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Relationship between the urinary excretion rates of the analyzed modifications and specific metabolic rates (SMR) of six different mammalian species.
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DNA damage and DNA repair may mediate several cellular processes, like replication and transcription, mutagenesis and apoptosis and thus may be important factors in the development and pathology of an organism, including cancer. DNA is constantly damaged by reactive oxygen species (ROS) and reactive nitrogen species (RNS) directly and also by produ...
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... DNA damage and repair can influence several cellular processes, such as replication and transcription, mutagenesis, and apoptosis. Therefore, they may play crucial roles in an organism's development and pathology, including cancer [60]. ...
Background and Objectives: Nucleotide Excision Repair (NER), the most extensively researched DNA repair mechanism, is responsible for repairing a variety of DNA damages, and Xeroderma Pigmentosum (XP) genes participate in NER. Herein, we aimed to update the previous results with a meta-analysis evaluating the association of XPA, XPB/ERCC3, XPF/ERCC4, and XPG/ERCC5 polymorphisms with the susceptibility to HNC. Materials and Methods: PubMed/Medline, Web of Science, Scopus, and Cochrane Library databases were searched without any restrictions until 18 November 2023 to find relevant studies. The Review Manager 5.3 (RevMan 5.3) software was utilized to compute the effect sizes, which were expressed as the odds ratio (OR) with a 95% confidence interval (CI). Results: Nineteen articles were involved in the systematic review and meta-analysis that included thirty-nine studies involving ten polymorphisms. The results reported that the CC genotype of rs17655 polymorphism showed a significantly decreased risk of HNC in the recessive model (OR: 0.89; 95%CI: 0.81, 0.99; p-value is 0.03). In addition, the CT genotype (OR: 0.65; 95%CI: 0.48, 0.89; p-value is 0.008) of the rs751402 polymorphism was associated with a decreased risk, and the T allele (OR: 1.28; 95%CI: 1.05, 1.57; p-value is 0.02), the TT (OR: 1.74; 95%CI: 1.10, 2.74; p-value is 0.02), and the TT + CT (OR: 2.22; 95%CI: 1.04, 4.74; p-value is 0.04) genotypes were associated with an increased risk of HNC. Conclusions: The analysis identified two polymorphisms, rs17655 and rs751402, as being significantly associated with the risk of HNC. The study underscored the influence of various factors, such as the type of cancer, ethnicity, source of control, and sample size on these associations.
... Exposure to cytotoxic drugs, inflammatory processes, ionization, and cigarette smoking are predisposing factors for ROS production (11). Some genetic mutations, such as those in Ras and p53 tumor suppressor genes, are associated with ROS activation (12,13). Additionally, the tumor angiogenesis of gliomas is induced by ROS, upregulating epidermal growth factor (EGF) and plateletderived growth factor (PDGF) expression (14). ...
... Of all the canonical nucleosides, 2'-deoxyguanosine (dG) is most easily one-electron-oxidized thanks to its low ionization potential [11]. The formed dG radical cation can be converted to dG, or after reaction with a water molecule, to 7,8-dihydro-8-oxo-2 -deoxyguanosine ( OXO dG), one of the most abundant DNA lesions [12]. OXO dG can be further converted to various subsequent products, such as 2 -deoxyspirodi(iminohydantoin) (Sp) (Figure 1) [13]. ...
... Of all the canonical nucleosides, 2'-deoxyguanosine (dG) is most easily oneelectron-oxidized thanks to its low ionization potential [11]. The formed dG radical cation can be converted to dG, or after reaction with a water molecule, to 7,8-dihydro-8-oxo-2′deoxyguanosine ( OXO dG), one of the most abundant DNA lesions [12]. OXO dG can be further converted to various subsequent products, such as 2′-deoxyspirodi(iminohydantoin) (Sp) (Figure 1) [13]. ...
