TR Dizin İndeksli Yayınlar Koleksiyonu / TR Dizin Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14365/4
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Article The Evaluation of Health Status of Familial Mediterranean Fever Patients with Homozygous M694V Mutation(2025-09-02) Kehribar, Demet Yalcin; Ozgen, Metin; Baraz, Lale Saka; Çakar, AyşegülAim: Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder characterized by recurrent episodes of fever, serositis, and systemic inflammation. The M694V mutation in the MEFV gene is associated with a more severe disease phenotype, including early onset, frequent attacks, and an increased risk of amyloidosis. This study aimed to evaluate the clinical features, comorbidities, and treatment outcomes of FMF patients homozygous for the M694V mutation. Material and Methods: A retrospective analysis was conducted on 183 FMF patients homozygous for the M694V mutation, diagnosed and followed at our hospital between 2014 and 2022. Data on demographics, clinical characteristics, laboratory findings, and treatment modalities were collected. Results: The most common symptoms were abdominal pain (88%), joint pain (78%), and arthritis (46%). Proteinuria and amyloidosis were detected in 22.4% and 7.1% of patients, respectively. The average age of symptom onset was 14.1 years, with a mean annual attack frequency of 2.75. Comorbidities were present in 24% of patients, including spondyloarthritis and inflammatory bowel disease. Colchicine was the mainstay treatment (94.5%), while 21.8% required IL-1 inhibitors. Eight patients (4.4%) died during follow-up, five due to amyloidosis-related complications. Conclusion: M694V homozygous FMF patients exhibit a severe disease presentation associated with this variant with frequent attacks, high amyloidosis risk, and significant comorbidities. While colchicine remains essential, biologics are increasingly used for colchicine-resistant cases. Early diagnosis, individualized treatment, and regular monitoring are crucial to improving patient outcomes.Article Bibliometric Analysis on Methods and Tools Developed for DGE Analysis: Current Trends and Future Perspectives(2025-04-29) Kochan, NeclaDiferansiyel gen ekspresyonu (DGE) analizi, yeni nesil dizileme teknolojilerinin ortaya çıkışıyla önemli bir ilgi kazanmıştır. Bu durum, DGE analizi için çeşitli yöntemlerin ve araçların geliştirilmesine yol açmıştır. Bu çalışmada, Biblioshiny ve VOSviewer yazılımları kullanılarak, incelenen dönem boyunca eğilimleri araştırmak amacıyla bibliyometrik analiz yapılmıştır. 2005-2023 yılları arasında Web of Science veri tabanından, diferansiyel gen ekspresyonu ile ilgili terimleri konu alan ilgili makaleler taranmıştır. İncelenen dönem boyunca yayımlanan eğilimleri göstermek için Biblioshiny ve VOSviewer yazılımları kullanılarak ağ haritaları oluşturulmuştur. Toplamda 729 çalışma, DGE analizi metodolojilerindeki, araçlarındaki ve paketlerindeki eğilimleri ortaya koymak amacıyla incelenmiştir. Bu amaçla, ülke, kurum, kaynak, yazar ve anahtar kelime üretkenliği açısından eş-yazarlık, bibliyografik eşleşme ve eş-oluşum analizleri yapılmıştır. 