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Öğe Activation of Proteolysis During Oocyte In Vitro Maturation(2025) Tepeköy, Filiz; Bulut, Berk; Karaöz, ErdalIn vitro maturation (IVM) is a form of assisted reproductive technology (ART) applied to obtain mature oocytes in culture. Decline in IVM success rates by age has led consideration of novel approaches based on cellular dynamics. Our aim was to achieve proteostasis in old bovine oocytes from 13 to 16-year-old bovine with a lower potential for fertilization. Lysosomal activation was achieved through increasing concentrations of proton pump activators PIP2 (0.1, 0.5, 1, and 5 μM), PMA (0.1, 1, 10, and 50 μM), and DOG (0.1, 1, 10, and 50 μM) at 6, 12, 18, and 24 h of IVM in old bovine oocytes. Morphological analysis was performed and IVM rates were determined. DQ-Red BSA was applied to live oocytes to determine proteolytic activation while lysosome density was determined by Lysotracker probe. Protein carbonylation was detected through oxyblot analysis. Polar body extrusion (PBE), through which a haploid nonfunctional polar body is released in the perivitelline space after completion of the first meiotic division, was observed in PIP2-0.1 μM, -0.5μM-6h; PIP2-5μM-12h; PMA-0.1μM-18h; PIP2-0.1μM, -0.5μM-24h groups. Oocyte diameter was the highest in DOG-1μM-6h, PMA-0.1μM-12h, PIP2-1μM-18h, and PIP2-0.5μM-24h groups. Morphological scores of oocytes were higher in young and old control groups. PIP2, PMA, and DOG affected oocyte quality positively after 6 h of IVM yielding in oocyte scores similar to the control group oocytes. However, they had a negative impact on the oocyte scores in longer periods of IVM, except for lower doses PMA (0.1 and 1 μM) at 12 h and PIP2 (0.5 μM) and PMA (0.1 μM) at 18 h, which were able to maintain the scores relatively closer to the control oocytes. Proteolytic activation was achieved in all groups at 6 h of culture. At all other time points PIP2 and PMA groups showed a better response to proteolytic activation. Lysosome density was increased in PIP2-5μM-6h; PIP2-0.1μM, -1μM-12h; PIP2-1μM, -5μM-18h as well as PMA-0.1μM-6h; PMA-1μM, -10μM-12h; PMA-1μM-18h; DOG-50μM-6h and DOG-0.1μM-12h. Protein carbonylation was the lowest in PIP2-0.1 μM groups at 12, 18, and 24 h. This study suggests that proton pump activators PIP2 and PMA was found to have a positive impact on IVM in terms of both morphological scores and proteolytic activation in a time and dose dependant manner.Öğe Antimicrobial peptides: Could cecropin A and nisin be new promising agents for the treatment of anaerobic infections(2024) Kurt, Zeynep; Demirci, Mehmet; Arı, Şule; Tokuç, Edip; Kılınçaslan, Ayşe Ceylan; Ziyad, Muhuyedin Abdirahman; Kocazeybek, Bekir Sami; Toman, Hrisi BaharAntimicrobial peptides (AMPs) may mitigate the danger of increasing antimicrobial resistance. We aimed to determine the activities of catestatin, temporin A, nisin and cecropin A against Bacteroides fragilis ATCC 25285, Prevotella melaninogenica ATCC 25845, Cutibacterium acnes ATCC 6919, Peptostreptococcus anaerobius ATCC 27337 and Peptostreptococcus stomatis DSM 17678. strains. The susceptibility of all anaerobic bacteria was determined by Kirby-Bauer disc diffusion method, agar dilution and broth microdilution method, recommended by CLSI. By broth microdilution the MIC of temporin A for P. anaerobius was 500µg/mL, and MBC >500µg/mL. The MIC of nisin for P. melaninogenica was 200µg/mL, with a MBC of 400µg/mL, for C. acnes, P. anaerobius, and P. stomatis, MIC were 40mg/mL. The MIC of cecropin A for B. fragilis was 50µg/mL, MBC was 500µg/mL. For C. acnes, the MIC was 4µg/mL, MBC was 8µg/mL. The MIC for P. melaninogenica, P. anaerobius and P. stomatis were 8µg/mL, with corresponding MBC values of 16, 32 and 50µg/mL, respectively. Conversely, catestatin proved ineffective against all strains. In conclusion, our study, demonstrated that cecropin A and nisin showed promising results against anaerobic standard strains. We believe thatfurther research conducted to explore those AMPs could hold promise as a treatment option for anaerobic bacterial infections.