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"Adenosine" AND "Emergency"

Chiachen Chen, Mary Beth Breslin, Jessie J Guidry, Michael S Lan
Insulinoma associated-1 (INSM1) is a key protein functioning as a transcriptional repressor in neuroendocrine differentiation and is activated by N-Myc in human neuroblastoma (NB). INSM1 modulates the phosphoinositide 3-kinase (PI3K)-AKT Ser/Thr kinase (AKT)-glycogen synthase kinase 3β (GSK3β) signaling pathway through a positive-feedback loop, resulting in N-Myc stabilization. Accordingly, INSM1 has emerged as a critical player closely associated with N-Myc in facilitating NB cell growth. Here, an INSM1 promoter-driven luciferase-based screen revealed that the compound 5'-iodotubercidin suppresses adenosine kinase (ADK), an energy pathway enzyme, and also INSM1 expression and NB tumor growth...
February 12, 2019: Journal of Biological Chemistry
Kazunari Tsuyuguchi, Yuka Sasaki, Satoshi Mitarai, Ken Kurosawa, Yuki Saito, Tadaishi Koh
BACKGROUND: Bedaquiline, a diarylquinoline with a novel mode of action that specifically inhibits mycobacterial adenosine 5׳-triphosphate (ATP) synthase, has been approved in over 50 countries including the USA and EU for the treatment of pulmonary multidrug-resistant tuberculosis (pMDR-TB) in adults. METHODS: This study was conducted to evaluate the safety, efficacy, and pharmacokinetics of bedaquiline in adult Japanese patients with pMDR-TB. In this study, patients received bedaquiline for 24 weeks or more (maximum 48 weeks) with an individualized background regimen (BR)...
February 7, 2019: Respiratory Investigation
Barbara Cacciari, Pamela Crepaldi, Chun Yan Cheng, Elena Bossi, Giampiero Spalluto, Stephanie Federico, Kenneth A Jacobson, Marco Cattaneo
BACKGROUND: Platelet aggregation plays a pathogenic role in the development of arterial thrombi, which are responsible for common diseases caused by thrombotic arterial occlusion, such as myocardial infarction and stroke. Much efforts is directed toward developing platelet aggregation inhibitors that act through several mechanisms: the main antiplatelet family of COX-inhibitors, phosphodiesterase inhibitors, and thrombin inhibitors. Recently, the important role in the platelet aggregation of adenosine diphosphate (ADP)-activated P2Y12 and P2Y1 receptors, G-protein coupled receptors of the P2 purinergic family, has emerged, and their inhibitors are explored as potential therapeutic antithrombotics...
February 8, 2019: Medicinal Chemistry
Charles E Samuel
Herbert "Herb" Tabor, who celebrated his 100th birthday this past year, served the Journal of Biological Chemistry as a member of the Editorial Board beginning in 1961, as an Associate Editor, and as Editor-in-Chief for 40 years, from 1971 until 2010. Among the many discoveries in biological chemistry during this period was the identification of RNA modification by C6 deamination of adenosine (A) to produce inosine (I) in double-stranded (ds) RNA. This posttranscriptional RNA modification by adenosine deamination, known as A-to-I RNA editing, diversifies the transcriptome and modulates the innate immune interferon response...
February 1, 2019: Journal of Biological Chemistry
Samantha N Muellers, Juliana A Gonzalez, Abinash Kaur, Vital Sapojnikov, Annie Laurie Benzie, Dean G Brown, David W Parkin, Brian J Stockman
Trichomoniasis is caused by the parasitic protozoan Trichomonas vaginalis and is the most prevalent, nonviral sexually transmitted disease. The parasite has shown increasing resistance to the current 5-nitroimidazole therapies indicating the need for new therapies with different mechanisms. T. vaginalis is an obligate parasite that scavenges nucleosides from host cells and then uses salvage pathway enzymes to obtain the nucleobases. The adenosine/guanosine preferring nucleoside ribohydrolase was screened against a 2000-compound diversity fragment library using a 1 H NMR-based activity assay...
