TR-Dizin

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Citation - Scopus: 0
Cytoplasmically localized tRNA-derived fragments inhibit translation in Drosophila S2 cells
(TUBITAK, 2022) Hamid,S.M.; Akgül,B.; Akgül, Bünyamin; Moleküler Biyoloji ve Genetik Bölümü; Moleküler Biyoloji ve Genetik Bölümü
Transfer ribonucleic acids (tRNAs) serve not only as amino acid carriers during translation but also as a template for the biogenesis of short fragments that can regulate gene expression. Despite recent progress in the function of tRNA-derived fragments (tRFs), their intracellular localization, protein partners, and role in regulating translation are not well understood. We used synthetic tRFs to investigate their localization and function in Drosophila S2 cells. Under our experimental setting, all synthetic tRFs tested were localized at distinct sites within the cytoplasm in a similar manner in Drosophila S2 cells. Cytoplasmically-localized tRFs were positioned in close proximity to GW182 and XRN1 proteins. Functionally, tRFs, which slightly suppressed proliferation in S2 cells, inhibited translation without any major shift in the polysome profile. These results suggest that 5’-tRFs are cytoplasmically-localized and regulate gene expression through inhibition of translation in Drosophila. © TÜBİTAK.
Citation - WoS: 6
Effect of CNT incorporation on PAN/PPy nanofibers synthesized by electrospinning method
(Tubitak Scientific & Technological Research Council Turkey, 2020) Ince Yardimci, Atike; Tanoglu, Metin; Yilmaz, Selahattin; Selamet, Yusuf; Tanoğlu, Metin
In this study, carbon nanotubes (CNTs) added polyacrylonitrile/polypyrrole (PAN/PPy) electrospun nanofibers were produced. Average diameters of the nanofibers were measured as 268 and 153 nm for 10 and 25 wt% of PPy contents, respectively. A relatively higher strain to failure values (23.3%) were observed for the low PPy content. When as-grown CNTs (1 and 4 wt%) were added into the PAN/PPy blends, disordered nanofibers were observed to form within the microstructure. To improve the interfacial properties of CNTs/PAN/PPy composites, CNTs were functionalized with H2SO4/HNO3/HCl solution. The functionalized CNTs were well dispersed within the nanofibers and aligned along the direction of nanofibers. Therefore, beads formation on nanofibers decreased. The impedance of the nanofibers was found to decrease with the PPy content and CNT addition. These nanofibers had a great potential to be used as an electrochemical actuator or a tissue engineering scaffold.
Endogenous heat shock protein GroEL of A. actinomycetemcomitans preferentially targets primary human CD8+ T cells
(2015) Aldanmaz Nalbant, AYTEN; Akgül, Bünyamin; Akgül, Bünyamin; Kant, Melis
Apoptosis can be used to manipulate host cells by bacterial products such as bacterial heat shock proteins (Hsp). One of the virulence factors of periodontal pathogen Aggregatibacter actinomycetemcomitans is heat shock protein GroEL (AaGroEL), which has been shown to interact with host cells. AaGroEL (Hsp64) also has the potential to modulate immune system cells. In this study we used endogenous AaGroEL protein as an antigen to study bacterial Hsp-induced apoptosis in different immune system cells. Human peripheral blood mononuclear cells and cell lines were cultured with different doses (50-1000 ng/mL) of endogenous AaGroEL at various time points. Apoptosis of the cells was measured by Annexin V and 7AAD labeling. Apoptotic cells were analyzed by flow cytometry. Our data suggested that AaGroEL-responding primary CD8+ T cells were more susceptible to apoptosis than CD4+ T cells. Furthermore, the magnitude of apoptosis in the Jurkat T cell line was higher than that in primary CD8+ T cells. There was no statistically significant level of apoptosis in the chronic myeloid leukemia (K562) cell line, which belongs to myeloid lineages. Thus, A. actinomycetemcomitans GroEL protein has more potent apoptotic effect on cells that are derived from a lymphoid progenitor.
