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Publication Metadata only A proteomic analysis of mitochondrial complex iii inhibition in SH-SY5Y human neuroblastoma cell line(Bentham Science, 2019) Acioglu, Cigdem; Tuzuner, Mete Bora; Serhatli, Muge; Sahin, Betul; Akgun, Emel; Adiguzel, Zelal; Gurel, Busra; Baykal, Ahmet Tarik; Ayhan, Ceyda Açılan; Faculty Member; School of Medicine; 219658Background and Objective: Antimycin A (AntA) is a potent Electron Transport System (ETS) inhibitor exerting its effect through inhibiting the transfer of the electrons by binding to the quinone reduction site of the cytochrome bcl complex (Complex III), which is known to be impaired in Huntington's Disease (HD). The current studies were undertaken to investigate the effect of complex III inhibition in the SH-SY5Y cell line to delineate the molecular and cellular processes, which may play a role in the pathogenesis of HD. Method: We treated SH-SY5Y neuroblastoma cells with AntA in order to establish an in vitro mitochondrial dysfunction model for HD. Differential proteome analysis was performed by the nLC-MS/MS system. Protein expression was assessed by western blot analysis. Results: Thirty five differentially expressed proteins as compared to the vehicle-treated controls were detected. Functional pathway analysis indicated that proteins involved in ubiquitin-proteasomal pathway were up-regulated in AntA-treated SH-SY5Y neuroblastoma cells and the ubiquitinated protein accumulation was confirmed by immunoblotting. We found that Prothymosin alpha (ProT alpha) was down-regulated. Furthermore, we demonstrated that nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression was co-regulated with ProT alpha expression, hence knockdown of ProT alpha in SH-SY5Y cells decreased Nrf2 protein level. Conclusion: Our findings suggest that complex III impairment might downregulate ubiquitin-proteasome function and NRF2/Keapl antioxidant response. In addition, it is likely that downregulation of Nrf2 is due to the decreased expression of ProT alpha in AntA-treated SH-SY5Y cells. Our results could advance the understanding of mechanisms involved in neurodegenerative diseases.Publication Metadata only An investigation of the relationship between TMPRSS6 gene expression, genetic variants and clinical findings in breast cancer(Springer, 2020) Mete, Meltem; Trabulus, Didem Can; Talu, Canan Kelten; Mutlu, Tuba; Tekin, Bülent; Güven, Mehmet; N/A; Özoran, Emre; Teaching Faculty; School of Medicine; Koç University Hospital; 307296Breast cancer is one of the most common types of cancer among women worldwide. The TMPRSS6 (Transmembrane Serine Protease 6) gene encodes matriptase-2, which plays an important role in iron hemostasis as the hepcidin regulator and may play a role in breast cancer susceptibility. In this study, we examined the expression levels of the TMPRSS6 gene in healthy tissues and tumor tissues of breast cancer patients; and the relationship between these levels and pathological findings. The relationship between TMPRSS6 polymorphisms (rs733655, rs5756506, rs2413450, rs855791, rs2235324, rs4820268) and patients' hematological parameters. The gene expression study encompassed 47 breast cancer patients and the gene polymorphism study consisted of 181 breast cancer patients and 100 healthy controls. Gene expression analysis was performed by qRT-PCR. The genotyping of TMPRSS6 polymorphisms was performed by RT-PCR. TMPRSS6 gene expression levels in tumor tissues were found to be 1.88 times higher than the expression levels in the control tissues. We examined the relationship between TMPRSS6 gene expression levels and pathological data, statistically significant relationship was found between patient's estrogen receptor (ER) and HER2 findings and TMPRSS6 gene expression (respectively p = 0.02, p = 0.002). When the relationship between TMPRSS6 gene polymorphisms related genotypes distributions and hematological findings was investigated, a significant relationship was identified between mean corpuscular hemoglobin concentration (MCHC) parameter and the polymorphism