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    Effect of Atypical Antipsychotic Usage at Therapeutic Doses on Daytime Sleepiness
    (2023) Alan, Meltem; Yuksel, Tugba Nurcan; Topcu, Birol
    The aim of this study is to determine the effect of using atypical antipsychotic drug usage at therapeutic doses on daytime sleepiness. One hundred twenty volunteers who met the inclusion-exclusion criteria were divided into two equal groups. Group 1: patient group (60 patients volunteers used atypical antipsychotic in therapeutic doses and hospitalized in the psychiatry clinic of Tekirdağ Namık Kemal University Hospital and Group 2: control group (60 control volunteers). Socio-demographic and Clinical Information Form consist of 14 questions was administration all volunteers. Also, Epworth Sleepiness Scale which is a survey that determines the degree of sleepiness in eight different situations during the day was administered to all volunteers. Atypical antipsychotic drug usage at therapeutic doses significantly increased patients’ daytime sleepiness compared to the control group. Among the atypical antipsychotic drugs usage in therapeutic dose, the drug that caused the most daytime sleepiness was clozapine. Also, using of atypical antipsychotic drugs in therapeutic doses markedly decreased patients’ life quality compared to the control group. Atypical antipsychotic drug usage at therapeutic doses could cause daytime sleepiness and reduce patients’ quality of life.
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    Effect of PDE 5 Inhibitor-Avanafil on Renal Ischemia/Reperfusion Injury in Rats
    (Galenos Publ House, 2023) Yuksel, Tugba Nurcan; Halici, Zekai; Kaya, Cihangir; Bozkurt, Ayse; Tavaci, Taha; Civelek, Maide Sena; Ozdemir, Bengul
    Aim: Renal ischemia-reperfusion injury (RI/RI) damages many organs, especially the kidney. Phosphodiesterase (PDE) 5 inhibitors has antioxidant and anti-inflammatory effects. Avanafil (AVA) is a second-generation PDE 5 inhibitor with greater PDE isoform selectivity. The aim of this study is to investigate the effects of AVA on RI/RI in rats. Materials and Methods: Forty rats were randomly divided into five groups (n=8): Sham; AVA 10; RI/RI; RI/RI + 5 mg/kg AVA, and RI/RI + 10 mg/ kg AVA. RI/RI in rats was established by clamping renal artery. An acute surgical experiment was performed for the induction of renal ischemia for 45 min by renal artery clamping followed by reperfusion for 24 h. Kidney tissues were investigated biochemically [malondialdehyde (MDA) and glutathione (GSH) with ELISA], molecularly [relative quantification of IL-113, nuclear factor-kappa B (NF-KB), and tumor necrosis factor-alpha (TNF-a) mRNA gene expression with qRT-PCR], and histopathologically (staining with Harris hematoxylin and eosin Y). Results: AVA administration ameliorated disturbances in MDA and GSH levels caused by RI/RI. AVA treatment improved the increase in the mRNA expressions of IL-113, NF-KB, and TNF-a in kidney tissues induced ischemia/reperfusion injury. AVA administration ameliorated histopathologic injury in kidney tissues caused by renal ischemia reperfusion. Moreover, the values closest to those of the sham group were obtained by administering 10 Conclusion: AVA administration improved renal ischemia/reperfusion-induced tissue injury by alleviating oxidative stress and inflammatory cascades that could be important in ischemia-reperfusion injury. These findings may provide a mechanistic basis for using AVA to treat RI/RI.
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    Effect of trimetazidine against ovarian ischemia/reperfusion injury in rat model: A new pathway: JAK2/STAT3
    (Mashhad Univ Med Sciences, 2023) Yuksel, Tugba Nurcan; Halici, Zekai; Cadirci, Elif; Toktay, Erdem; Ozdemir, Bengul; Bozkurt, Ayse
    Objective(s): Ovarian ischemia/reperfusion (I/R) is an extremely complex pathological problem that begins with oxygen deprivation, progresses to excessive free radical production, and intensifies inflammation. The JAK2/STAT3 signaling pathway is a multipurpose signaling transcript channel that plays a role in several biological functions. Trimetazidine (TMZ) is a cellular anti-ischemic agent. This study aims to investigate the effects of TMZ on ovarian I/R injury in rats. Materials and Methods: sixty four rats were divided into 8 groups at random: healthy(group1); healthy+TMZ20(group2); ischemia (I) (group 3); I+TMZ10(group4); I+ TMZ20(group5); I/R(group6); I/R+TMZ10(group7); I/R+TMZ20(group8). Vascular clamps were placed just beneath the ovaries and over the uterine horns for 3 hr to induce ischemia. The clamps were removed for the reperfusion groups, and the rats were reperfused with care to ensure that the blood flowed into the ovaries, subjecting them to reperfusion for 3 hr. TMZ was administered orally by gavage 6 and 1 hr before operations. At the end of the experiment, ovarian tissues were removed for biochemical, molecular, and histopathological investigation. Results: TMZ administration ameliorated ischemia/reperfusion-induced disturbances in GSH and MDA levels. TMZ treatment inhibited I/R-induced JAK2/STAT3 signaling pathway activation in ovarian tissues. TMZ administration also improved the increase in the mRNA expressions of IL1 beta, TNF-alpha, and NF-KB caused by ischemia/reperfusion injury. Moreover, TMZ treatment improved histopathologic injury in ovarian tissues caused by ischemia/reperfusion. Conclusion: TMZ treatment protected rats against ovarian ischemia/reperfusion injury by alleviating oxidative stress and inflammatory cascades. These findings may provide a mechanistic basis for using TMZ to treat ovarian ischemia-reperfusion injury.