Citation - WoS: 4
The importance of protein profiling in the diagnosis and treatment of hematologic malignancies
(Galenos Yayincilik, 2011) Sanli-Mohamed, Gulsah; Turan, Taylan; Ekiz, Huseyin Atakan; Baran, Yusuf; Baran, Yusuf
Proteins are important targets in cancer research because malignancy is associated with defects in cell protein machinery. Protein profiling is an emerging independent subspecialty of proteomics that is rapidly expanding and providing unprecedented insight into biological events. Quantitative assessment of protein levels in hematologic malignancies seeks a comprehensive understanding of leukemia-associated protein patterns for use in aiding diagnosis, follow-up treatment, and the prediction of clinical outcomes. Many recently developed high-throughput proteomic methods can be applied to protein profiling. Herein the importance of protein profiling, its exploitation in leukemia research, and its clinical usefulness in the treatment and diagnosis of various cancer types, and techniques for determining changes in protein profiling are reviewed. (Turk J Hematol 2011; 28: 1-14)
Citation - WoS: 1
Investigation of Potential Anticarcinogenic Effects of Corilagin in Lung Cancer Cells
(Marmara Univ, inst Health Sciences, 2019) Rencuzogullari, Cagla; Cincin, Zeynep Birsu; Iplik, Elif Sinem; Baran, Yusuf; Cakmakoglu, Bedia; Baran, Yusuf
Objective: Lung cancer (LC) is the most extensive reason of cancer associated deaths in men and women in the world. LC categorizes into two main groups due to their molecular clinicopathological features and therapeutic responses. Non-small cell lung cancer (NSCLC) is the main subgroup that consists of nearly 85% of all lung cancer types. Corilagin, a biologically active ellagitannin, could be extracted from Phyllanthus species which are known as Chinese medicinal plant. It has been recently shown that Corilagin could exert anti-inflammatuar and antioxidative effects in different experimental cancer models. However, the molecular effects of Corilagin in NSCLC remain unclear. Methods: In this study, the antiproliferative and apoptotic effects of Corilagin were identified by WST-1 cell proliferation test, caspase-3 and mitochondrial membrane potential (MMP). Results: We found that Corilagin significiantly suppressed the proliferation of NSCLC cells. Furthermore, we also showed that Corilagin could contribute apoptosis by inducing activity of caspase-3 molecule and loss of MMP. Conclusion: Taken together, our study first showed that Corilagin could be a new treatment method for NSCLC after verifying its effects with in vivo and clinical studies.
Citation - WoS: 0
Citation - Scopus: 0
Knockdown of death receptor 5 antisense long noncoding RNA and cisplatin treatment modulate similar macromolecular and metabolic changes in HeLa cells
(Tubitak Scientific & Technological Research Council Turkey, 2022) Gurer, Dilek Cansu; Erdogan Vatansever, Ipek; Ceylan, Cagatay; Akgul, Bunyamin; Akgül, Bünyamin
Background/aim: Despite great progress in complex gene regulatory mechanisms in the dynamic tumor microenvironment, the potential contribution of long noncoding RNAs (lncRNAs) to cancer cell metabolism is poorly understood. Death receptor 5 antisense (DR5-AS) is a cisplatin inducible lncRNA whose knockdown modulates cell morphology. However, its effect on cell metabolism is unknown. The aim of this study is to examine metabolic changes modulated by cisplatin and DR5-AS lncRNA in HeLa cells.Materials and methods: We used cisplatin as a universal cancer therapeutic drug to modulate metabolic changes in HeLa cervix cancer cells. We then examined the extent of metabolic changes by Fourier transform infrared spectroscopy (FTIR). We also performed transcriptomics analyses by generating new RNA-seq data with total RNAs isolated from cisplatin-treated HeLa cells. Then, we compared cisplatin-mediated transcriptomics and macromolecular changes with those mediated by DR5-AS knockdown.Results: Cisplatin treatment caused changes in the unsaturated fatty acid and lipid-to-protein ratios and the glycogen content. These observations in altered cellular metabolism were supported by transcriptomics analyses. FTIR spectroscopy analyses have revealed that DR5-AS knockdown causes a 20.9% elevation in the lipid/protein ratio and a 76.6% decrease in lipid peroxidation. Furthermore, we detected a 3.42% increase in the chain length of the aliphatic lipids, a higher content of RNA, and a lower amount of glycogen indicating relatively lower metabolic activity in the DR5-AS knockdown HeLa cells. Interestingly, we observed a similar gene expression pattern under cisplatin treatment and DR5-AS knockdown HeLa cells. Conclusion: These results suggest that DR5-AS lncRNA appears to account for a fraction of cisplatin-mediated macromolecular and metabolic changes in HeLa cervix cancer cells.
