73,273 results match your criteria purine kinase

Investigating the Role of Guanosine on Human Neuroblastoma Cell Differentiation and the Underlying Molecular Mechanisms.

Front Pharmacol 2021 27;12:658806. Epub 2021 Apr 27.

Department of Medical, Oral and Biotechnological Sciences, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy.

Neuroblastoma arises from neural crest cell precursors failing to complete the process of differentiation. Thus, agents helping tumor cells to differentiate into normal cells can represent a valid therapeutic strategy. Here, we evaluated whether guanosine (GUO), a natural purine nucleoside, which is able to induce differentiation of many cell types, may cause the differentiation of human neuroblastoma SH-SY5Y cells and the molecular mechanisms involved. Read More

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Deazapurine Nucleoside Analogues for the Treatment of .

ACS Infect Dis 2021 May 11. Epub 2021 May 11.

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, U.K.

Trichomoniasis is the most common nonviral sexually transmitted disease in humans, but treatment options are limited. Here, we report a resorufin-based drug sensitivity assay for high-throughput microplate-based screening under hypoxic conditions. A 5203-compound enamine kinase library and several specialized compound series were tested for the inhibition of growth at 10 μM with ' values of >0. Read More

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The current role of interferon in hairy cell leukaemia: clinical and molecular aspects.

Br J Haematol 2021 May 1. Epub 2021 May 1.

Haematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.

We investigated the current role of interferon-alpha (IFNα) in hairy cell leukaemia (HCL) in a retrospective analysis of patients with HCL. A cohort of 74 patients with HCL was divided in to three groups: (A) patients aged >65 years with first-line treatment; (B) patients with comorbidities with first-line treatment; (C) patients who were purine analogues resistant. In total, 94% achieved a response, with a complete response rate of 24%. Read More

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Noncanonical DNA polymerization by aminoadenine-based siphoviruses.

Science 2021 04;372(6541):520-524

Génomique Métabolique, Genoscope, Institut François Jacob, CEA, CNRS, Univ. Evry, Université Paris-Saclay, 2 Rue Gaston Crémieux, 91057 Evry, France.

Bacteriophage genomes harbor the broadest chemical diversity of nucleobases across all life forms. Certain DNA viruses that infect hosts as diverse as cyanobacteria, proteobacteria, and actinobacteria exhibit wholesale substitution of aminoadenine for adenine, thereby forming three hydrogen bonds with thymine and violating Watson-Crick pairing rules. Aminoadenine-encoded DNA polymerases, homologous to the Klenow fragment of bacterial DNA polymerase I that includes 3'-exonuclease but lacks 5'-exonuclease, were found to preferentially select for aminoadenine instead of adenine in deoxynucleoside triphosphate incorporation templated by thymine. Read More

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4E Interacting Protein as a Potential Novel Drug Target for Nucleoside Analogues in .

Microorganisms 2021 Apr 13;9(4). Epub 2021 Apr 13.

Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium.

Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets. Read More

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High uric acid induces liver fat accumulation via ROS/JNK/AP-1 signaling.

Am J Physiol Endocrinol Metab 2021 Apr 26. Epub 2021 Apr 26.

Department of Internal Medicine, Xiang`an Hospital of Xiamen University, China.

Uric acid is the end metabolite derived from the oxidation of purine compounds. Overwhelming evidence shows the vital interrelation between hyperuricemia (HUA) and non-alcoholic fatty liver disease (NAFLD). However, the mechanisms for this association remain unclear. Read More

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How cyanophage S-2L rejects adenine and incorporates 2-aminoadenine to saturate hydrogen bonding in its DNA.

Nat Commun 2021 04 23;12(1):2420. Epub 2021 Apr 23.

Unit of Structural Dynamics of Biological Macromolecules, CNRS UMR 3528, 25-28 rue du Docteur Roux, Institut Pasteur, Paris, France.

Bacteriophages have long been known to use modified bases in their DNA to prevent cleavage by the host's restriction endonucleases. Among them, cyanophage S-2L is unique because its genome has all its adenines (A) systematically replaced by 2-aminoadenines (Z). Here, we identify a member of the PrimPol family as the sole possible polymerase of S-2L and we find it can incorporate both A and Z in front of a T. Read More

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Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD.

Nat Commun 2021 04 23;12(1):2426. Epub 2021 Apr 23.

Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.

To adapt to fluctuating protein folding loads in the endoplasmic reticulum (ER), the Hsp70 chaperone BiP is reversibly modified with adenosine monophosphate (AMP) by the ER-resident Fic-enzyme FICD/HYPE. The structural basis for BiP binding and AMPylation by FICD has remained elusive due to the transient nature of the enzyme-substrate-complex. Here, we use thiol-reactive derivatives of the cosubstrate adenosine triphosphate (ATP) to covalently stabilize the transient FICD:BiP complex and determine its crystal structure. Read More

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Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex.