February 1, 2019: ACS Infectious Diseases
Polyxeni Ntontsi, Aggeliki Detta, Petros Bakakos, Stelios Loukides, Georgios Hillas
Severe, inadequately-controlled asthma remains a clinical challenge. For this reason, clinical trials and preclinical experimental studies on novel agents as an add-on therapies continue emerge. Phosphodiesterases (PDEs) are enzymes that regulate the function of immune cells by hydrolyzing cyclic guanosine monophosphate/cGMP and cyclic adenosine monophosphate/cAMP. PDEs are divided into subfamilies [PDE3, PDE4, PDE5 and PDE7] which are mainly found in the respiratory tract. Inhibitors of PDEs have already been approved for COPD and pulmonary hypertension...
January 24, 2019: Expert Opinion on Investigational Drugs
Kristoffer Navred, Myriam Martin, Lina Ekdahl, Eva Zetterberg, Nadine Gretenkort Andersson, Karin Strandberg, Eva Norstrom
BACKGROUND: Flow cytometric platelet activation has emerged as an alternative diagnostic test for inherited platelet disorders. It is, however, labor intensive and few studies have directly compared the performance of flow cytometric platelet activation (PACT) to light transmission aggregometry (LTA). The aims of this study were 1/ to develop a simplified flow cytometric platelet activation assay using microtiter plates and 2/ to correlate the outcome to gold standard method LTA, and to clinical bleeding assessment tool scores (BAT score)...
2019: PloS One
Kaoru Okishige, Takatoshi Shigeta, Takuro Nishimura, Rena A Nakamura, Tatsuhiko Hirao, Hiroshi Yoshida, Yasuteru Yamauchi, Tetsuo Sasano, Kenzo Hirao
INTRODUCTION: Adenosine triphosphate (ATP) sensitive atrial tachycardia (AT) has been treated by radiofrequency catheter ablation. Cryofreezing energy has emerged as a novel energy source for catheter ablation. The aim of this study was to investigate the efficacy and safety of cryofreezing ablation for ATP-sensitive AT. METHODS AND RESULTS: A total of six patients with ATP-sensitive ATs were included in this study. A single atrial extra-stimulation was able to initiate and terminate these ATs in all six patients...
January 17, 2019: Journal of Cardiovascular Electrophysiology
Monil Majmundar, Tikal Kansara, Akash Jain, Palak Shah, Priyam Mithawala, Rupak Desai, Priyank Shah, Rajkumar Doshi
Inhibition of the P2Y12 receptor by an oral P2Y12 inhibitor with loading doses along with Cyclooxygenase-1 inhibition by aspirin is considered a first-line treatment strategy in patients with the acute coronary syndrome and patients undergoing percutaneous coronary intervention (PCI). Limitations associated with oral P2Y12 receptor inhibitors include a requirement for in vivo conversion (thienopyridines), delayed onset of action, suboptimal inhibition, irreversible inhibition (thienopyridines), and delayed offset...
January 5, 2019: American Journal of Cardiology
Jun Oda, Tetsuo Yukioka, Kazunari Azuma, Takao Arai, Junji Chida, Hiroshi Kido
Aim: In serious heatstroke, elevated body temperature (>40°C) is considered the main cause of illness. Mitochondrial carnitine palmitoyltransferase II (CPT II) plays an important role in adenosine triphosphate (ATP) generation from long-chain fatty acids, and its thermolabile phenotype of CPT2 polymorphisms leads to ATP production loss under high fever. Whether by heatstroke or influenza, high fever suppresses mitochondrial ATP production in patients with the thermolabile phenotype of CPT2 polymorphisms...