Citation - WoS: 3
A minimally invasive transfer method of mesenchymal stem cells to the intact periodontal ligament of rat teeth: a preliminary study
(Tubitak Scientific & Technological Research Council Turkey, 2018) Gul Amuk, Nisa; Kurt, Gokmen; Kartal Yandim, Melis; Adan, Aysun; Baran, Yusuf; Baran, Yusuf
The aim of this study was to introduce a minimally invasive procedure for mesenchymal stem cell (MSC) transfer into the intact periodontal ligament (PDL) of the molar teeth in rats. Ten 12-week-old Wistar albino rats were used for this preliminary study. MSCs were obtained from bones of two animals and were labeled with green fluorescent protein (GFP). Four animals were randomly selected for MSC injection, while 4 animals served as a control group. Samples were prepared for histological analysis, Cox-2 mRNA expression polymerase chain reaction analysis, and fluorescent microscopy evaluation. The number of total cells, number of osteoclastic cells, and Cox-2 mRNA expression levels of the periodontal tissue of teeth were calculated. The number of total cells was increased with MSC injections in PDL significantly (P < 0.001). The number of osteoclastic cells and Cox-2 mRNA expression were found to be similar for the two groups. GFP-labeled MSCs were observed with an expected luminescence on the smear samples of the PDL with transferred MSCs. The results of this preliminary study demonstrate successful evidence of transferring MSCs to intact FIX in a nonsurgical way and offer a minimally invasive procedure for transfer of MSCs to periodontal tissues.
Citation - WoS: 7
Citation - Scopus: 7
Multidrug resistance in chronic myeloid leukemia
(Tubitak Scientific & Technological Research Council Turkey, 2014) Unlu, Miray; Kiraz, Yagmur; Kaci, Fatma Necmiye; Ozcan, Mehmet Ali; Baran, Yusuf; Baran, Yusuf
Chronic myeloid leukemia (CML) is characterized by the accumulation of Philadelphia chromosome-positive (Ph+) myeloid cells. Ph+ cells occur via a reciprocal translocation between the long arms of chromosomes 9 and 22 resulting in constitutively active Bcr-abl fusion protein. Tyrosine kinase inhibitors (TKIs) are used against the kinase activity of Bcr-abl fusion protein for the effective treatment of CML. However, the development of drug resistance, directed by different genetic mechanisms, is the major problem of clinical applications of TKIs. These mechanisms include mutations in the TKI binding site of Bcr-abl, overexpression of Bcr-abl, overexpression of ATP binding cassette transporters, aberrant ceramide metabolism, inhibition of apoptosis, and changes in expression levels of microRNAs. Recently, many studies have focused on understanding the molecular mechanisms of drug resistance in cancer while targeting therapies providing reversal of resistance. Cancer stem cells also have roles in tumor initiation, maintenance, progression, metastasis, and drug resistance. Uncovering the mechanisms of drug resistance can provide more efficient treatment of cancer since these findings may provide novel targets for a complete cure. In this review, we discuss recent findings on the mechanisms of multidrug resistance and its reversal in CML.
Citation - WoS: 2
Citation - Scopus: 1
Mutant selection by using Fourier expansion
(Tubitak Scientific & Technical Research Council Turkey, 2020) Takan, Savas; Ayav, Tolga; Ayav, Tolga; Bilgisayar Mühendisliği Bölümü
Mutation analysis is a widely used technique to evaluate the effectiveness of test cases in both hardware and software testing. The original model is mutated systematically under certain fault assumptions and test cases are checked against the mutants created to see whether the test cases can detect the faults or not. Mutation analysis is usually a computationally intensive task, particularly in finite state machine (FSM) testing due to a possibly huge amount of mutants. Random selection could be a practical reduction method under the assumption that each mutant is identical in terms of the probability of occurrence of its associating fault. The present study proposes a mutant selection method based on Fourier analysis of Boolean functions. Fourier helps to identify the most effective transitions on the output so that the mutants related to those transitions can be selected. Such mutants are considered more important since they are more likely to be killed. To evaluate the method, test cases are generated by the well-known W method, which has the capability of detecting every potential fault. The original and reduced sets of mutants are compared with respect to their importance values. Evaluations show that the mutants selected by the proposed technique are more effective, which reduces the cost of mutation analysis without sacrificing the performance of the mutation analysis.
