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Öğe Apo E Genotyping İn Tuberculosis Patients From Malatya(Turgut Özal Tıp Merkezi Dergisi, 2015) Acar, Ceren; Giray, Aslı Kurt; Vaizoğlu, R.Dilara; Gözükara, G.Harika; Arıca, Zeynep; Durmaz, Bekir; Kayabaş, Üner; Otlu, BarışÖz: Tinea inkognito, topikal veya sistemik steroidlerin uygunsuz kullanımı sonucu tipik dermatofit kliniğinden uzaklaşan dermatofit enfeksiyonudur. Tinea inkognito klinik görünüm olarak egzema, psoriasis, alerjik kontakt dermatit, rozasea, seboreik dermatit, atopik dermatit gibi birçok dermatozu taklit edebilmektedir. Tinea inkognito tanısı, lezyondan direkt KOH (potasyum hidroksit) incelemesi (nativ preperatı), lezyondan mantar kültürü yapılması ve bazı olgularda histopatolojik inceleme ile konulur. Tinea inkognito tedavisinde sistemik antifungal tedavi önerilmektedir. Burada, kliniğimizde 2014 yılı içinde çeşitli dermatozları taklit eden tinea inkognito tanısı almış ve tedavi edilmiş 10 olgu sunulmaktadırÖğe The association between TLR4 polymorphisms and pulmonary tuberculosis(2019) Vaizoğlu, Reika Dilara; Gözükara Bağ, Harika; Acar, CerenAbstract: Tuberculosis (TB) is a major health problem which causes many deaths every year in the world. According to the World Health Organization (WHO) report, 1.5 million people lose their lives due to tuberculosis in every year. Although some of the infected people are showing the symptoms, in some the disease never develops, even about 90% of the affected ones are improved by the immune system's response. As in many infectious diseases, the difference between the number of infected people and the number of sick people is caused by differences in balance between the host defense and the virulence of the organism. In this case, the genetic basis of the response to infectious agents needs to be investigated in order to understand the relationship between infectious diseases and host. For this purpose; we investigated the effects of TLR4 polymorphisms (rs4986790 & rs4986791) that are involved in immune system mechanisms against susceptibility to Mycobacterium tuberculosis (MTB). In order to understand the association we did genotyping in 65 TB patients from Malatya. The results of the genotyping showed no significant association to the single nucleotide polymorphisms (SNPs) mentioned, for rs4986790 the p value was 0.80 and for rs4986791 p value was 0,517 for the genotypes. The population size was the limiting factor for the statistical analysis and it should be also taken into account that a number of genes are taking part in the signal transduction pathway that TLR4 is involved.Öğe The association between vitamin D receptor polymorphisms and multiple sclerosis in a Turkish population(Elsevier Sci Ltd, 2018) Kamisli, Ozden; Acar, Ceren; Sozen, Mert; Tecellioglu, Mehmet; Yucel, Fatma Ebru; Vaizoglu, Dilara; Ozcan, CemalBackground: Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS). Genetic and environmental factors are important in disease development. Many studies have investigated the relationship between MS and VDR polymorphisms. VDR gene polymorphism has not been previously studied in Turkish MS patients. We aimed to investigate the relationship between MS and VDR genotypes Taq I, Apa I and Fok I polymorphisms in a Turkish population. Methods: 167 MS patients and 146 healthy control subjects were included in the present study. MS and the VDR TaqI (rs731236), ApaI (rs7975232), and FokI (rs2228570) polymorphisms were investigated. Results: The study enrolled 167 patients (121 females, 46 males) with MS and 146 healthy individuals (88 females, 58 males). The frequency of only the Fok I polymorphism differed significantly between the two groups (p = 0.002). The TaqI (rs731236) and ApaI (rs7975232) genotype distributions were not significantly different between MS patients and healthy controls (p = 0.626 and p = 0.990, respectively). Also there were no significant gender difference between patients and controls for Taq I and Apa I. Conclusion: In conclusion, we found a significant association between MS and the FokI polymorphism in our region of Turkey. However, the results may be different in other populations. More epidemiological and genetic studies are needed to explain the association between genetic factors and MS.