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https://www.readbyqxmd.com/read/28330104/purification-and-characterization-of-the-enzymes-involved-in-nicotinamide-adenine-dinucleotide-degradation-by-penicillium-brevicompactum-nrc-829
#1
Thanaa Hamed Ali, Dina Helmy El-Ghonemy
The present study was conducted to investigate a new pathway for the degradation of nicotinamide adenine dinucleotide (NAD) by Penicillium brevicompactum NRC 829 extracts. Enzymes involved in the hydrolysis of NAD, i.e. alkaline phosphatase, aminohydrolase and glycohydrolase were determined. Alkaline phosphatase was found to catalyse the sequential hydrolysis of two phosphate moieties of NAD molecule to nicotinamide riboside plus adenosine. Adenosine was then deaminated by aminohydrolase to inosine and ammonia...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28325877/dual-utility-nls-drives-rnf169-dependent-dna-damage-responses
#2
Liwei An, Yiyang Jiang, Howin H W Ng, Ellen P S Man, Jie Chen, Ui-Soon Khoo, Qingguo Gong, Michael S Y Huen
Loading of p53-binding protein 1 (53BP1) and receptor-associated protein 80 (RAP80) at DNA double-strand breaks (DSBs) drives cell cycle checkpoint activation but is counterproductive to high-fidelity DNA repair. ring finger protein 169 (RNF169) maintains the balance by limiting the deposition of DNA damage mediator proteins at the damaged chromatin. We report here that this attribute is accomplished, in part, by a predicted nuclear localization signal (NLS) that not only shuttles RNF169 into the nucleus but also promotes its stability by mediating a direct interaction with the ubiquitin-specific protease USP7...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28325600/synthesis-and-anti-cancer-activities-of-new-sulfonamides-4-substituted-triazolyl-nucleosides
#3
Soukaina Alaoui, Maeva Dufies, Mohsine Driowya, Luc Demange, Khalid Bougrin, Guillaume Robert, Patrick Auberger, Gilles Pagès, Rachid Benhida
Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell lines, AICAR is under clinical development for several pathologies, thanks to its original mode of action. Indeed, AICAR induced autophagy cell death and is able, following this mechanism, to circumvent resistance to apoptotic drugs including kinase inhibitors currently on the market...
March 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28324644/synthesis-of-the-t-705-ribonucleoside-and-ribonucleotide-and-studies-on-the-chemical-stability
#4
Johanna Huchting, Matthias Winkler, Hiba Nasser, Chris Meier
T-705 (favipiravir) is a fluorinated hydroxypyrazine carboxamide that exhibits antiviral activities against a variety of RNA viruses. Due to the lack of potent agents to combat these infections caused by a large number of these high-impacting pathogens, huge emphasis has been put on the studies of T-705's antiviral properties and its mechanism of action. T-705 acts as a nucleobase analogue; hence, it is metabolized to the corresponding ribonucleoside triphosphate intracellularly. We herein report a reliable synthesis of T-705-ribonucleoside and its 5'-monophosphate...
March 21, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28323865/the-microrna-302b-inhibited-insulin-like-growth-factor-binding-protein-2-signaling-pathway-induces-glioma-cell-apoptosis-by-targeting-nuclear-factor-ia
#5
Chin-Cheng Lee, Peng-Hsu Chen, Kuo-Hao Ho, Chwen-Ming Shih, Chia-Hsiung Cheng, Cheng-Wei Lin, Kur-Ta Cheng, Ann-Jeng Liu, Ku-Chung Chen
MicroRNAs are small noncoding RNAs that post-transcriptionally control the expression of genes involved in glioblastoma multiforme (GBM) development. Although miR-302b functions as a tumor suppressor, its role in GBM is still unclear. Therefore, this study comprehensively explored the roles of miR-302b-mediated gene networks in GBM cell death. We found that miR-302b levels were significantly higher in primary astrocytes than in GBM cell lines. miR-302b overexpression dose dependently reduced U87-MG cell viability and induced apoptosis through caspase-3 activation and poly(ADP ribose) polymerase degradation...