2005 yılından sonra çıktı ve atıf sayılarında artış gözlenmiştir. Çalışma süresince ABD ve Çin, DGE analizine en çok katkı sağlayan ülkeler olarak öne çıkmıştır. Zamansal çalışmalar, belirli aralıklarla bir miktar azalma olmakla birlikte, zaman içinde yayınlarda önemli bir artış olduğunu ortaya koymuştur. En büyük düşüş, 2008 ile 2010 yılları arasında gözlenmiştir. Bu düşüşlere rağmen, DGE analizi, herhangi bir hastalığın mekanizmalarını, gen işlevlerini ve terapötik hedefleri anlamadaki temel rolü nedeniyle genomikte kritik bir konu olmaya devam etmektedir. Bu eğilim, mevcut yöntemlerin ve araçların, çeşitli hastalıklarla ilişkili anahtar bilgilendirici genleri tanımlamak için yeterince güçlü kabul edildiğini göstermektedir.Research Project G Protein Kenetli Östrojen Reseptör 1 (Gper1)'In Gastrointestinal Adenokarsinom Hücrelerindeki Proliferatif ve Apoptotik Etkilerinin Araştırılması(2016) Kurt, Akif Hakan; Tosun, Metiner; Cetintas, Vildan BozokÇalışmamızda kadın hastalardan elde edilen AGS ve HT-29, mide ve kolorektal adenokarsinom hücre hatlarında GPER1 reseptörünün proliferatif ve apoptotik etkilerinin belirlenmesi ve hücreiçi sinyal yolaklarını araştırmak için GPER1 agonisti G-1 maddesi tek başına ve GPER1 protein kinaz ve kalsiyum kanal inhibitörleri varlığında hücre hatlarına uygulandı. Etken maddemiz G-1?in hangi hücre içi yolaklarla ilişkili olabileceğini bulmak için 10-5 M konsantrasyonda G-1 ile kombine olarak hücre içi sinyal yolaklarını inhibe eden inhibitörler; GPER1 inhibitörü G-15, protein kinaz A inhibitörü H-89, protein kinaz C (PKC) inhibitörü GF109203, fosfotidilinozitol 3-kinaz (PI3K) inhibitörü LY-294002, Rho-kinaz (ROCK) inhibitörü Y-27632, kalsiyum ATPaz inhibitörü tapsigargin ve inositol 1,4,5 trifosfat (IP3)inhibitörü 2-APM kullanıldı. Kombine uygulamaların hücre canlılığı üzerine etkisi 48. ve 72. saatlerde MTT yöntemiile değerlendirildi. MTT ve Xcelligance sonuçlarına göre, GPER1 agonisti G-1, AGS ve HT-29 hücreleri üzerinde konsantrasyona ve zamana bağlı olarak sitotoksik ve antiproliferatif etki göstermiştir. Hücre proliferasyon deney sonuçlarına göre AGS mide kanser hücre hattında GPER1 agonisti G-1'in oluşturduğu sitotoksik ve antiproliferatif etki inositol 1,4,5 trifosfat (IP3) bağımlı görünmektedir. HT-29 kolon kanser hücre hattında, GPER1 agonisti G-1'in oluşturduğu sitotoksik ve antiproliferatif etki fosfotidilinozitol 3-kinaz (PI3K) ve inositol 1,4,5 trifosfat (IP3) bağımlı görünmektedir. Yapılan denemelerde G-1 maddesinin en yüksek konsantrasyonu ile 72 saat inkübasyon sonunda AGS kanser hücre hattında % 49.1 oranında nekroz, % 9.9 erken apoptoz, % 4.1 geç apoptoz;HT-29 kanser hücre hattında % 32.6 nekroz, % 2.2 erken apoptoz, % 2.2 geç apoptoz gözlenmiştir. GPER1 agonisti G-1 in p53, Bcl-2 ve Bax ekspresyon üzerine etkisi sonuçlarına göre; G-1 in oluşturduğu apoptotik etkiye, p53 sinyal iletim yolağının aracılık ettiği görülmektedir (Bax ekspresyon artışı ve Bcl-2 ekspresyon azalması). Real-Time PCR ve görüntüleme sonuçlarına göre HT-29 ve AGS hücrelerinde siRNA kullanarak GPER1 ekspresyonubaşarılı bir şekilde baskılanmıştır. MTT hücre proliferasyon deney sonuçlarında, GPER1 agonisti G-1, siRNA uygulanmamış ve uygulanmış hücreler üzerinde benzer etki göstermiştir. GPER1 agonisti G-1'in oluşturduğu sitotoksik ve antiproliferatif etki GPER1 reseptör bağımlı görünmemektedir. Sonuç olarak; GPER1 agonisti G-1, AGS ve HT-29 kanser hücrelerinde yüksek dozda belirgin olarak sitotoksik ve antiproliferatif etki oluşturmuştur. Bu çalışma GPER1 agonisti G-1? i mide ve kolorektal kanser hastaları için yeni bir hedef haline getirebilir; mide ve kolorektal kanser hastaları üzerinde ikinci basamak çalışmaların yapılmasına öncülük edebilir.Research Project Hepatoselüler Karsinoma Hücrelerinde Telomerik Dna Replikasyonu Proteini Ctc1'in Kuadrupleks Dna (G4) Stabilizatörleri ile Kombine Olarak Hedeflenmesi(2021) Karagonlar, Zeynep Fırtına; Yandım, Cihangir; Sezan, Sıla; Karpat, ÖzümDNA onarım mekanizmaları, sağlıklı hücrelerin