Genetic information stored in a DNA base sequence is continuously exposed to harmful factors. It has been determined that 9 × 104 different DNA damage events occur in a single human cell every 24 h. Of these, 7,8-dihydro-8-oxo-guanosine (OXOG) is one of the most abundant and can undergo further transformations towards spirodi(iminohydantoin) (Sp). Sp is highly mutagenic in comparison to its precursor if not repaired. In this paper, the influence of both Sp diastereomers 4R and 4S as well as their anti and syn conformers on charge transfer through the double helix was taken into theoretical consideration. In addition, the electronic properties of four modelled double-stranded oligonucleotides (ds-oligos) were also discussed, i.e., d[A1Sp2A3oxoG4A5] * [T5C4T3C2T1]. Throughout the study, the M06—2X/6—31++G** level theory was used. Solvent–solute non-equilibrated and equilibrated interactions were also considered. The subsequent results elucidated that the 7,8-dihydro-8-oxo-guanosine:cytidine (OXOGC) base pair is the settled point of a migrated radical cation in each of the discussed cases, due to its low adiabatic ionization potential, i.e., ~5.55 [eV]. The opposite was noted for excess electron transfer through ds-oligos containing anti (R)-Sp or anti (S)-Sp. The radical anion was found on the OXOGC moiety, whereas in the presence of syn (S)-Sp or syn (R)-Sp, an excess electron was found on the distal A1T5 or A5T1 base pair, respectively. Furthermore, a spatial geometry analysis of the discussed ds-oligos revealed that the presence of syn (R)-Sp in the ds-oligo caused only a slight deformation to the double helix, while syn (S)-Sp formed an almost ideal base pair with a complementary dC. The above results are in strong agreement with the final charge transfer rate constant, as calculated according to Marcus’ theory. In conclusion, DNA damage such as spirodi(iminohydantoin), especially when becoming part of clustered DNA damage, can affect the effectiveness of other lesion recognition and repair processes. This can lead to the acceleration of undesired and deleterious processes such as carcinogenesis or aging. However, in terms of anticancer radio-/chemo- or combined therapy, the slowing down of the repair machinery can result in increased effectiveness. With this in mind, the influence of clustered damage on charge transfer and its subsequent effect on single-damage recognition by glycosylases justifies future investigation.
... The reaction of the ROS hydroxyl groups with some chromatin protein purines and pyrimidines results in genomic instability and mutated oncogene overexpression via ROS activation [31]. The increased expression of the mutated Ras and p53 oncogenes commonly involves ROS in high-grade gliomas [32,33]. Glioblastoma neoangiogenesis resulting from changes in EGFR, PDGFR, and VEGFR expression is commonly associated with phosphatidylinositide-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways under ROS activation [34,35]. ...
Glioblastoma is notorious for its rapid progression and neovascularization. In this study, it was found that KDEL (Lys-Asp-Glu-Leu) containing 2 (KDELC2) stimulated vasculogenic factor expression and induced human umbilical vein endothelial cell (HUVEC) proliferation. The NLRP3 inflammasome and autophagy activation via hypoxic inducible factor 1 alpha (HIF-1α) and mitochondrial reactive oxygen species (ROS) production was also confirmed. The application of the NLRP3 inflammasome inhibitor MCC950 and autophagy inhibitor 3-methyladenine (3-MA) indicated that the above phenomenon activation correlated with an endothelial overgrowth. Furthermore, KDELC2 suppression decreased the endoplasmic reticulum (ER) stress factors’ expression. The ER stress inhibitors, such as salubrinal and GSK2606414, significantly suppressed HUVEC proliferation, indicating that ER stress promotes glioblastoma vascularization. Finally, shKDELC2 glioblastoma-conditioned medium (CM) stimulated TAM polarization and induced THP-1 cells to transform into M1 macrophages. In contrast, THP-1 cells co-cultured with compensatory overexpressed (OE)-KDELC2 glioblastoma cells increased IL-10 secretion, a biomarker of M2 macrophages. HUVECs co-cultured with shKDELC2 glioblastoma-polarized THP-1 cells were less proliferative, demonstrating that KDELC2 promotes angiogenesis. Mito-TEMPO and MCC950 increased caspase-1p20 and IL-1β expression in THP-1 macrophages, indicating that mitochondrial ROS and autophagy could also interrupt THP-1-M1 macrophage polarization. In conclusion, mitochondrial ROS, ER stress, and the TAMs resulting from OE-KDELC2 glioblastoma cells play important roles in upregulating glioblastoma angiogenesis.
... In addition to containing vitamin C and E and their role as antioxidants, they have the ability to reduce oxidative stress and reduce the high damage to DNA that was measured by comet test (19). The presence of antioxidants in the body helps control the damage to DNA (20). The results showed that animals with diabetes and treated with plant diet, animal diet, and nutritional supplements, clarified a marked improvement in DNA compared to the group of untreated infected animals as shown in the following figures: ...
