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    Ameliorative effect of vitamin C on diabetes-induced damages in nucleic acids of testicular tissues
    (2023) Doğan, Ayça; Ergun, Sercan; Bilgin, Mehmet Dinçer; Severcan, Mete; Severcan, Feride
    Background: Diabetes mellitus (DM) can be characterized by over-production and under-utilization of carbohydrates and varying degrees of abnormal lipid and protein metabolism. The complications of diabetes mellitus affect various organs and systems in the body including the reproductive system. Vitamin C (ascorbic acid) is an essential micronutrient for maintaining normal metabolic processes and homeostasis within the human body. In the current study, the diabetes-induced alterations on the nucleic acids of rat testicular tissues and the effects of low and high doses of ascorbic acid administration were investigated using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy coupled with an unsupervised technique, namely principal component analysis (PCA). Methods: Male Wistar rats were treated with streptozotocin (STZ) to induce DM. One week after STZ administration, the diabetic rats were treated with a low dose of ascorbic acid (15 mg/kg) and a high dose of ascorbic acid (100 mg/kg) for 6 weeks. The dissected testicular tissues were studied by FTIR spectroscopy. PCA was applied to their spectra. Results: This study revealed diabetes-induced global contextual alterations on nucleic acids, particularly RNAs and DNAs in diabetic samples. Low dose ascorbic acid administration was found to be more effective than higher doses in restoring the effect of diabetes on nucleic acids. The PCA results presented a successful discrimination of the diabetic group from the control and Vitamin C treated groups, and showed especially the ameliorative effect of low dose Vitamin C. Conclusion: Low dose Vitamin C was found to be more effective in combating diabetes-induced alterations in nucleic acids. ATRFTIR spectroscopy combined with multivariate data analyses demonstrated the beneficial effect of Vitamin C administration on nucleic acid content of diabetic testicular tissue based on the spectral differences.
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    Aspects of silver tolerance in bacteria: infrared spectral changes and epigenetic clues
    (Wiley-V C H Verlag Gmbh, 2018) Gurbanov, Rafig; Özek, Nihal S.; Tuncer, Sinem; Severcan, Feride; Gözen, Ayşe G.
    In this study, the molecular profile changes leading to the adaptation of bacteria to survive and grow at inhibitory silver concentration were explored. The profile obtained through infrared (IR)-based measurements indicated extensive changes in all biomolecular components, which were supported by chemometric techniques. The changes in biomolecular profile were prominent, including nucleic acids. The changes in nucleic acid region (1350-950 cm(-1)) were encountered as a clue for conformational change in DNA. Further analysis of DNA by IR spectroscopy revealed changes in the backbone and sugar conformations. Moreover, Enzyme-Linked Immunosorbent Assay-based measurements of DNA methylation levels were performed to see if epigenetic mechanisms are in operation during bacterial adaptation to this environmental challenge. The results indicated a notable demethylation in Escherichia coli and methylation in Staphylococcus aureus likely to be associated with their elaborate adaptation process to sustain survival and growth.
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    Biomolecular changes and subsequent time-dependent recovery in hippocampal tissue after experimental mild traumatic brain injury
    (2021) Garip Ustaoğlu, Şebnem; Mohamed H. M.A, Ali; Rakib, Fazle; Blezer, Erwin L. A.; Heijningen, Caroline L.Van; Dijkhuizen, Rick M.; Severcan, Feride
    Traumatic brain injury (TBI) is the main cause of disability and mortality in individuals under the age of 45 years. Elucidation of the molecular and structural alterations in brain tissue due to TBI is crucial to understand secondary and long-term efects after traumatic brain injury, and to develop and apply the correct therapies. In the current study, the molecular efects of TBI were investigated in rat brain at 24 h and 1 month after the injury to determine acute and chronic efects, respectively by Fourier transform infrared imaging. This study reports the time-dependent contextual and structural efects of TBI on hippocampal brain tissue. A mild form of TBI was induced in 11-week old male Sprague Dawley rats by weight drop. Band area and intensity ratios, band frequency and bandwidth values of specifc spectral bands showed that TBI causes signifcant structural and contextual global changes including decrease in carbonyl content, unsaturated lipid content, lipid acyl chain length, membrane lipid order, total protein content, lipid/protein ratio, besides increase in membrane fuidity with an altered protein secondary structure and metabolic activity in hippocampus 24 h after injury. However, improvement and/or recovery efects in these parameters were observed at one month after TBI.
