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Öğe Decoding myasthenia gravis: advanced diagnosis with infrared spectroscopy and machine learning(2024) Severcan, Feride; Özyurt, İpek; Doğan, Ayça; Severcan, Mete; Gurbanov, Rafig; Küçükcankurt, Fulya; Elibol, Birsen; Tiftikçioğlu, İrem; Gürsoy, Esra; Yangın, Melike Nur; Zorlu, YaşarMyasthenia Gravis (MG) is a rare neurological disease. Although there are intensive efforts, the underlying mechanism of MG still has not been fully elucidated, and early diagnosis is still a question mark. Diagnostic paraclinical tests are also time-consuming, burden patients financially, and sometimes all test results can be negative. Therefore, rapid, cost-effective novel methods are essential for the early accurate diagnosis of MG. Here, we aimed to determine MG-induced spectral biomarkers from blood serum using infrared spectroscopy. Furthermore, infrared spectroscopy coupled with multivariate analysis methods e.g., principal component analysis (PCA), support vector machine (SVM), discriminant analysis and Neural Network Classifier were used for rapid MG diagnosis. The detailed spectral characterization studies revealed significant increases in lipid peroxidation; saturated lipid, protein, and DNA concentrations; protein phosphorylation; PO2-asym + sym /protein and PO2-sym/lipid ratios; as well as structural changes in protein with a significant decrease in lipid dynamics. All these spectral parameters can be used as biomarkers for MG diagnosis and also in MG therapy. Furthermore, MG was diagnosed with 100% accuracy, sensitivity and specificity values by infrared spectroscopy coupled with multivariate analysis methods. In conclusion, FTIR spectroscopy coupled with machine learning technology is advancing towards clinical translation as a rapid, low-cost, sensitive novel approach for MG diagnosis.Öğe Effects of prenatal binge-like ethanol exposure and maternal stress on postnatal morphological development of hippocampal neurons in rats(Pergamon-Elsevier Science Ltd, 2017) Jakubowska-Dogru, Ewa; Elibol, Birsen; Dursun, İlknur; Yürüker, SinanBackground: Alcohol is one of the most commonly used drugs of abuse negatively affecting human health and it is known as a potent teratogen responsible for fetal alcohol syndrome (FAS), which is characterized by cognitive deficits especially pronounced in juveniles but ameliorating in adults. Searching for the potential morphological correlates of these effects, in this study, we compared the course of developmental changes in the morphology of principal hippocampal neurons in fetal-alcohol (A group), intubated control (IC group), and intact control male rats (C group) over a protracted period of the first two postnatal months. Methods: Ethanol was administered to the pregnant Wistar dams intragastrically, throughout gestation days (GD) 7-20, at a total dose of 6 g/kg/day resulting in the mean blood alcohol concentration (BAC) of 246.6 +/- 40.9 mg/dl. Ten morphometric parameters of Golgi-stained hippocampal neurons (pyramidal and granule) from CA1, CA3, and DG areas were examined at critical postnatal days (PD): at birth (PD1), at the end of the brain growth spurt period (PD10), in juveniles (PD30), and in young adults (PD60). Results: During postnatal development, the temporal pattern of morphometric changes was shown to be region dependent with most significant alterations observed between PD1-30 in the CA region and between PD10-30 in the DG region. It was also parameter-dependent with the soma size (except for CA3 pyramids), number of primary dendrites, dendrite diameter, dendritic tortuosity and the branch angle demonstrating little changes, while the total dendritic field area, dendritic length, number of dendritic bifurcations, and spine density being highly increased in all hippocampal regions during the first postnatal month. Moderate ethanol intoxication and the maternal intubation stress during gestation, showed similar, transient effects on the neuron development manifested as a smaller soma size in granule cells, reduced dendritic parameters and lower spine density in pyramidal neurons at PD1. Full recovery from these effects took place within the first 10 postnatal days. Conclusions: This study showed regional and temporal differences in the development of different morphometric features of principal hippocampal neurons in intact subjects over a protracted 2-months postnatal period. It also demonstrated an overlap in the effects of a moderate fetal ethanol intoxication and a mild maternal stress produced by the intragastric intubation, a commonly used method of ethanol administration to the pregnant dams. Fast recovery from the adverse effects on the soma size, dendritic arborization and spines density observed at birth indicates towards the fetal ethanol/stress induced developmental retardation.