genomunun bütünlüğünün korunmasında çalışsa da, bu mekanizmalar kanser hücrelerine uygulanan tedavilerin verimini azaltmakta ve direnç geliştirmektedir. Bu sebeple kanserli hücreleri hedefleyerek geliştirilen DNA hasarı onarımının inhibisyon stratejisi meme ve over gibi kanserlerde PARP inhibitörleri (ör. Olaparib) kullanılarak başarıya ulaşmıştır. Fakat, karaciğer kanserinde bu stratejiler henüz sonuç vermemiştir. Karaciğer kanserinin en yaygın türü olan Hepatosellüler Karsinoma (HCC) tedaviye dirençli, çoklu moleküler karsinogenez basamağına sahip bir malignitedir. İleri HCC hastaları için Sorafenib ve Regorafenib gibi HCC?de öncelikli olan güdümlü terapiler geliştirilmesine rağmen, kansere yönelik tedavileri büyük ölçüde mevcut gereksinimin gerisindedir ve kanserin dirençle nüksetmesi gibi problemler mevcuttur. Bu projede yeni bir yaklaşımla, ilaç dirençli HCC hücrelerinde G-kuadruplekslerin neden olduğu DNA hasarının onarımından sorumlu telomerik replikasyon proteini CTC1 üzerinden telomerik DNA?nın hedeflenmesi amaçlanmaktadır. Literatürde, CTC1?in telomerlerin stabilitesi için kritik olduğu gösterilmiştir. CTC1?in susturulması, hatalı telomer replikasyonu, kök hücre tükenmesi ve telomerlerin kaybı ile sonuçlanmıştır. Kanserli hücrelerde CTC1 geninin susturulmasının diğer önemli sonucu hücrelerde artan radyosensitivitedir. Ayrıca, dirençli olmayan kontrollere kıyasla radyoterapi-dirençli melanom hücrelerinde CTC1 ekspresyonunun kritik artışı gözlemlenmiştir, yani tümörojenik hücrelerde CTC1 geninin direnç gelişiminde önemi gösterilmiştir. Bu projede, CTC1 inhibisyonuna sahip hücrelerde G4 stabilizatörleri ile ilave telomer DNA hasar yüklemesi indüklenerek kanser hücresi canlılığını azaltabilecek antitümör oluşum mekanizmaları araştırılmıştır. Ayrıca, bu çalışmada Sorafenib?e duyarlı hatların yanında, aynı hatların Sorafenib-dirençli klonları da kullanılarak önerilen stratejinin sorafenib direncine yönelik hassasiyete sebep olup olmadığı incelenmiştir. Kısaca, Epitelyal-benzeri (Huh-7) ve Mezenkimal-benzeri (Mahlavu) HCC hücre hatları ile öncesinde oluşturduğumuz Sorafenib-dirençli klonlarında da CTC1 geni susturularak, G4 stabilizatörleri ve Sorafenib ile tekli ve kombine ilaç uygulaması gerçekleştirilmiştir. Bu stratejinin kanserli hücre canlılığı ve DNA hasarına etkileri, immünositokimyasal boyama ve MTT Assay ile incelenmiştir. Ayrıca, susturulan hücrelerin büyüme hızı, sferoid ve koloni oluşumları incelenmiştir. Böylece, çalışmanın sonuçları hem Sorafenib dirençli hastalarda yeni tedavilerin planlanmasına hem de geleneksel kemoterapi seçeneklerinin veriminin artırılmasında translasyonel potansiyele sahiptir.Article Upregulated Acute Systemic Inflammation-Related Genes Based on Endotoxin Exposure Provide ‘Survival Benefit’ or Create ‘High Risk of Death’ in Leukaemia and Colon Cancer(Istanbul University, 2024-07-10) Duran, Gizem Ayna; Duran, Assist. Prof. Dr. Gizem Ayna; Ayna Duran, GizemObjective: Although endotoxin exposure has been shown to trigger innate immune responses and promote cancer, it has also been shown to prevent cancer formation. In our study, survival analysis was performed to determine whether the upregulated genes triggered by endotoxins have hazardous effects on cancers or provide a survival benefit. Materials and Methods: Gene intensity values of control and bacterial endotoxin-administered individuals were obtained from the Gene Expression Omnibus database. Using the R "Linear Models for Microarray Data" package, differentially expressed gene analyses were conducted to determine genes