Öğe Hyperbolic and trigonometric generators of archimedean copulas: characteristics and performance(University of Maragheh, 2025) Kazemirad, Amirmasoud; Golshani, Leila; Najjari, Vadood; Kokabinezhad, MohsenIn this paper, hyperbolic and trigonometric functions, based on cosecant and cotangent as generator function for the family of Archimedean copula, are proposed. For these families, the dependence characteristics are compared. Also, to show the performance of these copulas, we investigate the stochastic frontier model based on them. Then we conclude that the copulas based on hyperbolic and trigonometric cosecant and cotangent are more suitable for modeling dependence structure.Öğe Optimization of Morris Water Maze protocols : effects of water temperature and hypothermia on spatial learning and memory in aged female rats(Turkish Geriatrics Society, 2024) Oran, Duygu Sultan; Temel, Zeynep; Başer, İbrahim Gökşin; Temizyürek, Arzu; Selcan, AyşinIntroduction: Aging is a highly complex process driven by a multitude of factors. The use of humans in aging research is complicated by many factors (ethical issues; environmental and social factors; long natural life span). Therefore, rats are common models for the study of aging and age-related diseases. The Morris water maze test is one of the most common cognitive tests in studies investigating age-related learning and memory. However, standardized protocols are lacking, which could influence results. This study investigated the effects of water temperature and inter-trial interval on physiological parameters, hippocampus-dependent learning, and memory in aged female rats performing the Morris Water Maze. Materials and Methods: Thirty-two female Wistar Hannover rats, aged over 18 months, were divided into four groups based on water temperature (20 °C or 24 °C) and inter-trial interval (30 seconds or 13 minutes). Results: Rats exposed to 24 °C demonstrated better spatial learning and memory retention than those at 20 °C. The interaction between inter-trial interval and water temperature significantly affected memory, with higher temperatures improving memory, especially with shorter intervals. Inter-trial interval alone did not significantly affect learning, but longer durations were associated with more stable body temperatures. Neither water temperature nor inter-trial interval significantly influenced body weight. Conclusion: These findings emphasize the need to standardize environmental conditions in Morris water maze protocols to enhance research validity and reliability. Optimizing these protocols is crucial to upholding ethical standards and ensuring animal welfare, advancing more effective and scientifically sound practices in gerontological research, and fostering a better understanding of aging processes.Öğe Changes in secondary structure of protein in skeletal muscle due to high-carbohydrate of high-fat diets(2024) Özer, Nazlı Ezer; Mollaoğlu, Ayça DoğanObjective: Obesity, which arises from changes in lifestyle and feeding habits, poses a threat to human health. One essential contributor to the increase in obesity rates is the popularity of high-calorie diets. This study aims to investigate high-fat (HFD) and high-carbohydrate (HCD) diet-induced molecular changes in protein secondary structure in longissimus dorsi skeletal muscle tissues of female inbred C57BL/6J mice by utilizing Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy. Materials and Methods: Mice were fed a control diet, HCD, or HFD for 24 weeks. Their skeletal muscle tissues were collected, and their spectra were recorded using a Bruker Invenio S ATR-FTIR spectrometer in the 4000-400 cm-1 region. Results: The protein secondary structure profiles of the HCD group demonstrated a significant rise in antiparallel beta-sheet and beta-turn and a decline in parallel beta-sheets, together with the insignificant increase in aggregated beta-sheets and a decrease in alpha-helix. The impact of an HFD on protein conformation is less pronounced than HCD. The HFD diet led to an increase in antiparallel beta-sheets and a decrease in parallel beta sheets. Although insignificant, an increase was observed in beta-turn and alpha-helix. Conclusion: These results propose the appearance of protein aggregation and/or formation of protein- protein intermolecular interaction in skeletal muscle tissues of female inbred C57BL/6J mice. Collectively, these data suggest that both high-calorie diets impair secondary structures of protein in skeletal muscle that may affect its metabolic function.