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    Comparison of human breast milk vs commercial formula-induced early trophic enteral nutrition during postoperative prolonged starvation in an animal model
    (2024) Doğan, Ayça; Severcan, Feride; Tuzlacı, Ayşe; Güvenç, B. Haluk
    The present study aimed to characterize the changes in macromolecular composition and structure in ileal tissue induced by postoperative prolonged starvation (PS), human breast milk feeding (HM) and commercial formula feeding (CF) for 48 and 72 h (h). Forty-two Wistar albino rats underwent an ileal transection and primary anastomosis and were then divided into six subgroups. Two groups of seven rats were food-deprived for 48 and 72 h with free access to water only in metabolic cages (48 h PS, 72 h PS). Then, two groups of seven rats received early enteral trophic nutrition (EEN) either using HM, and CF at 48 h post-operation (48 h HM, 48 h CF). The other two groups of seven rats received the same trophic enteral nutrition at 72 h post-operation (72 h HM, 72 h CF). An additional seven rats were fed normal rat chow (control), after which the ileal tissues were harvested and freeze-dried overnight. Then sample spectra were recorded by Fourier transform infrared (FTIR) spectroscopy. PS at 48 and 72 h resulted in an increase in the concentration of lipids and a decrease in the concentration of proteins. CF and HM trophic feeding induced a decrease in membrane fluidity and an increase in lipid order. Ileal tissues showed similar compositional and structural changes in lipids and proteins in the PS and CF groups after 48 and 72 h. A marked decrease in nucleic acid concentration was seen in CF at 48 h compared to HM. The human milk feeding groups did not induce any significant alterations and showed compositional and structural data similar to the controls. In conclusion, EEN application seems to be safer when introduced at 48 h rather than 72 h and time of this nutrition is crucial to maintain ileum structure and therefore immunity and well-being. HM-induced trophic nutrition is seen to protect the ileal tissue from significant alterations within lipid and protein compositions, whereas CF caused notable changes. HM is absolutely the best nutritional source for gut health in this animal model.
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    CoronaVac (Sinovac) COVID-19 vaccine-induced molecular changes in healthy human serum by infrared spectroscopy coupled with chemometrics
    (TÜBİTAK, 2021) Doğan, Ayça; Gurbaov, Rafig; Severcan, Mete; Severcan, Feride
    From the beginning of the COVID-19 coronavirus pandemic in December of 2019, the disease has infected millions of people worldwide and caused hundreds of thousands of deaths. Since then, several vaccines have been developed. One of those vaccines is inactivated CoronaVac-Sinovac COVID-19 vaccine. In this proof of concept study, we first aimed to determine CoronaVac-induced biomolecular changes in healthy human serum using infrared spectroscopy. Our second aim was to see whether the vaccinated group can be separated or not from the non-vaccinated group by applying chemometric techniques to spectral data. The results revealed that the vaccine administration induced significant changes in some functional groups belonging to lipids, proteins and nucleic acids. In addition, the non-vaccinated and vaccinated groups were successfully separated from each other by principal component analysis (PCA) and linear discriminant analysis (LDA). This proof-of-concept study will encourage future studies on CoronaVac as well as other vaccines and will lead to make a comparison between different vaccines to establish a better understanding of the vaccination outcomes on serum biomolecules.
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    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, Yaşar
    Myasthenia 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.
