Fakülteler / Faculties
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Item Associations between IL-1 alpha, IL-1 beta, TNF alpha, and IL-6 variations, and susceptibility to transposition of the great arteries(2022) Atasoy Karakas, Latife; Tugrul, Duygu; Sahin Uysal, Nihal; Esin, Sertac; Tokel, Niyazi Kursat; Terzi, Yunus Kasim; 35590253; AEY-5060-2022Background: To evaluate the relationship between IL-1 alpha-889UT (rs1800587), IL-1 beta -511 C >T (rs16944), TNF alpha-308G > A (rs1800629), TNF alpha-238G > A (rs361525), IL-6 -174G> C (rs1800795), and IL-6 -572G > C (rs1800796) polymorphisms and the susceptibility to transposition of the great arteries (TGA). Methods: A prospective analysis was performed on mothers whose newborns were diagnosed as having TGA. For each case of TGA, a mother who gave birth to a healthy neonate in the same period was randomly selected for the control group. The sample size was calculated before planning the study with 80% power and 5% alpha. Results: Twenty-seven mothers whose newborn had TGA anomalies (group 1) and 27 mothers whose newborn had no TGA (group 2) were included in the study. There were no significant differences between the groups in terms of maternal age, pregestational body mass index, gestational age at birth and infant sex (p> 0.05). The genotype and allele distributions of IL-1 alpha -889C/T (rs1800587), IL-1 beta -511C >T (rs16944), TNF alpha -308G >A (rs1800629), TNF alpha -238G > A (rs361525), IL-6 -174G> C (rs1800795) and IL-6 -572G > C (rs1800796) gene variants were not different between the two groups (p> 0.05). Conclusions: There was no relation between IL-1 alpha, IL-1 beta, IL-6, and TNF alpha promoter gene polymorphisms and TGA occurrence in our study group.Item The Influence of Sex on Brain Development Genetics and the Possible Relationship with Sex-Dependent Differences in Psychiatric Disorders(2021) Bagcaz, Arda; Terzi, Yunus Kasim; Sahin, Feride Iffet; 0000-0001-5947-0179; 0000-0001-7308-9673; AAK-2321-2021; AAC-7232-2020There are sex-dependent differences in the prevalence, age of onset, and course of psychiatric disorders and cognitive abilities. Although it has been assumed that the direct effect of gonadal hormones in sensitive periods leads to sexually dimorphic brain development, current evidence suggests that another possible factor may be sex-specific regulations at the gene level. Understanding the sex differences at the gene level can be promising to identify the mechanisms that predispose or trigger psychiatric disorders, and may provide new prevention or treatment strategies. This paper aims to review the findings on the mechanisms that affect the sex-specific differences in brain development at the gene level and to discuss the relationship of these findings with different cognitive characteristics of the sexes and psychiatric disorders.Item A newborn case diagnosed as isolated TBX1 deletion with 22q11 deletion syndrome(2020) Turan, Ozden; Celik, Zerrin Yilmaz; Ince, Deniz Anuk; Terzi, Yunus Kasim; Ecevit, Ayse; 0000-0002-2232-8117; 0000-0002-7707-1881; 0000-0002-4369-2110; AAJ-4616-2021; AAJ-2333-2021; I-6746-2016Item Persistent Hyperinsulinemic Hypoglycemia with Pancreatic Teratoma in Infancy: A Case Report(2020) Cemeroglu, Ayse Pinar; Sarialioglu, Faik; Belen-Apak, Fatma Burcu; Terzi, Yunus Kasim; 0000-0002-8257-810X; 32782239; AAL-7766-2021Objective: Unusual clinical course Background: Pediatric intraabdominal pancreatic teratomas have been rarely reported. This is the first case of severe hyper-insulinemic hypoglycemia in a 6-month-old infant secondary to an intraabdominal teratoma. The hypoglycemia resolved after surgical removal. Case Rreport: A 6-month-old infant was seen in a pediatric emergency department with complaints of lethargy and abnormal eye movements. She was diagnosed with hyperinsulinemic hypoglycemia and started on diazoxide. A CT and MRI of the abdomen revealed a 165x77x72 mm cyst with a 51x45x30 mm solid structure connecting to the wall of the cyst by a stalk, raising suspicion of a fetus in fetu. The mass had no connection to her pancreas. Following total excision of the intraabdominal mass, her hypoglycemia resolved. Histopathological examination showed immature fetal pancreatic tissue consistent with a mature teratoma. Whole exon sequencing of the infant's peripheral blood showed a negative mutation of ABCC8 and presence of heterozygous variations of HNF1b and IRS1 genes. Conclusions: This is the first case report of an infant with severe hyperinsulinemic hypoglycemia secondary to a pancreatic teratoma. The heterozygous variations of HNF1b and IRS1 genes likely played a role in the embryogenesis, causing a pancreatic teratoma and hyperinsulinemic hypoglycemia.Item