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Citation Count: 30
Apoptotic Effects of Quercitrin on DLD-1 Colon Cancer Cell Line
(Frontiers Media Sa, 2015) Cincin, Zeynep Birsu; Unlu, Miray; Kiran, Bayram; Bireller, Elif Sinem; Baran, Yusuf; Cakmakoglu, Bedia; Baran, Yusuf
Quercetin, which is the most abundant bioflavonoid compound, is mainly present in the glycoside form of quercitrin. Although different studies indicated that quercitrin is a potent antioxidant, the action of this compound is not well understood. In this study, we investigated whether quercitrin has apoptotic and antiproliferative effects in DLD-1 colon cancer cell lines. Time and dose dependent antiproliferative and apoptotic effects of quercitrin were subsequently determined by WST-1 cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, detection of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine (PS) in the plasma membrane. There were significant increases in caspase-3 activity, loss of MMP, and increases in the apoptotic cell population in response to quercitrin in DLD-1 colon cancer cells in a time- and dose-dependent manner. These results revealed that quercitrin has antiproliferative and apoptotic effects on colon cancer cells. Quercitrin activity supported with in vivo analyses could be a biomarker candicate for early colorectal carcinoma.
Citation Count: 7
Comparative development of knowledge-based bioeconomy in the European Union and Turkey
(informa Healthcare, 2014) Ozan, Didem Celikkanat; Baran, Yusuf; Baran, Yusuf
Biotechnology, defined as the technological application that uses biological systems and living organisms, or their derivatives, to create or modify diverse products or processes, is widely used for healthcare, agricultural and environmental applications. The continuity in industrial applications of biotechnology enables the rise and development of the bioeconomy concept. Bioeconomy, including all applications of biotechnology, is defined as translation of knowledge received from life sciences into new, sustainable, environment friendly and competitive products. With the advanced research and eco-efficient processes in the scope of bioeconomy, more healthy and sustainable life is promised. Knowledge-based bioeconomy with its economic, social and environmental potential has already been brought to the research agendas of European Union (EU) countries. The aim of this study is to summarize the development of knowledge-based bioeconomy in EU countries and to evaluate Turkey's current situation compared to them. EU-funded biotechnology research projects under FP6 and FP7 and nationally-funded biotechnology projects under The Scientific and Technological Research Council of Turkey (TUBITAK) Academic Research Funding Program Directorate (ARDEB) and Technology and Innovation Funding Programs Directorate (TEYDEB) were examined. In the context of this study, the main research areas and subfields which have been funded, the budget spent and the number of projects funded since 2003 both nationally and EU-wide and the gaps and overlapping topics were analyzed. In consideration of the results, detailed suggestions for Turkey have been proposed. The research results are expected to be used as a roadmap for coordinating the stakeholders of bioeconomy and integrating Turkish Research Areas into European Research Areas.
Citation Count: 445
Flow cytometry: basic principles and applications
(Taylor & Francis Ltd, 2017) Adan, Aysun; Alizada, Gunel; Kiraz, Yagmur; Baran, Yusuf; Nalbant, Ayten; Baran, Yusuf
Flow cytometry is a sophisticated instrument measuring multiple physical characteristics of a single cell such as size and granularity simultaneously as the cell flows in suspension through a measuring device. Its working depends on the light scattering features of the cells under investigation, which may be derived from dyes or monoclonal antibodies targeting either extracellular molecules located on the surface or intracellular molecules inside the cell. This approach makes flow cytometry a powerful tool for detailed analysis of complex populations in a short period of time. This review covers the general principles and selected applications of flow cytometry such as immunophenotyping of peripheral blood cells, analysis of apoptosis and detection of cytokines. Additionally, this report provides a basic understanding of flow cytometry technology essential for all users as well as the methods used to analyze and interpret the data. Moreover, recent progresses in flow cytometry have been discussed in order to give an opinion about the future importance of this technology.
