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    Downregulatory effect of miR-342-3p on epileptogenesis in the PTZ-kindling model
    (Springer, 2022) Pala, Mukaddes; Meral, Ismail; Acikgoz, Nilgun Pala; Yilmaz, Senay Gorucu; Okur, Semra Karaca; Acar, Seyma; Polat, Yalcin
    Background Epileptogenesis is a process that results in neurons firing abnormally, causing seizures. Increasing evidence has shown that miRNAs expressed in the epileptic hippocampus are involved in epileptogenesis. We demonstrated the expression changes of miRNAs that may be effective in epileptogenesis in silico analysis in the kindling model created with Pentylenetetrazole (PTZ). Thus, we aimed to identify the target genes responsible for epileptogenesis. Methods and results Fifteen male Wistar-albino rats (200-230 g) were randomly divided into two groups control (n = 6) and PTZ (n = 9). The control group received 0.5 ml saline, and the PTZ group (35 mg/kg i.p.) intraperitoneally (i.p.) (11 times, every other day) to induce tonic-clonic seizures. Seizures were observed and scored 30 min after PTZ injection. After the last dose of PTZ (75 mg/kg) administration, the hippocampus tissues of the rats were removed by anesthesia. Analysis of miRNAs was performed with the Affymetrix gene chip miRNA sequence (728 miRNA) and confirmed by the Real-Time Polymerase Chain Reaction (Real-Time PCR) method (29 miRNAs). We evaluated the expression change of the target gene of miRNA, whose expression change was detected using in silico analysis, by q-RT PCR. Eight miRNAs with changes in expression were detected. Of these miRNAs, miR-342-p was downregulated in the PTZ group and was statistically significant (p < 0.005). Ultimately, we determined that the target gene of miR-342-p is a metabotropic glutamate receptor 2 (GRM2) and that GRM2 expression is upregulated. Conclusions Downregulation of miR-342-3p in the PTZ kindling model may result in the upregulation of GRM2.
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    Pentylenetetrazole-induced kindling rat model: miR-182 and miR-27b-3p mediated neuroprotective effect of thymoquinone in the hippocampus
    (Taylor & Francis Ltd, 2022) Pala, Mukaddes; Meral, Ismail; Acikgoz, Nilgun Pala; Yilmaz, Senay Gorucu; Taslidere, Elif; Okur, Sema Karaca; Acar, Seyma
    Objectives: Epilepsy is a neurological disease that pathologically affects brain functions. The epileptic hippocampus has modified microRNA(miRNA) levels. Therefore, we aimed to evaluate the neuroprotective effect of thymoquinone (TQ) in PTZ-induced epilepsy and to demonstrate the overlap between miRNA and mRNA expression profiles. Methods: Male adult Wistar albino rats (200-230 g, n = 20) were divided into three groups as control (n = 6), PTZ (n = 7), and TQ + PTZ (n = 7). The PTZ kindling model was created by injecting PTZ in sub convulsive doses to rats on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, and 24 of the study into animals. Clonic and tonic seizures were induced by injecting a convulsive dose of PTZ on day 26 of the study. Rats in the TQ+PTZ group were treated by oral gavage with a 20 mg/kg TQ 2 h before each PTZ injection. The rats in the control group were treated with 0.5 ml saline. Seizure severity was evaluated with the Racine scale. The genes and signaling pathways targeted by miRNAs were determined by bioinformatics analysis. Results: In the rat hippocampus, mature 728 miRNAs were analyzed by microarray and the nine miRNA were verified by quantitative Real-Time PCR. rno-miR-182 and rno-miR-27b-3p were up-regulated in the PTZ group and down-regulated in the TQ + PTZ group. Discussion: In the PTZ kindling epilepsy model, the expression of these two miRNAs was regulated by TQ and exerted a neuroprotective effect by controlling the activities of target genes.
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    The Prolidase Activity, Oxidative Stress, and Nitric Oxide Levels of Bladder Tissues with or Without Tumor in Patients with Bladder Cancer
    (Springer, 2017) Gecit, Ilhan; Eryilmaz, Recep; Kavak, Servet; Meral, Ismail; Demir, Halit; Pirincci, Necip; Gunes, Mustafa
    This study was designed to evaluate the malondialdehyde (MDA), glutathione (GSH) and nitric oxide (NO) levels, and also prolidase, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) enzyme activities in malignant and benign cancers of bladder tissue. A total of 59 patients admitted to our clinic due to microscopic or macroscopic haematuria, were prospectively included in the study. Because of some reasons (no request to participate in the study, the inability to reach, other malignancies, alcohol consumption, metabolic disease), eight patients were excluded from study. Of the 51 patients, 25 were bladder tumor patients, and 26 were patients without cancers. The bladder tissue samples were obtained from all patients under anesthesia (spinal, epidural or general) for the measurement of MDA, GSH and NO levels, and prolidase, GSH-Px and SOD enzyme activities. Among the patients with bladder cancers, 7 patients were females and 18 patients were males, with an average age of 68.4 +/- 2.49. Among patients without tumors, 6 patients were females and 20 patients were males, with an average age of 58 +/- 2.05. In patients with bladder tumors, the oxidants (MDA, NO, prolidase) were higher, and the antioxidants (SOD, GSH, GSH-Px) were lower than those in patients without tumors. It was concluded that the oxygen free radicals play a role in the etiology of bladder cancers similar to many other tumors and inflammatory conditions. Therefore, we assume that antioxidants may provide benefits in the prevention and treatment of bladder cancer.