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    Diagnosis and treatment methods of autoimmune myasthenia gravis : a systematic review
    (Altınbaş Üniversitesi, 2022) Yangın, Melike Nur; Zorlu, Yaşar; Severcan, Feride
    Myasthenia Gravis (MG), which is an autoimmune disorder, causes abnormalities in the neuromuscular junction and has a prevalence of 15-20 per 100,000 people. Although skeletal and extraocular muscles are commonly affected by the disease, approximately 10% of patients have severe involvement in the muscles necessary for respiration. A myasthenic crisis may cause life-threatening consequences. The prevalence and incidence of autoimmune MG increase with age. Women’s disease incidence peaks between the ages of 30 and 40, while men’s incidence peaks between the ages of 60 and 80. The existence of autoantibodies against postsynaptic membrane proteins is the most crucial indicator of MG. Anti-AChR (acetylcholine receptor antibody) positive is a distinct feature of MG (% 80). While antiMuSK (muscle-specific kinase antibody) positivity is detected in 1-10% of all patients, LRP4 (low density lipoprotein receptor related protein 4) antibody positivity is seen in 3-25% of MG patients without AChR and MuSK antibodies (anti-LRP4). Despite many methods used in the diagnosis of MG, it is not possible to make the diagnosis in some patients because of conditions that may vary from patient to patient, such as fluctuation in symptoms and clinical findings. Rapid diagnosis is crucial in patients with MG, because effective treatment must begin as early as possible to prevent potentially fatal complications. Moreover, rapid diagnosis of patients and determination of the patient’s subtype is an important step in the treatment process. Therefore, the aim of this study is to summarize the techniques used in the diagnosis and treatment of MG which is one of the rare diseases.
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    Diagnosis of malignant pleural mesothelioma from pleural fluid by Fourier transform-infrared spectroscopy coupled with chemometrics
    (Spie-Soc Photo-Optical Instrumentation Engineers, 2018) Abbas, Sherif; Özek, Nihal Şimşek; Emri, Salih; Köksal, Deniz; Severcan, Mete; Severcan, Feride
    This study was conducted to differentiate malignant pleural mesothelioma (MPM) from lung cancer (LC) and benign pleural effusion (BPE) from pleural fluids using the diagnostic power of Fourier transform-infrared spectroscopy with attenuated total reflectance mode coupled with chemometrics. Infrared spectra of MPM (n = 24), LC (n = 20), and BPE (n = 25) were collected, and hierarchical cluster analysis (HCA) and principal component analysis (PCA) were applied to their spectra. HCA results indicated that MPM was differentiated from LC with 100% sensitivity and 100% specificity and from BPE, with 100% sensitivity and 88% specificity, which were also confirmed by PCA score plots. PCA loading plots indicated that these separations originated mainly from lipids, proteins, and nucleic acids-related spectral bands. There was significantly higher lipid, protein, nucleic acid, and glucose contents in the MPM and LC. However, the significant changes in triglyceride and cholesterol ester content, protein and nucleic acid structure, a lower membrane fluidity, and higher membrane order were only observed in the MPM. To check the classification success of some test samples/each group, soft independent modeling of class analogies was performed and 96.2% overall classification success was obtained. This approach can provide a rapid and inexpensive methodology for the efficient differentiation of MPM from other pleural effusions. (C) 2018 Society of Photo-Optical Instrumentation Engineers (SPIE)
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    Discrimination of heavy metal acclimated environmental strains by chemometric analysis of FTIR spectra
    (Academic Press Inc Elsevier Science, 2020) Kepenek, Eda Şeyma; Severcan, Mete; Gözen, Ayşe Gül; Severcan, Feride
    Heavy metal acclimated bacteria are profoundly the preferred choice for bioremediation studies. Bacteria get acclimated to toxic concentrations of heavy metals by induction of specific enzymes and genetic selection favoring new metabolic abilities leading to activation of one or several of resistance mechanisms creating bacterial populations with differences in resistance profile and/or level. Therefore, to use in bioremediation processes, it is important to discriminate acclimated bacterial populations and choose a more resistant strain. In this study, we discriminated heavy metal acclimated bacteria by using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy and multivariate analysis methods namely Hierarchical Cluster Analysis (HCA), Principal Component Analysis (PCA) and Soft Independent Modeling of Class Analogy (SIMCA). Two acclimation methods, acute and gradual, were used which cause differences in molecular changes resulting in bacterial populations with different molecular and resistance profiles. Brevundimonas sp., Gordonia sp., and Microbacterium oxydans were exposed to the toxic concentrations of Cd (30 mu g/ml) or Pb (90 mu g/ml) by using broth medium as a growth media. Our results revealed that PCA and HCA clearly discriminated the acute-acclimated, gradual acclimated, and control bacteria from each other in protein, carbohydrate, and whole spectral regions. Furthermore, we classified acclimated (acute and gradual) and control bacteria more accurately by using SIMCA with 99.9% confidence. This study demonstrated that heavy metal acclimated and control group bacteria can be discriminated by using chemometric analysis of FTIR spectra in a powerful, cost-effective, and handy way. In addition to the determination of the most appropriate acclimation procedure, this approach can be used in the detection of the most resistant bacterial strains to be used in bioremediation studies.