Background: The comet analysis (electromagnetic relay analysis of a single cell) is ahighly sensitive method for determining DNA damage because to exposure tocarcinogens and other substances that consequently affect fertility.Objective: the aim of this study is to Evaluation the broken DNA in male diabeticmice. Created by alloxan and knowledge of the effect of some nutritional systems onthe treatment and repair of genetic material due to diabetes.Materials and methods: In this study were used, 42 male Albino mice labs at the ageof 2-3 months and weight (25-30) g then 6 animals were isolated to represent thecontrol group, The remaining animals were injected between the thighs by alloxan 150mg / kg and left the next day to make sure hit by diabetes and randomly distributed tosix groups in addition to a set of Not affected control transactions.Results and conclusion: It was found from the results of the statistical analysis shownin figure(1) showed the presence of the highest percentage of injuries in the geneticmaterial that was in the group of animals with diabetes and untreated for the durationof the experiment, as it was clear from the photos of this group that the tail lengthresulting from the migration of the genetic material DNA to outside the nucleusbecause to its damage, as well as the results showed that the group of animals affectedby diabetes and the treatment by adding the Salvia officinalis plant to both plant andanimal nutrition had a significant decrease (<0.05> P) in the proportion of geneticmaterial injuries where the proportion of high (long guilt) infections was low in thesetwo The two groups compared to the group of animals with diabetes and untreated forthe duration of the experiment.
... Furthermore, mutations occurring due to impaired repair processes are seen in tumor suppressor genes such as Ras and P53. P53 plays a crucial role in genomic integrity surveillance and apoptosis regulation [85]. ...
This thesis presents all my contributions to scientific field, being a real proof of my achievements, in order to be qualified for PhD coordinator.
... It was known that SIRT-3 regulated the key enzyme activities for acetylation and reactive oxygen species (ROS) detoxification (Ilari et al., 2020). Since ROS is one of the important factors to impact the occurrence and development of tumors (Tudek et al., 2010;McDonnell et al., 2015), we presumed that RES + cis-DDP inhibits the growth of SiHa cells by regulating the ROS expression through the SIRT3dependent pathway. Indeed, it was found in our study that the Frontiers in Pharmacology | www.frontiersin.org ...
Background: Cervical cancer exerts considerable mortality in the world. The combinations of chemotherapy with cis-platinum were the first-line treatment in late-stage cervical cancer but may cause severe adverse effects. Resveratrol (RES, 3,5,4′-trihydroxy-trans-stilbene) is a phytoalexin, and it showed anti-cancer effects but with low toxicity and side effects. Herein, we examined the anti-cancer effects of cis-platinum combined with RES in human cervical cancer cell lines.
Methods: The antiproliferative effect was examined by cell counting and short-term MTT assay. Cell apoptosis was detected. The cell cycle distribution was determined by flow cytometry. Intracellular reactive oxygen species and mitochondrial transmembrane potential change were observed and calculated by confocal microscopy. The Si-RNA interference of SIRT3 in cancer cells was performed. Protein expression was checked by Western blotting.
Results: RES inhibited the growth of SiHa cell lines, and it significantly enhanced the cis-platinum-induced cell apoptosis and cell cycle arresting in 48 h. The activation of the SIRT3 relative anti-oxidative pathway was proved to be the reason for the enhanced anti-cancer effects of cis-platinum and RES combination. Si-RNA interference of SIRT3 compromised the anti-cancer effect of cis-platinum and RES combination. Furthermore, the silencing of SIRT3 RNA inhibited the expression of the anti-oxidant enzyme (MnSOD, GPx, SOD-1, and CAT) and decreased the generation of H 2 O 2 in the cis-platinum and RES combination group.
Conclusion: RES enhances the anti-cancer effects of cis-platinum on SiHa cells by activating the SIRT3 relative anti-oxidative pathway. RES may act as a potential synergistic agent and be useful in the treatment of cervical cancer.
... For example, endogenously derived ROS activate the ERK1/2 MAPK signaling pathway and the AKT signaling pathway in OC, both of which promote cell proliferation [52,53]. The increased ROS generation also contributes to a genetic mutation in cancer cells, further contributing to cell transformation [54,55]. As opposed to the traditional view of ROS generation in cancer as a harmful secondary by-product, the increasing knowledge of cancer cell metabolism and signal transduction is exposing ROS as a positive contributing factor in tumorigenesis and cancer development. ...
