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Öğe 4-Vinylbenzyl and 2-morpholinoethyl substituted ruthenium (II) complexes: Design, synthesis, and biological evaluation(Elsevier, 2020) Sari, Yakup; Gurses, Canbolat; Celepci, Duygu Barut; Kelestemur, Unzile; Aktas, Aydin; Yuksel, Sengul; Ates, BurhanRecently, the medical applications of organoruthenium complexes have attention attracted to organometallic chemists and biochemists. In this study, 4-vinylbenzyl and 2-morpholinoethyl substituted (NHC) Ru(II)(eta(6)-p-cymene) complexes were synthesized and in vitro DNA binding, cell cytotoxicity (anticancer activity) and genotoxicity properties were determined in order to understand the biological activities. These complexes have been prepared from the 4-vinylbenzyl and 2-morpholinoethyl substituted Ag(I) NHC complexes via transmetallation method. The characterization of the new (NHC)Ru(II)(eta(6)-p-cymene) complexes was performed by using H-1 NMR, C-13 NMR, FTIR spectroscopy and elemental analysis techniques. Also, molecular structure of complex 1b was obtained with single-crystal X-ray diffraction method. IC50 value of 1b against MCF-7 cell line was determined as 3.61 mu M and for 1b, an oxidation effect was observed in the concentrations higher than 50 mu g/mL. Comet assay unlike sister chromatid exchange (SCE) analysis data showed correlated results with cytotoxicity as well as DNA binding properties of the complexes. (C) 2019 Elsevier B.V. All rights reserved.Öğe Altered adrenomedullin levels of the rats exposed to constant darkness and light stress(Elsevier Science Sa, 2008) Yuksel, SengulAlthough a variety of physiological and psychological stressors stimulate a significant increase in adrenomedullin (ADM) levels, suggesting a regulatory or protective role for ADM in countering the hypothalamo-pituitary-adrenal (HPA) axis activation following these stressors, it is still unknown whether light or darkness stress is involved in the endogenous ADM production systems. This study is aimed to investigate the effects of constant light or darkness for 60 days on ADM level in the plasma of adult male rats. ADM concentrations were assessed before and after the stressors in tail arterial blood by using HPLC. In the both groups, ADM levels greatly increased in the first week and than continued with lesser changes from the control levels. In conclusion, the study showed that keeping the rats in constant darkness and light vicinity for a long time altered ADM synthesis and secretion from the plasma or other tissues. (C) 2008 Elsevier B.V. All rights reserved.Öğe Antioxidative and metabolic responses to extended cold exposure in rats(Akademiai Kiado Zrt, 2008) Yuksel, Sengul; Asma, Dilek; Yesilada, OzferIn this work, we investigated whether extended cold exposure increases oxidative damage and susceptibility to oxidants of rat liver, heart, kidney and lung which are metabolically active tissues. Moreover in this study the effect of cold stress on some of the lipid metabolic mediators were studied in rat experimental model. Male albino Sprague-Dawley rats were randomly divided into two groups: The control group (n = 12) and the cold-stress group (n = 12). Tissue superoxide dismutase (SOD), catalase (CAT), glutathion S-transferase (GST) and glutathion reductase (GR) activities and glutathion (GSH) were measured using standard protocols. The biochemical analyses for total lipid, cholesterol, trigliceride, HDL, VLDL and LDL were done on autoanalyzer. In cold-stress groups SOD activity was decreased in the lung whereas it increased in the heart and kidney. CAT activity was significantly decreased (except liver) in all the tissues in treated rats. GST activity of cold-induced rats increased in liver and heart while decreased in the lung. GR activity was significantly decreased (except in liver) in all the tissues in cold-stressed rats. GSH level was significantly increased in the heart but decreased in the lung of animals exposed to cold when compared to controls. It was found that among the groups trigliceride, total lipid, HDL and VLDL parameters varied significantly but cholesterol and LDL had no significant variance. In this study, we found that exposure of extended (48 h) cold (8 C) caused changes both in the antioxidant defense system (as tissue and enzyme specific) and serum lipoprotein profiles in rats.