Öğe Association of Vitamin D Receptor Polymorphisms to Pulmonary Tuberculosis in Turkish Patients: An Up-to-date Meta-Analysis and A Case-Control Study(2021) Gözükara Bağ, Harika; Acar, Ceren; Vaizoğlu, Refika DilaraAbstract: Introduction: Tuberculosis is a major global health issue, threatening millions of lives every year. To understand the interactions between host and the pathogenic factors, many association studies are being held in different populations and most of the time results are controversial. Vitamin D receptor is one of the immunomodulatory molecules that may have an effect on susceptibility to tuberculosis. Up to now, there was no positive association reported with the tuberculosis and Fok I or Taq I polymorphisms of VDR gene in tuberculosis patients of Turkish origin. The aim of this study was to make an updated meta-analysis and a case-control study in our group of patients for figuring out the association between Fok I and Taq I polymorphisms of VDR and TB. Materials and Methods: In the present study, association of pulmonary tuberculosis and VDR gene’s Fok I (rs 2228570) and Taq I (rs20731236) polymorphisms were investigated in our patient group from Malatya, and a comparison was made by a meta-analysis with the mentioned polymorphisms. Ninety-four healthy controls and 80 patients are subjects of case control study. The samples are genotyped for Taq I and Fok I polymorphisms by using TaqMan SNP genotyping kits. The allelic and genotypic distributions were analyzed by exact significance of the Pearson’s test or Fisher’s exact tests. Meta-analyses for each SNP were conducted under four different genetic models. The statistical significance of the pooled ORs was determined by a Z test and publication bias was evaluated by Egger’s test. Results: Our case control study Taq I polymorphism showed no significant association to TB which also matched with our meta-analysis. On the other hand, for Fok I polymorphism, genotypes and allele frequencies were significantly different in our focus group (p 0.044). Sex based analysis gave significantly different results in women with TB as well even though our meta-analysis showed no association to that polymorphism. Conclusion: The reasons underlying the susceptibility to TB is still not clear. The immune response process is so complex and many molecules are taking part in these reactions. So, there are a lot of candidate molecules to be checked in the association studies. VDR is still one of those molecules and may be other than by checking single SNPs, haplotypes could be under investigation with bigger populations.Öğe An association study of D-amino acid oxidase and D-amino acid oxidase activator polymorphisms and schizophrenia in patients from Turkey(Cumhuriyet Univ Tip Fak Psikiyatri Anabilim Dali, 2016) Kartalci, Sukru; Acar, CerenObjective: Schizophrenia is a highly heritable complex disease. The genetic interactions underlying this heritability is still needs to be understood. Linkage studies pointed out the D-amino acid oxidase (DAO) and D-amino acid oxidase activator (DAOA-G72) genes as candidate genes in susceptibility to schizophrenia. The association studies of interaction partners D-amino acid oxidase and D-amino acid oxidase activator gene polymorphisms and schizophrenia has been performed in different studies with different ethnic origins. However these studies showed conflicting results. In this study, it is aimed to examine the effects of several DAO and DAOA polymorphisms in Turkish schizophrenia patients. Methods: In the present study two single nucleotide polymorphisms (SNPs) within DAO gene (rs2111902 and rs3741775) and one in DAOA gene (rs2391191) were genotyped in individuals with Turkish origin from Malatya region on eastern part of Turkey. 