2017: PloS One
https://www.readbyqxmd.com/read/28323499/antiproliferative-activity-of-egg-yolk-peptides-in-human-colon-cancer-cells
#6
Marwa N Yousr, Akram A Aloqbi, Ulfat M Omar, Nazlin K Howell
Egg yolk peptides were successfully prepared from egg yolk protein by-products after lecithin extraction. Defatted egg yolk protein was hydrolyzed with pepsin and pancreatin and purified by gel filtration to produce egg yolk gel filtration fraction (EYGF-33) with antiproliferative activity. The highlight of this study was that the peptide EYGF-33 (1.0 mg/ml) significantly inhibits cell viability of colon cancer cells (Caco-2) with no inhibitory effects on the viability of human colon epithelial normal cells (HCEC) after 48 h...
March 21, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28323334/the-emerging-role-of-homologous-recombination-repair-and-parp-inhibitors-in-genitourinary-malignancies
#7
REVIEW
Kalen J Rimar, Phuoc T Tran, Richard S Matulewicz, Maha Hussain, Joshua J Meeks
As cells age and are exposed to genotoxic stress, preservation of the genomic code requires multiple DNA repair pathways to remove single-strand or double-strand breaks. Loss of function somatic genomic aberrations or germline deficiency in genes involved in DNA repair can result in acute cell death or, after a latency period, cellular transformation. Therapeutic exploitation of DNA repair by inhibition of poly (adenosine diphosphate [ADP]) ribose polymerases (PARP), a family of enzymes involved in the repair of single-strand and in some cases double-strand breaks, has become a novel cancer treatment...
March 21, 2017: Cancer
https://www.readbyqxmd.com/read/28322442/systems-analysis-of-dynamic-transcription-factor-activity-identifies-targets-for-treatment-in-olaparib-resistant-cancer-cells
#8
Joseph T Decker, Eric C Hobson, Yining Zhang, Seungjin Shin, Alexandra L Thomas, Jacqueline S Jeruss, Kelly B Arnold, Lonnie D Shea
The development of resistance to targeted therapeutics is a challenging issue for the treatment of cancer. Cancers that have mutations in BRCA, a DNA repair protein, have been treated with poly (ADP-ribose) polymerase (PARP) inhibitors, which target a second DNA repair mechanism with the aim of inducing synthetic lethality. While these inhibitors have shown promise clinically, the development of resistance can limit their effectiveness as a therapy. This study investigated mechanisms of resistance in BRCA-mutated cancer cells (HCC1937) to Olaparib (AZD2281) using TRACER, a technique for measuring dynamics of transcription factor (TF) activity in living cells...
March 21, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28322157/diabetes-related-neurological-implications-and-pharmacogenomics
#9
Rojas Carranza Camilo Andrés, Bustos Cruz Rosa Helena, Pino Pinzón Carmen Juliana, Ariza Marquez Yeimy Viviana, Gómez Bello Rosa Margarita, Cañadas Garre Marisa
Diabetes mellitus (DM) is the most commonly occurring cause of neuropathy around the world and is beginning to grow in countries where there is a risk of obesity. DM Type II, (T2DM) is a common age-related disease and is a major health concern, particularly in developed countries in Europe where the population is aging. T2DM is a chronic disease which is characterised by hyperglycemia, hyperinsulinemia and insulin resistance, together with the body's inability to use glucose as energy. Such metabolic disorder produces a chronic inflammatory state, as well as changes in lipid metabolism leading to hypertriglyceridemia, thereby producing chronic deterioration of the organs and premature morbidity and mortality...