Öğe Diyastometamiyeli Polimasti(İnönü Üniversitesi Tıp Fakültesi Dergisi, 2011) Yuksel, Sengul; Coban, Yusuf KenanÇoklu meme oluşumu ile diğer konjenital anomaliler arasında olası ilişkiler gösterilmiş olmasına karşın diastometamyeli ve polimasti anomalilerinin ilişkisi daha önce bildirilmemiştir. Bu vakada, diastometamyeli ve polymastili on bir yaşındaki bir kız hasta kompleks fenotipinin genetik etiyolojisi ile birlikte araştırılarak sunuldu.Öğe THE EFFECTS OF EXOGENOUS ADRENOMEDULLIN AND L-NAME ON ANTIOXIDANT DEFENCE SYSTEM OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND LIPID PARAMETERS OF SERUM IN RAT(Parlar Scientific Publications (P S P), 2011) Asma, Dilek; Yuksel, SengulThe aim of our study was to investigate the contribution of exogenous adrenomedullin (ADM): an antioxidant, and N sup omega nitro-L-arginine methyl ester (L-NAME); the nitric oxide synthase (NOS) enzyme inhibitor, to balance the oxidant/antioxidant status in hypothalamus and adrenal medulla, which are both key components of the hypothalamic-pituitary-adrenal (HPA) axis and affects some lipid metabolic mediators. Thirty six male albino Spraque-Dawley rats were randomly divided into three groups: the control group, the ADM group (8 nmol/kg, i.p.), and the L-NAME group (2 ml/kg, i.p.). Measurements of tissue superoxide dismutase (SOD), catalase (CAT), glutathion S-transferase (GST) and glutathion reductase (GR) activities and glutathione (GSH) were performed in tissues using chemical protocols. The biochemical analyses for total lipid, cholesterol, triglycerides, HDL, VLDL, and LDL were conducted on an auto-analyser. Administering exogenous ADM and L-NAME caused synergic changes in the tissues, antioxidative enzyme activities, and altered serum lipoprotein profiles in rats. In the adrenal medulla and hypothalamus of the experimental groups, SOD and GST activities decreased significantly, while the CAT and GR activities increased. The amount of GSH was enhanced in the both tissues in the ADM group only, while the amount was decreased for the hypothalamus of the L-NAME group. After the treatment, the cholesterol (of L-NAME group), triglyceride, total lipid, and VLDL parameters varied significantly, but there was no significant difference between the HDL and LDL among the groups.Öğe Evaluation of genotoxic and mitotoxic effects of TAF-loaded chitosan nanoparticles in HepG2 cells(Taylor & Francis Ltd, 2024) Sezer, Selcen Korkmaz; Yuksel, Sengul; Koc, Ahmet; Ulu, Ahmet; Ates, BurhanTenofovir alafenamide (TAF) is a new drug from the nucleotide reverse transcriptase inhibitor group approved for the treatment of chronic Hepatitis B in 2016. With this study, we aimed to test whether possible cellular toxicity can be reduced by controlled drug release as a result of loading with chitosan nanoparticles (CHS). We investigated the genotoxic and mitotoxic effects of 45 mu M TAF-loaded CHS and TAF-only on HepG2 cells by micronucleus (MN), comet assay, determination of mtDNA quantification, mitochondrial membrane potential (Delta Psi m), and ROS levels. Additionally, we compared the samples by RNAseq analyses to reveal the transcriptional responses to each regimen. In terms of genotoxic tests, although MN and comet were found higher in all experimental treatment conditions, the encapsulation of CHS reduced the genotoxicity of TAF. MtDNA level was found to be lower in the TAF treatment, whereas it was higher in CHS and CHS-TAF treatments. The TAF-loaded CHS and TAF treatments had an impaired Delta Psi m value. Cellular ROS levels were higher in all treatment conditions. According to the analyses of gene expression patterns; CHS-only changed the expression of relatively few genes (187 genes), while TAF changed the expression of the 1974 genes and TAF-loaded CHS changed the expression of 734 genes. Considering the gene expression numbers, CHS encapsulation of TAF significantly reduced the number of genes that were differentially expressed by TAF-only. Overall, we observed that TAF has genotoxic and mitotoxic effects on HepG2 cells, and upon encapsulation with CHS, its genotoxic and mitotoxic effects were decreased.