96 schizophrenia patients and 100 mentally healthy individuals are the subjects of this study. Results: No significant difference was found in between the controls and schizophrenia sample for the SNPs rs2111902 and rs3741775 of DAO gene but a significant association was found on the allelic level of rs2391191 of DAOA gene. The relationship between aggressive behaviour, suicide attempts and genotypes were also evaluated in the patient group. Discussion: A significant association for the G allele of rs2391191 at the allelic level (p=0.036) was found, on the other hand no association could be shown between the examined rs2111902 and rs3741775 polymorphisms and the pathology of the disorder in the group of Turkish schizophrenia patients included in this study.Öğe A case of adult-onset metachromatic leukodystrophy beginning with behavioral symptoms(Klinik Psikiyatri Dergisi, 2023) Tunali, Cemile Hazan; Unal, Sueheyla; Acar, Ceren; Ozer, Emel SaglarMetachromatic leukodystrophy is a rare inherited disor-der of the nervous system with great clinical variability characterized by loss of both cognitive and motor func-tions upon extensive white matter damage by the accu-mulation of sulfatides. Although metachromatic leukodystrophy usually affects children, many cases of adult leukodystrophy have been reported in the litera-ture in the last few years. Adult-onset leukodystrophy typically presents with a progressive syndrome that includes various combinations of cognitive impairment, spasticity, apraxia, ataxia, and upper motor neuron ma-nifestations. In this article, we decided to present this case to draw attention to the fact that the adult form of metachromatic leukodystrophy, which presents with psychotic symptoms and behavioural problems, should be considered in the differential diagnosis of psychotic pictures. In a 48-year-old male patient who did not have any psychiatric or neurological problems before, symp-toms such as meaningless shouting, running away from home, restlessness, and audio-visual hallucinations were added to the clinical picture that started with confusion and disorganized behaviour in a short time. MRI, plasma aryl sulfatase A level (ARSA) and gene analysis were per-formed for differential diagnosis in the patient. It is known that the patient has a sibling who died before the age of one, and two nephews diagnosed with an autism spectrum disorder. Heterozygous c.1283C>A (p P428Q) mutation was detected in the patient, which was not previously reported in the literature or mutation databases. The chromosomal region -22q13.33-in which the ARSA gene with this mutation is located is also a can-didate region for autism. In this respect, it was thought that this mutation might be related to disorganized behavioural problems.Öğe Composition of the colon microbiota in the individuals with inflammatory bowel disease and colon cancer(Springer, 2024) Acar, Ceren; Celik, Sibel Kucukyildirim; Ozdemirel, H. Ozgur; Tuncdemir, Beril Erdem; Alan, Saadet; Mergen, HaticeThe human intestine is a habitat for microorganisms and, recently, the composition of the intestinal microbiota has been correlated with the etiology of diseases such as inflammations, sores, and tumors. Although many studies have been conducted to understand the composition of that microbiota, expanding these studies to more samples and different backgrounds will improve our knowledge. In this work, we showed the colon microbiota composition and diversity of healthy subjects, patients with inflammatory bowel disease (IBD), and colon cancer by metagenomic sequencing. Our results indicated that the relative abundance of prokaryotic and eukaryotic microbes differs between the healthy vs. tumor biopsies, tumor vs. IBD biopsies, and fresh vs. paraffin-embedded tumor biopsies. Fusobacterium, Escherichia-Shigella, and Streptococcus genera were relatively abundant in fresh tumor biopsies, while Pseudomonas was significantly elevated in IBD biopsies. Additionally, another opportunist pathogen Malasseziales was revealed as the most abundant fungal clade in IBD biopsies, especially in ulcerative colitis. We also found that, while the Basidiomycota:Ascomycota ratio was slightly lower in tumor biopsies compared to biopsies from healthy subjects, there was a significant increase in IBD biopsies. Our work will contribute to the known diversity of prokaryotic and eukaryotic microbes in the colon biopsies in patients with IBD and colon cancer.