March 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28321181/rnf146-inhibits-excessive-autophagy-by-modulating-the-wnt-%C3%AE-catenin-pathway-in-glutamate-excitotoxicity-injury
#10
Yuefan Yang, Peng Luo, Haoxiang Xu, Shuhui Dai, Wei Rao, Cheng Peng, Wenke Ma, Jiu Wang, Hongyu Xu, Lei Zhang, Sai Zhang, Zhou Fei
Glutamate induced excitotoxicity is common in diverse neurological disorders. RNF146 as an E3 ubiquitin ligase protects neurons against excitotoxicity via interfering with Poly (ADP-ribose) (PAR) polymer-induced cell death (parthanatos). However, the neuroprotective role of RNF146 has not been fully understood. We aimed to investigate the role of RNF146 in modulating autophagy in HT22 cells under glutamate excitotoxicity injury. Here we found that induction of RNF146 decreased the cellular damage and excitotoxicity induced by glutamate...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28320298/sodium-orthovanadate-inhibits-proliferation-and-triggers-apoptosis-in-oral-squamous-cell-carcinoma-in-vitro
#11
A A Khalil, M J Jameson
Sodium orthovanadate (SOV) is a general inhibitor of tyrosine phosphatases, a large family of enzymes that catalyze the removal of phosphate groups from tyrosine residues. SOV is commonly used in the laboratory to preserve the protein tyrosyl phosphorylation state of proteins under study. It has shown promising antineoplastic activity in some human cancer cell lines; this effect has not been fully investigated in head and neck squamous cell carcinoma. In this study, the effect of SOV on cell growth, proliferation, viability, and apoptosis was assessed in Cal27 cells, an oral squamous cell carcinoma (OSCC) cell line...
February 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28320285/cells-resistant-to-toxic-concentrations-of-manganese-have-increased-ability-to-repair-dna
#12
K A Zakharcheva, L V Gening, K Yu Kazachenko, V Z Tarantul
Manganese (Mn) is crucially important for vital activity of cells and has many biological functions. Nevertheless, high doses of Mn taken up by an organism over a long period may cause neurodegenerative diseases such as manganism and Parkinsonism. The molecular mechanisms of this Mn toxicity are still poorly studied. It is now believed that Mn-induced pathophysiological neural processes are multifaceted and affect several metabolic pathways. In particular, Mn ions might affect the processes of DNA replication and repair...
January 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28319807/targeting-nf-kappa-b-signaling-by-artesunate-restores-sensitivity-of-castrate-resistant-prostate-cancer-cells-to-antiandrogens
#13
Jessica J Nunes, Swaroop K Pandey, Anjali Yadav, Sakshi Goel, Bushra Ateeq
Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells...
March 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319392/scaffold-repurposing-of-nucleosides-adenosine-receptor-agonists-enhanced-activity-at-the-human-dopamine-and-norepinephrine-sodium-symporters
#14
Dilip K Tosh, Aaron Janowsky, Amy J Eshleman, Eugene Warnick, Zhan-Guo Gao, Zhoumou Chen, Elizabeth Gizewski, John A Auchampach, Daniela Salvemini, Kenneth A Jacobson
We have repurposed (N)-methanocarba adenosine derivatives (A3 adenosine receptor (AR) agonists) to enhance radioligand binding allosterically at the human dopamine (DA) transporter (DAT) and inhibit DA uptake. We extended the structure-activity relationship of this series with small N(6)-alkyl substitution, 5'-esters, deaza modifications of adenine, and ribose restored in place of methanocarba. C2-(5-Halothien-2-yl)-ethynyl 5'-methyl 9 (MRS7292) and 5'-ethyl 10 (MRS7232) esters enhanced binding at DAT (EC50 ∼ 35 nM) and at the norepinephrine transporter (NET)...
