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Öğe Alteration of butyrylcholinesterase level in cholelithiasis patients after laparoscopic cholecystectomy: Do butyrylcholinesterase levels affect lipid metabolism?(Bayrakol Medical Publisher, 2021) Ayan, Durmus; Bolat, Haci; Ozmen, Esma; Sari, IsmailAim: Cholelithiasis (gallbladder stone) is a disease with a high incidence worldwide. The disease is multifactorial and various factors such as gender, age, obesity and use of oral contraceptives are held responsible for the development of the disease. In addition, lipid disorder is observed in more than 50% of patients with cholelithiasis. Laparoscopic cholecystectomy (LC) is one of the most frequently used surgical methods in the treatment of cholelithiasis, and there are data indicating that lipid profile changes and metabolic syndrome (MetS) develop after the operation. In this study, we aimed to investigate whether there is a change in lipid profile and Butyrylcholinesterase (BChE) activity, which affects lipid metabolism, in cholelithiasis patients after LC. Material and Methods: In our study, 31 patients (obese and non-obese) who applied to the general surgery clinic of Nigde Omer Halisdemir University Training and Research Hospital were included. Blood samples were taken from the patients before LC and 6 months after the operation, and the lipid levels and BChE enzyme activity were examined using spectrophotometric method. Results: According to the results, it was determined that the total cholesterol (p=0.015) and LDL (p=0.010) levels significantly decreased after LC, while no significant difference was found in the other parameters examined (p>0.05). In addition, it was observed that there was no significant correlation between the lipid profile examined both before and after LC and BChE activity level. Discussion: According to the data obtained, the significant decrease in LDL and total cholesterol after LC indicates that this operation causes a positive change at least within a period of 6 months in the lipid profile of patients.Öğe Are VEGF and SCUBE1 gene expressions increased in diabetic retinopathy?(Walter De Gruyter Gmbh, 2023) Ayan, Durmus; Zor, Kuersad Ramazan; Ozmen, Esma; Bicer, Gamze Yildirim; Onder, Cagatay Emir; Sari, IsmailObjectives: In the current study, we synergistically evaluated vascular endothelial growth factor (VEGF) gene expression levels and signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) gene expression levels in diabetic patients without retinopathy, non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR).Methods: 94 blood samples from 26 healthy controls, 29 non-DR, 22 NPDR, and 17 PDR patients were collected in sterile EDTA tubes. Total RNA was obtained from these samples without waiting and then converted to cDNA. The expression levels of the VEGF and SCUBE1 genes were determined by quantitative real-time polymerase chain re-action (qPCR).Results: SCUBE1 gene expression levels were 2.15 (p=0.015), 1.75 (p=0.799), 2.37 (p=0.037) times higher, and VEGF gene expression levels were 1.71 (p=0.023), 1.75 (p=0.012), 1.85 (p=0.031) times higher in the non-DR, NPDR, and PDR groups compared to the control group, respectively. VEGF gene expression levels were significantly higher in participants with HbA1c levels >= 5.7% compared to those with < 5.7. SCUBE1 and VEGF gene expression levels were significantly higher in participants with fasting plasma glucose (FPG) levels >= 126 mg/dL than those with < 126 mg/dL.Conclusions: As a result, SCUBE1 gene expression levels are higher than VEGF gene expression levels, especially in the PDR group. Therefore, SCUBE1 may contribute to the pathology of DR just like VEGF by generating angiogenesis. However, we believe there isa need for experimental animal model studies with DR examining SCUBE1 gene expression levels in tissue samples.