Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Article Citation - WoS: 15Citation - Scopus: 13Cascade Therapy With Doxorubicin and Survivin-Targeted Tailored Nanoparticles: an Effective Alternative for Sensitization of Cancer Cells To Chemotherapy(Elsevier Ltd., 2019) Dağlıoğlu, Cenk; Kacı, Fatma NecmiyeChemotherapy frequently involves combination treatment protocols to maximize tumor cell killing. Unfortunately these intensive chemotherapeutic regimes, often show disappointing results due to the development of drug resistance and higher nonspecific toxicity on normal tissues. In cancer treatment, it is critically important to minimize toxicity while preserving efficacy. We have previously addressed this issue and proposed a nanoparticle-based combination therapy involving both a molecularly targeted therapy and chemotherapeutic agent for neutralizing antiapoptotic survivin (BIRC5) to potentiate the efficacy of doxorubicin (DOX). Although the particles exhibited strong anticancer effect on the lung carcinoma A549 and the cervical carcinoma HeLa cells, there were lower-level therapeutic outcomes on the colon carcinoma HCT-116, the leukemia Jurkat and the pancreatic carcinoma MIA PaCa-2 cells. Since targeted therapies are one of the key approaches for overcoming drug resistance, tailoring the treatment of cancer cells with distinct characteristics is necessary to improve the therapeutic outcome of cancer therapy and to minimize potential pharmacokinetic interactions of drugs. In the light of this issue, this study examined whether a cascade therapy with low-dose DOX and survivin-targeted tailored nanoparticles is more effective at sensitizing HCT-116, Jurkat and MIA PaCa-2 cancer cells to DOX-chemotherapy than simultaneous combination therapy. The results demonstrated that the sequential therapy with the protocol comprising addition of the nanoparticles after incubation of cells with DOX clearly advanced the therapeutic outcome of related cancer cells, whereas the reverse protocol resulted in a reduction or delay in apoptosis, emphasizing the critical importance of formulating synergistic drug combinations in cancer therapy.Article Citation - WoS: 15Citation - Scopus: 15Identification of Stable Qtls for Fiber Quality and Plant Structure in Upland Cotton (g. Hirsutum L.) Under Drought Stress(Elsevier Ltd., 2018) Akköse Baytar, Asena; Peynircioğlu, Ceng; Sezener, Volkan; Basal, Hüseyin; Frary, Anne; Frary, Amy; Doğanlar, SamiCotton is an economically important commodity for nearly fifty industries including the textile sector which is largely based on cotton fiber. Identification of markers linked to loci for fiber traits under drought stress may be particularly beneficial because such loci could provide the genetic adaptability needed to produce good fiber under water limitation. In the present study, 177 simple sequence repeat (SSR) markers were used to detect significant quantitative trait loci (QTLs) linked to 11 fiber quality and plant structure traits in a panel of 99 Upland cotton (Gossypium hirsutum L.) genotypes using GLM and MLM analysis. The fiber quality traits, including fiber length (FL), fiber fineness (FF), fiber strength (FS), fiber elasticity (FE), fiber uniformity (FU), spinning conversion index (SCI), earliness (EAR), 1st position boll retention (1st PBR), 2nd position boll retention (2nd PBR), total boll number (TBN) and plant height (PH), were tested under both well-watered and water-limited irrigations in two locations. At both locations, GLM identified a total of 74 and 70 QTLs under well-watered and water limited conditions, respectively, at p ≤ 0.005. MLM detected seven and 23 QTLs under well-watered and water-limited conditions, respectively. Of the identified QTLs, some QTLs were detected in both locations: three for well-watered and two for water-stress conditions. Moreover, a total of 19 QTLs were stable under both watering-regimes. The QTLs identified herein could be useful in the development of cotton cultivars that have adaptability to drought conditions worldwide.Article Citation - WoS: 14Citation - Scopus: 16Transcriptomic Analysis of Boron Hyperaccumulation Mechanisms in Puccinellia Distans(Elsevier Ltd., 2018) Öztürk, Saniye Elvan; Göktay, Mehmet; Has, Canan; Babaoğlu, Mehmet; Allmer, Jens; Doğanlar, Sami; Frary, AnnePuccinellia distans, common alkali grass, is found throughout the world and can survive in soils with boron concentrations that are lethal for other plant species. Indeed, P. distans accumulates very high levels of this element. Despite these interesting features, very little research has been performed to elucidate the boron tolerance mechanism in this species. In this study, P. distans samples were treated for three weeks with normal (0.5 mg L−1) and elevated (500 mg L−1) boron levels in hydroponic solution. Expressed sequence tags (ESTs) derived from shoot tissue were analyzed by RNA sequencing to identify genes up and down-regulated under boron stress. In this way, 3312 differentially expressed transcripts were detected, 67.7% of which were up-regulated and 32.3% of which were down-regulated in boron-treated plants. To partially confirm the RNA sequencing results, 32 randomly selected transcripts were analyzed for their expression levels in boron-treated plants. The results agreed with the expected direction of change (up or down-regulation). A total of 1652 transcripts had homologs in A. thaliana and/or O. sativa and mapped to 1107 different proteins. Functional annotation of these proteins indicated that the boron tolerance and hyperaccumulation mechanisms of P. distans involve many transcriptomic changes including: alterations in the malate pathway, changes in cell wall components that may allow sequestration of excess boron without toxic effects, and increased expression of at least one putative boron transporter and two putative aquaporins. Elucidation of the boron accumulation mechanism is important in developing approaches for bioremediation of boron contaminated soils.Article Citation - WoS: 7Citation - Scopus: 8Protein Based Flushing Related Blood Urea Nitrogen Effects on Ovarian Response, Embryo Recovery and Embryo Quality in Superovulated Ewes(Elsevier Ltd., 2017) Tur, İrfan; Dinç, Dursun