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Öğe Deep phenotyping of miRNAs in exercise-induced cardiac hypertrophy and fibrosis(Indian Acad Sciences, 2023) Pala, Mukaddes; Yilmaz, Senay Gorucu; Altan, Mehmet; Sonmez, Osman Fuat; Dincer, Sensu; Mengi, Murat; Karabulut, AydinCardiac hypertrophy (CH) is an adaptational enlargement of the myocardium, in exposure to altered stress conditions or in case of injury which can lead to heart failure and death. MicroRNAs (miRNAs) are non-coding RNAs that play a significant role in modulating gene expression. Here, we aimed to identify new miRNAs effective in an experimental CH model and to find an epigenetic biomarker that could demonstrate therapeutic targets responsible for the pathology of heart tissue and serum. In this study, Sprague-Dawley male rats were divided into the training group (TG, n=9) and the control group (CG, n=6). Systolic and diastolic dimensions of the left ventricle and myocardial wall thickness were measured by echocardiography to assess CH. After the exercise program of the rats, miRNA expression measurements and histological analyses were performed. The 25,000 genes in the rat genome were searched using microarray analysis. A total of 128 miRNAs were selected according to the fold change rates, and nine miRNAs were validated for expression analysis. The terminal deoxynucleotidyl transferase dUTP nick (TUNEL) method was used to detect apoptotic cells. Cell proliferation was evaluated by the proliferative cell nuclear antigen (PCNA) method. Necrosis, bleeding, and intercellular edema were detected in TG. The mean histopathological score was higher in TG (p=0.03). There were rarely positive cells for apoptosis of both groups in cardiomyocytes. In the receiver characteristic curve analysis (ROC), the heart tissue rno-miR-290 had an area under the curve (AUC) of 0.920 with 100% sensitivity and 89.90% specificity (p=0.045), rno-miR-194-5p had AUC of 0.940 with 83.33% sensitivity and 100% specificity (p=0.003), and the serum rno-miR-132-3p AUC was 0.880 with 66.67% sensitivity and 100% specificity (p=0.004) in TG. miR-194-5p was used as a therapeutic target for remodeling the cardiac process. While miR-290 contributes to CH as a negative regulator, miR-132 in serum is effective in the pathological and physiological cardiac remodeling process and is a candidate biomarker.Öğe Effects of Tianeptine Pretreatment on Stress-Induced Trace Element Alterations in Rats(Kure Iletisim Grubu A S, 2009) Karakoc, Yunus; Kasar, Muzaffer; Mengi, Murat; Yildirim, Ejder Akgun; Yurdakos, Ertan; Barutcu, U. BoraIntroduction: Although the alterations in trace elements levels were shown in chronically restrainted rats, the association between stress-induced changes in trace element levels and the effects of psychopharmacological agents has not been well documented yet. Tianeptine has been a widely used antidepressant in experimental studies investigating stress related behavioral changes. In this study, we aimed to search the effects of tianeptine pretreatment on stress-induced trace element alterations in rat brain. Methods: The animals were divided into three groups: controls (n=9), chronic restraint stress group (n=7), chronic restraint stress+tianeptine group (n=9). Restraint stress procedure was 6 hours per day for 21 consecutive days and the rats had either intraperitoneal 1 ml saline injection or 10 mg/kg tianeptine twice a day within an interval of 8 hours. The rats were decapitated 30 minutes after the last restraint period. Following digestion procedures, Zn, Cu and Fe levels of the frontal lobe, temporal lobe, brain stem, liver and spleen were determined by flame atomic absorption spectrophotometer. Results: We found that Cu and Fe levels were significantly increased in the frontal lobe, temporal lobe and brain stem whereas Zn levels did not change significantly following chronic restraint stress. With tianeptine pretreatment Zn levels were significantly increased in all tissues investigated, whereas Cu and Fe levels were significantly decreased when compared with those of control and chronic restraint stress groups. Conclusions:We assume that the decreases in Cu and Fe levels might be the result of decreased induction of metallothionein-I due to inhibition of stress-evoked HPA axis by tianeptine. Increased levels of Zn might be associated with possible interaction between Zn and tianeptine through NMDA receptors. Consequently, it may be suggested that the effects of tianeptine pretreatment on trace element levels might account for its preventive effects on stress-induced behavioral disturbances.