Öğe Bioinformatic analysis of genetic changes CLOCK, BMAL1, CRY1, CRY2, PER1, PER2, PER3, and NPAS2 proteins in HCC patients(Kare Publ, 2023) Ayan, Durmus; Ak, CagatayBackground and Aim: Genes related to the circadian rhythm control various biological processes. The aim of this study was to comprehensively investigate the mutational and mRNA profile of core circadian rhythm genes Materials and Methods: In this study, the gene profile of a total of 369 patients with HCC was examined over the data obtained from the cancer genome atlas database through-cBioPortal. The effects of mutations on protein were examined by scoring the Polymorphism Phenotyping v2, Mutation Assessor, and SIFT-databases. While the association of genes with other genes was determined with the GeneMANIA-database, the association of expression levels in the genes with overall survival (OS) was evaluated with the Kaplan-Meier Plot database. Results: As a result of the analyses, there were a total of 25 mutations. Decreased expression levels of PER1 (1.3e-05), PER3 (p=0.046), and CRY2 (p=1.8e-06) genes were found statistically associated with shorter OS. It was also found that increased expression levels of the PER2 (p=0.045) gene were associated with longer OS, and increased expression levels of the NPAS2 (p=9e-04) gene were associated with shorter OS. Conclusion: In particular, changes in the PER1, PER2, CRY2, and NPAS2 genes may provide possible molecular targets in chemotherapy and immunotherapy for HCC patients.Öğe Bioinformatic analysis of neuropeptide related genes in patients diagnosed with invasive breast carcinoma(Elsevier Ltd, 2024) Yay, Fatih; Ayan, DurmusPurpose: Neuropeptide receptors are expressed in many malignancies. Effectors involved in the action mechanisms of HCRTR1, HCRTR2, NPY4R (PPYR1) may be related to breast cancer (BC). Genes encoding these receptors and PPY and PTPN11 genes were aimed to examine via bioinformatics tools in the BRCA cohort. To our knowledge, this is the first study in which these receptor genes and PP, which have not found much research in BC, are examined together with PTPN11 and analyzed comprehensively in large patient cohorts from public databases. Methods: cBioPortal was used for gene alteration analyses, GeneMania for association analyses with other genes, Kaplan-Meier Plotter for Overall Survival (OS) and Relapse Free Survival (RFS) analyses, UALCAN for methylation analyses, TIMER2.0 for expression analyses, The Human Protein Atlas database for expression validations, TIMER for immune infiltration analyses, WEKA 3.8.6 for diagnostic classification performances of the genes based on Random Forest Classifier and Enrichr-KG for Gene Ontology (GO) Biological Process (BP) and KEGG analysis. Results: 19 (1.9 %) nucleotide changes were found in 996 cases. Missense mutation is most common. Decreased expression levels of the HCRTR1 gene were associated with shorter OS and RFS, but decreased expression levels of the PTPN11 gene were associated with longer OS and RFS. Decreased expression levels NPY4R (PPYR1) gene were associated with shorter RFS. Increased expression levels of HCRTR2 and PPY genes were associated with longer RFS. HCRTR1 and NPY4R (PPYR1) genes were statistically hypermethylated; conversely HCRTR2 and PPY genes were hypomethylated. There was no significant change in PTPN11 gene promoter methylation level. HCRTR1, NPY4R (PPYR1) and PTPN11 gene expressions were downregulated; conversely, HCRTR2 and PPY gene expressions upregulated. Weak correlations were observed between NPY4R (PPYR1) gene expression and CD4+ T Cell, Neutrophil, Dendritic Cell and between PTPN11 gene expression and CD8+ T Cell, Macrophage, Neutrophil, Dendritic Cell infiltrations. Area under the receiver operating characteristics curve values of the 10-fold cross-validation and by splitting the dataset in a ratio of 80:20 models were 0.930 and 0.963 respectively. HCRTR2 and HCRTR1 belong to regulation of cytosolic calcium ion concentration, cellular calcium ion homeostasis GO BPs. Conclusion: In BC patients, increases in HCRTR2 and PPY gene expressions could be considered as positive prognostic factors. Decreases in HCRTR1 and NPY4R (PPYR1) gene expressions could be considered as negative prognostic factors. Decreased expression of PTPN11 gene may have a positive prognostic factor. Changes in existing genes are likely to be both a biomarker and therapeutic target for BC. However, experimental and clinical studies are needed to elucidate the mechanisms underlying these neuropeptide receptors in terms of breast carcinogenesis. © 2024 Elsevier LtdÖğe Bioinformatic assessment of the relationship between breast cancer and autophagy-related protein Ambra1 mutation(Kare Publishing, 