Öğe Evaluation of the genotoxicity and cytotoxicity in the buccal epithelial cells of patients undergoing orthodontic treatment with three light-cured bonding composites by using micronucleus testing(Korean Assoc Orthodontists, 2014) Toy, Ebubekir; Yuksel, Sengul; Ozturk, Firat; Karatas, Orhan Hakki; Yalcin, VuhammetObjective: This study evaluated the cytotoxicity and genotoxicity of fixed orthodontic treatment with three different light-cured orthodontic bonding composites by analyzing micronucleus (MN) formation in the buccal mucosa during a 6-month period. Methods: Thirty healthy volunteers were selected from consecutive patients referred for orthodontic treatment. Equilibrium 2 brackets and molar tubes (Dentaurum) were bonded with three different lightcured orthodontic bonding composites Transbond XT (3M Unitek), Kurasper F (Kuraray Europe), or GrenGloo (Ormco Corporation) to all teeth in both arches. Exfoliated buccal epithelial cells were scraped from the middle part of the inner cheeks with sterile cement spatulas before treatment and at 1, 3, and 6 months after treatment. MNs and nuclear alterations, such as karyorrhexis (KR), karyolysis (KL), and binucleated cells (BNs), were scored under a light microscope. Repeated measure ANOVA was used to calculate statistical differences in degenerative nuclear abnormalities. Results: MN rates did not significantly differ among different time points within the same cell type (p > 0.05). in contrast, the number of BNs in buccal epithelial cells significantly increased in all composite groups (p < 0.01, Transbond XT; p < 0.001, Kurasper F and GrenGloo). KL frequency significantly increased between the beginning and end of the study in the Kurasfer F (0.80 + 0.79 to 1.90 + 1.10; p <0.05) and GrenGloo (1.30 + 1.06 to 2.40 + 1.08; p <0.05) groups. Conclusions: After 6 months of fixed orthodontic treatment with different light-cured composites, morphological signs of cytotoxicity were observed but genotoxic effects were absent.Öğe Genotoxic effects of banding procedure with different orthodontic cements on human oral mucosa cells(Tubitak Scientific & Technological Research Council Turkey, 2012) Ozturk, Firat; Yuksel, Sengul; Toy, Ebubekir; Kurtoglu, Elcin Latife; Kucuk, Eyup BurakAim: To assess the genotoxic and cytotoxic effects of banding procedure with 5 different orthodontic cements on human oral buccal epithelium cells. Materials and methods: Fifty healthy volunteers (mean age: 14.54 +/- 2.37 years) were randomly divided into 5 groups of 10. Preformed stainless steel molar bands (3M Unitek) were cemented to the upper and lower first molar teeth with 5 different orthodontic cements (Durelon, GC Fuji Ortho Band LC Paste Pak, Meron, Ultra Band Lok, and 3M Unitek Multi Cure) in each group. Genotoxic effects of the banding procedure for a 1-month period were evaluated using the micronucleus test (MNT). To monitor cytotoxic effects, binucleated cells (BNs), karyolysis (KL), and karyorrhexis (KR) were also evaluated in this setting. Results: Analysis of micronuclei in buccal epithelial cells revealed a significant increase in chromosomal damage in all groups (P < 0.01). Significant differences were found in the number of BNs in the groups receiving treatment with Meron, Ultra Band Lok, Durelon, and 3M Multi Cure (P < 0.01). Banding with GC Fuji and Durelon significantly elevated KL frequencies (P <0.05). Durelon had a significant effect on KR (P < 0.01). Conclusion: Band cementation with conventional glass ionomer cement (Meron) showed the least genotoxic effects. The highest cytotoxic effects on human oral buccal epithelium cells were found in the polycarboxylate cement (Durelon) group.