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    Dose-dependent differentiation of gamma-irradiated hazelnut samples by mid-infrared spectroscopy coupled with chemometrics
    (Hindawi Ltd, 2020) Doğan, Ayça; Severcan, Mete; Severcan, Feride
    Gamma irradiation is used as a food preservation method. It is known that high-dose irradiation causes several structural and functional damages. Therefore, the detection of high-dose irradiated food samples is a critical issue in international trade. The objective of this work is to evaluate the potential of Fourier transform infrared (FTIR) spectroscopy for the differentiation of gamma-irradiated hazelnuts at higher doses (3 kGy and 10 kGy) from the lower (1.5 kGy) and nonirradiated ones using multivariate statistical analysis, namely, principal component analysis (PCA) and hierarchical cluster analysis (HCA). This study showed that high-dose irradiated hazelnut samples can be clearly differentiated from the low-dose irradiated samples using unsupervised methods based on the spectral differences. Furthermore, dose-dependent discrimination was also achieved. In conclusion, FTIR spectroscopy combined with multivariate statistical analysis has potential for the development of a reliable and fast methodology for separation of high-dose irradiated food samples.
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    Embryo quality assessment in in vitro fertilization (IVF) using metabolite footprints secreted to human embryo culture media by ATR-FTIR spectroscopy and multivariate analysis
    (Oxford Univ Press, 2016) Garip, S.; Ceyhan, S. T.; Korkmaz, C.; Müge, A.; Güney, E.; Bal, E.; Severcan, Feride
    Objective of this study is the embryo quality can be determined noninvasively using FTIR spectroscopy to analyze human embryo culture media in IVF treatment. In this prospective, double-blind study, embryo quality was determined by analyzing spent culture media after fertilization by ATR-FTIR spectroscopy and hierarchical cluster analysis (HCA). For each patient, transferred embryos were selected according to morphological assessment and ATR-FTIR studies were carried out collaterally without knowing the morphological grading of each embryo.
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    Epileptic seizure-induced structural and functional changes in rat femur and tibia bone tissues: A fourier transform infrared imaging study
    (Spie-Soc Photo-Optical Instrumentation Engineers, 2013) Garip, Şebnem; Şahin, Deniz; Severcan, Feride
    The disease- and drug- related bone disorders are rapidly increasing in the population. It is previously reported that anti-epileptic drugs (AEDs) may cause osteopenia, osteoporosis, and fractures in epilepsy patients. However, it cannot be determined whether the bone disorders in epileptic patients are due to AED therapy and/or to epilepsy and epileptic seizures. There is no study in the literature which investigates the sole effects of epilepsy and epileptic seizures on bone tissues. The current study provides the first report on determination of the possible effects of epilepsy and epileptic seizures on long bone tissues. Wistar Albino Glaxo/Rijswijk rats, which are accepted as genetic rat models for human absence epilepsy, were compared with the healthy Wistar rats to get information about the sole effects of epilepsy and epileptic seizures on bones. Cortical regions of tibia and femur bones were studied by Fourier transform infrared microspectroscopy (FTIRM). According to FTIRM parameters, variation on bone mineral and matrix composition, including decreased mineral content, decreased collagen cross-links, increased carbonate substitution, and larger crystals in epileptic group compared to the healthy one, show severe effects of epilepsy and seizures on bone tissues for the first time. (C) 2013 Society of Photo-Optical Instrumentation Engineers (SPIE)
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    Fourier transform infrared imaging—A novel approach to monitor bio molecular changes in subacute mild traumatic brain injury
    (MDPI, 2021) Rakib, Fazle; Al-Saad, Khalid; Garip Ustaoğlu, Şebnem; Ullah, Ehsan; Mall, Raghvendra; Thompson, Richard; Abdelalim, Essam M.; Ahmed, Tariq; Severcan, Feride; Ali, Mohamed H. M.