Öğe Mitochondria-specific targeting to overcome imatinib resistance in chronic myeloid leukemia cells(Elsevier, 2024) Hekmatshoar, Yalda; Özkan, Tülin; Karabay, Arzu Zeynep; Koç, Aslı; Gürel, A. Karadağ; Vignais, Marie-Luce; Sunguroğlu, A....Öğe 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. HalukThe 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.Öğe Web Server-based structure prediction as a supplementary tool for basic and acidic FGF secondary structure analysis using FTIR spectroscopy and a case study comparing curve-fit with the model-based structure inspection of the FTIR data(DergiPark, 2023) Korkmaz, Filiz; Mollaoğlu, Ayça; Adıgüzel, YekbunFourier Transform Infrared (FTIR) spectroscopy can provide relative proportion of secondary structure elements in a protein. However, extracting this information from the Amide I band area of an FTIR spectrum is difficult. In addition to experimental methods, several protein secondary structure prediction algorithms serving on the Web can be used as supplementary tools requiring only protein amino acid sequences as inputs. In addition, web-server based docking tools can provide structure information when proteins are mixed and potentially interacting. Accordingly, we aimed to utilize web-server based structure predictors in fibroblast growth factor (FGF) protein structure determination through the FTIR data. Seven such predictors were selected and tested on basic FGF (bFGF) protein, to predict FGF secondary structure. Results were compared to available structure-files deposited in the Protein Data Bank (PDB). Then, FTIR spectra of bFGF and the acidic form of the protein with 50 folds more bovine serum albumin as carrier protein (1FGFA/50BSA) were collected. Optimized Amide I curve-fit parameters of bFGF with low (<5) root mean square deviation (RMSD) in the PDB data and the predictions were obtained. Those parameters were applied in curve-fitting of 1FGFA/50BSA data. Secondary structure was inspected also through applying models derived from the previously established methods. Results of model-based secondary structure estimation from FTIR data were compared with secondary structure calculated as 1 part contribution from 1FGFA/1BSA complex and 49 parts contribution from BSA. Complex structure was obtained through docking. RMSD in the PDB data and the predictions were respectively 3.05 and 2.39 with the optimized parameters. Those parameters did not work well for the 1FGFA/50BSA data. Models are better in this case, wherein one model (Model-1’) with the lowest average RMSD has 8.38 RMSD in the bFGF and 4.78 RMSD in the 1FGFA/50BSA structures. Model-based secondary structure predictions are better for determining bFGF and 1FGFA/50BSA secondary structures through the curve-fit approach that we followed, under non-optimal conditions like protein/BSA mixtures. Web servers can assist experimental studies investigating structures with unknown structures. Any web-based structure prediction supporting the experimental results would be enforcing the findings, but the unsupported results would not necessarily falsify the experimental data.Öğe Gene expression profile as a precursor of inflammation in mouse models: BFMI860 and C57BL/6NCrl(Istanbul University Press, 2024) Doğan, Ayça; Brockmann, Gudrun A.Objective: We aimed to investigate the differences in the immune response to body fat content between the genetically mutant obese BFMI860 (BFMI) mouse strain and the lean C57BL/6Ncrl (B6) mouse strain as a control and the effects of obesity on gene expression on inflammation-related pathways in epididymal adipose tissue. Materials and Methods: Six males from each strain were maintained on a standard maintenance diet (SMD) or a high-fat diet (HFD). At the age of 10 weeks, serum and epididymal adipose tissue samples were collected for cytokine and gene expression analyses. RNA samples from epididymal adipose tissue were hybridized using the microarray technique to study the quantitative transcript amounts of genes. Results: Pathway analysis of gene expression data revealed no considerable development of inflammatory state