2024) Karabay, Umut; Ayan, DurmusObjectives: Autophagy protein 1, regulated by Beclin 1 (Ambra1), promotes tumor formation and development by modulating autophagy. Therefore, in situ intervention in autophagy is a promising new strategy for tumor therapy. We aimed to evaluate the possible effects of changes in the Ambra1 gene on breast cancer (BC) treatment in the BRCA cohort. Methods: The gene profile of a total of 996 patients with BC was examined using data obtained from the Cancer Genome Atlas database via cBioPortal. The effects of mutations on proteins were examined by scoring the Polymor-phism Phenotyping v2, Mutation Assessor, and Sorting Intolerant from Tolerant databases. The association of genes with other genes was determined with the STRING database. Kaplan-Meier Plot database was used by evaluating the overall survival (OS). The promoter methylation was evaluated by the UALCAN database. Results: Eleven mutations were detected. Four of these mutations were truncated proteins. Ambra1 tissue expression levels were upregulated compared to healthy tissue in the BRCA cohort; this was not statistically significant (p>0.05). Decreased Ambra1 expression levels were associated with a shorter OS (p=0.038). Ambra1 promoter region hyperme-thylation was significant in the BRCA cohort compared to healthy tissue (p<0.001). Conclusion: To our best knowledge, our study is the first to examine the relationship between BC and Ambra1 using bioinformatic tools. Ambra1 may be a candidate target molecule within the treatment strategy due to the mutations evaluated in the BRCA cohort, hypermethylation status, and the association of Ambra1 with shorter OS. However, these situations need to be confirmed by further studies. © 2024, Kare Publishing. All rights reserved.Öğe Bioinformatic Investigation of Genetic Changes in Paraoxonase Genes in Breast Cancer and Breast Cancer Subtypes(Galenos Publ House, 2024) Ayan, Durmus; Gul, Mehmet Ali; Karabay, Umut; Bulut, Seyyid MehmetObjective: Among women, breast cancer (BC) is the most prevalent form of cancer. Many molecular targets have been discovered for BC prognosis and treatment. However, new markers still need to be identified, as cancer pathogenesis is triggered by different mechanisms. The aim of this study was to examine the changes in the paraoxonase genes ( PON1 , PON2 , and PON 3 ) involved in the pathogenesis of BC. Materials and Methods: The characteristics of the mutations were evaluated with the Cbioportal database. Kaplan-Meier Plot evaluated recurrence-free survival (RFS). The UALCAN database determined the promoter methylation. Gene expression was evaluated by GEPIA2.0 database. Results: PON1 harbored the most mutations. There was a significant decrease in PON3 expression levels in BC samples compared with healthy samples. PON1 and PON2 expression levels did not differ between BC tissue and normal adjacent tissue. Elevated expression levels of PON1 and PON2 genes were correlated with longer RFS, whereas reduced expression of the PON2 gene showed an association with longer RFS. Moreover, the promoter regions of PON1 and PON 3 were found to be hypermethylated, while the promoter region of PON 2 was found to be hypomethylated. The PON3 promoter region was significantly hypermethylated in luminal and human epidermal growth factor receptor 2 (HER2) + BC subtypes. However, the PON3 promoter region was significantly hypomethylated in the triple negative breast cancer (TNBC) subtype. Conclusion: These results suggest that methylation and expression status of PON3 in BC and BC subtypes (TNBC, luminal and HER2) may indicate a poor prognosis. The PON3 gene could be a negative prognostic marker in BC. However, the results should be supported by prospective studies.