    Traumatic brain injury (TBI) can be defined as a disorder in the function of the brain after a bump, blow, or jolt to the head, or penetrating head injury. Mild traumatic brain injury (mTBI) can cause devastating effects, such as the initiation of long-term neurodegeneration in brain tissue. In the current study, the effects of mTBI were investigated on rat brain regions; cortex (Co) and corpus callosum (CC) after 24 h (subacute trauma) by Fourier transform infrared (FTIR) imaging and immunohistochemistry (IHC). IHC studies showed the formation of amyloid-β (Aβ) plaques in the cortex brain region of mTBI rats. Moreover, staining of myelin basic protein presented the shearing of axons in CC region in the same group of animals. According to FTIR imaging results, total protein and lipid content significantly decreased in both Co and CC regions in mTBI group compared to the control. Due to this significant decrease in both lipid and protein content, remarkable consistency in lipid/protein band ratio in mTBI and control group, was observed. Significant decrease in methyl content and a significant increase in olefinic content were observed in Co and CC regions of mTBI rat brain tissues. Classification amongst distinguishable groups was performed using principal component analysis (PCA) and hierarchical clustering (HCA). This study established the prospective of FTIR imaging for assessing biochemical changes due to mTBI with high sensitivity, precision and high-resolution.
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    FTIR imaging of structural changes in visceral and subcutaneous adiposity and brown to white adipocyte transdifferentiation
    (Royal Soc Chemistry, 2015) Baloğlu, Fatma Küçük; Garip, Şebnem; Heise, Sebastian; Brockmann, Gudrun; Severcan, Feride
    Obesity is a heterogeneous disorder which increases risks for multiple metabolic diseases, such as type 2 diabetes. The current study aims to characterize and compare visceral and subcutaneous adipose tissues in terms of macromolecular content and investigate transdifferentiation between white and brown adipocytes. Regarding this aim, Fourier transform infrared (FTIR) microspectroscopy and uncoupling protein 1 (UCP1) immunohistological staining were used to investigate gonadal (visceral) and inguinal (subcutaneous) adipose tissues of male Berlin fat mice inbred (BFMI) lines, which are spontaneously obese. The results indicated a remarkable increase in the lipid/protein ratio, accompanied with a decrease of UCP1 protein content which might be due to the transdifferentiation of brown adipocytes to white adipocytes in obese groups. It has been widely reported that brown adipose tissue has a strong effect on fatty acid and glucose homeostasis and it could provide an opportunity for the therapy of obesity. When the amount of brown adipose tissue was decreased, lower unsaturation/saturation ratio, qualitatively longer hydrocarbon acyl chain length of lipids and higher amount of triglycerides were obtained in both adipose tissues of mice lines. The results also revealed that subcutaneous adipose tissue was more prone to obesity-induced structural changes than visceral adipose tissue, which could originate from it possessing a lower amount of brown adipose tissue. The current study clearly revealed the power of FTIR microspectroscopy in the precise determination of obesity-induced structural and functional changes in inguinal and gonadal adipose tissue of mice lines.