in BFMI and B6 on SMD. Both strains responded to HFD distinctly; the inflammatory state was more prominent in the obese BFMI group than in the lean B6 group. Several genes, such as Adipoq, NFkbia, Plaur, F2r, C3ar1, and Nfatc4 in pathways involved in the immune system have been found to be differentially regulated in BFMI mice. Under the condition of obesity in BFMI mice, the induction of inflammation-related pathways indicates an increased risk of insulin resistance, atherosclerosis, and cardiovascular disease. Conclusion: This study identified distinct expression patterns of genes involved in inflammatory pathways, particularly those associated with the adipocytokine signaling pathway and complement and coagulation cascades, in the epididymal adipose tissue of BFMI and B6 mice. The BFMI strain is a valuable and promising model for clarifying the mechanisms underlying obesity and the activation of inflammation in adipose tissue.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 Methylsulfonylmethane induces caspase-dependent apoptosis in acute myeloid leukemia cell lines(2024) Hekmatshoar, Yalda; Karabay, Arzu Zeynep; Özkan, Tülin; Koç, Aslı; Sunguroğlu, AsumanBackground: Acute myeloid leukemia (AML) is a heterogeneous ailment in both biological and clinical concepts. Numerous efforts have been devoted to discover natural compounds for combating cancer, which showed great potential in cancer management. Methylsulfonylmethane (MSM), an organosulfur dietary supplement, is utilized for improving various clinical conditions, particularly osteoarthritis. MSM can exert antitumor activity in a wide range of cancers. Objectives: The molecular mechanisms of action underlying antileukemic activity of MSM remain unclear. In this regard, we aimed to investigate the anticancer properties of MSM on human AML cell lines (U937 and HL60) with focus on underlying cell death mechanism. Methods: Anticancer activity of the MSM was examined employing MTT assay, Annexin V-PE/7AAD staining, caspase3/7 activity test, and real-time qPCR. Both cell lines were treated with different concentrations (50-400 mM) of MSM for 24 h. Pretreatment of the cells with a caspase inhibitor (i.e., Z-VAD-fmk) was performed for the assessment of apoptosis induction. Results: The results of MTT assay revealed that in both cell lines, the MSM markedly reduced cell viability in comparison to the control cells. Additionally, findings of Annexin V-7AAD staining revealed that MSM induced apoptosis and activated caspase 3/7 in both cell lines markedly. Real-time quantitative PCR results also supported the induction of apoptosis in AML cells. MSM altered the expression levels of various apoptotic genes (BAX, BAD, and BIM). Conclusion: Overall, our results indicated that MSM could induce apoptosis in AML cell lines in a dose-dependent manner, which therefore could be utilized as an antileukemic agent.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 Therapeutic and prophylactic effects of fulvic acid on a breast cancer model established by MCF-7 cell line in SCID mice(2024) Gülçiçek, Osman Bilgin; Oran, Duygu Sultan; Temizyürek, Arzu; Yavuz, Erkan; Yiğitbaş, Hakan; Erçetin, Candaş; Solmaz, Ali; Yıldırım, Funda; Sönmez, Kıvılcım; Çelik, AtillaIntroduction. There is still minimal scientific understanding of effects of fulvic acid (FA) on breast cancer. We investigated the prophylactic, therapeutic, and combined effects of FA in a breast cancer model created using MCF-7 cell line in severe combined immunodeficiency disease (SCID) mice. Results. Four experimental groups were established as the control group (Group C), prophylaxis group (Group P), therapeutic group (Group T), and prophylaxis + therapeutic group (Group P + T). Tumor growth was observed by the in vivo imaging system and macroscopically in mammary glands of all mice (100%) of Group C, microscopically in only one mouse of Group P (12.5%), in four mice in Group T (50%), but only one animal (12.5%) in Group P + T. Immunohistochemistry (IHC) showed that p53 staining was significantly higher in tissues of Group C compared to other groups (P < 0.05). No difference was found in IHC scores for p53 between Group P and P + T (P > 0.05). Bcl-2 staining was significantly higher in Group C compared to Group P + T (P = 0.015) and higher in Group P + T compared to Group T (P = 0.021) but no significant difference was found between Group P and others (P > 0.05). Bax staining was significantly higher in Group C compared to others (P < 0.05) but no significant difference was found between FA groups (P > 0.05). Conclusion. Prophylactic FA treatment can prevent tumor formation by inducing variations in the expression of p53, BcL-2, and Bax proteins in mammary glands of SCID mice before tumor formation. This suggests that FA may be a powerful inhibitory candidate for the prevention of tumorigenesis in breast cancer.