January 2019: Acute Medicine & Surgery
Hua-Hua Zhong, Bo Yu, Dan Luo, Liang-Yan Yang, Jin Zhang, Sha-Sha Jiang, Shao-Jie Hu, Yun-Yun Luo, Mei-Wen Yang, Fen-Fang Hong, Shu-Long Yang
With aging, various factors deteriorate the normal sleep process that is essential for the restoration of functional and physical performance. Due to aging-related diseases, life changes, or aging itself, disturbances in normal sleep cycles can profoundly affect healthy aging. To understand the interconnections between aging and the factors influencing sleep, with emerging evidence accumulated in recent years, this study elaborates on the roles of aging in sleep from four perspectives: cortical thinning, white matter degeneration, neurotransmitter dysregulation, and circadian disorganization...
January 12, 2019: Neuroscience and Biobehavioral Reviews
Xiao-Ling Zhang, Zhen-Zhen Wang, Qian-Hang Shao, Zhao Zhang, Lin Li, Zhen-Yu Guo, Hong-Mei Sun, Yi Zhang, Nai-Hong Chen
Deletions or some mutations in the gene encoding the multifunctional protein, DJ-1, have been considered to be linked with autosomal recessive early onset Parkinson's disease (PD). Current emerging evidence suggests that DJ-1 is involved in the protection against oxidative stress-induced mitochondrial damage. However, the exact molecular mechanisms underlying this are not completely clear. The aim of this study was to investigate the effects of DJ-1 on the Akt pathway, nuclear factor erythroid 2-related factor (Nrf2), and c-Jun N-terminal kinase (JNK) with regard to modulating mitochondrial function...
January 8, 2019: Brain Research Bulletin
Tamara Berdyyeva, Chunfang Xia, Natalie Taylor, Yingbo He, Gang Chen, Chaofeng Huang, Wei Zhang, Hartmuth Kolb, Michael Letavic, Anindya Bhattacharya, Anna Katrin Szardenings
PURPOSE: The P2X7 receptor, an adenosine triphosphate (ATP)-gated purinoreceptor, has emerged as one of the key players in neuroinflammatory processes. Therefore, developing a positron emission tomography (PET) tracer for imaging of P2X7 receptors in vivo presents a promising approach to diagnose, monitor, and study neuroinflammation in a variety of brain disorders. To fulfill the goal of developing a P2X7 PET ligand as a biomarker of neuroinflammation, [18 F]JNJ-64413739 has been recently disclosed...
January 10, 2019: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Alberto Martire, Catia Lambertucci, Rita Pepponi, Antonella Ferrante, Nicholas Benati, Michela Buccioni, Diego Dal Ben, Gabriella Marucci, Karl-Norbert Klotz, Rosaria Volpini, Patrizia Popoli
Cerebral ischemia is the second most common cause of death and a major cause of disability worldwide. Available therapies are based only on anticoagulants or recombinant tissue plasminogen activator. Extracellular adenosine increases during ischemia and acts as a neuroprotective endogenous agent mainly by activating adenosine A1 receptors (A1 Rs) which control calcium influx, glutamate release, membrane potential, and metabolism. Accordingly, in many experimental paradigms it has been already demonstrated that the stimulation of A1 R with full agonists is able to reduce ischemia-related structural and functional brain damage; unfortunately, cardiovascular side effects and desensitization of A1 R induced by these compounds have strongly limited their exploitation in stroke therapy so far...
January 7, 2019: Journal of Neurochemistry
Àlbert Rafels-Ybern, Adrian Gabriel Torres, Noelia Camacho, Andrea Herencia-Ropero, Helena Roura Frigolé, Thomas F Wulff, Marina Raboteg, Albert Bordons, Xavier Grau-Bove, Iñaki Ruiz-Trillo, Lluís Ribas de Pouplana
The modification of adenosine to inosine at the first position of transfer RNA (tRNA) anticodons (I34) is widespread among bacteria and eukaryotes. In bacteria, the modification is found in tRNAArg, and is catalysed by tRNA adenosine deaminase A (TadA), a homodimeric enzyme. In eukaryotes I34 is introduced in up to eight different tRNAs by the heterodimeric adenosine deaminase acting on tRNA (ADAT). This substrate expansion significantly influenced the evolution of eukaryotic genomes in terms of codon usage and tRNA gene composition...