Öğe Can immature granulocytes and neutrophil-lymphocyte ratio be biomarkers to evaluate diabetic nephropathy?: A cross-sectional study(Elsevier Science Inc, 2024) Yay, Fatih; Bayram, Ergul; Aggul, Hunkar; Guclu, Ceren Onal; Ayan, DurmusAims: We aimed to examine the role of circulating immature granulocytes (IGs) in assessing Diabetic Nephropathy (DN) mainly and also associations of other leukocyte parameters with DN. Methods: In this retrospective cross-sectional study, a total of 164 Diabetes Mellitus patients were grouped as normoalbuminuric and microalbuminuric according to urinary albumin excretion in the course of admission. Neutrophil-lymphocyte ratio (NLR), IG count (IG#) and IG percentage (IG%) levels were compared between the groups. The value of IG# and IG% levels in detecting microalbuminuria was analyzed with the Receiver operating characteristic (ROC) curve. Results: NLR was remarkably higher in the microalbuminuric group (p = 0.036). Correlation results in the microalbuminuric group were as follows: A feeble positive correlation between neutrophil count (NEU#) and serum creatinine and albumin-to- creatinine ratio (ACR) (p = 0.036, r = 0.261; p = 0.005, r = 0.347, respectively), a feeble positive correlation between lymphocyte count (LYM#) and estimated glomerular filtration rate (p = 0.021, r = 0.285). Correlation results in the normooalbuminuric group were as follows: A feeble positive correlation between NEU# and ACR (p = 0.043, r = 0.204), a feeble negative correlation between LYM# and serum creatinine (p = 0.042, r = -0.205), a poor positive correlation between IG# and ACR and HBA1C% (p = 0.048, r = 0.199; p = 0.004, r = 0.290, respectively), a positive poor correlation between IG% and HBA1C% (p = 0.019, r = 0.235). Area under the ROC curve values for IG# and IG% were not statistically noteworthy in detecting microalbuminuria (p = 0.430; p = 0.510, respectively). Conclusions: IG# and IG% values are insufficient to predict immediate microalbuminuria, but could be considered a weak biomarker for renal damage in normoalbuminuric (<30 mg/g) diabetic patients. Further researches are needed for the use of leukocyte parameters in evaluating DN.Öğe Changes in arginine metabolism in advanced Alzheimer?s patients: Experimental and theoretical analyses(Elsevier, 2023) Saria, Ismail; Ersan, Serpil; Ozmen, Esma; Ayan, Durmus; Ersan, Erdal; Berisha, Avni; Kayae, SavasLimited data obtained in studies conducted in recent years suggest that changes in arginine metabolism may be associated with the pathogenesis of Alzheimer's disease (AD). However, the underlying mecha-nisms of this pathway's effects on the disease are not clear and there are conflicting data. Therefore, in this study, we aimed to determine the levels of L-arginine and its important metabolites and enzymes involved in the pathway in advanced AD patients to examine the change in L-arginine metabolism as inclusively as possible.Serum and plasma samples were obtained from 51 patients diagnosed with advanced AD and 30 volunteer controls. Arginase, Ornithine Decarboxylase (ODC), Arginine Decarboxylase (ADC), and Agmati-nase levels in serum samples were determined by enzyme-linked immunosorbent assay (ELISA) and, L- arginine, Ornithine and nitric oxide (NO) levels were determined by colorimetric method. Agmatine levels were measured by high-performance liquid chromatography in the plasma samples of the study groups. Furthermore, in silico molecular docking studies were performed to get preliminary knowledge about the binding interactions of the agmatine with various targets such as AChE, butyrylcholinesterase (BuChE), BACE-1 and tau protein kinase 1 which play an important role in AD pathogenesis.Agmatine and L-arginine levels were found to be significantly lower in the patient group than in the control group. Milder but not statistically significant reductions were observed in all other param-eters we measured involved in L-arginine metabolism. Furthermore, NO levels were found to be sig-nificantly lower in men with advanced AD patients than in control men. It has been analyzed that agmatine ligand interacts effectively with the studied proteins which play an important role in AD pathogenesis; these interactions were significant and, based on the docking score, occurred in the fol-lowing order: butyrylcholinesterase (PDB id: 1P0I) > Human acetylcholinesterase > Human tau-protein kinase I.In conclusion, in advanced AD patients, the activity of the L-arginine pathway decreased in gen-eral, especially agmatine formation, and this may be due to the decrease in L-arginine levels. Therefore, arginine de novo synthesis may be decreased in advanced AD patients. Furthermore, according to the MolDock binding score, agmatine ligand has a high binding affinity for proteins involved in AD manage-ment and/or pathogenesis. Therefore, agmatine may play a role in the pathogenesis of AD by inhibit-ing the activity of these proteins. However, additional comprehensive studies are needed to clarify these thoughts.