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    A comparative meta-analysis of peripheral 8-hydroxy-2?-deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2?-deoxyguanosine (8-Oxo-DG) levels across mood episodes in bipolar disorder
    (Wiley, 2023) Arat Çelik, H. E.; Tuna, Gamze; Ceylan, Deniz; Kucukgoncu, Suat
    [Abstract Not Available]
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    A comparative meta-analysis of peripheral 8-hydroxy-2?-deoxyguanosine mood episodes in bipolar disorder
    (Pergamon-Elsevier Science Ltd, 2023) Arat Çelik, Hidayet Ece; Tuna, Gamze; Ceylan, Deniz; Kucukgoncu, Suat
    Objective: Oxidative DNA damage has been associated with the pathophysiology of bipolar disorder (BD) as one of the common pathways between increased medical comorbidity and premature aging in BD. Previous evidence shows increased levels of oxidatively induced DNA damage markers, 8-hydroxy-2 '-deoxyguanosine (8-OHdG) or its tautomer 8-oxo-7,8-dihydro-2 '-deoxyguanosine (8-oxo-dG), in patients with BD in comparison to healthy individuals. With the current research, we aim to analyze data on peripheral (blood or urine) 8-OHdG/8-oxo-dG levels across mood states of BD using a meta-analytical approach.Method: A literature search was conducted using the databases PubMed, Scopus, and Web of Science to identify eligible studies (January 1989 to July 2022). Relevant studies were systematically reviewed; a random-effects meta-analysis and a meta-regression analysis were conducted.Results: The current meta-analysis included 12 studies consisting of 808 BD patients (390 in euthymia, 156 in mania, 137 in depression, 16 in mixed episode, 109 not specified) and 563 healthy controls. BD patients that were currently depressed had significantly higher levels of 8-OHdG/8-oxo-dG than healthy controls, while euthymic or manic patients did not differ from healthy controls. A meta-regression analysis showed sex distri-bution (being female) and older age to be significantly related to increased 8-OHdG/8-oxo-dG levels.Conclusion: Our findings suggest that 8-OHdG/8-oxo-dG may be a state-related marker of depression in BD and may be affected by older age and female gender.
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    Oxidative DNA base damage and base excision repair abnormalities in siblings of individuals with bipolar disorder
    (Research Square, 2023) Çelik, Hidayet Ece; Yılmaz, Seda; Kendirlioğlu, Burcu Kök; Çörekli, Esma; Bekar, Nazlı Dal; Çelik, Ömer; Yorguner, Neşe; Öztürk, Bilge Targıtay; İşlekel, Hüray; Özerdem, Ayşegül; Akan, Pınar; Ceylan, Deniz; Tuna, Gamze
    Previous evidence suggests elevated levels of oxidative DNA damage, particularly 8-hydroxy-2'- deoxyguanosine (8-OH-dG), and abnormalities in the repair of 8-OH-dG by the base excision repair (BER) in BD. However, the genetic disposition of these abnormalities remains unknown. In this study, we aimed to investigate the levels of oxidative DNA damage and BER mechanisms in individuals with BD and their siblings, as compared to healthy controls (HCs). 46 individuals with BD, 41 siblings of individuals with BD, and 51 HCs were included in the study. Liquid chromatography-tandem mass spectrometry was employed to evaluate the levels of 8-OH-dG in urine, which were then normalized based on urine creatinine levels. The real-time-polymerase chain reaction was used to measure the expression levels of 8-oxoguanine DNA glycosylase 1 (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), poly ADP-ribose polymerase 1 (PARP1), and DNA polymerase beta (POL?). The levels of 8-OH-dG were found to be elevated in both individuals with BD and their siblings when compared to the HCs. The OGG1 and APE1 expressions were downregulated, while POL? expressions were upregulated in both the patient and sibling groups compared to the HCs. Age, smoking status, and the number of depressive episodes had an impact on APE1 expression levels in the patient group while body mass index, smoking status, and past psychiatric history had an impact on 8-OH-dG levels in siblings. Both individuals with BD and unaffected siblings presented similar abnormalities regarding oxidative DNA damage and BER, suggesting a link between abnormalities in DNA damage / BER mechanisms and familial susceptibility to BD. Our findings suggest that targeting the oxidative DNA damage and BER pathway could offer promising therapeutic strategies for reducing the risk of age-related diseases and comorbidities in individuals with a genetic predisposition to BD.