Citation Count: 7
HER2-Targeted, Degradable Core Cross-Linked Micelles for Specific and Dual pH-Sensitive DOX Release
(Wiley-v C H verlag Gmbh, 2022) Bayram, Nazende Nur; Ulu, Gizem Tugce; Topuzogullari, Murat; Baran, Yusuf; Isoglu, Sevil Dincer; Baran, Yusuf
Here, a targeted, dual-pH responsive, and stable micelle nanocarrier is designed, which specifically selects an HER2 receptor on breast cancer cells. Intracellularly degradable and stabilized micelles are prepared by core cross-linking via reversible addition-fragmentation chain-transfer (RAFT) polymerization with an acid-sensitive cross-linker followed by the conjugation of maleimide-doxorubicin to the pyridyl disulfide-modified micelles. Multifunctional nanocarriers are obtained by coupling HER2-specific peptide. Formation of micelles, addition of peptide and doxorubicin (DOX) are confirmed structurally by spectroscopical techniques. Size and morphological characterization are performed by Zetasizer and transmission electron microscope (TEM). For the physicochemical verification of the synergistic acid-triggered degradation induced by acetal and hydrazone bond degradation, Infrared spectroscopy and particle size measurements are used. Drug release studies show that DOX release is accelerated at acidic pH. DOX-conjugated HER2-specific peptide-carrying nanocarriers significantly enhance cytotoxicity toward SKBR-3 cells. More importantly, no selectivity toward MCF-10A cells is observed compared to HER2(+) SKBR-3 cells. Formulations cause apoptosis depending on Bax and Caspase-3 and cell cycle arrest in G2 phase. This study shows a novel system for HER2-targeted therapy of breast cancer with a multifunctional nanocarrier, which has higher stability, dual pH-sensitivity, selectivity, and it can be an efficient way of targeted anticancer drug delivery.
Citation Count: 36
A novel mechanism of dasatinib-induced apoptosis in chronic myeloid leukemia; ceramide synthase and ceramide clearance genes
(Springer, 2011) Gencer, Emel B.; Ural, Ali U.; Avcu, Ferit; Baran, Yusuf; Baran, Yusuf
Sphingolipids are bioeffector molecules that control various aspects of cell growth, proliferation, apoptosis, and drug resistance. Ceramides, the central molecule of sphingolipid metabolism, are inducer of apoptosis and inhibitors of proliferation. Sphingosine-1-phosphate (S1P) and glucosyleceramide, converted from ceramides by sphingosine kinase-1 (SK-1) and glucosyleceramide synthase (GCS) enzymes, respectively, inhibit apoptosis and develop resistance to chemotherapeutic drugs. In this study, we examined the therapeutic potentials of bioactive sphingolipids in chronic myeloid leukemia (CML) alone and in combination with dasatinib in addition to investigate the roles of ceramide-metabolizing genes in dasatinib-induced apoptosis. Cytotoxic effects of dasatinib, C8:ceramide, PDMP, and SK-1 inhibitor were determined by XTT cell proliferation assay. Changes in caspase-3 enzyme activity and mitochondrial membrane potential (MMP) were measured using caspase-3 colorimetric assay and JC-1 MMP detection kit. Expression levels of ceramide-metabolizing genes were examined by qRT-PCR. Application of ceramide analogs and inhibitors of ceramide clearance genes decreased cell proliferation and induced apoptosis. Targeting bioactive sphingolipids towards generation/accumulation of ceramides increased apoptotic effects of dasatinib, synergistically. It was shown for the first time that dasatinib induces apoptosis through downregulating expression levels of antiapoptotic SK-1 but not GCS, and upregulating expression levels of ceramide synthase (CerS) genes, especially CerS1, in K562 cells. On the other hand, dasatinib downregulates expression levels of both GCS and SK-1 and upregulate apoptotic CerS2, -5 and -6 genes in Meg-01 cells. Increasing endogenous ceramide levels and decreasing prosurvival lipids, S1P, and GC, can open the way of more effective treatment of CML.
Citation Count: 27
Polarized emission from CsPbBr₃ nanowire embedded-electrospun PU fibers
(Iop Publishing Ltd, 2018) Guner, Tugrul; Topcu, Gokhan; Savaci, Umut; Genc, Aziz; Turan, Servet; Sari, Emre; Demir, Mustafa M.; Demir, Mustafa
Interest in all-inorganic halide perovskites has been increasing dramatically due to their high quantum yield, band gap tunability, and ease of fabrication in compositional and geometric diversity. In this study, we synthesized several hundreds of nanometer long and similar to 4 nm thick CsPbBr3 nanowires (NWs). They were then integrated into electrospun polyurethane (PU) fibers to examine the polarization behavior of the composite fiber assembly. Aligned electrospun fibers containing CsPbBr3 NWs showed a remarkable increase in the degree of polarization from 0.17-0.30. This combination of NWs and PU fibers provides a promising composite material for various applications such as optoelectronic devices and solar cells.