Öğe Genotoxic effects of sulfur dioxide in human lymphocytes(Sage Publications Inc, 2014) Uren, Nihal; Yuksel, Sengul; Onal, YunusSulfur dioxide (SO2), which is used as food preservative in apricot sulfurization and several fabricated foods, is a common air pollutant. The aim of this study was to reveal the possible genotoxic effects of SO2 using in vitro human lymphocytes. The different endpoints of genotoxicity: sister chromatid exchange (SCE), micronuclei (MN) tests and cell growth kinetics such as mitotic index (MI) and replication index (RI) were studied. The cells were treated with 0.1, 0.5 and 1.0 ppm concentrations of SO2. It was shown that SO2 caused significant increases in the frequency of SCE and MN in the middle and high dosage groups and also induced mitotic delays and decreased MI and RI. In conclusion, the results have confirmed that SO2 has potent mutagenicity and it can cause genetic damage leading to a malignancy.Öğe Preparation, Controlled Drug Release, and Cell Viability Evaluation of Tenofovir Alafenamide-Loaded Chitosan Nanoparticles(Wiley-V C H Verlag Gmbh, 2024) Ulu, Ahmet; Sezer, Selcen Korkmaz; Yuksel, Sengul; Koc, Ahmet; Ates, BurhanTenofovir alafenamide (TAF) is used as a hepatitis B virus (HBV) nucleotide reverse transcriptase inhibitor for the treatment of chronic HBV infection. However, the use of TAF suffers from its poor solubility and low bioavailability. Therefore, this study prepared and characterized chitosan nanoparticles (CHS NPs) loaded with TAF. Morphological findings demonstrated that CHS NPs are roughly spherical and homogeneous in shape. Besides, TAF-loaded CHS NPs displayed the hydrodynamic diameter, zeta potential, and PDI of approximately 340 nm, 48.9 mV, and 0.65, respectively. The encapsulation efficiency is at about 50%, and TAF is released about 93% at the end of 80 hours at pH 7.4. In addition, human hepatocellular carcinoma cells (HepG2) are used for cell viability studies and it is observed that TAF-loaded CHS NPs has 1.24 times less viable cells as compared to the control. Collectively, TAF-loaded CHS NPs could be used as an efficient formulation for the treatment of chronic HBV infection.Öğe Prevalence of Pericentric Inversion of Chromosome 9 in Eastern Anatolia Region and Relationship to Reproductive Efficiency(Kare Publ, 2018) Yuksel, Sengul; Savaci, Serap; Ekici, Cemal; Kurtoglu, Elcin Latife; Korkmaz, Selcen; Yesilada, ElifObjectives: One of the most common, structurally balanced chromosome rearrangements is the pericentric inversion of chromosome (inv[9]). It is considered to be a variant of the normal karyotype, and has been found in both normal populations and patients with various abnormal phenotypes. The aim of this study was to determine the frequency of chromosome 9 rearrangement in the Malatya Province and check whether it is correlated with certain diseases. Methods: In this study, we investigated the karyotype analysis of 4168 patients admitted in the Turgut Ozal Medical Center and Research Hospital, Genetic Disease Diagnosis Center Laboratory, between 2014 and 2016 and retrospectively reviewed their clinical data. Chromosomes from cultured peripheral blood lymphocytes were analyzed using Giemsa Trypsin-Giemsa (GTG) banding. Results: Pericentric inversion was detected in 71 (1.7 %) of 4168 cases, including 32 (45.1%) cases with inv(9) causing infertilty, 21 (29.6%) causing growth retardation, four (5.6%) causing multiple spontaneous abortion, and 14 (19.7%) causing other abnormalities, all of which were referred to our laboratory. Conclusion: In this study, the distribution of inv (9) in the Malatya Province was shown, and it is believed that these results would contribute to the knowledge regarding the incidence of inv (9) in the Eastern Anatolia Region and Turkey.