December 27, 2018: Molecular Biology and Evolution
Edoardo Giacopuzzi, Massimo Gennarelli, Chiara Sacco, Alice Filippini, Jessica Mingardi, Chiara Magri, Alessandro Barbon
BACKGROUND: A-to-I RNA editing is a co-/post-transcriptional modification catalyzed by ADAR enzymes, that deaminates Adenosines (A) into Inosines (I). Most of known editing events are located within inverted ALU repeats, but they also occur in coding sequences and may alter the function of encoded proteins. RNA editing contributes to generate transcriptomic diversity and it is found altered in cancer, autoimmune and neurological disorders. Emerging evidences indicate that editing process could be influenced by genetic variations, biological and environmental variables...
December 27, 2018: BMC Genomics
Amy C Burke, Dawn E Telford, Murray W Huff
PURPOSE OF REVIEW: Bempedoic acid has emerged as a potent inhibitor of ATP-citrate lyase (ACLY), a target for the reduction of LDL cholesterol (LDL-C). We review the impact of bempedoic acid treatment on lipoprotein metabolism and atherosclerosis in preclinical models and patients with hypercholesterolemia. RECENT FINDINGS: The liver-specific activation of bempedoic acid inhibits ACLY, a key enzyme linking glucose catabolism to lipogenesis by catalyzing the formation of acetyl-CoA from mitochondrial-derived citrate for de novo synthesis of fatty acids and cholesterol...
February 2019: Current Opinion in Lipidology
Li-Di Xu, Marie Öhman
It is well established that somatic mutations and escape of immune disruption are two essential factors in cancer initiation and progression. With an increasing number of second-generation sequencing data, transcriptomic modifications, so called RNA mutations, are emerging as significant forces that drive the transition from normal cell to malignant tumor, as well as providing tumor diversity to escape an immune attack. Editing of adenosine to inosine (A-to-I) in double-stranded RNA, catalyzed by adenosine deaminases acting on RNA (ADARs), is one dynamic modification that in a combinatorial manner can give rise to a very diverse transcriptome...
December 25, 2018: Genes
Mohammad B Uddin, Kartik R Roy, Salman B Hosain, Sachin K Khiste, Ronald A Hill, Seetharama D Jois, Yunfeng Zhao, Alan J Tackett, Yong-Yu Liu
Mutant p53 proteins that promote cancer cell invasive growth, metastasis and drug resistance emerge as therapeutic targets. Previously, we reported that suppression of ceramide glycosylation restored wild-type p53 protein and tumor suppressing function in cancer cells heterozygously carrying p53 R273H, a hot-spot missense mutation; however, the mechanisms underlying the control of mutant protein expression remain elusive. Herein, we report that an N6 -methyladenosine (m6 A) at the point-mutated codon 273 (G>A) of p53 pre-mRNA determines the mutant protein expression...
December 19, 2018: Biochemical Pharmacology
Yun Jiang, Zhancheng Wang, Xu Chen, Wei Wang, Xiaowei Wang
Background: The adenosine deaminase acting on RNA 1 (ADAR1) specifically deaminates adenosine to inosine in double-stranded RNA (dsRNA). Emerging evidence indicated that under hypoxia condition, such as tumor microenvironment, ADAR1 level was increased. Interestingly, we found FGFR2 was also increased under hypoxia stress. The purpose of this study was to investigate the regulation mechanism of ADAR1 and the potential role of ADAR1-FGFR2 axis in cell proliferation and apoptosis. Methods: Using human umbilical vein endothelial cells as cellular model, we explored the function of ADAR1 in regulating cell survival...
2018: Drug Design, Development and Therapy
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