Proc Natl Acad Sci U S A 2021 05;118(19)

Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10065;

Backtracking, the reverse motion of the transcriptase enzyme on the nucleic acid template, is a universal regulatory feature of transcription in cellular organisms but its role in viruses is not established. Here we present evidence that backtracking extends into the viral realm, where backtracking by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) may aid viral transcription and replication. Structures of SARS-CoV-2 RdRp bound to the essential nsp13 helicase and RNA suggested the helicase facilitates backtracking. Read More

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Severe acute myopathy following SARS-CoV-2 infection: a case report and review of recent literature.

Skelet Muscle 2021 04 21;11(1):10. Epub 2021 Apr 21.

Bangladesh Specialized Hospital, Dhaka, Bangladesh.

Background: SARS-CoV2 virus could be potentially myopathic. Serum creatinine phosphokinase (CPK) is frequently found elevated in severe SARS-CoV2 infection, which indicates skeletal muscle damage precipitating limb weakness or even ventilatory failure.

Case Presentation: We addressed such a patient in his forties presented with features of severe SARS-CoV2 pneumonia and high serum CPK. Read More

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Nano-TiO₂ Reduces Testosterone Production in Primary Cultured Leydig Cells from Rat Testis Through the Cyclic Adenosine Phosphate/Cyclic Guanosine Phosphate/Epidermal Growth Factor Receptor/Matrix Metalloproteinase Signaling Pathway.

J Biomed Nanotechnol 2021 Mar;17(3):477-486

Nano-titanium dioxide (nano-TiO₂) has been shown to inhibit testosterone synthesis in male mice or rats; however, the mechanisms underlying these effects have yet to be elucidated. In this study, we investigated whether the inhibition of testosterone synthesis by nano-TiO₂ on Leydig cells (LCs) was related to the dysfunction of the cAMP/CGMP/EGFR/MMP signaling pathway in primary cultures of LCs prepared from rat testis exposed to nano-TiO₂. We found that the early apoptotic rate of LCs increased by 4. Read More

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Mitochondrial NADP is essential for proline biosynthesis during cell growth.

Nat Metab 2021 04 8;3(4):571-585. Epub 2021 Apr 8.

Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Nicotinamide adenine dinucleotide phosphate (NADP) is vital to produce NADPH, a principal supplier of reducing power for biosynthesis of macromolecules and protection against oxidative stress. NADPH exists in separate pools, in both the cytosol and mitochondria; however, the cellular functions of mitochondrial NADPH are incompletely described. Here, we find that decreasing mitochondrial NADP(H) levels through depletion of NAD kinase 2 (NADK2), an enzyme responsible for production of mitochondrial NADP, renders cells uniquely proline auxotrophic. Read More

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Watching a double strand break repair polymerase insert a pro-mutagenic oxidized nucleotide.

Nat Commun 2021 04 6;12(1):2059. Epub 2021 Apr 6.

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA.

Oxidized dGTP (8-oxo-7,8-dihydro-2´-deoxyguanosine triphosphate, 8-oxodGTP) insertion by DNA polymerases strongly promotes cancer and human disease. How DNA polymerases discriminate against oxidized and undamaged nucleotides, especially in error-prone double strand break (DSB) repair, is poorly understood. High-resolution time-lapse X-ray crystallography snapshots of DSB repair polymerase μ undergoing DNA synthesis reveal that a third active site metal promotes insertion of oxidized and undamaged dGTP in the canonical anti-conformation opposite template cytosine. Read More

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Protein kinase D, ubiquitin and proteasome pathways are involved in adenosine receptor-stimulated NR4A expression in myeloid cells.

Biochem Biophys Res Commun 2021 May 31;555:19-25. Epub 2021 Mar 31.

School of Veterinary Medicine, University College Dublin, Ireland; UCD Conway Institute, University College Dublin, Ireland. Electronic address:

Adenosine is a purine nucleoside pivotal for homeostasis in cells and tissues. Stimulation of the adenosine receptors (AR) has been shown to regulate the nuclear orphan receptor 4A (NR4A1-3) family, resulting in attenuation of hyper-inflammatory responses in myeloid cells. The NR4A1-3 orphan receptors are early immediate response genes and transcriptional regulators of cell and tissue homeostasis. Read More

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Muscle Damage in Systemic Sclerosis and CXCL10: The Potential Therapeutic Role of PDE5 Inhibition.

Int J Mol Sci 2021 Mar 12;22(6). Epub 2021 Mar 12.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS9 7TF, UK.