Öğe Effects of Electroconvulsive Therapy on Some Inflammatory Factors in Patients With Treatment-Resistant Schizophrenia(Lippincott Williams & Wilkins, 2016) Kartalci, Sukru; Karabulut, Aysun Bay; Erbay, Lale Gonenir; Acar, CerenObjectives Electroconvulsive therapy (ECT) is the most effective option for several psychiatric conditions, including treatment-resistant schizophrenia. However, little is known about the molecular mechanism of action of ECT. The link between inflammatory system and schizophrenia is the focus of recent studies. However, the impact of ECT on inflammatory functioning in this disorder remains elusive. Whether ECT could modulate inflammatory factors in patients with schizophrenia was examined. Methods Plasma levels of interleukin-4 (IL-4), transforming growth factor- (TGF-), myeloperoxidase (MPO), and nuclear factor-B (NF-B) activation were analyzed in 20 schizophrenic patients, mainly with resistant to antipsychotic medication disorders, and in 20 sex- and age-matched healthy controls. Disease severity was evaluated using the Brief Psychiatric Rating Scale. All patients were followed with measurement of the inflammatory factors before and after ECT treatment and compared with the controls. Results Patients with schizophrenia had markedly raised NF-B and but decreased TGF- levels compared with healthy controls. On the other hand, no significant differences were found for the levels of IL-4 and MPO levels. The clinical improvement during repeated ECT was accompanied by a gradual and significant increase in IL-4 and TGF- level, but MPO and NF-B activation were left unaffected. Increases in TGF- were negatively correlated with the change in Brief Psychiatric Rating Scale scores after ECT. Conclusions It is shown that ECT, while increasing the anti-inflammatory response such as the levels of IL-4 and TGF-, it did not affect the levels of MPO and NF-B activation in this study.Öğe Epigenetic Perspective in Schizophrenia: DNA Methylation Patterns(2022) Karaaslan, Ezgi; Kartalcı, Şükrü; Acar, CerenSchizophrenia is a mental disorder characterized by delusions, hallucinations and various behavioral disorders. Affecting approximately 1% of the world's population, schizophrenia not only affects patients, but also other members of the society. Genetic and environmental factors play roles in the etiology of the disorder.Genetics, neurodevelopmental disorder, drug use, urban life, alone or together can be counted as the factors that cause the disorder. Despite increasing studies in recent years, the factors causing the formation of schizophrenia have not been fully clarified and more research is needed. Although genetic factors are risk factors for schizophrenia, it is thought that some environmental factors affect the emergence of the disorder. Epigenetic mechanisms regulate gene functions without changing the nucleotide sequence of DNA. DNA methylation is associated with schizophrenia, and methylation status studies have been conducted in many schizophrenia candidate genes. Examination of DNA methylation states will contribute significantly to psychiatric research.In this review, data published in global databases obtained from DNA methylation studies related with schizophrenia are summarized and their importance in schizophrenia is briefly discussed.