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Molecules (Basel, Switzerland) Jan 2013The advantages and disadvantages of existing approaches to the synthesis of oligodeoxyribonucleotides (ODN) are discussed focusing on large-scale methods. The liquid... (Review)
Review
The advantages and disadvantages of existing approaches to the synthesis of oligodeoxyribonucleotides (ODN) are discussed focusing on large-scale methods. The liquid phase and solid supported synthesis and the synthesis on soluble polymers are discussed. Different problems concerning the methods and implementation of the ODN synthesis are outlined depending on goals of using target oligomers.
Topics: Click Chemistry; Deoxyribonucleosides; Oligodeoxyribonucleotides; Solid-Phase Synthesis Techniques
PubMed: 23322070
DOI: 10.3390/molecules18011063 -
International Journal of Molecular... Jan 2023The guanine base in nucleic acids is, among the other bases, the most susceptible to being converted into 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) when exposed to... (Review)
Review
The guanine base in nucleic acids is, among the other bases, the most susceptible to being converted into 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) when exposed to reactive oxygen species. In double-helix DNA, 8-oxodG can pair with adenine; hence, it may cause a G > T (C > A) mutation; it is frequently referred to as a form of DNA damage and promptly corrected by DNA repair mechanisms. Moreover, 8-oxodG has recently been redefined as an epigenetic factor that impacts transcriptional regulatory elements and other epigenetic modifications. It has been proposed that 8-oxodG exerts epigenetic control through interplay with the G-quadruplex (G4), a non-canonical DNA structure, in transcription regulatory regions. In this review, we focused on the epigenetic roles of 8-oxodG and the G4 and explored their interplay at the genomic level.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Deoxyguanosine; DNA Damage; DNA Repair; DNA
PubMed: 36768357
DOI: 10.3390/ijms24032031 -
Molecules (Basel, Switzerland) Jan 2021A major obstacle in tumor treatment is associated with the poor penetration of a therapeutic agent into the tumor tissue and with their adverse influence on healthy... (Review)
Review
A major obstacle in tumor treatment is associated with the poor penetration of a therapeutic agent into the tumor tissue and with their adverse influence on healthy cells, which limits the dose of drug that can be safely administered to cancer patients. Gemcitabine is an anticancer drug used to treat a wide range of solid tumors and is a first-line treatment for pancreatic cancer. The effect of gemcitabine is significantly weakened by its rapid plasma degradation. In addition, the systemic toxicity and drug resistance significantly reduce its chemotherapeutic efficacy. Up to now, many approaches have been made to improve the therapeutic index of gemcitabine. One of the recently developed approaches to improve conventional chemotherapy is based on the direct targeting of chemotherapeutics to cancer cells using the drug-peptide conjugates. In this work, we summarize recently published gemcitabine peptide-based conjugates and their efficacy in anticancer therapy.
Topics: Animals; Cell-Penetrating Peptides; Deoxycytidine; Humans; Molecular Targeted Therapy; Nanoparticles; Neoplasms; Peptides; Gemcitabine
PubMed: 33445797
DOI: 10.3390/molecules26020364 -
The Journal of Biological Chemistry Nov 2021Detection of thymidine analogues after their incorporation into replicating DNA represents a powerful tool for the study of cellular DNA synthesis, progression through... (Review)
Review
Detection of thymidine analogues after their incorporation into replicating DNA represents a powerful tool for the study of cellular DNA synthesis, progression through the cell cycle, cell proliferation kinetics, chronology of cell division, and cell fate determination. Recent advances in the concurrent detection of multiple such analogues offer new avenues for the investigation of unknown features of these vital cellular processes. Combined with quantitative analysis, temporal discrimination of multiple labels enables elucidation of various aspects of stem cell life cycle in situ, such as division modes, differentiation, maintenance, and elimination. Data obtained from such experiments are critically important for creating descriptive models of tissue histogenesis and renewal in embryonic development and adult life. Despite the wide use of thymidine analogues in stem cell research, there are a number of caveats to consider for obtaining valid and reliable labeling results when marking replicating DNA with nucleotide analogues. Therefore, in this review, we describe critical points regarding dosage, delivery, and detection of nucleotide analogues in the context of single and multiple labeling, outline labeling schemes based on pulse-chase, cumulative and multilabel marking of replicating DNA for revealing stem cell proliferative behaviors, and determining cell cycle parameters, and discuss preconditions and pitfalls in conducting such experiments. The information presented in our review is important for rational design of experiments on tracking dividing stem cells by marking replicating DNA with thymidine analogues.
Topics: Animals; Cell Cycle; Cell Self Renewal; Cell Tracking; DNA Replication; Humans; Stem Cells; Thymidine
PubMed: 34717955
DOI: 10.1016/j.jbc.2021.101345 -
ACS Chemical Biology Mar 2019Genomic integrity is constantly challenged by exposure to environmental and endogenous genotoxic agents. Reactive oxygen species (ROS) represent one of the most common...
