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    Bioinformatic analysis of neuropeptide related genes in patients diagnosed with invasive breast carcinoma
    (Elsevier Ltd, 2024) Yay, Fatih; Ayan, Durmus
    Purpose: 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 Ltd
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    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, Durmus
    Aims: 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.
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    Verification of enzymatic ethanol analysis method and method comparison with headspace gas chromatography
    (Walter De Gruyter Gmbh, 2022) Ozturk, Alpaslan; Temel, Ismail; Yalcindag, Ali; Ucar, Fatma; Yay, Fatih
    Objectives This study aimed to verify the enzymatic ethanol analysis method and compare the technique with headspace gas chromatography (HS/GC). Materials and methods The limit of the blank, limit of detection, and limit of quantification, precision, linearity, and accuracy of the enzymatic process were evaluated based on the data obtained. In addition, a method comparison was made between the enzymatic method and the HS/GC analysis method. Results It was seen that the enzymatic method was linear in the range of 14-450 mg/dL, the coefficient of variation and bias values ranged between 0.5-1.09% and 4.52-9.78%, respectively. The quantitative accuracy was 2.13% and 2.23% at concentrations of 41.16 and 95.82 mg/dL, respectively. When the regression analysis was performed between the results obtained using the enzymatic alcohol dehydrogenase (ADH) and HS/GC methods, y=0.966x + 2.084 linear relationship formula and regression coefficient of r(2)=0.9987, it was found that it showed a good agreement at a confidence interval of 5%. Conclusions The findings showed that the enzymatic method had good linearity, excellent precision, and a high correlation with the higher-order comparator method, the HS/GC method, in the ethanol analysis.