Öğe Escherichia Coli O157:H7 Suşuna Özgü Potansiyel Litik Bakteriyofaj Araştırılması(2015) Otlu, Barış; Yakupoğulları, Yusuf; Bayındır, Yaşar; Doruk, Evren Engin; Gürsoy, Nafia; Gül, Mehmet; Acar, Ceren[Abstract Not Available]Öğe Identification of a Novel Deletion in AVP-NPII Gene in a Patient with Central Diabetes Insipidus(Assoc Clinical Scientists, 2015) Deniz, Ferhat; Acar, Ceren; Saglar, Emel; Erdem, Beril; Karaduman, Tugce; Yonem, Arif; Cagiltay, EylemCentral Diabetes Insipidus (CDI) is caused by a deficiency of antidiuretic hormone and characterized by polyuria, polydipsia and inability to concentrate urine. Our objective was to present the results of the molecular analyses of AVP-neurophysin II (AVP-NPII) gene in a large familial neurohypophyseal (central) DI pedigree. A male patient and his family members were analyzed and the prospective clinical data were collected. The proband applied to hospital for eligibility to be a recruit in Armed Forces. The patient had severe polyuria (20 L/day), polydipsia (20.5 L/day), fatique, and deep thirstiness. CDI was confirmed with the water deprivation-desmopressin test according to an increase in urine osmolality from 162 mOsm/kg to 432 mOsm/kg after desmopressin acetate injection. To evaluate the coding regions of AVP-NPII gene, polymerase chain reactions were performed and amplified regions were submitted to direct sequence analysis. We detected a heterozygous three base pair deletion at codon 69-70 (207_209delGGC) in exon 2, which lead to a deletion of the amino acid alanine. A three-dimensional protein structure prediction was shown for the deleted AVP-NPII and compared with the wild type. The three base pair deletion may yield an abnormal AVP precursor in neurophysin moiety, but further functional analyses are needed to understand the function of the deleted protein.Öğe Lack of association between catechol-Omethyltransferase and schizophrenia in a Turkish population(Turkish Biochemistry Society, 2015) Acar, Ceren; Sözen, Mustafa Mert; Gözükara, Harika; Orman, Kübra; Kartalcı, ŞükrüObjective: Catechol-O-methyltransferase (COMT) is the key molecule in the catabolism of catecholamines like dopamine which is an important molecule in schizophrenia. Due to its function and location COMT gene is a strong candidate gene for schizophrenia. The aim of this study was to investigate the possible associations of 3 COMT single nucleotide polymorphisms (SNPs) and schizophrenia in our population. COMT enzyme activity is regulated by a widely known Val158Met polymorphism (rs4680), along with the variation of the SNPs rs737865 and rs165599. Methods: Val158Met polymorphism (rs4680), the SNPs rs737865 and rs165599 were the targets of this study. The study was performed with 96 patients (66 male and 30 female) and 100 controls (47 male and 53 female) from Malatya region on eastern part of Turkey by using TaqMan genotyping assays. Results: We couldn’t find a significant difference between the schizophrenia patients and normal controls for any of the SNPs that were studied. The genotype frequencies in both the patient and control groups satisfied the Hardy– Weinberg equilibrium. No significant gender differences were observed for the SNPs that were investigated. No significant difference was observed in the allele or genotype frequencies as well. Conclusion: COMT gene doesn’t appear to be a risk factor in this population of schizophrenia patients in Turkey. © 2015, Turkish Biochemistry Society. All rights reserved.Öğe Lipoid proteinosis and epilepsy: Molecular analysis(2019) Tecellioglu, Mehmet; Kamisli, Ozden; Acar, Ceren; Merge, Hatice; Sozen, Mert; Karaduman, Tugce; Sarac, Gulbahar; Erbay, Mehmet FatihAim: Lipoid proteinosis (LP) is also known as Urbach-Wiethe disease which is a rare autosomal recessive disorder characterized by intracellular accumulation of hyaline material in skin and mucosae. LP has typical neurological, dermatological and radiological findings. The pathogenesis of disease is unknown. In literature several cases have been reported up to date. Mutations in extracellular matrix protein 1 (ECM1) gene have been found to cause the disease. We evaluated the molecular features of a family diagnosed with LP and evaluate the known and novel mutations of LP. Material and Methods: Genomic DNA was extracted from peripheral blood of the patients and family members including clinically normal parents and two siblings of the two affected subjects by using a commercial DNA extraction kit. Polymerase chain reaction was performed for all 10 exons of ECM1 gene by using the primers defined. Results: All of the exons of the ECM1 gene were sequenced and this revealed a 2-bp deletion in exon 7 of the ECM1 gene in both patients and both parents. Patients have the homozygous 2-bp deletions (c735del TG) and the parents and two healthy siblings showed heterozygous 2-bp deletion. Conclusions: Our patients found to be homozygous for the deletion in ECM1 gene. In order to understand the molecular pathology of the disease in detail, further functional analysis of the mutations should be performed.