Öğe PROTECTIVE EFFECT OF MYRICETIN AGAINST E2-INDUCED GENOTOXIC DAMAGE IN HUMAN LYMPHOCYTES(Parlar Scientific Publications (P S P), 2012) Yuksel, Sengul; Yesilada, Elif; Gulbay, Gonca; Kurtoglu, Elcin; Savaci, S. SerapProtective effect of myricetin (MRY) against the cytotoxic and genotoxic effects of a hormonal steroid, 17 beta-estradiol (E-2), was assessed in peripheral blood human lymphocyte culture. Sister chromatid exchanges (SCE), mitotic index (MI) and replication index (RI) were scored as genetic endpoints. Firstly, the genotoxic effect of different amounts (5, 10 and 20 mu M final concentration) of E2 was tested, and 10 and 20 mu M E-2 levels were detected as genotoxic. In the second set, E-2 groups were treated with 10 mu M MRY. MRY reduced the SCE but increased MI as well as RI, suggesting its protective action on human lymphocytes in vitro against E-2-induced genotoxic damage.Öğe A Rare Mosaic Karyotype of 45,X/46,X,psu idic(Y)(p11.32)/46, XY with SHOX Haploinsufficiency, External Male Genitalia, and Short Stature(Karger, 2019) Ekici, Cemal; Esener, Zeynep; Korkmaz, Selcen; Salturk, Nihal; Yuksel, Sengul; Koc, AhmetIn this case study, we describe a 3-year-old boy who was referred to the Inonu University Hospital with short stature complaint. His height was 86 cm (-2.96 SDS), weight was 12 kg (-2.43 SDS), and head circumference was 46.5 cm (-2.34 SDS). Chromosomal analyses were performed on cultured peripheral blood lymphocytes of the patient and his parents and showed the patient's karyotype mos 45, X[20]/46, X, idic(Y)(p11.32)[29]/46, XY[1]. The karyotypes of the parents were normal. Subsequently, specific FISH probes were hybridized to the related regions of the sex-determining region Y (SRY), centromere X/Y (CEP X/Y), and short stature homeobox (SHOX) genes. Simultaneous SNP array-CGH was conducted. As to our knowledge, we present the first patient with mosaic isodicentric Y chromosome with 3 different cell lines and normal male external genitalia. Our results suggest that it would be beneficial to study cytogenetic and molecular cytogenetic methods together for better diagnostic accuracy and treatment. (C) 2018 S. Karger AG, BaselÖğe Use of microfluidic sperm extraction chips as an alternative method in patients with recurrent in vitro fertilisation failure(Springer/Plenum Publishers, 2019) Yildiz, Koray; Yuksel, SengulPurpose It is known that sperm preparation techniques in in vitro fertilisation (IVF) are intended to select the best-quality sperm. The aim of this study is to compare sperm the density gradient method and microfluidic chip (Fertile Plus) method in infertile patients by analysing fertilisation rates, pregnancy rates, and sperm morphology and DNA fragmentation rates posed by these two methods. Methods Using semen samples obtained from the patients, sperms were prepared with gradient (n = 312) and microfluidic chip methods (n = 116). Fertilisation and pregnancy rates were compared in the first time and in the recurrent IVF trial patients. In addition, the morphology and DNA fragmentation comparison of sperm samples were evaluated by Toluidine blue in situ chemical staining method. Results There was no statistically significant difference between fertilisation and pregnancy rates when compared with study groups in first-time IVF treatment patients. However, in recurrent IVF failure patients, there was a significant difference in fertilisation rates but no statistically significant difference was found in pregnancy rates. The microfluidic chip method significantly decreased sperm DNA fragmentation index according to density gradient method. Conclusions Microfluidic chip method may be recommended in patients with recurrent unsuccessful in vitro trials. The sperm DNA fragmentation test prior to the treatment will be helpful in selecting the appropriate sperm-washing method.