Öğe Identification of exosomal microRNAs and related hub genes associated with imatinib resistance in chronic myeloid leukemia(2024) Karabay, Arzu Zeynep; Özkan, Tülin; Gürel, Aynur Karadağ; Koç, Aslı; Hekmatshoar, Yalda; Sunguroğlu, Asuman; Aktan, Fügen; Büyükbingöl, ZelihaChemotherapy resistance is a major obstacle in cancer therapy, and identifying novel druggable targets to reverse this phenomenon is essential. The exosome-mediated transmittance of drug resistance has been shown in various cancer models including ovarian and prostate cancer models. In this study, we aimed to investigate the role of exosomal miRNA transfer in chronic myeloid leukemia drug resistance. For this purpose, firstly exosomes were isolated from imatinib sensitive (K562S) and resistant (K562R) chronic myeloid leukemia (CML) cells and named as Sexo and Rexo, respectively. Then, miRNA microarray was used to compare miRNA profiles of K562S, K562R, Sexo, Rexo, and Rexo-treated K562S cells. According to our results, miR-125b-5p and miR-99a-5p exhibited increased expression in resistant cells, their exosomes, and Rexo-treated sensitive cells compared to their sensitive counterparts. On the other hand, miR-210-3p and miR-193b-3p were determined to be the two miRNAs which exhibited decreased expression profile in resistant cells and their exosomes compared to their sensitive counterparts. Gene targets, signaling pathways, and enrichment analysis were performed for these miRNAs by TargetScan, KEGG, and DAVID. Potential interactions between gene candidates at the protein level were analyzed via STRING and Cytoscape software. Our findings revealed CCR5, GRK2, EDN1, ARRB1, P2RY2, LAMC2, PAK3, PAK4, and GIT2 as novel gene targets that may play roles in exosomal imatinib resistance transfer as well as mTOR, STAT3, MCL1, LAMC1, and KRAS which are already linked to imatinib resistance. MDR1 mRNA exhibited higher expression in Rexo compared to Sexo as well as in K562S cells treated with Rexo compared to K562S cells which may suggest exosomal transfer of MDR1 mRNA.Öğe Exploring free amino acid profiles in CCHF patients: Implications for disease progression(2024) Büyüktuna, Seyit Ali; Yerlitaş, Serra İlayda; Zararsız, Gözde Ertük; Doğan, Kübra; Kablan, Demet; Bağcı, Gökhan; Özer, Selda; Baysal, Cihad; Çakır, Yasemin; Cephe, Ahu; Koçhan, Necla; Zararsız, Gökmen; Doğan, Halef OkanThis study investigated the intricate interplay between Crimean-Congo hemorrhagic fever virus (CCHFV) infection and alterations in amino acid metabolism. Our primary aim is to elucidate the impact of Crimean-Congo hemorrhagic fever (CCHF) on specific amino acid concentrations and identify potential metabolic markers associated with viral infection. One hundred ninety individuals participated in this study, comprising 115 CCHF patients, 30 CCHF negative patients, and 45 healthy controls. Liquid chromatography-tandem mass spectrometry techniques were employed to quantify amino acid concentrations. The amino acid metabolic profiles in CCHF patients exhibit substantial distinctions from those in the control group. Patients highlight distinct metabolic reprogramming, notably characterized by arginine, histidine, taurine, glutamic acid, and glutamine metabolism shifts. These changes have been associated with the underlying molecular mechanisms of the disease. Exploring novel therapeutic and diagnostic strategies addressing specific amino acids may offer potential means to mitigate the severity of the disease.