The diverse repertoires of cellular mechanisms that progress certain cancer types are being uncovered by recent research and leading to more effective treatment options. Ovarian cancer (OC) is among the most difficult cancers to treat. OC has limited treatment options, especially for patients diagnosed with late-stage OC. The dysregulation of miRNAs in OC plays a significant role in tumorigenesis through the alteration of a multitude of molecular processes. The development of OC can also be due to the utilization of endogenously derived reactive oxygen species (ROS) by activating signaling pathways such as PI3K/AKT and MAPK. Both miRNAs and ROS are involved in regulating OC angiogenesis through mediating multiple angiogenic factors such as hypoxia-induced factor (HIF-1) and vascular endothelial growth factor (VEGF). The NAPDH oxidase subunit NOX4 plays an important role in inducing endogenous ROS production in OC. This review will discuss several important miRNAs, NOX4, and ROS, which contribute to therapeutic resistance in OC, highlighting the effective therapeutic potential of OC through these mechanisms.
... However, most of the studies, if not all of them involving antioxidant-vitamins, have not been effective. The oxidative stress hypothesis is partly linked to another theory of natural aging, which is related to chromosomal changes (Tudek et al., 2010). Research showing that mitochondrial DNA mutations in the gene in the oxidative stress pathway may help reduce resistance to oxidative stress supports this theory (Gardner, Sutherland, & Shaffer, 2011). ...
Aging is psychosocially and biologically defined as being older. An aged or geriatric patient is defined as a person whose biological age is advanced. Aging can be characterised as a deterioration of the physiological functions essential for survival and fertility that is time-related. Aging is a complex spatial and temporal hierarchy of dynamic activities that are integrated over the life cycle of a complex dance. Thus, aging is not easily dissected into disjoint subprocesses; it is a dynamic, multidimensional, hierarchical process. In most body structures, aging is followed by incremental modifications. Aging biology research focuses on understanding both the cellular and molecular mechanisms that underlie these changes and those that accompany the onset of age-related diseases. As time passes, aging takes place in a cell, an organ, or the whole body. It is a phase of every living thing that goes on through the whole adult life cycle. Aging is an organism's sequential or incremental transition that results in an increased risk of fatigue, illness, and death. Aging is multifaceted. Therefore, there are various hypotheses each of which may clarify one or more aspects of aging. Ageing in humans reflects the accumulation over time of changes in a human being that may involve social, psychological, and physical changes. Recent hypotheses are assigned to the concept of damage, whereby the accumulation of damage (including DNA oxidation) may cause biological systems to fail, or to the concept of programmed ageing, whereby problems with internal processes (epigenomic maintenance can cause ageing such as DNA methylation) are correlated with the causes of ageing.
... The direct genetic effects arising from radiation-induced DNA lesions are singlestrand breaks or double-strand breaks, which lead, respectively, to the activation of the DNA repair process and apoptosis [21,22]. Furthermore, accumulation of ROS can also lead to indirect effects of ionising radiation that can cause structural and functional defects of the cellular nucleic acids, proteins, and lipids. ...
... This intracellular damage accumulation can lead to tumour development due to the increased DNA mutation rate [23]. In other cases, ROS-mediated oxidation can result in chromosomal rearrangements and errors in recombination processes [21,22] or damage to mitochondrial DNA. All these events have important roles in the development of secondary malignancies after radiotherapy [24]. ...
... The uncovering that the TP53 gene physiologically expresses, in a tissue-dependent manner, several p53 splice variants (isoforms) provides an explanation for its pleiotropic biological activities [83]. In fact, among the different isoforms of p53, some have oncogenic potential, while others show oncosuppressor properties or, in some cases, can have both functions, depending on the cellular context [22]. The p53 family of proteins also includes p63 and p73 that can induce apoptosis by mediating cell cycle arrest at G2/M and G1/S [84]. ...
In the framework of space flight, the risk of radiation carcinogenesis is considered a “red” risk due to the high likelihood of occurrence as well as the high potential impact on the quality of life in terms of disease-free survival after space missions. The cyclic AMP response element-binding protein (CREB) is overexpressed both in haematological malignancies and solid tumours and its expression and function are modulated following irradiation. The CREB protein is a transcription factor and member of the CREB/activating transcription factor (ATF) family. As such, it has an essential role in a wide range of cell processes, including cell survival, proliferation, and differentiation. Among the CREB-related nuclear transcription factors, NF-κB and p53 have a relevant role in cell response to ionising radiation. Their expression and function can decide the fate of the cell by choosing between death or survival. The aim of this review was to define the role of the CREB/ATF family members and the related transcription factors in the response to ionising radiation of human haematological malignancies and solid tumours.