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    Infrared spectroscopy and imaging in stem cells and aging research
    (Humana Press Inc., 2019) Aksoy, Ceren; Severcan, Feride
    The effect of aging process on stem cell function is crucial because of their critical role in tissue regeneration and repair. The impact of aging on stem cells needs to be understood clearly for the success of clinical application and obtaining desired therapeutic outcome throughout the novel stem cell based therapies. The existing methods used to monitor and characterize the stem cells have some unwanted effects on the properties of stem cells and these methods also do not provide real-time information about cellular conditions. These challenges enforce the usage of nondestructive, rapid, sensitive, high-quality, label-free, cheep, and innovative chemical monitoring methods. In this context, vibrational spectroscopy provides promising alternative to get new information into the field of stem cell biology for chemical analysis, quantification, and imaging of stem cells. Infrared spectroscopy and imaging coupled with chemometric methods can be used as novel and complimentary methods to obtain new insight into stem cell studies for future therapeutic and regenerative medicine. © Springer Science+Business Media New York 2018.
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    Infrared spectroscopy offers tremendous potential in cancer diagnosis
    (Cell Press, 2019) Severcan, Feride; Abbas, Sherif; Yonar, Dilek; Emri, Salih
    All over the word, scientists are actively engaged in the characterization, screening and diagnosis of different pathological conditions. Ideally, the aim is to monitor the system of interest, without disturbing it, in a sensitive, rapid and operated manner at minimum cost.
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    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, Sevinç
    Myasthenia 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.
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    Interaction of the cholesterol reducing agent simvastatin with zwitterionic DPPC and charged DPPG phospholipid membranes
    (Elsevier B.V., 2019) Sarıışık, Ediz; Koçak, Mustafa; Küçük, Baloğlu, Fatma; Severcan, Feride
    Simvastatin is a lipid-lowering drug in the pharmaceutical group statins. Interaction of a drug with lipids may define its role in the system and be critical for its pharmacological activity. We examined the interactions of simvastatin with zwitterionic dipalmitoyl phosphatidylcholine (DPPC) and anionic dipalmitoyl phosphatidylglycerol (DPPG) multilamellar vesicles (MLVs) as a function of temperature at different simvastatin concentrations using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The FTIR results indicate that the effect of simvastatin on membrane structure and dynamics depends on the type of membrane lipids. In anionic DPPG MLVs, high simvastatin concentrations (12, 18, 24 mol%) change the position of the CH 2 antisymmetric stretching mode to lower wavenumber values, implying an ordering effect. However, in zwitterionic DPPC MLVs, high concentrations of simvastatin disorder systems both in the gel and liquid crystalline phases. Moreover, in DPPG and DPPC MLVs, simvastatin has opposite dual effects on membrane dynamics. The bandwidth of the CH 2 antisymmetric stretching modes increases in DPPG MLVs, implying an increase in the dynamics, whereas it decreases in DPPC MLVs. Simvastatin caused broadening of the phase transition peaks and formation of shoulders on the phase transition peaks in DSC curves, indicating multi-domain formations in the phospholipid membranes. Because physical features of membranes such as lipid order and fluidity may be changed with the bioactivity of drugs, opposing effects of simvastatin on the order and dynamics of neutral and charged phospholipids may be critical to deduce the action mechanism of the drug and estimate drug-membrane interactions. © 2019 Elsevier B.V.
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    Investigation of the structural effects of radiotherapy dose rate on rat lung tissue: An FTIR imaging study
    (Cell Press, 2019) Özyurt, İpek; Garip, Şebnem; Baloğlu, Fatma Küçük; Zorlu, Faruk; Severcan, Feride
    Radiotherapy is widely used to cure cancer. During treatment, ionizing radiation is applied by a linear accelerator to the area that is being treated. During this process normal cells can also be damaged by radiotherapy.
