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    Evaluation of the Antioxidative and Protective Effects of Thymoquinone in a Pentylenetetrazole-induced Epilepsy Model
    (2025) Pala, Mukaddes; Meral, Ismail; acikgoz, nilgun; Hanikoglu, Ferhat; Kucukcetin, Ikbal Ozen; OZDEM, SEBAHAT; Yılmaz, Şenay Görücü
    Objective: Epilepsy is a common neurological disorder that leads to neuronal excitability and provokes various forms of cellular reorganization in the brain. We investigated the antioxidative and protective effects of thymoquinone (TQ) from the perspective of biomarkers in serum samples of rats using a pentylenetetrazol (PTZ)-induced epilepsy model. Methods: Twenty-one adult, male Wistar albino rats were randomly assigned to three groups. (1) Control (n=6); 0.5 mL saline (i.p.). (2) PTZ (n=7); 35 mg/kg PTZ (i.p.). (3) TQ+PTZ (n=8); 20 mg/kg TQ orally (p.o.)+ 35 mg/kg PTZ (i.p.). To induce kindling, PTZ was injected at a subconvulsive dose (35 mg/kg, i.p.) every other day for 24 days. Then, on the 26th day of the study, a single loading dose of PTZ (75 mg/kg) was injected into the animals. Seizure severity was evaluated with the Racine scale. Blood samples were taken from rats under anesthesia by the cardiac puncture method. The serum levels of myeloperoxidase (MPO), ischemia-modified albumin, total oxidant status (TOS), total antioxidant status (TAS), advanced oxidation protein products (AOPP), total sulfhydryl (T. sulfhydryl), and paraoxonase-1 (PON-1) were evaluated colorimetrically by the ELISA method, using a spectrophotometer. Results: A significant relationship was found between PTZ and TQ+PTZ groups for TAS (p=0.020), TOS (p=0.006), AOPP (p=0.015), and T. sulfhydryl (p=0.009). MPO and PON-1 were not significant (p>0.05). Conclusion: TQ may be used as an adjuvant agent in the regulation of epileptic seizures with its antioxidative and protective functions in the PTZ-induced epilepsy model. At the same time, serum parameters can potentially be diagnostic tools for the effective managing of treatment.
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    How does social media impact the number of citations? An altmetric analysis of the 50 most-cited MicroRNA articles
    (Gaziantep Üniversitesi, 2021) Pala, Mukaddes; Demirbilek, Mahmut; Pala Açıkgöz, Nilgün; Dokur, Mehmet
    Objective: Altmetric analysis is web-based a metric analysis. Social media platforms affect medical literature over the last few years. The altmetric Attention Score (AAS) is an automatically calculated metric for monitoring social media. This study aimed to determine the correlation between AAS and the number of citations received from important articles published in the last 11 years with microRNAs. Methods: MicroRNA as a search term was entered into the Web of Science database to identify all articles. The most 50 cited articles were analyzed by Topic, Journal Name, First Author, Publication Year, Citation, Average Citation Per Year (ACPY), Impact Factor (IF), Quartile (Q) Category, H Index, and AAS. Results: Altmetric explorer identified 45.911 articles as being referred to online. Correlation analysis revealed that there was a weak correlation between AAS and the number of citations (p<0.15), while a very strong correlation was found between the number of citations and ACPY (p<0.01). Conclusion: These results give some clues about the articles studied did not lose their currency. They are cited regularly each year so they are very popular in academia. This study provides a detailed list of 50 most cited microRNA articles and social media interest using the Altmetric.com database. miRNAs can be used in the diagnosis, prognosis, or treatment of various diseases.
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    mTOR signaling pathway genes effect in COVID-19 infection
    (Inonu University, 2024) Pala, Mukaddes; Yılmaz, Şenay Görücü; Tanriverdi, Elif Seren; Gunduz, Ayten; Delen, Leman Acun; Ozturk, Dilara Altay; Öterkuş, Mesut
    Coronavirus disease 2019 (Covid-19) is an infectious disease that causes severe acute respiratory illness caused by coronavirus 2 (SARS-CoV-2). SARS-CoV-2 uses host-specific metabolic pathways, including mTOR. The mTOR pathway is hyperactive in viral respiratory tract infections and contributes positively to viral replication. 100 samples were evaluated, 50 patients (Female=23, Male=27), and 50 controls (Female=29, Male=21). The patients were individuals who were COVID-19 positive. We detected expression changes of 5 genes in mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) (MLST8, mTOR, RPTOR, MAPKAP1 and RICTOR). Serum samples were obtained from all patients. The expression changes of mTORC1 and mTORC2 Complex genes were evaluated with Real-time PCR method. Receiver operating curve (ROC) analysis was performed to define the diagnostic power of these genes. Expression changes of five genes in the mTORC1 and mTORC2 complex were statistically significant (p =0.001) and upregulated in serum. The area under the ROC Curve values indicating the diagnostic power of genes were 0.948, 0.771, 0.851, 0.798, and 0.805, respectively. These genes may be candidate for treatment targets. The high discriminative power of these genes in patients from controls indicates their diagnostic potential in serum samples.