Öğe Lipoid proteinosis and epilepsy: Molecular analysis(2019) Tecellioğlu, Mehmet; Kamışlı, Özden; Acar, Ceren; Mergen, Hatice; Sözen, Mustafa Mert; Karaduman, Tuğçe; Saraç, Gülbahar; Erbay, Mehmet FatihAbstract: Aim: Lipoid proteinosis (LP) is also known as Urbach-Wiethe disease which is a rare autosomal recessive disorder characterized by intracellular accumulation of hyaline material in skin and mucosae. LP has typical neurological, dermatological and radiological findings. The pathogenesis of disease is unknown. In literature several cases have been reported up to date. Mutations in extracellular matrix protein 1 (ECM1) gene have been found to cause the disease. We evaluated the molecular features of a family diagnosed with LP and evaluate the known and novel mutations of LP. Material and Methods: Genomic DNA was extracted from peripheral blood of the patients and family members including clinically normal parents and two siblings of the two affected subjects by using a commercial DNA extraction kit. Polymerase chain reaction was performed for all 10 exons of ECM1 gene by using the primers defined. Results: All of the exons of the ECM1 gene were sequenced and this revealed a 2-bp deletion in exon 7 of the ECM1 gene in both patients and both parents. Patients have the homozygous 2-bp deletions (c735del TG) and the parents and two healthy siblings showed heterozygous 2-bp deletion. Conclusions: Our patients found to be homozygous for the deletion in ECM1 gene. In order to understand the molecular pathology of the disease in detail, further functional analysis of the mutations should be performed.Öğe Malatya daki tüberkülozlu hastalarda apo e genotiplendirmesi(İnönü Üniversitesi Tıp Fakültesi Dergisi, 2015) Acar, Ceren; Kurt, Aslı Giray; Vaizoğlu, R.Dilara; Gözükara, G.Harika; Arıca, Zeynep; Durmaz, Bekir; Kayabaş, Üner; Otlu, BarışAmaç: Bu çalışmadaki amacımız, ülke geneline göre tüberkülozlu hasta prevelansı yüksek olan bölgemizde, tüberküloz tanısı konmuş hasta populasyonunda ve sağlıklı gönüllülerde Apo E polimorfizmlerini genotiplendirmek ve varyasyonları göstermektir. Bu veriler ve normal bireylere ait veriler karşılaştırılarak olası Apo E-tübeküloz bağlantısına yönelik bir profil çıkarılması hedeflenmektedir. Gereç ve Yöntem: Çalışmaya Turgut Özal Tıp Merkezi Mikrobiyoloji Anabilim Dalı ve Malatya İl Sağlık Müdürlüğü tarafından toplanan 60 tüberkülozlu (TB) hasta ve 160 sağlıklı birey dahil edildi. Periferal kan örneklerinden DNA izole edildi. Apo E genotiplendirmesi, Real-Time PCR temelli hazır kit kullanılarak gerçekleştirildi. Genotip ve allel frekanslarını karşılaştırmak için Fisher kesin ki-kare testi ve olabilirlik oranı kullanılmıştır. Bulgular: Önceki çalışmaların aksine bizim çalışmamıza dahil ettiğimiz populasyonda tüberküloz ve Apo E genotipleri arasında bir bağlantı bulunamamıştır. Veriler hasta ve normallerin karşılaştırılması ve hasta ve sağlıklı bireylerin cinsiyetleri arasındaki farklılıkların karşılaştırılması ile analiz edilmiştir ve istatistiki açıdan anlamlı bir sonuca ulaşılamamıştır. Sonuç: Bu çalışma, Apo E genotipleri ve tüberküloz arasındaki bağlantıyı araştıran Türkiye’de yapılmış ilk çalışmadır. Diğer populasyonlarda bağlantı bulunmuş olmasına rağmen biz tüberküloz ve Apo E allelleri ve genotipleri arasında bir bağlantı bulunamamıştır. Çalışmaya, Malatya ilinde ulaşılabilen tüm hastalar dahil edilmiş olmasına rağmen kısıtlayıcı etkenlerden bir tanesi hasta sayısının az olmasıdır. Daha büyük örnek grubu ile çalışarak daha bilgilendirici bir sonuca ulaşılabileceği düşünülmektedir.