that differ between healthy and bacterial endotoxin-administered samples. "ShinyGo 0.80" web-based tool was used to determine the disease types indicated by these genes. The "Kaplan-Meier Plotter" web-based tool was used to conduct survival analysis. Results: Genes that create an innate immune response to bacterial endotoxin exposure and are upregulated differently than in individuals without exposure were identified. According to gene enrichment analyses, the two main types of cancer identified were leukaemia/lymoma and colon cancer. We detected that MLF1, STAT5B, and BCL3 genes led to poor survival; however, the ARHGAP26 gene was protective for acute myeloid leukaemia patients. In the case of colon cancer, SMAD7 and TLR2 genes were determined as leading to "high risk of death". Conclusion: Once the systemic inflammation-related genes identified in our study are confirmed through laboratory experiments in samples taken from solid tissue in the case of colon cancer and at the level of genes obtained from blood samples in leukemias, genetically targeted treatments will also be possible.Article Evaluation of Blood and Cerebrospinal Fluid Biochemistry, Cytology and Haematological Parameters in Head-And Form of Malignant Catarrhal Fever in Cattle(2023-08-01) Uzlu, Erdoğan; Erkılıç, Ekin Emre; Adalı, Yasemen; Öğün, Metin; Can Şahna, Kezban; Eryeğen, Nilhan; Eroğlu, Hüseyin Avni; Abayli, Hasan; Ermutlu, Celal ŞahinIn this study, it was aimed to examine the biochemical changes, hematological changes and cerebrospinal fluid (CSF) cytology and blood serum of cattle with head-eye form of Malignant Catarrhal Fever (MCF). For this pur- pose, 22 cattle diagnosed with "head-eye form" of MCF and clinically healthy 10 cattle were evaluated. Blood and cere- brospinal fluid (CSF) were collected from all cattle. In sera, AST, urea, glucose, CK (P<0.05), LDH levels (P<0.01) were found be high, ALT, ALP, cholesterol (P<0.05), Ca, total protein (P<0.01) and Mg, albumine and Fe levels (P<0.001) were found to be low in MCF group when compared to the control group. In CSF, Ca (P<0.01) and total protein levels (P<0.001) were found high glucose level (P<0.05) was found low in MCF group when compared to the control group. In haematology, some parameters were determined to be different between the groups. In cytological results of CSF in MCF group, polymorphonuclear leucocytes, lymphocytes, erytrocytes, macrophages and plasma cells were determined. In conclusion, since there were a limited number of studies examining biochemical, cytologic and hematological results of MCF especially in CSF, the results from our study were thought to be important for future stud- ies in which viral diseases affects the nervous system of cattles.Article Experimental Intravaginal and Intrauterine Endometritis Model: Which Model Is More Useful?(2022-12-31) Beşeren, Hatice; Makav, Mustafa; Kuru, Mushap; Adalı, Yasemen; Coşkun, Mustafa Reha; Eroğlu, Hüseyin AvniThis study aims to compare the newly created intravaginal endometritis model (IVM) with the intrauterine endometritis model (IUM). E. coli infusion was used as intravaginally for IVM and intrauterinally for IUM model. The animals were exeuted on the 7th day. Histopathological and biochemical analyses [malondialdehyde (MDA), glutathione (GSH), Endocan, Endoglin] were performed. A significant inflammation was determined in IVM and IUM compared to the control. A significant decrease in GSH and a significant increase in MDA and Endoglin were determined in IVM and IUM compared to the control. There was a statistically