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Öğe Resveratrol and quercetin-induced apoptosis of human 232B4 chronic lymphocytic leukemia cells by activation of caspase-3 and cell cycle arrest(Taylor & Francis Ltd, 2013) Gokbulut, Aysun Adan; Apohan, Elif; Baran, YusufChronic lymphocytic leukemia (CLL), defined by accumulation of pathogenic B cells, has a very complex biology due to various factors such as inherited, host, and enviromental factors. Recently, finding new therapeutic agents or development of novel treatment strategies have been paid attention. Resveratrol and quercetin, important phytoalexins found in many plants, have been reported to have cytotoxic effects on various types of cancer. In this study, we examined cytotoxic, cytostatic, and apoptotic effects of these two important phenolic compounds on 232B4 human CLL cells. Cytotoxic effects of resveratrol and quercetin were determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using caspase-3 colorimetric assay. Annexin V-FITC/PI double staining was performed to measure apoptotic cell population. Effects of resveratrol and quercetin on cell cycle profiles of CLL cells were investigated by flow cytometry. Treatment of CLL cells with resveratrol and quercetin caused dose dependent inhibition of cell proliferation and increased apoptotic cell population through induction of caspase-3 activity. Cell cycle analysis displayed cell cycle arrest mainly in G0/G1 for both polyphenols. Our data, in total, showed for the first time that resveratrol and quercetin might block CLL growth through inducing apoptosis and cell cycle arrest.Öğe scMAGS: Marker gene selection from scRNA-seq data for spatial transcriptomics studies(Pergamon-Elsevier Science Ltd, 2023) Baran, Yusuf; Dogan, BeratSingle-Cell RNA sequencing (scRNA-seq) has provided unprecedented opportunities for exploring gene expres-sion and thus uncovering regulatory relationships between genes at the single-cell level. However, scRNA-seq relies on isolating cells from tissues. Therefore, the spatial context of the regulatory processes is lost. A recent technological innovation, spatial transcriptomics, allows for the measurement of gene expression while preser-ving spatial information. An initial step in the spatial transcriptomic analysis is to identify the cell type, which requires a careful selection of cell-specific marker genes. For this purpose, currently, scRNA-seq data is used to select a limited number of marker genes from among all genes that distinguish cell types from each other. This study proposes scMAGS (single-cell MArker Gene Selection), a novel method for marker gene selection from scRNA-seq data for spatial transcriptomics studies. scMAGS uses a filtering step in which the candidate genes are identified before the marker gene selection step. For the selection of marker genes, cluster validity indices, the Silhouette index, or the Calinski-Harabasz index (for large datasets) are utilized. Experimental results showed that, in comparison to the existing methods, scMAGS is scalable, fast, and accurate. Even for large datasets with millions of cells, scMAGS could find the required number of marker genes in a reasonable amount of time with fewer memory requirements. scMAGS is made freely available at https://github.com/doganlab/scmags and can be downloaded from the Python Package Directory (PyPI) software repository with the command pip install scmags.Öğe Synthesis, cytotoxic and antimicrobial activities of novel cobalt and zinc complexes of benzimidazole derivatives(Elsevier Science Sa, 2017) Apohan, Elif; Yilmaz, Ulku; Yilmaz, Ozgur; Serindag, Ayfer; Kucukbay, Hasan; Yesilada, Ozfer; Baran, YusufIn this study fourteen novel cobalt (II) or zinc (II) complexes of benzimidazoles were synthesized from the 1-(4-substitutedbenzyl)-1H-benzimidazoles and CoCl2.6H(2)O or ZnCl2. Cytotoxic activities of novel complexes were investigated against lung cancer cells (A549) and BEAS-2B. Three of the examined compounds (1, 4 and 5) showed high cytotoxic activity against A549. While the IC50 of the cisplatin was 2.56 pg/mL for A549 cells at 72 h, the IC50 values of compounds 1, 4 and 5 were 1.97, 1.87 and 1.9 mu g/mL, respectively. IC50 values of these compounds for BEAS-2B cells were higher than the IC50 values for A549. While the IC50 values for BEAS-2B cells were 59.8, 24.5 and 32.67 mu g/mL, respectively, the IC50 of the cisplatin was determined as 2.53 pgimL in the present work. Three of the compounds have also high antimicrobial activity against all the microorganisms used. (C) 2016 Elsevier B.V. All rights reserved.Öğe Therapeutic potential of targeting ceramide/glucosylceramide pathway in cancer(Springer, 2013) Yandim, Melis Kartal; Apohan, Elif; Baran, YusufSphingolipids including ceramides and its derivatives such as ceramide-1-phosphate, glucosylceramide (GlcCer), and sphingosine-1-phosphate are essential structural components of cell membranes. They now recognized as novel bioeffector molecules which control various aspects of cell growth, proliferation, apoptosis, and drug resistance. Ceramide, the central molecule of sphingolipid metabolism, generally mediates anti-proliferative responses such as inhibition of cell growth, induction of apoptosis, and/or modulation of senescence. There are two major classes of sphingolipids. One of them is glycosphingolipids which are synthesized from the hydrophobic molecule, ceramide. GlcCer, generated by glucosylceramide synthase (GCS) that transfers the glucose from UDP-glucose to ceramide, is an important glycosphingolipid metabolic intermediate. GCS regulates the balance between apoptotic ceramide and antiapoptotic GlcCer. Downregulation or inhibition of GCS results in increased apoptosis and decreased drug resistance. The mechanism underlying the drug resistance which develops with increased glucosylceramide expression is associated with P-glycoprotein. In various types of cancers, overexpression of GCS has been observed which renders GCS a good target for the treatment of cancer. This review summarizes our current knowledge on the structure and functions of glucosylceramide synthase and glucosylceramide and on the roles of glucosylceramide synthase in cancer therapy and drug resistance.Öğe Uzamsal transkriptomiks analizleri için tek hücre RNA sekanslama verilerinden hareketle işaretçi gen seçimi yapan yeni bir yöntemin geliştirilmesi(İnönü Üniversitesi, 2022) Baran, YusufSon birkaç yılda geliştirilen teknolojiler ile birlikte artık herhangi bir anda hücre içerisindeki transkriptomun uzamsal olarak analiz edilebilmesi mümkün hale gelmiştir. Hücrelerin gen ifadesine ilişkin konum bilgisinin artık elde edilebiliyor olması hücrelerin uzamsal olarak birbirleriyle olan ilişkilerini ve dolayısıyla hücresel düzeyde vücutta meydana gelen birçok biyolojik süreci daha iyi anlamamıza imkân tanımaktadır. Ancak gelişmekte olan uzamsal teknolojilerin deneysel maliyetleri hala yüksektir ve bu teknolojilerin bazıları deney öncesinde hücre tiplerini birbirlerinden ayırt edebilen kısıtlı sayıdaki işaretçi genin önceden belirlenmesine ihtiyaç duymaktadır. Bu tez kapsamında literatürde in situ uzamsal transkriptomik deneyleri için gen seçimi işlemini gerçekleştiren yöntemler incelenmiş, eksiklikleri belirlenmiş ve eksiklikleri gidermek için bir yöntem geliştirilmiştir. Geliştirilen yöntem literatürde önerilen diğer yöntemler ile birçok açıdan karşılaştırılmış, üstünlükleri ve eksiklikleri tartışılmıştır. Sonuçlar, önerilen yöntemin değerlendirilen birçok parametre için mevcut yöntemlerden üstün olduğunu açıkça göstermektedir. Ayrıca önerilen yöntem açık erişimli bir yazılım paketi haline getirilerek araştırmacıların kullanımına sunulmuştur.
