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Nanomaterials for Theranostics: Recent Advances and Future Challenges *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Eun-Kyung Lim, Taekhoon Kim, Soonmyung Paik, Seungjoo Haam, Yong-Min Huh, Kwangyeol Lee
MTX inhibits the action of the FA reductase, which is responsible for conversion of FA to tetrahydrofolic acid [362, 363]. In the absence of tetrahydrofolic acids, DNA, RNA, and proteins cannot be synthesized, leading to blockage of cell division. Hydroxyurea (hyhdroxycarbamide) reduces production of deoxyribonucleotides through inhibition of the enzyme ribonucleotidereductase [361–366]. This enzyme catalyzes the reduction of ribonucleotide into their corresponding deoxyribonucleotides, which are required for DNA synthesis. 5-FU, a thymidylate synthase inhibitor, is widely used in the treatment of patients with breast or gastrointestinal tract cancer. Interrupting the action of this enzyme blocks the synthesis of pyrimidine thymidine, which is a nucleoside required for DNA replication, in the S phase of the cell cycle [367]. Thymidylate synthase converts deoxyuridine monophosphate (dUMP) into deoxythymidine monophosphate (dTMP), which is crucial in production of pyrimidine base for synthesis of DNA; thus, it is a viable target for cancer chemotherapy [367]. 5-FU causes a scarcity of dTMP. Therefore, rapidly dividing cancer cells undergo apoptosis via thymine-less death. 5-FU can arrest unlimited proliferation of cancer cells and also lead to production of faulty rRNA [368, 369]. The immunosuppressive drug 6-MP alters the synthesis and function of DNA and RNA by inhibiting purine nucleotide synthesis and metabolism and interferes with nucleotide interconversion and glycoprotein synthesis [370, 371].
Notes on Genetic and Radiation Control of Senescence
Published in Nate F. Cardarelli, The Thymus in Health and Senescence, 2019
Metal interactions with DNA are fairly well known. For instance, DNA will bind magnesium.170–175 The enzymatic incorporation of ribonucleotides into RNA requires the presence of divalent ions, magnesium and manganese being stimulatory at low concentrations and inhibitory at higher ones.173 An enzyme fraction from calf thymus nuclei catalyzed incorporation of deoxyribonucleotides into the terminal regions of DNA.174 This material required the presence of Mg++ for such activity to occur. Mg++ also induces ribosome subunit association, which is critical for mRNA translation.176 Watanabe and Iso noted that magnesium ion induces conformational changes in DNA.177 They also found that histone H1 inhibits Mg++ binding to chromatin.
Thymus Influence on Differentiation and Functional Maturation of T Lymphocytes
Published in Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein, Immunoregulatory Role of Thymus, 2019
Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein
Proposed by Ma et al.,63 biochemical mechanism of thymocyte selection is basically outlined as follows: High ADA and PNP activities protect prothymocytes and cortical thymocytes from toxic dATP and dGTP accumulation. Additionally, TdT-dependent DNA polymers formation utilizes free excess deoxyribonucleotides, particularly dATP and dGTP.The late stage of cortical thymocyte maturation involves another enzymatic combination. Sudden fall in TdT activity, low PNP and 5′ NT activities, and high kinase activity lead to the jeopardy of excessive level of purine deoxynucleotides, especially dGTP.Developing thymocytes may escape biochemical death if they represent the appropriate combination of the surface receptors for self la molecule recognition, which provides close contact with thymic epithelial and accessory cells. The thymic matrix cells may deliver to a thymocyte both metabolic help with transfer of nucleotides and enzyme molecules, as well as a stimulus (TH) for rapid differentiation to the developmental stage of medullary thymocyte which contains higher levels of PNP and 5′ NT.
Role of silymarin (Silybum marianum) in the prevention of colistin-induced acute nephrotoxicity in rats
Published in Drug and Chemical Toxicology, 2022
Burak Dumludag, Mehmet Kursat Derici, Osman Sutcuoglu, Betul Ogut, Ozge Tugce Pasaoglu, Ipek Isık Gonul, Ulver Derici
Apoptosis (DNA fragmentation) was studied on paraffine embedded tissue sections by use of the TUNEL (terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling) assay method (Apoptag reagent, Q-Biogene, Strasbourg, France). Briefly, kidney sections were digested by proteinase K followed by H2O2- inactivation of endogenous peroxidase. The sections were incubated with residues of digoxigenin nucleotide and terminal deoxynucleotide transferase (which catalyzes a template-independent addition of deoxyribonucleotide triphosphate to the 39-end of double single-stranded DNA). After that, the sections were incubated with the antidigoxygenin antibody coupled to peroxidase. The cells with evidence of nuclear DNA fragmentation could be identified, and the labeling index calculated, after incubating the sections with diaminobenzidine and H2O2. The number of TUNEL positive cells was determined in the tubular epithelial cells, both in the cortex and medulla. More than 1000 tubular epithelial cells per patient were counted, and cells were considered to be positive when the staining intensity was moderate to strong.
Transcriptome analysis identifies key regulators and networks in Acute myeloid leukemia
Published in Hematology, 2019
Jiaxin Ye, Daliang Luo, Jianhong Yu, Sibo Zhu
Next, we observed that the target genes of hub miRNAs were related to cell growth, proliferation, death, and survival. Pathway analysis demonstrated that the ATP enzyme was significantly affected by miRNA regulation. The ATP was involved in biosynthesis pathways which were significantly enriched. Salvage Pathways of Pyrimidine Deoxyribonucleotides was a pathway related to the biosynthesis of deoxyribonucleotides. ATP played a very important role in this biological procedure [19–23]. Deoxyribonucleotides were essential to DNA synthesis/repair. The previous study demonstrated that the biosynthesis of deoxyribonucleotides was an important target for anticancer therapy [24,25].
Relationship between G proteins coupled receptors and tight junctions
Published in Tissue Barriers, 2018
Lorenza González-Mariscal, Arturo Raya-Sandino, Laura González-González, Christian Hernández-Guzmán
Nucleotides contain either a purine (adenine or guanine) or a pyrimidine (thymine, uracil or cytosine) nitrogenous base, and are termed ribonucleotides if the sugar is ribose or deoxyribonucleotides if the sugar is deoxyribose. Nucleotides have several functions: 1) as monomer units for forming the nucleic acid polymers DNA and RNA, 2) as packets of chemical energy in the form of the nucleoside triphosphates ATP, GTP, CTP and UTP, 3) as signaling molecules in the form of cyclic nucleotides cGMP and cAMP, and 4) as cofactors of enzymatic reactions.