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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, 2022) Pala, Mukaddes; Meral, İsmail; Açıkgöz Pala, Nilgün; Taşlıdere, Elif; Karaca Okur, Sema; Acar, Şeyma; Akbaş, Sabri
    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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    PTZ KINDLING MODEL: EVALUATION OF EEG FACTOR AND BIOCHEMISTRY PARAMETERS UNDER THE INFLUENCE OF RAMELTEON
    (2024) Pala, Mukaddes; kozan, ramazan; Kose, Hayrullah; Yılmaz, Şenay Görücü
    Many selective synthetic melatonin receptor agonists have anticonvulsant/anti-epileptogenic properties. These agonists bind to melatonin receptor 1 (MT1) and receptor 2 (MT2), causing their activation. Therefore, we evaluated the anticonvulsant effect of Ramelteon (RMLT) as a melatonin agonist in the PTZ (Pentylenetetrazol)-kindling model. In the study, 36 male Wistar Albino rats were assessed in 6 groups (Sham, PTZ, dimethylsulphoxide (DMSO), Valproic acid (VPA) (150 mg/kg) + PTZ, RMLT (30 mg/kg)+PTZ, VPA+RMLT+PTZ). Cortical electroencephalography (EEG) data were recorded for all groups. Seizures were scored according to the Racine scale. Seizure scores and onset times of the first myoclonic movements were compared in EEG traces. Total antioxidant status (TAS), total oxidant status (TOS), catalase, myeloperoxidase (MPO), and Thiol levels were measured in serum samples. Also, Calcineurin (CaN), Neuropeptide-Y (NPY), Neuron Specific Enolase (NSE), and S100B levels were measured in brain tissue samples. There was a significant difference between the PTZ and PTZ+Valproic acid+RMLT groups for the onset of the first myoclonic movements and the rate of spikes in the EEG traces in Racine's convulsion stages (P 0.05). RMLT has anticonvulsant properties. Additionally, the receptor preference of RMLT can be investigated.
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    The effect of regularly performed moderate-intensity exercise program on thiol/disulfide homeostasis, and ischemia-modified albumin
    (2022) Pala, Mukaddes; Altan, Mehmet; Hanikoglu, Ferhat; neselioglu, salim; EREL, Ozcan; Metin, Gökhan
    Aim: Thiol/disulfide homeostasis is an indicator of oxidative stress and antioxidant capacity. Ischemia-modified albumin (IMA) is an important marker for both oxidative stress and ischemia. We aimed to evaluate the possible effects of regularly performed moderate-intensity exercise on thiol/disulfide homeostasis, and IMA levels.Methods: Sprague Dawley rats were used. The study was composed of an Exercise group (EG, n=9) and Control group (CG, n=6). A 10-weeks swimming exercise was performed. Thiol/disulfide homeostasis measurement method was used in this study. IMA levels were measured by a cobalt-albumin binding method.Results: In the EG, total thiol levels were significantly higher compared to the CG (p<0.01). The disulfide/total thiol ratio was lower in the EG compared to the CG (p<0.01). We observed that there was a slight increase in IMA levels in EG (p=0.18). This increase was not statistically significant.Conclusion: Regularly performed moderate-intensity exercise has increased native and total thiol levels. Increase of thiol levels can prevent oxidative stress. Regularly performed moderate-intensity exercise programs appear to provide favourable effects on oxidative stress. 
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    The Effects of MicroRNAs on Cardiomyopathy in a Rat Model of Streptozotocin-induced Diabetes Mellitus
    (2025) Doğan, Aslıhan Şeyda; Pala, Mukaddes; Yılmaz, Şenay Görücü; BECEREN, AYFER; Karabulut, Aydın; Polat, Yalçın; ELÇIOGLU, HATICE KÜBRA
    Objective: Diabetic cardiomyopathy (DCM) is characterized by complex pathophysiological events. miRNAs play a role in the DCM. In our study, the potential of miRNAs as a biomarker in the diagnosis and treatment of DCM was evaluated in the diabetes model induced by streptozotocin in rats. Methods: Therefore, miRNAs obtained from rat heart tissue were analyzed by microarray, and twelve miRNAs (rno-miR-200c-3p, rno-miR-129-5p, rno-miR-150-3p, rno-miR-3584-5p, rno-miR-34c-3p, rno-miR-342-3p, rno-miR-466b-3p, rno-miR-466c-3p, rno-miR-31a-3p, rno-miR-15b-5p, rno-miR-196b-3p, and rno-miR-208a-5p) with changed expression levels were validated by real-time polymerase chain reaction analysis. Results: As a result of the validation, it was determined that three miRNAs (rno-miR-15b-5p, rno-miR-196b-3p, and rno-miR-208a-5p) were downregulated, one miRNA (rno-miR-200c-3p) was upregulated (p<0.05). MiR-15b-5p, miR-196b-3p, miR-200c-3p, and miR-15b-5p are involved in the regulation of DCM, and the GRAP2 gene is one of the possible targets of these miRNAs. Conclusion: miR-200c-3p has diagnostic value and may be a biomarker candidate.