significant increase in the IUM and a numerical increase in the IVM compared to the control. Endometritis was determined by histopathological and biochemical analyses in both IUM and IVM model. It is suggested that intravaginal administration, which is easier to perform, can be used in experimental endometritis model studies.Article Pathological and Biochemical Investigation of the Effects of L-Carnitine and Gemfibrozil on Peroxisome Proliferator Activated Receptors (ppars) and Lipidosis in Rabbits on a High-Fat Diet(2022-12-31) Erkılıc, Ekin Emre; Çitil, Mehmet; Tunca, Recai; Uzlu, Erdogan; Karapehlivan, Mahmut; Adalı, Yasemen; Yapar, Kürşad; Eroğlu, Huseyin Avni; Makav, MustafaObesity and fatty liver is a worldwide health problem in human with detrimental consequences where many investigations are undertaken to overcome this problem. In this study, gemfibrozil and L-carnitine were evaluated in prevention of obesity and lipidosis. The study involved 56 New-Zealand Albino rabbits, divided into 8 equal groups (n=7). The groups were as follow; group I (normal diet), II (normal diet +gemfibrozil), III (normal diet+L-carnitine) and IV (normal diet+gemfibrozil+L- carnitine), V (high fat diet), VI (high fat diet+gemfibrozil), VII (high fat diet+L- carnitine) and VIII (high fat diet+gemfibrozil+L-carnitine). Animals were blood sampled and wieght weekly during the experiment and at the end of the experiment for determination of biochemical parameters (glucose, total lipid). All rabbits were euthanised for histopathological examination and for distrubition of peroxisome proliferator activated receptors (PPARs) in tissues by immunohystochemistry. Gemfibrozil and L-carnitin treatment in rabbits given high fat diet resulted in statistically significant decrease in total lipid when compared to those only received high fat diet. Beta oxidation of high fat diet group was significantly higher than that of groups additionally received gemfibrozil and L-carnitine. Immunohistochemistry revealed an increase in PPAR, PPAR-α and β but not PPAR-γ expression in high fat diet group. On the contrary, L-carnitin administration had no effect on tissue PPAR expression. PPAR-α expression differed between groups received gemfibrozil and high fat diet and those did not. The most marked macroscopy finding was abdominal fat increase in high fat diet group (group V). On the other hand gemfibrozil administration resulted in significant abdominal fat decrease. Furthermore decreased abdominal fat was marked in gemfibrozil and L-carnitine given animals (group VIII) when compared to other groups. In conclusion, gemfibrozil and L-carnitine administration alleviated abdominal and hepatic fattening. Gemfibrozil also caused a significant increase in PPAR-α expression in the liver. It may be of use in avoiding abdominal fat (obesity) due to high fat diet by use of gemfibrozil, a synthetic PPAR-a ligand, and L-carnitine.Article Investigation of Cyclin-D1 Immunohistochemical Expression in Bladder Urethelial Carcinoma(2023-06-27) Adalı, Yasemen; Ezer, Mehmet; Yılmaz Ertürk, Fatma; Beşeren, Hatice; Ertürk, Fatma YılmazObjective: Cyclin D1 is a protein that is involved in the regulation of the cell cycle and is encoded by the CCND1 gene. There are few studies on Cyclin D1 in the literature, and the results differ in the studies. In this study, the relationship between Cyclin D1 expression and prognostic factors in bladder urothelial carcinomas was investigated. Materials and Methods: Forty-six patients who underwent TUR-M at the Kafkas University Health Research and