A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies(2019) Song, Yuanbin; Rongvaux, Anthony; Taylor, Ashley; Jiang, Tingting; Tabaldi, Toma; Balasubramanian, Kunthavai; Bagale, Arun; Terzi, Yunus Kasim; Gbyli, Rana; Wang, Xiaman; Fu, Xiaoying; Gao, Yimeng; Zhao, Jun; Podoltsev, Nikolai; Xu, Mina; Neparidze, Natalia; Wong, Elice; Torres, Richard; Bruscia, Emanuela M.; Kluger, Yuval; Manz, Markus G.; Flavell, Richard A.; Halene, Stephanie; 0000-0001-5612-9696; 30664659; B-4372-2018Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient "MISTRG" mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients' dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample's genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research.Item beta-Adrenoreceptor antagonists reduce cancer cell proliferation, invasion, and migration(2014) Iseri, Ozlem Darcansoy; Sahin, Feride Iffet; Terzi, Yunus Kasim; Yurtcu, Erkan; Erdem, S. Remzi; Sarialioglu, Faik; 25026350Context: Propranolol, atenolol, and ICI118,551 are non-selective beta-adrenergic receptor (AR), beta(1)-AR, and beta(2)-AR antagonists, respectively. Objective: We investigated the efficacy of propranolol, atenolol, and ICI118,551 on proliferation, migration, and invasion of non-stimulated breast (MCF7), colon (HT-29), and hepatocellular (HepG2) cancer cells. Materials and methods: beta-AR expression profiling of cells was performed by real time PCR. Cell proliferation was determined by MTT. Boyden chamber and scratch assays were performed to evaluate invasion and migration. Results and discussion: All cell lines expressed beta-ARs. ICI118,551 was the most cytotoxic, whereas atenolol was the least effective beta-AR antagonist for 24, 48, and 72 h. Cell invasion was inhibited by ICI118,551 (45, 46, and 50% for MCF7, HT29, and HepG2, respectively) and propranolol (72, 65, and 90% for MCF7, HT29, and HepG2, respectively). Propranolol, atenolol, and ICI118,551 reduced migration of MCF7, HT-29, and HepG2 cells to varying extents depending on the application concentration and duration. Propranolol and atenolol reduced migration of MCF7 and HT-29 in a concentration-dependent manner, whereas migration of these cells decreased after 48 and 72 h of ICI118,551 applications. Conclusion: Beta(2)-AR antagonist seemed to be the most cytotoxic beta-blocker on non-stimulated cancer cells. Propranolol and ICI118,551 were more effective than atenolol in inhibiting invasion and migration of non-stimulated MCF7 and HT-29 cells; ICI118,551 being the most potent. Concordantly, beta(2)-selective blockage seemed to be more effective for non-stimulated cells. Effect of the selective beta-AR antagonists showed variation depending on the concentration, incubation time, and histological origin of cells.Item Epigallocatechin 3-gallate applications on HT-29 and MCF-7 cell lines and evaluation of tumor suppressor gene methylation(2015) Terzi, Yunus Kasim; Kaya, Ozge Ozer; Iseri, Ozlem Darcansoy; Celik, Zerrin; Sahin, Feride IffetEpigallocatechin 3-gallate (EGCG) is an antitumor molecule and shows this activity by binding to the active center of a methyltransferase enzyme (DNMT1). The methylation of DNA sequences of tumor suppressor and DNA repair genes is observed in different stages of carcinogenesis. In this study, we analyzed the effect of EGCG on the methylation status of 25 tumor suppressor genes in cancer cell lines HT-29 and MCF-7. HT-29 and MCF-7 cells were incubated with 10 mu M, 20 mu M, and 50 mu M and 1 mu M, 5 mu M, and 10 mu M EGCG for 48 h, respectively. We found promoter hypermethylation of (1) CDH13, GATA5, and RAR beta genes in MCF-7 cell line and (2) RAR beta, ESR1, PAX6, WT1, CADM1, CHFR, CDH13, and GATA5 genes in HT-29 cell line. However, (3) after EGCG application, no changes in methylation status were detected in our samples. Our results suggest that methylation status of tumor suppressor genes did not change with different EGCG doses.Item Effect of Hereditary Hemochromatosis Gene H63D and C282Y Mutations on Iron Overload in Sickle Cell Disease Patients(2016) Terzi, Yunus Kasim; Balci, Tugce Bulakbasi; Boga, Can; Koc, Zafer; Celik, Zerrin Yilmaz; Ozdogu, Hakan; Karakus, Sema; Sahin, Feride Iffet; 27095682Objective: Hemochromatosis is an autosomal recessive disease that is one of the most important reasons for iron overload. Sickle cell disease is a hemoglobinopathy that occurs as a result of a homozygous mutation in the hemoglobin gene. Erythrocyte transfusion is frequently used in the treatment of this disease. Iron overload as a result of transfusion is important in the mortality and morbidity of sickle cell anemia patients as well as in other hemoglobinopathies. In this study, the effect of hemochromatosis gene (HFE) p.H63D and p.C282Y mutations on transfusion-related cardiac and liver iron overload in sickle cell disease patients who carry homozygous hemoglobin S