March 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28316110/proteasome-ubiquitin-receptor-psmd4-is-an-amplification-target-in-breast-cancer-and-may-predict-sensitivity-to-parpi
#15
Marlena S Fejzo, Lee Anderson, Hsiao-Wang Chen, Enrique Guandique, Ondrej Kalous, Dylan Conklin, Dennis J Slamon
Poly(ADP-ribose) polymerase 1 (PARP1) is an enzyme involved in DNA repair under investigation as a chemotherapeutic target. Current randomized phase 3 trials of PARPi in metastatic breast cancer are limited to patients with documented BRCA1/2 mutations and no biomarker of PARPi beyond BRCA status is available. In an effort to identify novel biomarkers for PARP inihibition, we created a cell line (HCC1187/TALRES) resistant to the PARP1 inhibitor talazoparib. Herein we show by array-CGH that HCC1187/TALRES has a selective loss of the proteasome ubiquitin receptor PSMD4 amplicon resulting in significant down-regulation of PSMD4...
March 18, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28315326/identification-of-parp14-inhibitors-using-novel-methods-for-detecting-auto-ribosylation
#16
Mariko Yoneyama-Hirozane, Shin-Ichi Matsumoto, Yukio Toyoda, Singh Saikatendu Kumar, Yumi Zama, Kazuko Yonemori, Motomi Oonishi, Tsuyoshi Ishii, Tomohiro Kawamoto
Poly(ADP-ribose) polymerases (PARPs) use nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate to transfer ADP-ribose when it releases nicotinamide as the metabolized product. Enzymes of the PARP family play key roles in detecting and repairing DNA, modifying chromatin, regulating transcription, controlling energy metabolism, and inducing cell death. PARP14, the original member of the PARP family, has been reported to be associated with the development of inflammatory diseases and various cancer types, making it a potential therapeutic target...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28314269/quantitative-structure-cytotoxicity-relationship-of-chalcones
#17
Hiroshi Sakagami, Yoshiko Masuda, Mineko Tomomura, Satoshi Yokose, Yoshihiro Uesawa, Naruhiko Ikezoe, Daiki Asahara, Koichi Takao, Taisei Kanamoto, Shigemi Terakubo, Hajime Kagaya, Hideki Nakashima, Yoshiaki Sugita
BACKGROUND: Fifteen chalcones were subjected to quantitative structure-activity relationship (QSAR) analysis based on their cytotoxicity and tumor specificity, in order to find their new biological activities. MATERIALS AND METHODS: Cytotoxicity against four human oral squamous cell carcinoma cell lines and three oral mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor specificity (TS) was evaluated by the ratio of the mean 50% cytotoxic concentration (CC50) against normal cells to that against tumor cell lines...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303528/human-mass-balance-study-and-metabolite-profiling-of-14-c-niraparib-a-novel-poly-adp-ribose-polymerase-parp-1-and-parp-2-inhibitor-in-patients-with-advanced-cancer
#18
Lotte van Andel, Z Zhang, S Lu, V Kansra, S Agarwal, L Hughes, M M Tibben, A Gebretensae, L Lucas, M J X Hillebrand, H Rosing, J H M Schellens, J H Beijnen
Niraparib is an investigational oral, once daily, selective poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor. In the pivotal Phase 3 NOVA/ENGOT/OV16 study, niraparib met its primary endpoint of improving progression-free survival (PFS) for adult patients with recurrent, platinum sensitive, ovarian, fallopian tube, or primary peritoneal cancer in complete or partial response to platinum-based chemotherapy. Significant improvements in PFS were seen in all patient cohorts regardless of biomarker status...
March 16, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28302823/parp-inhibitors-synthetic-lethality-in-the-clinic
#19
REVIEW
Christopher J Lord, Alan Ashworth
PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors arising in patients who carry germline mutations in either BRCA1 or BRCA2 are sensitive to PARPi because they have a specific type of DNA repair defect. PARPi also show promising activity in more common cancers that share this repair defect. However, as with other targeted therapies, resistance to PARPi arises in advanced disease...
March 17, 2017: Science
https://www.readbyqxmd.com/read/28302504/mitochondrial-nudix-hydrolases-a-metabolic-link-between-nad-catabolism-gtp-and-mitochondrial-dynamics
#20
Aaron Long, Nina Klimova, Tibor Kristian
NAD(+) catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD(+) catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism...
March 14, 2017: Neurochemistry International
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