Application Hospital were included in the study. General information about the cases and pathology reports were obtained from the hospital automation system. Tumor-containing sections were selected from the Hematoxylin and Eosin stained pathology slides, and immunohistochemical staining was performed manually with Cyclin D1 primary antibody on the blocks of the selected slides. Immunostained pathology slides were evaluated under light microscope by scoring 0-4 separately as nuclear and cytoplasmic scores. Results: The age range of the cases was 51-93, and the mean age was 69.2±11.7. Twelve (26.1%) cases were female and 34 (73.9%) were male. It was observed that 29 (63.0%) of the cases were low- grade and 17 (37.0%) were high-grade. Eighteen (39.1%) of the cases were invasive and 28 (60.9%) were noninvasive. In the statistical analyzes, it was noted that invasive tumors had a significantly higher grade compared to non-invasive tumors (pTa) (p= 0.007). Similarly, the presence of lymphovascular invasion in invasive tumors was statistically <0.005 higher than that of in non- invasive tumors. (p=0.001). It was observed that nuclear cyclin D1 expression (p=0.003) was significantly higher in invasive cases. In addition, nuclear cyclinD1 expression was found to be statistically significantly higher in low-grade tumors (p=0.044). Conclusion: As a result of the study, a relationship between Cyclin D1 expression and tumor grade and invasion status was observed in patients with bladder urothelial carcinoma, but studies with larger case series are needed to use Cyclin D1 as a biomarker.Article In Silico Approach for Identification of PI3K/MTOR Dual Inhibitors for Multiple Myeloma Treatment(Istanbul Univ, 2023-04-14) Masalaci, Ilke; Akdogan, Yaren; Mutlu, Ozge; Eyvaz, Hande; Kiraz, YagmurObjective: Multiple myeloma is a hematologic malignancy in which targeting phosphoinositide 3 kinase (PI3K) and/or the mammalian target of rapamycin (mTOR) individually has been shown to have anti-proliferative effects, however, inhibiting both proteins simultaneously has been reported to have more effective results for its treatment. The aim of this study is to determine the molecular interactions and predicted inhibitory effects of 40 different dual inhibitors on mTOR, PI3K delta, and PI3K gamma to propose potentially the most effective dual inhibitor that targets the PI3K delta and PI3K gamma isoforms as well as the mTOR proteins since those isoforms are known to be predominant in multiple myeloma patients. Therefore, the focus in this study is built around the specific targeting of the PI3K delta and PI3K gamma isoforms from the multiple myeloma perspective. Materials and Methods: In silico docking experiments were conducted to determine the binding energies for different ligands that target mTOR, PI3K delta, and PI3K gamma. Protein-dual inhibitor complexes and the amino acids and bond types were visualized to identify molecular interactions. The absorption, distribution, metabolism, and excretion properties of dual inhibitors were analyzed and evaluated. Results: The binding affinity values were found to be between -7 and -9.9 kcal/mol. The toxicity prediction values of the selected dual inhibitors were obtained from the Pro-Tox-II web tool and classified according to the globally harmonized system of classification of labeling of chemicals. Conclusion: Correspondingly, among all dual inhibitors, Vistusertib is determined to be a promising compound against multiple myeloma cells by inhibiting both PI3K delta and PI3K gamma as well as mTORC1/2.