Citation - WoS: 9
Citation - Scopus: 9
Noncoding RNAs in apoptosis: identification and function
(Tubitak Scientific & Technological Research Council Turkey, 2022) Tuncel, Ozge; Kara, Merve; Yaylak, Bilge; Erdogan, Ipek; Akgul, Bunyamin; Akgül, Bünyamin
Apoptosis is a vital cellular process that is critical for the maintenance of homeostasis in health and disease. The derailment of apoptotic mechanisms has severe consequences such as abnormal development, cancer, and neurodegenerative diseases. Thus, there exist complex regulatory mechanisms in eukaryotes to preserve the balance between cell growth and cell death. Initially, protein coding genes were prioritized in the search for such regulatory macromolecules involved in the regulation of apoptosis. However, recent genome annotations and transcriptomics studies have uncovered a plethora of regulatory noncoding RNAs that have the ability to modulate not only apoptosis but also many other biochemical processes in eukaryotes. In this review article, we will cover a brief summary of apoptosis and detection methods followed by an extensive discussion on microRNAs, circular RNAs, and long noncoding RNAs in apoptosis.
Stab and ballistic performances of aramid fabrics impregnated with silica based shear thickening fluids
(2021) Şenel, Fikret; Güneş, Deniz; Yildiz, Sema; Tanoğlu, Metin; Tanoğlu, Metin
This study focuses on the production of aramid fabric with improved stab and ballistic resistances treated with shear thickening fluids (STFs). The STFs were prepared by homogenization of various amount of silica particles within the PEG and ethyl alcohol, drying, and grinding steps. The rheological measurements showed that the addition of silica nanoparticles into the PEG, shear thickening behavior was enhanced. As silica concentration increased, the interparticle forces increased and so the friction between particles greatly increased, causing an enhanced shear- thickening property. Quasi-static and dynamic stab resistance tests showed that increasing shear thickening response corresponded to increased stab performance in the STF/aramid targets as compared to untreated aramid fabric. Ballistic test results showed that there was an increment in the ballistic resistance between untreated fabric and STF/aramid composites. It was also found that the flexibility of STF/aramid targets did not decrease significantly compared to the untreated aramid fabric
Therapeutic Potentials of Inhibition of Jumonji C Domaincontaining Demethylases in Acute Myeloid Leukemia
(2020) Engür, Selin; Koca, Duygu; Ki̇raz, Yağmur; Ulu, Tuğçe; Baran, Yusuf; Çekdemi̇r, Demet; Baran, Yusuf
Objective: Acute myeloid leukemia (AML) is a complex disease affected by both genetic and epigenetic factors. Histone methylation and demethylation are types of epigenetic modification in chromatin remodeling and gene expression. Abnormal expression of histone demethylases is indicated in many types of cancer including AML. Although many commercial drugs are available to treat AML, an absolute cure has not been discovered yet. However, inhibition of demethylases could be a potential cure for AML. Methylstat is a chemical agent that inhibits the Jumonji C domain-containing demethylases. Materials and Methods: The cytotoxic and apoptotic effects of methylstat and doxorubicin on HL-60 cells were detected by MTT cell viability assay, double staining of treated cells with annexin-V/ propidium iodide, and caspase-3 activity assay. Mitochondrial activity was analyzed using JC-1 dye. The expression levels of the BCL2 and BCL2L1 anti-apoptotic genes in HL-60 cells were determined using real-time polymerase chain reaction (PCR). Lastly, the cytostatic effect was determined by cell cycle analysis. Results: In our research, cytotoxic, cytostatic, and apoptotic effects of methylstat on human HL-60 cells were investigated. Cytotoxic and cytostatic analyses revealed that methylstat decreased cell proliferation in a dose-dependent cytotoxic manner and arrested HL60 cells in the G2/M and S phases. Methylstat also induced apoptosis through the loss of mitochondrial membrane potential and increases in caspase-3 enzyme activity. The expression levels of BCL2 and BCL2L1 were also decreased according to real-time PCR results. Finally, the combination of methylstat with doxorubicin resulted in synergistic cytotoxic effects on HL-60 cells. Conclusion: Taken together, these results demonstrate that methylstat may be a powerful candidate as a drug component of AML treatment protocols.

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