Skeletal muscle damage is a common clinical manifestation of systemic sclerosis (SSc). C-X-C chemokine ligand 10 (CXCL10) is involved in myopathy and cardiomyopathy development and is associated with a more severe SSc prognosis. Interestingly, the phosphodiesterase type 5 inhibitor (PDE5i) sildenafil reduces CXCL10 sera levels of patients with diabetic cardiomyopathy and in cardiomyocytes. Read More

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Downfalls of Chemical Probes Acting at the Kinase ATP-Site: CK2 as a Case Study.

Molecules 2021 Mar 31;26(7). Epub 2021 Mar 31.

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.

Protein kinases are a large class of enzymes with numerous biological roles and many have been implicated in a vast array of diseases, including cancer and the novel coronavirus infection COVID-19. Thus, the development of chemical probes to selectively target each kinase is of great interest. Inhibition of protein kinases with ATP-competitive inhibitors has historically been the most widely used method. Read More

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Collagen I Modifies Connexin-43 Hemichannel Activity via Integrin α2β1 Binding in TGFβ1-Evoked Renal Tubular Epithelial Cells.

Int J Mol Sci 2021 Mar 31;22(7). Epub 2021 Mar 31.

Joseph Banks Laboratories, School of Life Sciences, University of Lincoln, Lincoln LN6 7DL, UK.

Chronic Kidney Disease (CKD) is associated with sustained inflammation and progressive fibrosis, changes that have been linked to altered connexin hemichannel-mediated release of adenosine triphosphate (ATP). Kidney fibrosis develops in response to increased deposition of extracellular matrix (ECM), and up-regulation of collagen I is an early marker of renal disease. With ECM remodeling known to promote a loss of epithelial stability, in the current study we used a clonal human kidney (HK2) model of proximal tubular epithelial cells to determine if collagen I modulates changes in cell function, via connexin-43 (Cx43) hemichannel ATP release. Read More

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The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

Institute of Molecular Cell Biology, Jena University Hospital, D-07745 Jena, Germany.

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. Read More

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The PI3Kδ Inhibitor Idelalisib Diminishes Platelet Function and Shows Antithrombotic Potential.

Int J Mol Sci 2021 Mar 24;22(7). Epub 2021 Mar 24.

Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade Santiago de Compostela and Instituto de Investigación Sanitaria de Santiago, 15706 Santiago de Compostela, Spain.

Background: Clinical management of ischemic events and prevention of vascular disease is based on antiplatelet drugs. Given the relevance of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) as a candidate target in thrombosis, the main goal of the present study was to identify novel antiplatelet agents within the existing inhibitors blocking PI3K isoforms.

Methods: We performed a biological evaluation of the pharmacological activity of PI3K inhibitors in platelets. Read More

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P-Glycoprotein Inhibitor Tariquidar Plays an Important Regulatory Role in Pigmentation in Larval Zebrafish.

Cells 2021 Mar 20;10(3). Epub 2021 Mar 20.

Department of Animal Anatomy, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13 Street, Box 105J, 10-719 Olsztyn, Poland.

Zebrafish has emerged as a powerful model in studies dealing with pigment development and pathobiology of pigment diseases. Due to its conserved pigment pattern with established genetic background, the zebrafish is used for screening of active compounds influencing melanophore, iridophore, and xanthophore development and differentiation. In our study, zebrafish embryos and larvae were used to investigate the influence of third-generation noncompetitive P-glycoprotein inhibitor, tariquidar (TQR), on pigmentation, including phenotype effects and changes in gene expression of chosen chromatophore differentiation markers. Read More

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Polymeric Nanovectors Incorporated with Ganciclovir and HSV- Encoding Plasmid for Gene-Directed Enzyme Prodrug Therapy.

Molecules 2021 Mar 21;26(6). Epub 2021 Mar 21.

Department of Chemical and Biological Engineering, University of Idaho, Moscow, ID 83844, USA.

In the area of gene-directed enzyme prodrug therapy (GDEPT), using herpes simplex virus thymidine kinase (HSV-) paired with prodrug ganciclovir (GCV) for cancer treatment has been extensively studied. It is a process involved with two steps whereby the gene (HSV-) is first delivered to malignant cells. Afterward, non-toxic GCV is administered to that site and activated to cytotoxic ganciclovir triphosphate by HSV- enzyme expressed exogenously. Read More

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Piece of the puzzle: Remdesivir disassembles the multimeric SARS-CoV-2 RNA-dependent RNA polymerase complex.

Cell Biochem Biophys 2021 Jun 1;79(2):175-187. Epub 2021 Apr 1.

Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4001, South Africa.