of only the rs733655. According to our findings, the increase in TMPRSS6 gene expression in cancerous tissues shows that matriptase-2 may be effective in the cancer process. Thus TMPRSS6 gene polymorphisms may affect the disease process by affecting the blood parameters of patients.Publication Metadata only Comparison of spectrophotometric and fluorimetric methods in evaluation of biotinidase deficiency(Sciendo, 2016) Iseri-Erten, Sevgin Özlem; Dikmen, Zeliha Günnur; Ulusu, Nuriye Nuray; Faculty Member; School of Medicine; 6807Background: Biotin, a water-soluble vitamin, is used as a co-factor by enzymes involved in carboxylation reactions. Biotinidase (BTD) catalyzes the recycling of biotin from en do genous and dietary sources. Biotinidase deficiency (BD) is an autosomal recessively inherited disorder of biotin recycling that is associated with neurologic and cutaneous consequences when untreated. The aim of the study was to compare the results of spectrophotometric and fluorimetric methods, as well as to evaluate the advantages and disadvantages of both methods in current research practices. Methods: Study group was chosen among the BD suspected newborn, children and parents (n=52) who applied to Hacettepe University Pediatric Metabolism Unit. Results: BTD activity is stable for 2 hours at room temperature and at 4 degrees C, and for 4 months at -20 degrees C and -80 degrees C. Genetic and clinical results showed that 25% of the total number of patients had complete BD which was treated with 10 mg/day biotin, while 15.38% of the patients had partial BD, and they were prescribed biotin 5 mg/day. The area under the ROC curve was 0.960 +/- 0.25 and 0.927 +/- 0.41 for the fluorimetric and spectrophotometric method, respectively. Fluorimetric method showed 100% sensitivity and 97% specificity, whereas spectrophotometric method showed 90.5% sensitivity and 93.7% specificity. Conclusions: Fluorimetric method is superior to the spectro photo metric method due to higher sensitivity and specificity.Publication Metadata only Effects of alprazolam and haloperidol on thyroglobulin, antithyroglobulin, anti thyroid peroxidase and TSH in Rat(Walter De Gruyter Gmbh, 2018) Samadi, Afshin; Ansari, Mohammad Hassan Khadem; Ulusu, Nuriye Nuray; Faculty Member; School of Medicine; 6807Background: A large number of psychotropic drugs can interfere with the thyroid physiology, function and autoimmunity. Objective: The aim of the present study was to investigate the effects of alprazolam and haloperidol on thyroglobulin, antithyroglobulin (aTg), antithyroid peroxidase, and thyroid stimulating hormone levels on rats. Materials and Methods: First group of adult male Wistar rats was the control, second group received 0.5 mg kg(-1) haloperidol in physiological saline and the third group received 0.5 mg kg(-1) alprazolam, via gastric gavage once daily for 28 days. Plasma levels of all thyroid function tests were measured with chemiluminescent assay. Results: We have investigated a decrease in aTg amounts of control group (5.461 +/- 0.718) compared with drug treated rats with alprazolam (1.433 +/- 0.225) and haloperidol (1.21 +/- 0.228). (P-aTg = 0.00([ALP]), P-aTg = 0.01([HAL])). Although there were not any change in thyroglobulin levels in the haloperidol treated groups (0.9583 +/- 0.014) relative to control group (0.975 +/- 0.015); but in opposition Tg levels decreased significantly in response to alprazolam (0.36 +/- 0.16) compared with the control group (0.975 +/- 0.015), p-values are (P-Tg = 0. 001([ALP])), (P-Tg = 0. 