TR-Dizin İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/396
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Article Dalak Tirozin Kinaz ve Histon Deasetilaz Enzim İnhibisyonunun FLT3-ITD(+) Akut Miyeloid Lösemi Hücreleri Üzerindeki Anti-Lösemik Etkisi(2025) Akcok, E. Basak Gencer; Şansaçar, MerveSpleen Tyrosine Kinase (Syk) crosstalk with paramount signaling pathways which has a major contribution in the progress of acute myeloid leukemia (AML) such as PI3K, NFκB and JAK/STAT signaling pathways. Several studies recorded that deregulated Histone Deacetylase (HDAC) enzymes are involved in the pathogenesis of AML. The study aims to reveal the effect of Syk and HDAC co-inhibition on MOLM-13 and MV4-11 AML cells which are harboring the receptor of FMS-like Tyrosine Kinase's (FLT3) Internal Tandem Duplication (ITD). AML cells were incubated using both R406 and HDAC inhibitors alone and in combination, and increasing concentrations of R406 and HDAC inhibitors revealed a significant reduction of MOLM-13 and MV4-11 cells’ viability using MTT cell viability test. Furthermore, the combination of R406 and VPA resulted in a reduction in the proliferation of both cells correlated with the synergistic effect of the two drugs revealed by the combination index (CI). Moreover, investigating apoptosis for the combined administration of drugs resulted in induced apoptosis in AML cells using Annexin-V/PI double staining. We observed also changes in the mRNA expression level of MYC after combination treatment via Real-time PCR analysis. Even though further studies are needed, targeting Syk and HDAC enzymes in AML cells may be a good strategy in the treatment of patients suffering from AML with FLT3 ITD (+) mutation.Article Bazı Geleneksel Türk Gıdalarından Laktik Asit Bakterilerinin İzolasyonu(2021) Doğan, Osman; Aydın, Aysun CebeciAmaç: Bu çalışma ülkemizde geleneksel yöntemlerle üretilen gıda ürünlerindenlaktik asit bakterilerinin izolasyonunu ve tanımlanmasını sağlamak amacıylayapılmıştır.Materyal ve Yöntem: Çalışma kapsamında Van otlu peynir ve ekşi hamur örneğikullanılmıştır. Bu örnekler içerdikleri laktik asit bakterileri için çalışılmış vetanımlanmaları için biyokimyasal ve PCR bazlı moleküler biyolojik tekniklere tabitutulmuşlardır. Biyokimyasal testler kapsamında örnekler, Gram reaksiyonları,katalaz aktivitesi, gaz üretimi, 10oC ve 45oC'de, %6 ve %16 NaCl konsantrasyonda,pH 4.4 ve pH 9.6’da gelişim göstermeleri açısından incelenmiştir. Moleküler biyolojideneyleri kapsamında ise tür ve suş düzeyinde tanımlama için PCR-RFLP, 16SrRNA gen dizileme ve RAPD-PCR teknikleri kullanılmıştır.Araştırma Bulguları: Bir dizi mikrobiyolojik deneylerin sonucunda 26 adet bakteripotansiyel laktik asit bakterisi olarak izole edilmiştir. Bunlardan 25 adedininLactobacillus, Pediococcus ve Enterococcus cinslerine ait olduğu tespit edilmiş vetür ve suş düzeyinde tanımlanmaları sağlanmıştır. Kalan bir adet izolat iseStaphylococcus hominis olarak tanımlanmıştır.Sonuç: Çalışmamız sonucunda 25 adet laktik asit bakterisi gen dizileme ve RAPDPCR teknikleri kullanılarak tür ve suş düzeyinde başarıyla tanımlanmıştır.Research Project RNA İkincil Yapılarının Çok Boyutlu Gösterimi ve Pre-MiRNA Tespiti İçin Uygulamaları(2021) Demirci, Müşerref Duygu Saçar; Demirci, Yılmaz Mehmet-Article Investigation of Antiviral Potential of Food Carotenoids and Apocarotenoids Against RNA-Dependent RNA Polymerase of Hepatitis C Virus(2022-09-30) Fidan, OzkanHepatitis C disease have been a global health threat and affects a significant portion of world population. Hepatitis C have also been a silent health threat for Turkiye, where there are around half million people infected with Hepatitis C Virus (HCV). Disease burden and mortality are expected to increase gradually in the next 20 years in Turkiye. Unavailability of enough data on the currently-available drugs in routine clinical practice, their side effects and interactions with other drugs, and their efficacies on the less common genotypes indicates the necessity of alternative treatment options. Natural products from herbal and medicinal plants can indeed provide an alternative as being drug-like dietary supplements. In particular, the carotenoids and apocarotenoids are underexplored in their antiviral potential, including anti-HCV activities. Therefore, we focused on the virtual screening of various carotenoids and apocarotenoids against the RNA-dependent RNA polymerase (RdRp) of HCV. Molecular docking experiments showed strong binding affinities of the ligands to both palm and thumb domains of RdRp of HCV. In fact, some of them such as neoxanthin, crocin, canthaxanthin and cryptoflavin bound quite strongly to both domains compared to native ligands and current antiviral drugs. MD simulation for neoxanthin-RdRp complex confirmed the stability of the ligand within the binding cavity of RdRp throughout 100 ns simulation. This clearly indicated the potential of carotenoids, specifically neoxanthin, as RdRp inhibitor in treating HCV. Thus, this study not only discovered anti-HCV drug candidates with the properties of easy-to-access and low cost, but also paved the way for the development of carotenoid or apocarotenoid based dietary supplement candidates for the prevention and treatment of HCV.Article Enlightening the Molecular Mechanisms of Type 2 Diabetes With a Novel Pathway Clustering and Pathway Subnetwork