-
Disease Markers 2018The objective was to collect the available evidence on oxidative stress marker measurements in periodontal patients, focusing specifically on 8-hydroxy-2'-deoxyguanosine... (Meta-Analysis)
Meta-Analysis Review
The objective was to collect the available evidence on oxidative stress marker measurements in periodontal patients, focusing specifically on 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a salivary marker of periodontal disease, and to perform meta-analyses to calculate differences in concentration compared to healthy persons. A systematic search in PubMed, Cochrane Library, Embase, and Scopus identified 81 articles. Of these, 38 were duplicates. After reading the abstracts of the remaining 43, 42 were selected for full-text assessment. Finally, 17 articles were included in the qualitative synthesis. Those excluded were of low quality, did not answer the research question, or did not meet the inclusion and exclusion criteria. Of the 17 in the qualitative synthesis, 9 were included in the meta-analysis. The 9 studies in the meta-analysis were combined in a random effects model. Their heterogeneity was high ( = 3982.02, < 0.001, = 99.8%). The difference in mean 8-OHdG concentration in saliva between periodontal and healthy subjects was estimated at 2.11 ng/ml (95% CI 1.23-2.98). The different saliva collection methods (stimulated/unstimulated) did not explain the heterogeneity. The 8-OHdG levels in saliva of periodontal patients were almost double to those of healthy patients: 8-OHdG is clearly a powerful periodontal disease marker.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Aggressive Periodontitis; Biomarkers; Deoxyguanosine; Humans; Saliva
PubMed: 29854026
DOI: 10.1155/2018/7916578 -
Biochemistry. Biokhimiia Dec 20178-Oxo-7,8-dihydroguanine (8-oxo-G) is a key biomarker of oxidative damage to DNA in cells, and its genotoxicity is well-studied. In recent years, it has been confirmed... (Review)
Review
8-Oxo-7,8-dihydroguanine (8-oxo-G) is a key biomarker of oxidative damage to DNA in cells, and its genotoxicity is well-studied. In recent years, it has been confirmed experimentally that free 8-oxo-G and molecules containing it are not merely inert products of DNA repair or degradation, but they are actively involved in intracellular signaling. In this review, data are systematized indicating that free 8-oxo-G and oxidized (containing 8-oxo-G) extracellular DNA function in the body as mediators of stress signaling and initiate inflammatory and immune responses to maintain homeostasis under the action of external pathogens, whereas exogenous 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo) exhibits pronounced antiinflammatory and antioxidant properties. This review describes known action mechanisms of oxidized guanine and 8-oxo-G-containing molecules. Prospects for their use as a therapeutic target are considered, as well as a pharmaceutical agent for treatment of a wide range of diseases whose pathogenesis is significantly contributed to by inflammation and oxidative stress.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers; DNA Damage; DNA Repair; Deoxyguanosine; Guanine; Humans; Inflammation; Oxidative Stress
PubMed: 29523066
DOI: 10.1134/S0006297917130089 -
The Journal of Organic Chemistry Oct 2021Herein, we demonstrate an elegant multistep continuous flow synthesis for stavudine (d4T), a potent nucleoside chemotherapeutic agent for human immunodeficiency virus,...
Herein, we demonstrate an elegant multistep continuous flow synthesis for stavudine (d4T), a potent nucleoside chemotherapeutic agent for human immunodeficiency virus, acquired immunodeficiency syndrome (AIDS) and AIDS-related conditions. This was accomplished via six chemical transformations in five sequential continuous flow reactors from an affordable starting material, 5-methyluridine. In the first instance, single step continuous flow synthesis was demonstrated with an average of 97% yield, 21.4 g/h throughput per step, and a total of 15.5 min residence time. Finally, multistep continuous flow synthesis of d4T in 87% total yield with a total residence time of 19.9 min and 117 mg/h throughput without intermediate purification was demonstrated.
Topics: Humans; Stavudine
PubMed: 34060836
DOI: 10.1021/acs.joc.1c01013 -
Free Radical Biology & Medicine Sep 2023There is accumulating evidence that pro-inflammatory features are inherent to mitochondrial DNA and oxidized DNA species. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo)...
There is accumulating evidence that pro-inflammatory features are inherent to mitochondrial DNA and oxidized DNA species. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) is the most frequently studied oxidatively generated lesion. Modified DNA reaches the circulation upon cell apoptosis, necrosis or neutrophil extracellular trap (NET) formation. Standard chromatography-based techniques for the assessment of 8-oxodGuo imply degradation of DNA to a single base level, thus precluding the attribution to a nuclear or mitochondrial origin. We therefore aimed to establish a protocol for the concomitant assessment of oxidized mitochondrial and nuclear DNA from human plasma samples. We applied immunoprecipitation (IP) for 8-oxodGuo to separate oxidized from non-oxidized DNA species and subsequent quantitative polymerase chain reaction (qPCR) to assign them to their subcellular source. The IP procedure failed when applied directly to plasma samples, i.e. isotype control precipitated similar amounts of DNA as the specific 8-oxodGuo antibody. In contrast, DNA isolation from plasma prior to the IP process provided assay specificity with little impact on DNA oxidation status. We further optimized sensitivity and efficiency of qPCR analysis by reducing amplicon length and targeting repetitive nuclear DNA elements. When the established protocol was applied to plasma samples of abdominal aortic aneurysm (AAA) patients and control subjects, the AAA cohort displayed significantly elevated circulating non-oxidized and total nuclear DNA and a trend for increased levels of oxidized mitochondrial DNA. An enrichment of mitochondrial versus nuclear DNA within the oxidized DNA fraction was seen for AAA patients. Regarding the potential source of circulating DNA, we observed a significant correlation of markers of neutrophil activation and NET formation with nuclear DNA, independent of oxidation status. Thus, the established method provides a tool to detect and distinguish the release of oxidized nuclear and mitochondrial DNA in human plasma and offers a refined biomarker to monitor disease conditions of pro-inflammatory cell and tissue destruction.
