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    Investigation of the acute effect of the synthetic hemodialysis membrane on the expression of XRCC1 and PARP1 in chronic hemodialysis patients
    (Sage Publications Ltd, 2024) Unal, Selin; Yalin, Serkan Feyyaz; Altiparmak, Mehmet Riza; Batar, Bahadir; Guven, Mehmet
    Objective: The interaction between blood from end-stage renal failure patients undergoing hemodialysis treatment and the hemodialysis (HD) membranes used may lead to DNA damage, contingent upon the biocompatibility of the membranes. Given that this process could impact the disease's course, it is crucial to assess the efficacy of DNA repair mechanisms.Methods: In our study, we investigated the gene expression levels of XRCC1 and PARP1 enzymes, which are involved in the base excision repair (BER) repair mechanism crucial for repairing oxidative DNA damage, in 20 end-stage renal disease (ESRD) patients undergoing HD treatment both before and after dialysis sessions. Additionally, we compared our findings with those from 20 healthy controls. We assessed gene expression levels using real-time polymerase chain reaction (qRT-PCR).Results: We observed that the HD process utilizing a polysulfone membrane did not impact the expression levels of genes. However, we noted a lower expression level of the PARP1 gene in ESRD patients undergoing HD compared to the control group (0.021 +/- 0.005 vs 0.0019 +/- 0.0013, p = 0.0001).Conclusion: Although our study findings indicate that HD membranes do not affect gene expression overall, the specific decrease in PARPI gene expression suggests that the effectiveness of the BER DNA repair mechanism is impaired in ESRD patients, which may play a significant role in the progression of the disease.
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    MicroRNAs in cancer management
    (Nova Science Publishers, Inc., 2018) Batar, Bahadir; Ozoran, Emre; Guven, Mehmet
    MicroRNAs (miRNAs) are small non-coding single-stranded RNA molecules of 19- 25 nucleotides in length. miRNAs' main function is the post-transcriptional regulation of gene expression through messenger RNA (mRNA) repression or degradation by binding to 3' untranslated region (3'UTR) of target mRNAs. More than 60% of human proteincoding genes contain miRNA-binding regions within their 3' UTRs. miRNA-mRNA interactions are mediated by a 6 to 8 nucleotide long seed sequence in the miRNA 5' end. miRNAs can target different mRNAs. miRNAs have been linked to the etiology, initiation, progression, and prognosis of all kinds of human cancers. Experimental evidence showed that dysregulated miRNAs affect the hallmarks of malignant cells including, self-sufficiency in growth signals, evading apoptosis, sustaining proliferative signals, inducing angiogenesis, activating invasion, and metastases. miRNAs can have oncogenic or tumor suppressive function in the majority of cancers. Tumor suppressor miRNAs target cellular oncogenes and are downregulated in cancer. Oncogenic miRNAs regulate tumor suppressor genes and are overexpressed in cancer. Numerous human miRNA genes are located at fragile sites or in genomic regions that are deleted, amplified or translocated in cancer. miRNA expression is dysregulated in human malignancies through various mechanisms, containing miRNA gene amplification or deletion, aberrant transcriptional control of miRNAs, epigenetic alterations and defects in the miRNA biogenesis machinery. In addition to genomic alterations, dysregulated miRNA expression could be due to alterations in tumor suppressor or oncogenic transcription factors that function as transcriptional activators or repressors to control pri-miRNA transcription, such as c-myc and p53. Genome-wide profiling studies revealed that miRNA expression signatures are related with tumor type, tumor grade and clinical outcomes, so miRNAs could be potential candidates for diagnostic and prognostic biomarkers and development of therapeutic strategies. © 2018 Nova Science Publishers, Inc. All rights reserved.
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    The Long-Term Impact of Ionizing Radiation on DNA Damage in Patients Undergoing Multiple Cardiac Catheterizations
    (Humana Press Inc, 2023) Cimci, Murat; Batar, Bahadir; Bostanci, Merve; Durmaz, Eser; Karayel, Bahadir; Raimoglou, Damla; Guven, Mehmet
    Ionizing radiation (IR) exposures have increased exponentially in recent years due to the rise in diagnostic and therapeutic interventions. A number of small-scale studies investigated the long-term effect of IR on health workers or immediate effects of IR on patients undergoing catheterization procedures; however, the long-term impact of multiple cardiac catheterizations on DNA damage on a patient population is not known. In this study, the effects of IR on DNA damage, based on micronuclei (MN) frequency and 8-hydroxy-2 & PRIME;-deoxyguanosine (8-OHdG) as markers in peripheral lymphocytes, were evaluated in patients who previously underwent multiple cardiac catheterization procedures. Moreover, genetic polymorphisms in genes PARP1 Val762Ala, OGG1 Ser326Cys, and APE1 Asn148Glu as a measure of sensitivity to radiation exposure were also investigated in the same patient population. The patients who underwent & GE; 3 cardiac catheterization procedures revealed higher DNA injury in comparison to the patients who underwent & LE; 2 procedures, documented with the presence of higher level of MN frequency (6.4 & PLUSMN; 4.8 vs. 9.1 & PLUSMN; 4.3, p = 0.002) and elevated serum 8-OHdG levels (33.7 & PLUSMN; 3.8 ng/mL vs. 17.4 & PLUSMN; 1.9 ng/mL, p = 0.001). Besides, OGG1 Ser326Cys and APE1 Asn148Glu heterozygous and homozygous polymorphic types, which are related with DNA repair mechanisms, were significantly associated with MN frequency levels (p = 0.006 for heterozygous and p = 0.001 for homozygous with respect to OGG1 Ser326Cys, p = 0.007 for heterozygous and p = 0.001 for homozygous with respect to APE1 Asn148Glu). There was no significant difference in terms of PARP1 Val762Ala gene polymorphism between two groups.