The recently emerged SARS-like coronavirus (SARS-CoV-2) has continued to spread rapidly among humans with alarming upsurges in global mortality rates. A major key to tackling this virus is to disrupt its RNA replication process as previously reported for Remdesivir (Rem-P). In this study, we theorize, using computational simulations, novel mechanisms that may underlie the binding of Rem-P to SARS-CoV-2 RdRp-NSPs complex; a multimeric assembly that drives viral RNA replication in human hosts. Read More

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Treatment of COVID-19: a review of current and prospective pharmacotherapies.

Br J Hosp Med (Lond) 2021 Mar 12;82(3):1-9. Epub 2021 Mar 12.

Department of Intensive Care, Barnet Hospital, Royal Free London NHS Foundation Trust, London, UK.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread and have grave health and socioeconomic consequences worldwide. Researchers have raced to understand the pathophysiological mechanisms underpinning the disease caused by SARS-CoV-2 so that effective therapeutic targets can be discovered. This review summarises the key pharmacotherapies that are being investigated for treatment of COVID-19, including antiviral, immunomodulator and anticoagulation strategies. Read More

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Autophagy Induction by α-Santalol in Human Prostate Cancer Cells.

Anticancer Res 2021 Mar;41(3):1197-1202

Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA, U.S.A.

Background/aim: Previous studies have shown that the sandalwood oil constituent α-santalol inhibits growth of cultured human prostate cancer cells in vitro and PC-3 prostate cancer xenografts. Along with the studies from our laboratory, it is well established that α-santalol targets the phosphatidylinositol-4,5-bisphosphate 3-kinase-AKT serine/ threonine kinase 1 (AKT) pathway to induce apoptosis but its growth-suppressive effects have not been fully elucidated. The current study was undertaken to investigate the role of autophagy in α-santalol-induced prostate cancer cell death. Read More

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CD73 and Adenosine Receptor Signaling as a Potential Therapeutic Target in EGFR-Mutated NSCLC.

J Thorac Oncol 2021 04;16(4):509-511

Department of Internal Medicine, Division of Medical Oncology, University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

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mGDisAI: N7-methylguanosine (mG) sites and diseases associations inference based on heterogeneous network.

BMC Bioinformatics 2021 Mar 24;22(1):152. Epub 2021 Mar 24.

Engineering Research Center of Intelligent Control for Underground Space, Ministry of Education, China University of Mining and Technology, Xuzhou, 221116, China.

Background: Recent studies have confirmed that N7-methylguanosine (mG) modification plays an important role in regulating various biological processes and has associations with multiple diseases. Wet-lab experiments are cost and time ineffective for the identification of disease-associated mG sites. To date, tens of thousands of mG sites have been identified by high-throughput sequencing approaches and the information is publicly available in bioinformatics databases, which can be leveraged to predict potential disease-associated mG sites using a computational perspective. Read More

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The 11th Trial of a Cardiovascular Clinical Trialist: Coronavirus-2: Part 5.

Cardiol Rev 2021 May-Jun 01;29(3):109

Department of Cardiology and Medicine, New York Medical College, Westchester Health Care System, Valhalla, NY,

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Phase 2 Study of Ibrutinib in Classic and Variant Hairy Cell Leukemia.

Blood 2021 Mar 22. Epub 2021 Mar 22.

Ohio State University, Colmubus, Ohio, United States.

Hairy cell leukemia is a rare B-cell malignancy where there is a need for novel treatments for patients who do not benefit from purine analogues. Ibrutinib, an oral agent targeting Bruton tyrosine kinase in the B-cell receptor signaling pathway, is highly effective in several malignancies. Its activity in HCL was unknown. Read More

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Progesterone activates the cyclic AMP-protein kinase A signalling pathway by upregulating in fertile men.

J Int Med Res 2021 Mar;49(3):300060521999527

Shanghai JIAI Genetics & IVF Institute-China USA Center, Shanghai, China.

Objective: This was a prospective study to investigate whether progesterone affects sperm activity by regulating the cyclic AMP-protein kinase A (cAMP-PKA) signalling pathway via α/β hydrolase domain-containing protein 2 (ABHD2).

Methods: Spermatozoa were collected from healthy and infertile men (with oligoasthenospermia or abnormal acrosome; n = 30/group). The expression of and mutations in were detected by quantitative PCR, western blot, and gene sequencing. Read More

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Role of the chicken oligoadenylate synthase-like gene during in vitro Newcastle disease virus infection.

Poult Sci 2021 May 18;100(5):101067. Epub 2021 Feb 18.

Department of Animal Science, Iowa State University, 50011-3150 Ames, USA. Electronic address:

The enzyme 2'-5' oligoadenylate synthase (OAS) is one of the key interferon-induced antiviral factors that act through inhibition of viral replication. In chickens, there is a single well-characterized OAS gene, oligoadenylate synthase-like (OASL) that has been shown to be upregulated after infection with various viruses. However, a deeper understanding of how chicken OASL acts against viral infection is still necessary. Read More

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