Citation Count: 3
Regulation of mRNA stability through a pentobarbital-responsive element
(Elsevier Science inc, 2007) Akgul, Bunyamin; Tu, Chen-Pei D.; Akgül, Bünyamin
Pentobarbital, a general anesthetic and non-genotoxic carcinogen, can induce gene expression by activating transcription. In the Drosophila glutathione S-transferase D21 (gstD21) gene, pentobarbital's regulatory influence extends to the level of mRNA turnover. Transcribed from an intronless gene, gstD21 mRNA is intrinsically very labile. But exposure to pentobarbital renders it stabilized beyond what can be attributed to transcriptional activation. We aim here to identify cis-acting element(s) of gstD21 mRNA as contributors to the molecule's pentobarbital-mediated stabilization. In the context of hsp70 5'UTR and the 3'UTR of act5C, gstD21 mRNA, minus its native UTRs, is stable. Maintaining the same context of heterologous UTRs, we can reconstitute using the full-length gstD21 sequence the inherent instability of gstD21 mRNA and its stabilization by pentobarbital. Transgenic flies that express these chimeric gstD21 mRNA exhibit decay intermediates lacking 3'UTR, which are not stabilized by PB treatment. The 3'UTR sequence, when inserted downstream from a reporter transcript, stabilizes it 1.6-fold under PB treatment. The analysis of the decay intermediates suggests a polysome-associated decay pattern. We propose a regulatory model that features a 59-nucleotide pentobarbital-responsive element (PBRE) in the 3'UTR of gstD21 mRNA. (c) 2006 Elsevier Inc. All rights reserved.
Citation Count: 24
Role of autophagy in the progression and suppression of leukemias
(Elsevier Science inc, 2012) Ekiz, Huseyin Atakan; Can, Geylani; Baran, Yusuf; Baran, Yusuf
Autophagy is a physiological process in which cellular components are degraded by the lysosomal machinery. Thereby, organelles are recycled and monomers are produced in order to maintain energy production. Current studies indicate autophagy might suppress or augment survival of cancer cells. Therefore, by elucidating the role of autophagy in cancer pathogenesis, novel therapeutic intervention points may be revealed. Leukemia therapy has advanced in recent years; but a definitive cure is still lacking. Since autophagy often is deregulated in this particular type of cancer, it is clear that future findings will have clinical implications. This review will discuss the current knowledge of autophagy in blood cancers. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
Citation Count: 42
Therapeutic potential of targeting ceramide/glucosylceramide pathway in cancer
(Springer, 2013) Yandim, Melis Kartal; Apohan, Elif; Baran, Yusuf; Baran, Yusuf
Sphingolipids 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.
Citation Count: 12
An update on molecular biology and drug resistance mechanisms of multiple myeloma
(Elsevier Science inc, 2015) Mutlu, Pelin; Kiraz, Yagmur; Gunduz, Ufuk; Baran, Yusuf; Baran, Yusuf
Multiple myeloma (MM), a neoplasm of plasma cells, is the second most common hematological malignancy. Incidance rates increase after age 40. MM is most commonly seen in men and African-American population. There are several factors to this, such as obesity, environmental factors, family history, genetic factors and monoclonal gammopathies of undetermined significance (MGUS) that have been implicated as potentially etiologic. Development of MM involves a series of complex molecular events, including chromosomal abnormalities, oncogene activation and growth factor dysregulation. Chemotherapy is the most commonly used treatment strategy in MM. However, MM is a difficult disease to treat because of its marked resistance to chemotherapy. MM has been shown to be commonly multidrug resistance (MDR)-negative at diagnosis and associated with a high incidence of MDR expression at relapse. This review deals with the molecular aspects of MM, drug resistance mechanisms during treatment and also possible new applications for overcoming drug resistance. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Citation Count: 81
An update on molecular biology of thyroid cancers
(Elsevier Science inc, 2014) Omur, Ozgur; Baran, Yusuf; Baran, Yusuf
Differentiated thyroid cancer (DTC) is the most common endocrinological malignancy. There are several histological variants such as papillary and follicular thyroid carcinoma. Many patients with well-differentiated subtypes of DTC are cured by surgery alone or with radioiodine, while poorly differentiated types usually have a worse prognosis. The aggressiveness of thyroid tumors is closely linked to specific gene alterations. Several diagnostic and prognostic molecular markers such as BRAF and RAS point mutations; RET/PTC and PAX8/PPAR gamma gene rearrangements; MAPK, PI3K, p53, Wnt-beta catenin, HIF1 alpha and NF-kappaB signaling pathways; microRNA profiles and aberrant methylation have been demonstrated in more than 70% of DTC. Diagnostic use of these molecular markers may be optimized for identifying higher risks of mortality, tumor recurrence and metastatic potential. Understanding the molecular biology of thyroid cancers can be an important avenue for diagnosis and treatment of radioiodine-refractory or inoperable DTC patients with novel molecular targeted therapeutic agents. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

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