Öğe Matrix metalloproteinase 9 gene-MMP9-DNA methylation status in Turkish schizophrenia patients(Walter De Gruyter Gmbh, 2023) Karaaslan, Ezgi; Kartalci, Sukru; Bag, Harika Gozde Gozukara; Acar, CerenObjectives: Schizophrenia is a neuropsychiatric disease caused by disorders in brain development due to genetic and environmental factors. The interactions and mechanisms of the two main etiological factors are not fully understood despite neurobiological, clinical and genetic research and more research is needed. In this study, we aimed to investigate the DNA methylation differences in the matrix metalloproteinase 9 gene (MMP9) between schizophrenia and healthy control groups.Methods: Our study investigates DNA methylation patterns in the MMP9 gene in peripheral blood cells of schizophrenia patients. For this purpose, pyrosequencing method was used to analyze DNA methylation status of C-phosphate-G (CpG) regions in the 7th exon of MMP9 in 40 schizophrenia patients and 32 healthy individuals who admitted to our university hospital's psychiatry clinic.Results: In our results, it has been shown that there is a difference between MMP9 gene DNA methylations between healthy individuals and schizophrenia patients. Significant differences were found in the MMP9 gene exon 7 region in CpG 7-3, CpG 7-4, CpG 7-5 positions and mean methylation patterns between these two groups. Conclusions: This study provided evidence that DNA methylation differences may exist between schizophrenia patients and healthy individuals, and emphasized the epigenetic aspect of the disorder.Öğe The Novel Synthesized Pyridazinone Derivates Had the Antiproliferative and Apoptotic Effects in SHSY5Y and HEP3B Cancer Cell Line(Bentham Science Publ Ltd, 2018) Ciftci, Osman; Ozdemir, Zeynep; Acar, Ceren; Sozen, Mert; Basak-Turkmen, Nese; Ayhan, Idris; Gozukara, HarikaBackground: Brain cancer (neuroblastoma) and liver cancer (hepatocellular carcinoma) are common cancer types among others worldwide which do not have a radical treatment and cure. Objective: In the current study, five novel pyridazinone derivates bearing benzelhydrazone moiety at second position were synthesized and evaluated for their cytotoxic activity against neuroblastoma and hepatocellular carcinoma (SHSY5Y and HEP3B) and human fibroblast (HF) cell lines. The aim of the current study is to identify antiproliferative activity of five novel pyridazinone derivates against neuroblastoma and hepatocellular carcinoma (SHSY5Y and HEP3B) and human fibroblast (HF) cell lines. Method: The compounds were synthesized by the reacting 6-[4-(phenyl/4-chlorophenyl)piperazine-1yl]-3(2H)-pyridazinone-2-yl acetohydrazide with benzaldehyde in ethanol. The in vitro antiproliferative activities were determined with MTT assay. Bax, Bcl-2 and Casp3 gene expression levels were detected with RT-PCR analyses. Results: The lowest IC50 was observed for compound 4 in SHSY5Y and HEP3B cells. Apoptosis increased in cancer cells which was shown by changes inBax, Bcl-2 and Casp3 gene expression levels with 1-5 compound therapy. Conclusion: Novel pyridazinone derivates might be promising agents as new chemotherapeutic candidates in brain and liver cancer.Öğe Presence of a genetic association between NRG-3 SNP rs17101193 and schizophrenia(2020) Acar, Ceren; Sozen, Mustafa Mert; Kartalci, SukruAim: NRG-3 gene is a member of neuregulin signaling pathway and alleles of several single nucleotide polymorphisms (SNP) located in this gene are suspected to be associated with schizophrenia. During this work, we have done a study to investigate the potential association of the SNP rs17101193 of NRG-3 gene.Material and Methods: We used the DNA samples from 301 unrelated schizophrenia patients and 326 healthy control samples collected from Malatya-Turkey to determine the SNP genotypes. After genotyping, we compared the genotypes and alleles in terms of distributions between cases and controls. We also applied the recessive models for both alleles to get a more clarified result. We used