETs, and modulates oxylipin profiles. We investigated the changes of oxylipins and their impact on CRH in A2AAR(-/-) and wild type (WT) mice. We hypothesized that the attenuated CRH in A2AAR(-/-) mice is mediated by changes in oxylipin profiles, and that it can be reversed by either sEH- or ω-hydroxylases-inhibition...
September 7, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28887411/age-related-pacemaker-deterioration-is-due-to-impaired-intracellular-and-membrane-mechanisms-insights-from-numerical-modeling
#17
Joachim Behar, Yael Yaniv
Age-related deterioration of pacemaker function has been documented in mammals, including humans. In aged isolated sinoatrial node tissues and cells, reduction in the spontaneous action potential (AP) firing rate was associated with deterioration of intracellular and membrane mechanisms; however, their relative contribution to age-associated deficient pacemaker function is not known. Interestingly, pharmacological interventions that increase posttranslation modification signaling activities can restore the basal and maximal AP firing rate, but the identities of the protein targets responsible for AP firing rate restoration are not known...
September 8, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28887130/gender-specific-impairment-of-in-vitro-sinoatrial-node-chronotropic-responses-and-of-myocardial-ischemia-tolerance-in-rats-exposed-prenatally-to-betamethasone
#18
L R A Kiguti, C S Borges, A Mueller, K P Silva, C M Polo, J L Rosa, P V Silva, G Missassi, L Valencise, W G Kempinas, A S Pupo
Excessive fetal glucocorticoid exposure has been linked to increased susceptibility to hypertension and cardiac diseases in the adult life, a process called fetal programming. The cardiac contribution to the hypertensive phenotype of glucocorticoid-programmed progeny is less known, therefore, we investigated in vitro cardiac functional parameters from rats exposed in utero to betamethasone. Pregnant Wistar rats received vehicle (VEH) or betamethasone (BET, 0.1mg/kg, i.m.) at gestational days 12, 13, 18 and 19...
September 5, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28884118/the-role-of-adenosine-a2a-receptor-cyp450s-and-ppars-in-the-regulation-of-vascular-tone
#19
REVIEW
Maan T Khayat, Mohammed A Nayeem
Adenosine is an endogenous mediator involved in a myriad of physiologic functions, including vascular tone regulation. It is also implicated in some pathologic conditions. Four distinct receptor subtypes mediate the effects of adenosine, such as its role in the regulation of the vascular tone. Vascular tone regulation is a complex and continuous process which involves many mechanisms and mediators that are not fully disclosed. The vascular endothelium plays a pivotal role in regulating blood flow to and from all body organs...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28882563/adenosine-a1-receptor-potentiated-glycinergic-transmission-in-spinal-cord-dorsal-horn-of-rats-after-peripheral-inflammation
#20
Hu-Hu Bai, Jiang-Ping Liu, Li Yang, Ji-Yuan Zhao, Zhan-Wei Suo, Xian Yang, Xiao-Dong Hu
Adenosine is present at the extracellular space within spinal cord dorsal horn and engaged in the processing of nociceptive sensory signals. Systemic or spinal administration of exogenous adenosine produces a potent analgesia against pathological pain. Here we found that inhibitory glycinergic neurotransmission was an important target for adenosine regulation. In spinal cord slices from intact rats, adenosine increased the inhibitory postsynaptic currents mediated by glycine receptors (GlyRs). In spinal slices from Complete Freund's Adjuvant-injected rats, adenosine potentiated glycinergic transmission to a more degree than in control rats...
September 4, 2017: Neuropharmacology
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