(c) 2023 Elsevier B.V. All rights reserved.Öğe Comparison of the diagnostic accuracy of CKD-EPI cystatin-C, CKD-EPI creatinine and 24-hour creatinine clearance for estimating GFR: a preliminary study(Cukurova Univ, Fac Medicine, 2021) Ucucu, Suheyl; Ayan, Durmus; Serin, ErdincPurpose: Serum cystatin C level is a specific marker to estimate the glomerular filtration rate (GFR). Due to this specificity, we assume that GFR estimations based on cystatin C have higher diagnostic performances than GFR estimations using other biomarkers. In this study, we aimed to compared the diagnostic performances of CKDEPI cystatin C equation, CKD-EPI creatinine equation and 24-hour creatinine clearance to estimate GFR. Materials and Methods: A total of 130 participants who consisting of 101 acute and chronic renal disease patients and 29 healthy volunteers, who applied to the Nephrology Clinic, have been included in our study. Their urine creatinine levels and serum creatinine levels were measured by the colorimetric-Jaffe method, and cystatin C was by the nephelometric method. Results: There was a statistically significant relationship between CKD-EPI cystatin C, between CKD-EPI creatinine and standard creatinine clearance. The Area Under the Receiver Operating Characteristics curve (AUROC) was found to be 1, 0.995, and 0.954 respectively. Conclusion: According to the results, we think that serum cystatin C levels will present earlier findings in GFR decrease and may be a more effective marker than serum creatinine and standard creatinine clearance in the early period.Öğe Decreased butyrylcholinesterase and oxytocin levels versus increased dopamine levels in advanced Alzheimer’s patients(2022) Ayan, Durmus; Özmen, Esma; Erşan, Serpil; Sari, İsmail; Erşan, Etem Erdal; Söylemez, SibelAim: In this study, it was aimed to examine the serum levels of dopamine, oxytocin, and butyrylcholinesterase (BchE) enzyme activity in advanced Alzheimer’s disease (AD). Materials and Methods: For our preliminary study, a total of 40 participants were included in the study. 20 of the participants consisted of patients and the other 20 made up the control group. In the serum samples of the patient and control group, the lev- els of dopamine and oxytocin were measured by Enzyme-Linked Immuno Sorbent As- say (ELISA) method, while the BchE activity was measured by the spectrophotometric method. Results: We found that serum BchE and oxytocin levels in the AD group were sta- tistically lower than the controls (p<0.01, p=0.027), whereas serum dopamine levels in the AD group were statistically higher than the control group (p=0.02). Furthermore, we analyzed that there was no significant correlation between the measured parameters (p>0.05). Conclusion: Our results indicate that the decrease in BchE activity and oxytocin levels and the increase in dopamine levels may have a relationship with the progression of the disease in the AD group. However, we believe that studies are needed with larger numbers of patients with different levels of AD.Öğe Examination of the relationship between variants in the gene region encoding soluble epoxy hydrolase enzyme hydrolytic activity and type 2 diabetes(Bayrakol Medical Publisher, 2024) Ozmen, Esma; Ayan, Durmus; Onder, Cagatay Emir; Akin, Dilara Fatma; Kose, Burcu; Sari, Ismail; Yazici, CevatAim: Epoxyeicosanoids function as signal mediators in critical biological processes such as platelet aggregation, vasodilation, and anti -inflammation. With all these properties, Epoxyeicosanoids have been associated with many diseases. Metabolism of epoxyeicosanoids is carried out by soluble epoxide hydrolase enzymes, and as a result dihydroxyeicosatrienoic acids, which is a less active form than epoxyeicosanoids, are formed. In our study, SNP/mutation analysis was performed in the gene region responsible for the hydrolase activity of EPHX2, which encodes the soluble epoxide hydrolase enzyme. Material and Methods: The study consisted of two groups: a healthy group with 30 individuals and a T2DM patient group with 40 individuals. SNP/mutation analysis in the gene region responsible for the hydrolase activity of EPHX2 in