021([HAL])). Conclusion: We found that these two drugs may interfere with the thyroid physiology and metabolism.Publication Metadata only Identifying and solving scientific problems in the medicine: key to become a competent scientist(Walter De Gruyter Gmbh, 2020) N/A; Aydemir, Duygu; Ulusu, Nuriye Nuray; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; 6807The scientific method can be described as a multistep and detailed process, in which finding the best question is the first and most crucial step. Thus, scientific problem should be examined thoroughly in different ways and perspectives. The amount and diversity of scientific data are enormously increasing and becoming more specific day by day, therefore traditional observational biology is not sufficient on an individual basis to understand and treat multifactorial diseases. Moreover, protocols, documentations, information, outcomes, precisions, and considerations of evidence should be improved to answer scientific questions correctly during the scientific research. Because of the diversity of the data and the methods, statisticians and methodologists should be involved and contribute to the all stages of research. Besides that, all scientific data should be certainly reproducible and repeatable. Scientific knowledge is in a state of flux and becomes more complex day by day. Thus, becoming a competent scientist needs, abilities and skills such as creativity, hardworking and self-discipline that all requires lifelong learning, searching, and widening scientific horizons consistently. / Bilimsel yöntem, en iyi soruyu bulmanın ilk ve en önemli adım olduğu çok aşamalı ve ayrıntılı bir süreç olarak tanımlanabilir. Bu nedenle, bilimsel problem farklı şekillerde ve bakış açılarıyla ayrıntılı olarak incelenmelidir. Bilimsel verilerin sayısı ve çeşitliliği gün geçtikçe son derece hızlı bir biçimde artmakta ve daha belirgin hale gelmektedir, bu nedenle gelenekseli, gözlemsel biyoloji, çok faktörlü hastalıkları anlamak ve tedavi etmek için tek başına yeterli değildir. Ayrıca, bilimsel araştırma sırasında bilimsel sorulara doğru cevap verebilmek için protokoller, belgeler, bilgiler, sonuçlar, kesinlikler ve kanıtlar iyileştirilmelidir. Verilerin çeşitliliği ve yöntemlerden dolayı, istatistikçiler ve metod geliştirenler araştırmaya katılmalı ve araştırmanın her aşamasına katkıda bulunmalıdır. Bunun yanı sıra, tüm bilimsel veriler kesinlikle tekrarlanabilir olmalıdır. Bilimsel bilgi bir akış halindedir ve gün geçtikçe daha karmaşık hale gelir. Böylece, yetkin bir bilim insanının yaratıcılık, çalışkanlık ve öz disiplin gibi ihtiyaçları, yetenekleri ve becerileri herkesin yaşam boyu öğrenmeyi, aramayı ve bilimsel ufukları tutarlı bir şekilde genişletmeyi gerektiren bir hale gelir.Publication Metadata only Melatonin improves reduced activities of membrane atpases and preserves ultrastructure of gray and white matter in the rat brain ischemia/reperfusion model(Springer, 2021) Tuncer, Meltem; Pehlivanoğlu, Bilge; İsbir, Turgay; Sürücü, Hüseyin Selçuk; Faculty Member; School of Medicine; 21780Ischemia/reperfusion (I/R) is among the most frequent neurological problems and early intervention to limit the damage is crucial in decreasing mortality and morbidity. Based on reports regarding beneficial effects of melatonin, we investigated its impact on Na+-K+/Mg2+ ATPase and Ca2+/Mg2+ ATPase activities and ultrastructure of gray and white matter in the rat forebrain I/R model. Adult Wistar-albino rats (n = 78), were randomized into control, ischemia (I), ischemia/reperfusion (I/R), low (I/R + melatonin 400 mu g/kg), moderate (I/R + melatonin 1200 mu g/kg), and high (I/R + melatonin 2400 mu g/kg) dose melatonin. Two-vessel occlusion combined with hypotension (15 min) induced ischemia and reperfusion (75 min) achieved by blood reinfusion were performed. Activities of the membrane-bound enzyme, brain malondialdehyde levels, and brain matter ultrastructure were examined in frontoparietal cortices. Melatonin lowered production of malondialdehyde in a dose-dependently. The enzyme activities attenuated under I and I/R, improved with melatonin treatment. I and I/R severely disturbed gray and white matter morphology. Melatonin, in all applied doses, decreased ultrastructural damages in both gray and white matter. Favorable effects of melatonin can be attributed to its antioxidant properties suggesting that it could be a promising neuroprotective agent against I/R injury being effective both for gray and white matter due to favorable biological properties.Publication Metadata only Perceived barriers to diabetes management at home: a qualitative study(Walter