Genomic integrity is constantly challenged by exposure to environmental and endogenous genotoxic agents. Reactive oxygen species (ROS) represent one of the most common types of DNA damaging agents. While ROS mainly induce single-nucleobase lesions, epimeric 2-deoxyribose lesions can also be induced upon hydrogen atom abstraction from the C1', C3', or C4' carbon and the subsequent incorrect chemical repair of the resulting carbon-centered radicals. Herein, we investigated the replicative bypass of the C1'- and C3'-epimeric lesions of the four 2'-deoxynucleosides in HEK293T human embryonic kidney epithelial cells. Our results revealed distinct bypass efficiencies and mutagenic properties of these two types of epimeric lesions. Replicative bypasses of all C1'-epimeric lesions except α-dA are mutagenic in HEK293T cells, and their mutagenic properties are further modulated by translesion synthesis (TLS) DNA polymerases. By contrast, none of the four C3'-epimeric lesions are mutagenic, and the replicative bypass of these lesions is not compromised upon depletion of polymerase η, ι, κ, or ζ. Together, our results provide important new knowledge about the cytotoxic and mutagenic properties of C1' and C3' epimeric lesions, and reveal the roles of TLS DNA polymerases in bypassing these lesions in human cells.
Topics: Cell Survival; DNA; DNA Damage; DNA Repair; DNA Replication; DNA-Directed DNA Polymerase; Deoxyribonucleosides; HEK293 Cells; Humans; Mutagenesis; Mutagens; Reactive Oxygen Species
PubMed: 30768892
DOI: 10.1021/acschembio.8b01126 -
Medicina Oral, Patologia Oral Y Cirugia... Nov 2023The development and establishment of oral squamous cell carcinoma are confined to carcinogenesis, which involves oxidative stress via oxygen-free radical production as a...
BACKGROUND
The development and establishment of oral squamous cell carcinoma are confined to carcinogenesis, which involves oxidative stress via oxygen-free radical production as a hydroxyl radical (HO•), considered the most important cause of oxidative damage to basic biomolecules since it targets DNA strands. 8-Hydroxy-2´-deoxyguanosine (8-OHdG) is considered a free radical with a promutagenic capacity due to its ability to pair with adenosine instead of cytosine during replication.
MATERIAL AND METHODS
We collected 30 paraffin-embedded tissue samples of OSCC from patients treated between 2013 and 2018. We recorded risk habits, disease stage, disease free survival and death with at least 3 years of follow-up. 8-Hydroxyguanosine was evaluated by immunohistochemistry and subsequently classified as weak-moderate or strong positive expression. Additionally, we noted whether it was expressed in the cytoplasm and/or nucleus.
RESULTS
Most of the cases expressed 8-OHdG with a strong intensity (80%). All neoplastic cells were preferentially stained in only the cytoplasm (70.0%), but nuclear positivity was found in 30%, independent of the intensity. Based on the location in the cytoplasm and/or nucleus, tumors >4 cm showed a high frequency (95.5%) of 8-OHdG expression in only the cytoplasm, with a significant difference (p value 0.001). Additionally, overall survival was affected when immunoexpression was present in the cytoplasm and nucleus because all deaths were in this group were statistically significant (p value = 0.001).
CONCLUSIONS
All tumors showed DNA oxidative damage, and 8-OHdG was preferentially expressed in the cytoplasm. This finding was associated with tumor size and, when present in the nucleus, might also be related to death.
Topics: Humans; 8-Hydroxy-2'-Deoxyguanosine; Mouth Neoplasms; Deoxyguanosine; Carcinoma, Squamous Cell; DNA Damage; Oxidative Stress; Free Radicals
PubMed: 37471300
DOI: 10.4317/medoral.25924 -
FEBS Letters Jan 1995DNA of cancers such as renal cell carcinoma and mammary invasive ductal carcinoma, is persistently exposed to more oxidative stress than that of adjacent normal tissue.... (Review)
Review
DNA of cancers such as renal cell carcinoma and mammary invasive ductal carcinoma, is persistently exposed to more oxidative stress than that of adjacent normal tissue. We suggest that the concept of 'persistent oxidative stress in cancer' may open up a new research area, explaining part of the characteristic tumor biology of cancer such as activated transcription factors and proto-oncogenes, genomic instability, chemotherapy-resistance, invasion and metastasis.
Topics: 8-Hydroxy-2'-Deoxyguanosine; DNA, Neoplasm; Deoxyguanosine; Humans; Models, Biological; Neoplasms; Oxidative Stress; Reactive Oxygen Species
PubMed: 7821417
DOI: 10.1016/0014-5793(94)01368-b -
Characterization of deoxyribonucleoside transport mediated by concentrative nucleoside transporters.Biochemical and Biophysical Research... Jun 2021Human concentrative nucleoside transporters (CNTs) are responsible for cellular uptake of ribonucleosides; however, although it is important to better characterize...