both groups was performed by Sanger sequencing using appropriate primers. Result: A total of 12 mutations were detected in both groups as a result of Sanger sequencing. Two of the 12 detected mutations were missense mutations (p.Asn359Thr and p.Ser412Arg). It was determined that the pathogenic scores of these mutations were close to 1 for Poly-Phen2 and 0-100 for SNAP. In addition, two (c.1058+165C>T and c.1058+146G>A) SNPs were detected in the intron we observed in the T2DM group, which has not been detected and defined before in our study. Discussion: We believe that the mutations detected in our study, especially those that cause amino acid changes, may cause T2DM susceptibility in healthy individuals and progression of the disease pathogenesis in the T2DM group. We think that the detection of c.1058+165C>T and c.1058+146G>A mutations for the first time in our study will guide the next studies.Öğe NÖTROFİL/LENFOSİT ORANI PREDİYABETİK HASTALARDA İNSÜLİN DİRENCİ TAHMİNİNDE HOMA-IR İNDEKSİNE ALTERNATİF BİR BELİRTEÇ OLABİLİR Mİ?: BİR RETROSPEKTİF ÇALIŞMA(2023) Ayan, Durmus; Balcı, Tevfik; Aydoğan, Kader Zeybek; Özmen, Esma; Karabay, UmutAmaç: Çalışmamızda prediyabet ve diyabet olmayan hastalarda HOMA-IR indeksi ile Trigliserid/Glukoz (TyG) indeksi, LDL-K/HDL-K oranını, Trigliserid/ HDL-K oranını ve Nötrofil/ Lenfosit Oranını (NLO) bir biri ile karşılaştırmayı amaçladık. Gereç ve Yöntem: Çalışmamıza Niğde Ömer Halisdemir Üniversitesi Eğitim ve Araştırma Hastanesine 2019-2021 yılları arasında başvuran 18-75 yaş arasında 673’ü kadın 890’ü erkeklerden oluşan toplam 1433 hasta dahil edilmiştir. HOMA-IR indeksi, TyG indeksi, LDL-K/HDL-K oranı, Trigliserid/ HDL-K oranı, NLO hesaplamaları analizi yapılan testler vasıtasıyla yapılmış tır. Bulgular: Bulgularımıza göre diyabetik olmayan grupta Trigliserid/HDL-K oranının ve pre-diyabetik grupta NLO’nun rutinde kullanılan yöntem olan HOMA-IR indeksine göre hem de IR tahmininde kullanılan diğer indekslere göre duyarlılığı ve özgüllüğünün daha yüksek olduğu tespit edildi. Ayrıca diyabetik olmayan grupta Trigliserid/HDL-K oranı ile HOMA-IR indeksi arasında pozitif anlamlı bir korelasyon sonucuna ulaşılırken (r=0,219; p<0,001), pre-diyabetik grupta NLO ile HOMA-IR indeksi arasında anlamlı bir korelasyon sonucu bulunamadı (r=0,034; p=0,290). Sonuç: Sonuç olarak, NLO pre-diyabetik hastalarda IR tahmininde HOMA IR yerine alternatif bir parametre olabilir. Ancak bunun referans yöntem ile verifikasyonu yapılan prospektif çalışmalar ile doğrulanması gerektiği düşüncesindeyiz.Öğe Prevalence of Hemoglobinopathies in Premarital Screening in the Province of Nigde, Turkey(Taylor & Francis Ltd, 2023) Seydel, Gonul Seyda; Ayan, Durmus; Balci, Tevfik; Bayraktar, Muhammet; Gunturk, InayetHemoglobinopathies are one of the most widespread hereditary disorders in Turkey. The present study aimed to determine the prevalence of hemoglobinopathies in the Nigde province of Turkey. This study was conducted with 2013 individuals who applied for the premarital screening, between January 2019 and December 2021. The complete blood count was measured by an automated hematology analyzer. The types of hemoglobin were determined by high-performance liquid chromatography. A total of 2013 individuals including 951 (47.2%) females and 1062 (52.8%) males, were screened within the premarital screening program, and 67 (3.3%) of them were migrants. 53 out of 2013 (2.63%) individuals were identified as beta thalassemia carriers, and five of them were migrants including two from Afghanistan, two from Iran, and one from Georgia. HbC was observed in two cases, a couple from Syria (0.1%), HbD in two cases (0.1%), HbE in one case from Thailand (0.05%), HbS-beta-thalassemia in one case (0.05%), delta-beta thalassemia in one case (0.05%), and unidentified structural variant in one case (0.05%). Moreover, 183 individuals (9.1%) were considered to have iron deficiency, alpha-thalassemia, or silent beta-thalassemia carrier. These results indicate that the province of Nigde is a relatively risky region regarding hemoglobinopathies. Geographic location and immigrant population may have slightly affected the local prevalence of hemoglobinopathies and could be taken into consideration to ensure the effective implementation of the hemoglobinopathy prevention program.