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    Evaluation of the Antigenotoxic Effect of Quercetin Against Antiepileptic Drug Genotoxicity by Comet Analysis
    (2023) Canbolat, Fadime; Kenanoglu, Nihan Akıncı; Yuksel, Tugba Nurcan; Berber, Ahmet Ali
    Valproic acid (VPA) is among the most commonly used antiepileptic drugs in childhood and adult epilepsy. Although VPA is well tolerated, it can cause life-threatening side effects. VPA has toxic and genotoxic effects. Antioxidants can reverse drugs' toxic and genotoxic effects. Therefore, our study aimed to evaluate the antigenotoxic protective effect of quercetin (QUE) against VPA genotoxicity by in vitro comet assay analysis method. Comet assay analysis was performed in five different groups. Group I; negative control (Sterile H2O), Group II; positive control (H2O2), Group III; VPA was applied in four different dose ranges, Group IV; QUE was applied in four different dose ranges, Group V; For the simultaneous combined administration of VPA and QUE, three different doses of VPA + four different doses of QUE were administered. Low-dose administration of QUE was more effective in ameliorating the damage caused by low-dose VPA (62.5 ?g/ml) administration. It is seen that the genotoxic damage caused by the application of 125 ?g/ml VPA can be eliminated by QUE at all doses. It was determined that different doses of QUE exhibited a significant antigenotoxic effect against damage caused by 125 µg/mL VPA (P<0.05). In our study, the curative effect of QUE on DNA damage was determined by in vitro comet analysis. Our analysis results showed that QUE ameliorates VPA-induced genetic damage.
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    INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS
    (Trakya Univ Balkan Yerlesesi Enstituler Binasi, 2023) Yuksel, Tugba Nurcan; Yayla, Muhammed; Kose, Duygu; Ugan, Rustem Anil; Toktay, Erdem; Aksu Kilicle, Pinar; Cadirci, Elif
    Pomegranate peel contains bioactive ingredients such as flavonoids, ellagitannins, phenolics and proanthocyanidin compounds with high antioxidant activity. Pomegranate peel has antiapoptotic, antioxidant and anti-inflammatory effects due to its high punicalagin content. We aimed to determine the effect of pomegranate peel extract (PPE) on lipopolysaccharide (LPS)-induced uveitis. Sixty rats were seperated randomly into twelve groups (n = 5). The healthy group received intraperitoneal normal saline, the uveitis group received 200 mu g/kg LPS, the dexamethasone (DEX) group received 200 mu g/kg LPS plus 1 mg/kg DEX, the PPE100, PPE300 and PPE500 groups received 200 mu g/kg LPS plus 100, 300 and 500 mg/kg PPE, respectively. The eye tissues were collected at 3rd and 24th hour. and investigated molecularly (Relative quantification of gene expression), biochemically (Superoxide dismutase activity, Glutathione and Malondialdehyde levels) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Tumor Necrosis Factor-alpha, vascular endothelial growth factor, and Caspase-3 levels markedly decreased in a dose-dependent manner in the uveitic rats following PPE administration. PPE administration significantly ameliorated uveitic disorders in oxidative stress factors including Glutathione, Superoxide dismutase and Malondialdehyde, with its effects raising in a dose-dependent manner. PPE eliminated histopathological changes in eye tissues due to uveitis. PPE can be a promising agent by contributing to alternative preventive treatment methods for uveitis with its anti-inflammatory, antioxidative, antiapoptotic and antiangiogenic effects.
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    The Role and Antagonistic Effects of miR-16-5p in the Regulation of ADP-Ribosylation Factor-Like Tumor Suppressor Gene 1 in Lung Cancer Cells
    (Ataturk Univ, 2023) Yuksel, Tugba Nurcan; Bozgeyik, Esra; Bozgeyik, Ibrahim
    Objective: ADP-ribosylation factor-like tumor suppressor gene 1 is a member of the Ras superfamily of small guanosine triphosphatases that are known to be involved in multiple regulatory pathways in the multistage development of human cancers. Also, ADP-ribosylation factor-like tumor suppressor gene 1 expression levels have been reported to be dramatically lower in both cancer cell lines and tumor tissues compared to con-trols. Accordingly, defects in the regulation of the ADP-ribosylation factor-like tumor suppressor gene 1 gene seems have key tumor suppressive effects in the formation and development of human cancers including lung cancer. Moreover, microRNAs regulating the expression of ADP-ribosylation factor-like tumor suppressor gene 1 have not been described previously. Accordingly, the present study aimed to reveal the influence of miR-16-5p on the regulation of ADP-ribosylation factor-like tumor suppressor gene 1 gene. Materials and Methods: A549 lung adenocarcinoma cells were used. For the overexpression and silencing experiments of miR-16-5p synthetic microRNA mimics and inhibitors were used, respectively. Gene expres-sion analyses were achieved with the help of quantitative real-time polymerase chain reaction. Results: MiR-16-5p was identified to be predictive target of ADP-ribosylation factor-like tumor suppressor gene 1 and directly targets the expression of ADP-ribosylation factor-like tumor suppressor gene 1 as revealed by the overexpression and silencing experiments. Specifically, it was found that miR-1 6-5p- overe xpres sed A549 cells showed a decrease in ADP-ribosylation factor-like tumor suppressor gene 1 gene expression, whereas miR-16-5p-suppressed cells showed an increase in expression. These findings possibly suggest that miR-16-5p is the direct regulatory microRNA that posttranscriptionally regulates the expression of ADP-ribosylation factor-like tumor suppressor gene 1. Conclusion: Collectively, miR-16-5p seems to be a key regulatory molecule involved in the posttranscrip-tional regulation of the ADP-ribosylation factor-like tumor suppressor gene 1, and it might be responsible for the downregulation of this gene in lung cancer.