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    Kronik hipoperfüze sıçan beynine uygulanan stereotaktik ışın cerrahisinin (Radyocerrahi) beyin dokusu ve hücre membranında moleküler düzeyde oluşturduğu etkilerin biyofiziksel yöntemler ile araştırılması
    (2003) Zorlu, Abdullah Faruk; Öge, Halil Kamil; Boyar, Handan; Al-Otoibi, Toyran Neslihan; Severcan, Feride
    Arteriovenöz malfonnasyonlar (AVM), beyinde büyüyen normal olmayan kan damar demetleridir. Bu fızyopatolojik durum çevre beyin dokusunda, çalma olayı olarak da bilinen, hipoperfıizyona neden olur. AVM'lerin tedavi seçeneklerinden bir tanesi Stereotaktik radyocerrahidir. Çalma etkisiyle düşük perfüzyon ile beslenen beyin dokusunun iyonize radyasyona nasıl yanıt verdiği henüz aydınlanmamıştır. AVM lerin etrafında çalma fenomeni sonucu olan hipoksik bölgenin radyasyon etkilerine karşı dirençli olduğu düşüncesi ile radyasyonun bu hipoksik bölge üzerine olan etkisinin önemi hep gözardı edilmiştir. Literatürde hipoperfüze edilmiş beyin dokusunda, iyonize radyasyonun etkisini gösteren çalışma bulunmamaktadır. Bu projede, hipoperfüze beynin sağlıklı beyne göre iyonize radyasyondan ne derecede farklı etkilendiğini saptanarak literatürdeki bu eksiklik tamamlanmaya çalışılmıştır. Bu amaçla hipoperfüzyonun ve/veya radyocerrahinin sıçan beyin homojenat membranları ve kafatası kemik dokusu üzerine olan etkisi Fourier Transform Infrared (FTIR) spektroskop} tekniği kullanılarak incelenmiştir. Elde edilen FTIR sonuçları, hipoperfüzyonun sıçan beyin homojenat membranlarındaki lipit ve protein miktarlarını önemli derecede etkilediğini göstermiştir. Lipit miktarında artış, protein miktarında azalış, lipit/protein oranında artış, lipitlerin düzenli yapısında artış olduğu gözlemlenmiştir. Proteinlerin hem miktarları hem de ikincil yapıları, ß plakalı tabakalı yapı ve gelişi güzel kıvrımlarla meydana gelen yapılar artacak şekilde etkilenmiştir. Sağlıklı sıçan beyinlerine radyocerrahi uygulaması sonucunda lipit sentezinde artış, protein miktarında azalış, protein/lipit oranında küçük bir azalma olduğu anlaşılmıştır. Hipoperfüze beyinlere radyocerrahi uygulanması ile lipit sentezinde artış, protein miktarında önemli miktarda azalış, protein/lipit oranında önemli bir azalma olduğu elde edilen sonuçlar arasındadır. Ayrıca, radyasyonun hipoporfüze beyne uygulanması sonucu lipitlerin düzenliliğini ve sistemin iç derinliklerinin dinamiğinin önemli derecede arttığı, hipoperfüze olmamış beyin örneklerinde ise önemli bir değişiklik olmadığı görülmüştür. Bu bulgulardan elde edilen en önemli sonuç, protein-Amid I bölgesi hariç, radyasyon uygulamasının hipoperfüze edilmiş beyni, sağlıklı beyne göre daha belirgin bir şekilde etkiliyor olmasıdır. Bu bize hipoperfüze beynin, en azından yukarda bahsedilen parametreler açısından, radyasyona karşı daha hassas olduğunu göstermektedir. Bu çalışmadan elde edilen bulguların ortaya koyduğu diğer bir sonuç da, proteinlerin ikincil yapısının normal beyne radyasyon uygulaması sonucu etkilenerek $\\alpha$-heliks miktarının önemli derecede azalması ve gelişi güzel kıvrımların artması, dolay ısı ile denature olmasıdır. Hipoperfüze beyne radyocerrahi uygulanması sonucunda ise $\\alpha$-heliks ve ß plakalı tabakalı yapı miktarlarında önemli bir değişiklik olmazken, gelişi güzel kıvrımların miktarı azalmıştır. Hipoperfüze sıçanların kafatası kemiklerinde karbonat ve fosfat miktarlarında artış olduğu, protein miktarın azaldığı ve lipit/protein oranının arttığı görülmüştür. Radyocerrahi uygulamasıyla bu değerler kontrol grubununkine yakın değerlere ulaşmaktadır. Yani, radyasyon uygulaması ile hipoperfüzyonun neden olduğu değişiklikler azalarak sağlıklı beyin örneklerine ait olan değerlere yaklaşmıştır.