Öğe Evaluation of the first Candida auris isolates reported from Türkiye in terms of identification by various methods and susceptibility to antifungal drugs(2024) Erköse Genç, Gonca; Küçükkaya, Ilvana Caklovica; Komec, Selda; Önder, İlke Toker; Toptaş, Öykü; Teke, Leyla; Turan, Deniz; Aygün, Gökhan; Gülmez, Dolunay; Arıkan Akdağlı, Sevtap; Erturan, ZayrePurpose: Candida auris is increasingly being isolated from patients all over the world. It has five clades. In this study, it was aimed to compare the results of biochemical tests obtained using different methods and the antifungal susceptibility profiles of C. auris strains isolated from the first seven cases reported in Türkiye, and evaluate whether this information could be useful as preliminary data in determining the clade of strains in centers that lack the opportunity to apply molecular methods. Methods: Identification test results obtained using API ID 32 C, API 20 C AUX, VITEK-2 YST, and MALDI-TOF MS; colony color and morphology on Chromagar Candida, CHROMagar Candida Plus media, and cornmeal-Tween 80 agar; susceptibility to antifungals were tested and compared. Antifungal susceptibility test was studied using microdilution method according to the recommendations of EUCAST. Additionally, a pilot study was conducted to investigate the value of CHROMagar Candida Plus. Results: All seven strains were identified as Lachancea kluyveri with API ID 32 C, Rhodotorula glutinis; Cryptococcus neoformans with API 20 C AUX, and C. auris with both VITEK-2 YST and MALDI-TOF MS. MIC values for fluconazole were very high (≥64 mg/L) for all seven strains. It was observed that 11 (37.9%) of 29 Candida parapsilosis strains formed colonies with morphology similar to C. auris on CHROMagar Candida Plus medium, leading to false positivity. Conclusions: Although there have been many isolations of C. auris in our country in recent years, clade distribution of only a small number of strains is known yet. In this study, when the biochemical properties and antifungal susceptibility profiles of the seven strains were evaluated, it was concluded that they exhibited some characteristics compatible with clade I. It was also observed that strains 1 and 2 may belong to a different clade.Öğe The investigation of the molecular changes during lipopolysaccharide-induced systemic inflammation on rat hippocampus by using FTIR spectroscopy(2024) Çakmak-Arslan, Gülgün; Kaya, Yıldıray; Mamuk, Soner; Akarsu, Eyüp Sabri; Severcan, FerideThe aim of this study is to reveal the molecular changes accompanying the neuronal hyper-excitability during lipopolysaccharide (LPS)-induced systemic inflammation on rat hippocampus using Fourier transform infrared (FTIR) spectroscopy. For this aim, the body temperature of Wistar albino rats administered LPS or saline was recorded by radiotelemetry. The animals were decapitated when their body temperature began to decrease by 0.5°C after LPS treatment and the hippocampi of them were examined by FTIR spectroscopy. The results indicated that systemic inflammation caused lipid peroxidation, an increase in the amounts of lipids, proteins and nucleic acids, a decrease in membrane order, an increase in membrane dynamics and changes in the secondary structure of proteins. Principal component analysis successfully separated control and LPS-treated groups. In conclusion, significant structural, compositional and functional alterations occur in the hippocampus during systemic inflammation and these changes may have specific characteristics which can lead to neuronal hyper-excitability.Öğe Theranostic potential of a novel aptamer specifically targeting HER2 in breast cancer cells(Tübitak, 2024) Küçükcankurt, Fulya; Uçak, Samet; Altiok, NedretBackground/aim: The overexpression of HER2 is correlated with poorer outcomes and therapeutic resistance in breast cancer patients. While HER2-targeted therapies have shown improvement, prognosis remains poor for HER2-positive breast cancer patients, and these treatments have limitations. Therefore, it is crucial to explore effective molecular strategies for early detection and treatment of HER2-positive breast cancers. Materials and methods: In this study, we employed the cell-SELEX method to generate a selective aptamer capable of recognizing HER2 in its native conformation within breast cancer cells, for theranostic applications. Utilizing an adherent cell-SELEX approach, we developed and