mutation has been investigated. Materials and Methods: This is a prospective single-center cross-sectional study in patients with homozygous hemoglobin S mutation between the years 2008 and 2013. The patients were divided into two groups. The first group (group A, n=31) was receiving chelation therapy and the second group (group B, n=13) was not. Direct and indirect iron loads were analyzed by magnetic resonance imaging and biochemically, respectively. HFE gene mutations were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analyses were performed by independent samples t-test. Results: p.H63D mutation was detected in 10 (32.3%) patients in group A and in only 1 patient (7.7%) in group B. When the 2 groups were compared for iron overload, iron deposition in the liver was significantly higher in group B (p=0.046). In addition, in group A, iron deposition was significantly higher in HFE mutation carriers compared to patients without the mutation (p=0.05). Conclusion: Results of this study showed that HFE gene mutations are important in iron deposition in the liver in patients with sickle cell disease.Item BRCA1 and BRCA2 sequence variations detected with next-generation sequencing in patients with premature ovarian insufficiency(2016) Yilmaz, Nafiye Karakas; Karagin, Peren Hatice; Terzi, Yunus Kasim; Kahyaoglu, Inci; Yilmaz, Saynur; Erkaya, Salim; Sahin, Feride Iffet; 27403073Objective: Although the association between BRCA1 and BRCA2 gene mutations and breast and ovarian cancer is known, there is insufficient data about premature ovarian insufficiency (POI). However, several studies have reported that there might be a relationship between POI and BRCA1 and BRCA2 gene mutation. Therefore, in the present study, we aimed to investigate the role of BRCA1 and BRCA2 gene mutations in the etiology of POI in a Turkish population. Material and Methods: The cohort was classified into two groups: a study group, consisting of 56 individuals diagnosed with premature ovarian insufficiency (and who were younger than 40 years of age, had an antral follicle count <3-5, and FSH levels >12 IU/I), and a control group, consisting of 45 fertile individuals. A total of 101 individuals were analyzed by next-generation sequencing to detect BRCA1 and BRCA2 gene mutations. Results: We detected four new variations (p.T1246N and p.R1835Q in BRCA1 and p.I3312V and IVS-7T>A in BRCA2) that had not been reported before. Conclusion: We did not find an association between the BRCA1 and BRCA2 gene mutations and premature ovarian insufficiency. However, larger, functional studies are needed to clarify the association.Item Odontogenic effects of two calcium silicate-based biomaterials in human dental pulp cells(2018) Onay, Emel Olga; Yurtcu, Erkan; Terzi, Yunus Kasim; Ungor, Mete; Oguz, Yener; Sahin, Feride İffet; 30070078Background. The goal of treating exposed pulp with an appropriate pulp capping material is to promote the dentinogenic potential of the pulpal cells. There have been recent attempts to develop more effective pulp-capping materials. Objectives. The aim of this study was to evaluate the effect of newly developed calcium silicate-based material on odontogenic differentiation of primary human dental pulp cells (HDPCs), in comparison with a contemporary calcium silicate-based material. Material and methods. Human dental pulp cells isolated from dental pulps were cultured in standard culture conditions in Dulbecco's Modified Eagle's Medium (DMEM) and then the effects of Micro-Mega mineral trioxide aggregate (MM-MTA) (Micro-Mega, Besancon, France) and ProRoot MTA (MTA) (Dentsply Sirona, Tulsa, USA) (positive control) were evaluated on HDPCs at 1, 7 and 14 days. Untreated cells were used as a negative control. Odontoblastic differentiation was assessed by alkaline phosphatase (ALP) activity. Runtrelated transcription factor 2 (RUNX2), alkaline phosphatase liver/bone/kidney (ALPL), bone morphogenetic protein 2 (BMP2), dentin sialophosphoprotein (DSPP), and Distal-less homeobox 3 (DLX3), as odontoblastic/ osteoblastic expression markers, were evaluated by semi-quantitative real-time polymerase chain reaction (RT-PCR) analysis. Calcium levels of culture media were also determined. Results. The MM-MTA group significantly increased the expression of BMP2 compared with that of the MTA group at 3 different time periods (p < 0.05). The up-regulation of ALPL between day 1 and 14 and the up-regulation of DSPP between day 7 and 14 were significant in both groups (p < 0.05). Micro-Mega MTA and MTA exhibited similar messenger RNA (mRNA) expression levels of ALPL, DSPP, RUNX2, DLX3, and ALP activities, as well as calcium levels. Conclusions. Based on the cell responses observed in this study, MM-MTA might be used efficiently in dental pulp therapy as a potential alternative to MTA.