Approach(Tubitak Scientific & Technological Research Council Turkey, 2022-01-01) Bakir-Gungor, Burcu; Yazici, Miray Unlu; Goy, Gokhan; Temiz, Mustafa; Ünlü Yazici, MirayType 2 diabetes mellitus (T2D) constitutes 90% of the diabetes cases, and it is a complex multifactorial disease. In the last decade, genome-wide association studies (GWASs) for T2D successfully pinpointed the genetic variants (typically single nucleotide polymorphisms, SNPs) that associate with disease risk. In order to diminish the burden of multiple testing in GWAS, researchers attempted to evaluate the collective effects of interesting variants. In this regard, pathway-based analyses of GWAS became popular to discover novel multigenic functional associations. Still, to reveal the unaccounted 85 to 90% of T2D variation, which lies hidden in GWAS datasets, new post-GWAS strategies need to be developed. In this respect, here we reanalyze three metaanalysis data of GWAS in T2D, using the methodology that we have developed to identify disease-associated pathways by combining nominally significant evidence of genetic association with the known biochemical pathways, protein-protein interaction (PPI) networks, and the functional information of selected SNPs. In this research effort, to enlighten the molecular mechanisms underlying T2D development and progress, we integrated different in silico approaches that proceed in top-down manner and bottom-up manner, and presented a comprehensive analysis at protein subnetwork, pathway, and pathway subnetwork levels. Using the mutual information based on the shared genes, the identified protein subnetworks and the affected pathways of each dataset were compared. While most of the identified pathways recapitulate the pathophysiology of T2D, our results show that incorporating SNP functional properties, PPI networks into GWAS can dissect leading molecular pathways, and it could offer improvement over traditional enrichment strategies.Article Citation - WoS: 3Combined Effect of Midostaurin and Sphingosine Kinase-1 Inhibitor on FMS-Like Tyrosine Kinase 3 (FLT3) Wild Type Acute Myeloid Leukemia Cells(Walter de Gruyter Gmbh, 2022-02-01) Sahin, Hande Nur; Adan, AysunObjectives Therapeutic potential of clinically approved FLT3 inhibitor midostaurin has been neglected in wild-type FLT3 positive acute myeloid leukemia (AML). Sphingosine kinase-1 (SK-1) having anti-proliferative functions is studied in various cancers, but not in FLT3 wild-type AML. We aimed to develop new therapeutic strategies to combat FLT3 wild-type AML by combining midostaurin with SK-1 inhibitor (SKI II) in THP1 cells. Methods The anti-proliferative effects of midostaurin, SKI II and in combination on THP1 cells were determined by MTT assay. The combination indexes were calculated using calcusyn software. SK-1 expression and PARP cleavage were checked by western blot. Cell cycle distributions (PI staining) and apoptosis (annexin-V/PI dual staining) were assessed by flow cytometry for each agent alone and in combinations. Results Midostaurin decreased SK-1 protein level. Midostaurin, SKI II and certain combinations decreased cell viability in a dose dependent manner. The combined anti-leukemic effects of the aforementioned drug combination afforded additive effect. Co-administration induced both necrosis and apoptosis via phosphatidylserine externalization, PARP cleavage and cell cycle arrest at G0/G1 and S phases. Conclusions Targeting sphingosine kinase-1 together with FLT3 inhibition could be a novel mechanism to increase limited clinic response to midostaurin in wild-type FLT3 overexpressing AML after further pre-clinical studies.Article Green Synthesis of Silver Nanoparticles Using Walnut Shell Powder and Cynara sp. and Their Antibacterial Activities(2022-10-09) Erdem, İlker; Çakır, ŞerifeGümüş (Ag) ilgi çeken özellikleri ile (katalitik etkinlik, antimikrobiyal, vb.) bilinen bir malzemedir. Nano boyuttaki Gümüşartan yüzey alanı sebebiyle gelişmiş özellikler sunar. Yeşil üretim görece daha az zararlı malzemelerin kullanılması sebe - biyle umut veren daha çevre dostu bir malzeme hazırlama/üretme yöntemidir. Bu çalışmada, gümüş nano parçacıkların (Ag NP) hazırlanması için bitki özütleri (enginar, ceviz kabuğu tozu) hazırlama ortamı olarak kullanılmıştır. Farklı iki bitki özütüyle hazırlanan nano parçacıkların boyutları, sırasıyla ~46 nm ve ~109 nm olmuştur. Hazırlanan Ag NP’ların E.coli and S.aureus suşlarına karşı antibakteriyel etkileri belirlenmiş ve minimum etkili yoğunlukları araştırılmıştır.Article Tarhanadan Laktik Asit Bakterilerinin İzolasyonu(2020-07-14) Aydın, Aysun Cebeci; Çalış, Burak; Polat, Muhammet FatihTarhana is a staple food in Turkey and produced mainly by the fermentation of wheat flour and yogurt.There are variations in its use, it can be consumed as a snack, or as a soup, and its exact ingredients vary betweendifferent geographical regions. Our study aims to isolate and identify lactic acid bacteria in tarhana samples viabiochemical and molecular biology identification techniques. Three different tarhana samples were studied forbacterial Gram reactions, catalase activity, gas production, growth at 10°C and 45°C, in 6% and 16% NaClconcentrations and at pH 4,4 and pH 9,6 for the biochemical tests. For the molecular biology experiments, PCRRFLP, sequencing and RAPD-PCR were performed to identify organisms at the species and strain level.