explored a DNA aptamer, named HMAP7, which can specifically target HER2 in the MDA-MB-453 and SK-BR-3 human breast cancer cell lines. After sequencing, the binding affinities of 10 candidate aptamers to HER2 receptors were evaluated by measuring fluorescence intensities within intact cells using near-infrared optical imaging. The dissociation constant of HMAP7 was determined to be in the nanomolar range in both cell lines. Results: The cell-SELEX-derived aptamer sequence, HMAP7 (41-mer), exhibited the highest binding affinity and specificity for HER2. HMAP7 was rapidly internalized into breast cancer cells overexpressing HER2 but showed no uptake in the HER2 receptor-deficient breast cancer cell line MDA-MB-231. Moreover, HMAP7 demonstrated remarkable selectivity for HER2, rendering it suitable for use in complex biological systems. Conclusions: Our findings suggest that the novel DNA aptamer HMAP7 holds promise for both therapeutic and diagnostic applications, enabling selective delivery of therapeutic agents or imaging of HER2-positive breast tumors.Öğe Becoming temporarily protected, producing temporarily protecting places: how Syrian refugee women and children co-create place in Istanbul(Routledge, 2024) Yürür, GülkızılcaThe paper examines the usefulness of the Deleuzian concepts of smooth space and stratified space while capturing the experiences of refugee women and children as non-citizens under the temporary protection regime in Istanbul. Deleuze and Guattari, in their book ‘A Thousand Plateaus’, describe smooth space as the territory of the nomads, those who do not fit in neatly into forms of identity and division. Striated space on the other hand is created by the sedentary, the state, with an interest in blocking the speed of flows, movements of elements not rooted in a supposedly homogenous whole. Many refugee children acquire by birth the legal status of being under temporary protection, a liminal position which for many turns into a life-long arrangement. How do refugee women and children re-create community and culture as bounded to a place? What kind of space delivers itself to being transformed into a place of belonging for them? To work through these questions, interview data from several Syrian women and three Syrian children gathered through semi-structured interviews are embedded in the observations of social workers and psychologists working at the Kizilay community Centre the informants frequent in the Bagcilar district of Istanbul Province in Turkey.Öğe Quetiapine improves sensorimotor gating deficit in a sleep deprivation-induced rat model(Springer, 2023) Özcan, Öznur Özge; Çevreli, Burcu; Temizyürek, Arzu; Karahan, Mesut; Konuk, MuhsinBackground: Sleep deprivation (SD) impairs pre-stimulus inhibition, but the effect of quetiapine (QET) remains largely unknown. Objective: This study aimed to investigate the behavioral and cognitive effects of QET in both naïve and sleep-deprived rats. Materials and methods: Seven groups (n = 49) of male Wistar Albino rats were used in this study. SD was performed using the modified multiple platform technique in a water tank for 72 h. Our study consists of two experiments investigating the effect of QET on pre-pulse inhibition (PPI) of the acoustic startle reflex. The first experiment tested the effect of short- and long-term administration of QET on PPI response in non-sleeping (NSD) rats. The second experiment used 72 h REM sleep deprivation as a model for SD-induced impairment of the PPI response. Here, we tested the effect of QET on the % PPI of SD rats by short- and long-term intraperitoneal injection at the last 90 min of sleep SD and immediately subsequently tested for PPI. Results: 72 h SD impaired PPI, reduced startle amplitude, and attenuated the PPI% at + 4 dB, + 8 dB, and + 16 dB prepulse intensities. 10 mg/kg short and long-term QET administration completely improved sensorimotor gating deficit, increased startle amplitude, and restored the impaired PPI% at + 4 dB, + 8 dB, and + 16 dB after 72 h SD in rats. Conclusion: Our results showed short- and long-term administration of QET improved sensorimotor gating deficit in 72 h SD. Further research is required for the etiology of insomnia and the dose-related behavioral effects of QET.