De Gruyter Gmbh, 2019) Acil, Dilay; Bahar, Zühal; Faculty Member; School of Nursing; 3918Background: Diabetes is a complex and progressive disease and its treatment requires self-management strategies specific for each patient. The aim of the study was to determine perceived barriers to diabetes management at home in type II diabetes patients. Materials and methods: Inclusion criteria of this phenom-enological study included living in Izmir and a diagnosis for the last 1 year; 15 patients with diabetes participated the study. A semi-structured interview form based on Health Belief Model created by researchers with experts opinion, was used at in-depth face-to-face interviews. Data were analyzed with content analysis. Ethical and hospital approval was obtained. Participation of individuals is based on volunteerism; written informed consent from patients who accepted the study. Results: Perceived barriers to fulfilling home care needs and sustaining behavior of diabetes management included six themes, i.e. insufficient knowledge of diabetes, inability to accept diabetes, non-adherence to diabetes and exercise, problems with health care services, fear and effects of the family and the society and relevant subthemes. Conclusion: These findings about the barriers of the patients should provide guidance for patient specific nursing interventions.Publication Metadata only Possible mechanisms of transmissible cancers in tasmanian devils(Walter De Gruyter Gmbh, 2017) Ulusu, Nuriye Nuray; Faculty Member; School of Medicine; 6807Physical transfer of viable tumor cells from one organism to another is known as transmissible cancer, which is observed in dogs, Tasmanian devils, Syrian hamsters, and some soft-shell clams. Tasmanian devil facial tumor disease is transmitted like an infectious disease between individuals through biting and other close contact. This extinction type is quite different from the other extinction types such as ecological factors. Transmissible cancers' cellular metabolism is also different from the both normal cellular metabolism and other types of cancers' metabolism. The lack of an immune response against the Tasmanian devil facial tumor cells is the one of the key points in the transmission of the cancerous cells. The differentiated cellular metabolism and absence of immune reaction may be due to the organisms' enzymes. Cells may have altered surface proteins by altering enzymatic activities that cannot be recognized by both the innate and adaptive responses. The promiscuity of the key enzymes may be associated with unwanted side effects, such as cannot recognize molecular patterns on the transmitted cell or hypomethylation of DNA by altering catalytic properties enzymes or altered matrix metalloproteinases or cathelicidins.Publication Metadata only Understanding follicle growth in vitro: are we getting closer to obtaining mature oocytes from in vitro-grown follicles in human?(Wiley, 2017) Güzel, Yılmaz; N/A; Öktem, Özgür; Faculty Member; School of Medicine; 102627Obtaining and fertilizing mature oocytes from immature follicles that were grown outside the body has conceptually attracted scientists for centuries, with initial attempts first documented in the 19th century. Significant progress has been made since then, due in part to a better understanding of folliculogenesis and improved techniques of in vitro follicle growth. Indeed, in vitro growth is now considered a reasonable approach to preserve or restore fertility when immature follicles and their oocytes need to be grown and matured outside the body. Certain patients would benefit from in vitro follicle growth, particularly those who carry a risk of cancer re-seeding after grafting of frozen-thawed ovarian tissue or who are at the risk of premature ovarian failure due to several intrinsic ovarian defects and genetic mutations that lead to accelerated follicle atresia and early exhaustion of the ovarian reserve. This review provides an update on the current status of in vitro growth of preantral human follicles, from initial efforts to the most recent achievements.