Chi-Squared test and Fisher’s exact test for hypothesis testing.Results: Even though the difference between the case and control groups were not significant in context of distributions of two alleles of rs17101193, the distributions of genotypes were significantly different (p = 0.046). On the other hand, one of the genotypes (AA) was seen only in the patients. Conclusion: The results of our analyses and statistical test indicated that rs17101193 SNP of NRG-3 gene has a potential to be associated with schizophrenia and homozygosity of “A” allele seems to be a risk factor in our population. More evidence from separate case-control studies from different populations may be required to strengthen this idea.Öğe Presence of a genetic association between NRG-3 SNP rs17101193 and schizophrenia(2020) Sözen, Mustafa Mert; Acar, Ceren; Kartalcı, ŞükrüAbstract: Aim: NRG-3 gene is a member of neuregulin signaling pathway and alleles of several single nucleotide polymorphisms (SNP) located in this gene are suspected to be associated with schizophrenia. During this work, we have done a study to investigate the potential association of the SNP rs17101193 of NRG-3 gene. Material and Methods: We used the DNA samples from 301 unrelated schizophrenia patients and 326 healthy control samples collected from Malatya-Turkey to determine the SNP genotypes. After genotyping, we compared the genotypes and alleles in terms of distributions between cases and controls. We also applied the recessive models for both alleles to get a more clarified result. We used Chi-Squared test and Fisher’s exact test for hypothesis testing. Results: Even though the difference between the case and control groups were not significant in context of distributions of two alleles of rs17101193, the distributions of genotypes were significantly different (p = 0.046). On the other hand, one of the genotypes (AA) was seen only in the patients. Conclusion: The results of our analyses and statistical test indicated that rs17101193 SNP of NRG-3 gene has a potential to be associated with schizophrenia and homozygosity of “A” allele seems to be a risk factor in our population. More evidence from separate case-control studies from different populations may be required to strengthen this idea.Öğe Relationship between guanosine triphosphate pathway and tetrahydrobiopterin in gestational diabetes mellitus(Springer Int Publ Ag, 2020) Unuvar, Songul; Melekoglu, Rauf; Salva, Emine; Acar, Ceren; Yasar, SeymaPurpose The present study assesses the change in tetrahydrobiopterin (BH4), one of the most important products in the guanosine triphosphate (GTP) pathway and in other parameters that might affect nitric oxide (NO) production, in gestational diabetes mellitus (GDM). Methods The study included 100 healthy pregnant women and 100 women diagnosed with GDM. Serum levels of neopterin, BH4 and NO were measured. The levels of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and guanosine triphosphate cyclohydrolase I (GCHI/GTPCH) gene expression were determined. Results It was found that diabetes led to an increase in neopterin and NO levels, and a decrease in BH4 levels. A stimulation was observed in eNOS gene expression in the GDM group when compared to the control group, while GCHI levels were found to decrease when compared to the control group. iNOS gene expression was detected in neither the healthy controls nor the patient group. Conclusions Decreased NO bioavailability plays an important role in the progression of such macrovascular diseases as diabetes. BH4 levels decrease in diabetes patients, while the increased gene expression of GCHI reverses the diabetes-related BH4 deficiency and allows the endothelial cells to regain their ability to produce NO. Since GCHI is the rate-limiting enzyme in the biosynthesis of BH4, changes in GCHI levels directly affect the BH4 levels and the NO metabolism, leading to an increased risk of macrovascular complications. The significant increase in neopterin levels suggest that this is a potential biomarker for the early diagnosis of GDM.