Human concentrative nucleoside transporters (CNTs) are responsible for cellular uptake of ribonucleosides; however, although it is important to better characterize CNT-subtype specificity to understand the systemic disposition of deoxyribonucleosides (dNs) and their analogs, the involvement of CNTs in transporting dNs is not fully understood. In this study, using COS-7 cells that transiently expressed CNT1, CNT2, or CNT3, we investigated if CNTs could transport not only ribonucleosides but also dNs, i.e., 2'-deoxyadenosine (dAdo), 2'-deoxyguanosine (dGuo), and 2'-deoxycytidine (dCyd). The cellular uptake study demonstrated that dAdo and dGuo were taken up by CNT2 but not by CNT1. Although dCyd was taken up by CNT1, no significant uptake was detected in COS-7 cells expressing CNT2. Similarly, these dNs were transported by CNT3. The apparent K values of their uptake were as follows: CNT1, K = 141 μM for dCyd; CNT2, K = 62.4 μM and 54.9 μM for dAdo and dGuo, respectively; CNT3, K = 14.7 μM and 34.4 μM for dGuo and dCyd, respectively. These results demonstrate that CNTs contribute not only to ribonucleoside transport but also to the transport of dNs. Moreover, our data indicated that CNT1 and CNT2 selectively transported pyrimidine and purine dNs, respectively, and CNT3 was shown to transport both pyrimidine and purine dNs.
Topics: Animals; Biological Transport, Active; COS Cells; Chlorocebus aethiops; Deoxyadenosines; Deoxycytidine; Deoxyguanosine; Deoxyribonucleosides; Humans; Kinetics; Membrane Transport Proteins; Recombinant Proteins
PubMed: 33910126
DOI: 10.1016/j.bbrc.2021.04.075 -
Chinese Medical Journal Nov 2023Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative...
BACKGROUND
Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China.
METHODS
This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs . ≥100,000 copies/mL) and CD4 + cell count (<200 vs . ≥200 cell/µL). Median time to TND VL was assessed by Kaplan-Meier method. We also measured changes from baseline in CD4 + cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs).
RESULTS
We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND ( P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) ( P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) ( P <0.001). No differences were seen in CD4 + cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) ( P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain.
CONCLUSIONS
In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4 + cell count. CD4 + recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.
Topics: Adult; Humans; Anti-HIV Agents; China; Emtricitabine; HIV Infections; HIV-1; Lamivudine; Lipids; Retrospective Studies
PubMed: 37914678
DOI: 10.1097/CM9.0000000000002907 -
The Science of the Total Environment Apr 2023Selenium is an element present in trace amounts and different chemical forms. It may exert both beneficial and adverse effects on cellular redox status and on the...
Selenium is an element present in trace amounts and different chemical forms. It may exert both beneficial and adverse effects on cellular redox status and on the generation of reactive oxygen species. 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG) is an oxidized derivative of deoxyguanosine, and a sensitive biomarker of oxidative stress and genotoxicity. The present study assessed the extent to which selenium status was associated with urinary 8-oxodG concentrations in a Northern Italian population. We recruited healthy, non-smoking blood donors living in the Reggio Emilia province during 2017-2019. We measured urinary 8-oxodG concentrations and used restricted cubic spline regression analyses to investigate the association between selenium status (estimated using food frequency questionnaires, urinary concentrations, and serum concentrations of selenium and selenium species) and 8-oxodG/g creatinine. Among 137 participants aged 30-60 years, median urinary selenium and 8-oxodG concentrations were 22.02 μg/L and 3.21 μg/g creatinine, respectively. Serum samples and selenium speciation analyses were available for 104 participants. Median total serum selenium levels and dietary intake were 116.5 μg/L and 78.7 μg/day, respectively. In spline regression analysis, there was little association between dietary, serum, or urinary selenium with 8-oxodG concentrations. In sex-specific analyses, urinary selenium showed a positive association with the endpoint among males. For single selenium species, we observed positive associations with urinary 8-oxodG for serum organic selenium species, and negative associations for inorganic selenium forms. In the most adjusted analysis, urinary 8-oxodG concentrations showed a strong positive association with selenomethione-bound selenium (Se-Met) and a negative association with inorganic tetravalent selenium, selenite. In sex-specific analyses, these associations were considerably stronger in males than in females. Overall, study findings indicate that selenium species exhibited very different patterns of associations with the biomarker of oxidative stress, and that these associations also depended on sex. Background exposure to Se-Met appears to be strongly and positively associated with oxidative stress.
Topics: Male; Female; Humans; 8-Hydroxy-2'-Deoxyguanosine; Deoxyguanosine; Selenium; Creatinine; Oxidative Stress; Biomarkers
PubMed: 36702271
DOI: 10.1016/j.scitotenv.2023.161584