Topics: Humans; 8-Hydroxy-2'-Deoxyguanosine; Deoxyguanosine; DNA, Mitochondrial; Oxidation-Reduction; Aortic Aneurysm, Abdominal
PubMed: 37353175
DOI: 10.1016/j.freeradbiomed.2023.06.014 -
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 -
Bioorganic & Medicinal Chemistry Letters Feb 2019The synthesis of constrained nucleosides has become an important tool to understand the SAR in the interaction between biological and synthetic nucleotides in the...
The synthesis of constrained nucleosides has become an important tool to understand the SAR in the interaction between biological and synthetic nucleotides in the context of antisense oligonucleotide therapy. The incorporation of a cyclopropane into a furanose ring of a nucleoside induces some degree of constrain without affecting significantly the steric environment of a nucleoside. Here, we report a new, short and stereocontrolled synthesis of two constrained nucleosides analogues, 1',2'- methano-2',3'-dideoxyuridine 9, and the corresponding cytidine analog 12. X-ray crystallography revealed that the furanose ring in the constrained uridine and cytidine analogues was flattened with virtual loss of pseudorotation. The phosphoramidate esters of the novel constrained uridine and cytidine nucleosides, intended as prodrugs, were tested in cell-based assays for viral replication across the herpes virus family and HIV inhibition courtesy of Merck laboratories, Rahway. They were also tested in antiproliferative assays against colorectal and melanoma cell lines. Unfortunately, none of the compounds showed activity in these assays.
Topics: Antiviral Agents; Cell Line, Tumor; Crystallography, X-Ray; Dideoxynucleosides; Drug Screening Assays, Antitumor; HIV; Herpesviridae; Humans; Structure-Activity Relationship; Virus Replication
PubMed: 30612845
DOI: 10.1016/j.bmcl.2018.12.054 -
Advances in Clinical and Experimental... 2017Under homeostatic conditions, an equilibrium state between amounts of free radicals formed and their scavenging is observed. Free radicals are destructive only when... (Review)
Review
Under homeostatic conditions, an equilibrium state between amounts of free radicals formed and their scavenging is observed. Free radicals are destructive only when present in excess. Pathological changes within cells and tissues can result from a persistent excess of free radicals. Living organisms are increasingly exposed to oxidative stress, resulting in oxidative DNA modifications. One such modification is 8-hydroxy-2'-deoxyguanosine (8-OHdG). It is considered a biomarker of oxidative stress and oxidative DNA damage. It has been found both in physiological fluids and in cells. This paper presents methods found in the literature for determining 8-OHdG expression in various kinds of biological material - blood, urine or liver homogenates. Methods for determining the biomarker expression have been grouped into direct and indirect methods, and the various levels of 8-hydroxy-2'-deoxyguanosine that can be determined by the different techniques are presented. The basic pros and cons of the various techniques are also discussed.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers; DNA Damage; Deoxyguanosine; Free Radicals; Humans; Oxidative Stress
PubMed: 28397448
DOI: 10.17219/acem/43272 -
European Journal of Pharmaceutical... Oct 2016Gemcitabine (2',2'-difluoro-2'-deoxycytidine; dFdC) is an efficacious anticancer agent acting against a wide range of solid tumors, including pancreatic, non-small cell... (Review)
Review
Gemcitabine (2',2'-difluoro-2'-deoxycytidine; dFdC) is an efficacious anticancer agent acting against a wide range of solid tumors, including pancreatic, non-small cell lung, bladder, breast, ovarian, thyroid and multiple myelomas. However, short plasma half-life due to metabolism by cytidine deaminase necessitates administration of high dose, which limits its medical applicability. Further, due to its hydrophilic nature, it cannot traverse cell membranes by passive diffusion and, therefore, enters via nucleoside transporters that may lead to drug resistance. To circumvent these limitations, macromolecular prodrugs and nanocarrier-based formulations of Gemcitabine are gaining wide recognition. The nanoformulations based approaches by virtue of their controlled release and targeted delivery have proved to improve bioavailability, increase therapeutic efficacy and reduce adverse effects of the drug. Furthermore, the combination of Gemcitabine with other anticancer agents as well as siRNAs using nanocarriers has also been investigated in order to enhance its therapeutic potential. This review deals with challenges and recent advances in the delivery of Gemcitabine with particular emphasis on macromolecular prodrugs and nanomedicines.
Topics: Deoxycytidine; Drug Delivery Systems; Gemcitabine
PubMed: 27531553
DOI: 10.1016/j.ejps.2016.08.021 -
Child Development May 2017Urie Bronfenbrenner (1992) helped developmental psychologists comprehend and define "context" as a rich, thick multidimensional construct. His ecological systems theory...
Urie Bronfenbrenner (1992) helped developmental psychologists comprehend and define "context" as a rich, thick multidimensional construct. His ecological systems theory consists of five layers, and within each layer are developmental processes unique to each layer. The four articles in this section limit the exploration of context to the three innermost systems: the individual plus micro- and macrolayers. Rather than examine both the physical features and processes, the articles tend to focus solely on processes associated with a niche. Processes explored include social identity development, social network dynamics, peer influences, and school-based friendship patterns. The works tend to extend the generalization of extant theory to the developmental experience of various minority group experiences.
Topics: Capecitabine; Deoxycytidine; Friends; Humans; Pancreatic Neoplasms; Social Identification; Gemcitabine
PubMed: 28276582
DOI: 10.1111/cdev.12784