Öğe Effects of thymoquinone (TQ) on the molecular structure and total antioxidant capacity of cerebellum tissue of healthy rats(2022) Garip Ustaoğlu, Şebnem; Elibol, BirsenObjective: The neuroprotective effects of thymoquinone (TQ), the active compound of Nigella sativa, have been reported in accordance with the anti-inflammatory and antioxidant features of this drug. It has been suggested that the cerebellum plays a considerable role in neurodegenerative processes. In the current study, the possible effects of TQ on the structure and composition of cerebellum tissues and its total antioxidant capacity were studied dose-dependently. Materials and Methods: Fifteen adult Long Evans female rats were divided into groups as follows: G1: Control, G2: 10 mg/kg TQ treatment, G3: 20 mg/kg TQ treatment. TQ was injected into the rats intraperitoneally for two weeks. The control group only received corn oil used for the dissolving of TQ. Fourier-transform infrared spectroscopy (FTIR) studies and total protein, and antioxidant capacity measurements were carried out with cerebellum tissues which were removed following the decapitation of rats. Results and Conclusion: 10 mg/kg TQ treatment improved the saturated and unsaturated lipid and protein content in addition to decreasing nucleic acid content and lipid peroxidation and increasing the total antioxidant capacity of cerebellum tissues. However, 20 mg/kg TQ treatment did not have any significant effect.Öğe Insights from CD71 presentation and serum lipid peroxidation in myasthenia gravis - A small cohort study(2024) Çağlayan, Sinem Tuncer; Elibol, Birsen; Severcan, Feride; Gürsoy, Esra Başar; Tiftikçioğlu, Bedile İrem; Güngördü Dalar, Zeynep; Çelik, Ceren; Dai, Ayşe Suna; Karaçam, SevinçMyasthenia gravis (MG) is a multifaceted autoimmune disorder affecting the postsynaptic neuromuscular junction. In this study, we examined CD4+ and CD8+ T lymphocyte levels and ratios within peripheral blood mononuclear cells (PBMCs) in MG patients. Additionally, we assessed lymphocytes for the expression of CD71, which functions as a transferrin receptor mediating the uptake of iron into the cells. Building on recent discussions regarding CD20 depletion treatments in MG, we also scrutinized lymphocytes for CD20 expression. Comparative analyses were conducted among healthy controls, newly diagnosed MG patients, those undergoing pyridostigmine treatment alone, and MG patients receiving combination therapies. In the patients, the ratio of CD3+CD4+ T lymphocytes to CD3+ T lymphocytes was found to be decreased compared to the healthy controls, while the ratio of CD3+CD8+ cells to CD3+CD4+ cells increased. An increase in the percentage of CD71-expressing lymphocytes was observed in MG patients compared to the healthy control group, while CD20+ lymphocytes exhibited no statistical changes. Moreover, heightened serum lipid peroxidation levels were found in MG patients. These results suggest a possible relationship between iron metabolism, levels of CD71-expressing cells, and lipid peroxidation in MG. Conversely, pyridostigmine treatment reduced the levels of CD71-expressing cells and lipid peroxidation, suggesting potential immunomodulatory and antioxidant impacts of pyridostigmine in MG, either directly or indirectly.Öğe The structural effects of Vitamin A deficiency on biological macromolecules due to ethanol consumption and withdrawal: An FTIR study with chemometrics(2022) Elibol, Birsen; Severcan, Mete; Jakubowska-Dogru, Ewa; Dursun, Ilknur; Severcan, FerideThe structural effects of vitamin A-deficiency were examined on the molecular profiles of biomolecules of male rat hippocampus during prolonged ethanol intake/withdrawal using FT-IR spectroscopy coupled with chemometrics. Liquid ethanol diet with/without vitamin A was maintained to adult rats for 3-months. The rats were decapitated at different ethanol withdrawal times and FT-IR spectra were obtained. Ethanol consumption/withdrawal produced significant changes in proteins' conformations, while having insignificant structural effects on lipids. In vitamin A deficiency, ethanol produced structural changes in lipids by lipid ordering especially in the early-ethanol withdrawal. Furthermore, an increase in lipid and protein content, saturated/unsaturated lipid ratio, a decrease in nucleic acids content and decrease in membrane fluidity were observed. These changes were less severe in the presence of Vitamin A. This study is clinically important for individuals with vitamin A deficiency because they have to be more cautious when consuming alcohol to protect themselves from cognitive dysfunctions.