Ali; Semacan, AhmetThe present study is the first report that evaluates effects of nutritional effects of flushing with differing diet crude protein ratios on blood urea nitrogen (BUN) levels, related some reproductive parameters and embryo quality in ewe. During mating season, before synchronization protocol ewes were fed on alfalfa hay and additive concentrate feeding as flushing. Intra vaginal FGA containing sponges applied for 12 days for the purpose of synchronization and pFSH was administered by 8 declining doses for the purpose of superovulation. Uterus was flushed in the morning of the seventh day of mating and embryos were collected surgically. Collected embryos were qualified according to IETS criterion. There is no dependency found between BUN values measured at different days and at different diet crude protein concentrations. An increase in uterine pH levels due to increasing protein amounts was observed but this increase was not significant among groups. Ovarian function was evaluated by ovarian responses (CL + large follicle) showed difference between groups (p < 0.05) and the lowest protein intake group gave highest ovarian response. In addition, embryo recovery rates revealed difference between groups (p < 0.05) and it was observed that the lowest ovarian response group showed the highest rates of embryo recovery. It is concluded that, in some Anatolian native sheep breeds, the application of diet flushing with different crude protein concentrates influence ovarian responses and embryo recovery rates but has no effect on BUN levels; uterus physiology or embryonic quality.Article Citation - WoS: 39Citation - Scopus: 37Enhancing Tumor Cell Response To Multidrug Resistance With Ph-Sensitive Quercetin and Doxorubicin Conjugated Multifunctional Nanoparticles(Elsevier Ltd., 2017) Dağlıoğlu, CenkClassical chemotherapy uses chemotherapeutic agents as a mainstay of anticancer treatment. However, the development of multidrug resistance to chemotherapy limits the effectiveness of current cancer treatment. Nanosized bioconjugates combining a chemotherapeutic agent with a pharmacological approach may improve the curative effect of chemotherapeutic agents. Herein I addressed this issue by describing the synthesis, and testing of, pH-responsive Fe3O4@SiO2(FITC)-BTN/QUR/DOX multifunctional nanoparticles. The particles were designed to modulate resistance-mediating factors and to potentiate the efficacy of DOX against chemoresistance. The physicochemical properties of the nanoparticles were characterized based on the combination of several techniques: dynamic light scattering (DLS), zeta-potential measurement, Fourier transform infrared spectroscopy (FTIR), electron microscopy techniques (SEM and STEM with EDX) and an in vitro pH-dependent release study. Cellular uptake and cytotoxicity experiments demonstrated enhanced intracellular delivery and retention of nanoparticles in the cytoplasm and efficient reduction of cancer cell viability in drug-resistant lung carcinoma A549/DOX cell lines. This did not affect internalization and viability of an immortalized human lung epithelial cell line BEAS-2B. Moreover, proapoptotic and antiproliferative studies showed that Fe3O4@SiO2(FITC)-BTN/QUR/DOX nanoparticles can promote apoptosis, inhibit tumor cell proliferation, and enhance the chemotherapeutic effects of DOX against multidrug resistance. These results confirm that this multifunctional platform possesses significant synergy between QUR and DOX and is promising for development as an antitumor treatment in cancer therapy.Article Citation - WoS: 2Citation - Scopus: 5Pgminer: Complete Proteogenomics Workflow; From Data Acquisition To Result Visualization(Elsevier Ltd., 2017) Has, Canan; Allmer, JensIn parallel with the development of nucleotide sequencing an equally important interest in further describing the sequence in terms of function arose and the latter represents the current bottleneck in the overall research question. Sequencing the transcriptome allows determination of expressed nucleotide sequences and using mass spectrometry allows sequencing on the protein level. Both approaches can only sequence a subset of the existing transcripts. Moreover, for example post translational modification events can only be determined on the proteomics level. Therefore, it is essential to combine proteomics and genomics. For that purpose, proteogenomics data analysis pipelines have been described. Here, we describe a novel proteogenomics workflow which encompasses everything from the acquisition of data to result visualization in the Konstanz Information Miner (KNIME), a state of the art workflow management and data analytics platform. We amended KNIME with a number of processes like peptide consensus prediction, peptide mapping, and database equalizing, as well as result visualization. This enabled construction of our new workflow, entitled PGMiner, which not only includes all data analysis steps, but is highly customizable which is rather cumbersome for most existing pipelines. Furthermore, no burdensome installation processes have to be performed making PGMiner the most user friendly tool available.Article Citation - WoS: 8Citation - Scopus: 8Synthesis and Topoisomerase I Inhibitory Properties of Klavuzon Derivatives(Elsevier Ltd., 2017) Akçok, İsmail; Mete, Derya; Şen, Ayhan; Kasaplar, Pınar; Korkmaz, Kemal S.; Çağır, AliKlavuzon is a naphthalen-1-yl substituted α,β-unsaturated δ-lactone derivative, and is one of the anti-proliferative members of this class of compounds. Asymmetric and racemic syntheses of novel α,β-unsaturated δ-lactone derivatives are important to investigate their potential for the treatment of cancer. In this study, asymmetric and racemic syntheses of heteroatom-substituted klavuzon derivatives are reported. The syntheses were completed by a well-known three-step procedure. Anti-proliferative activity of seven novel racemic klavuzon derivatives were reported against MCF-7, PC3, HCT116 p53+/+ and HCT116 p53−/− cancer cell lines. Topoisomerase I inhibitory properties of 5,6-dihydro-2H-pyran-2-one derivatives were also studied. © 2017 Elsevier Inc.Article Citation - WoS: 46Citation - Scopus: 57Barcode Dna Length Polymorphisms Vs Fatty Acid Profiling for Adulteration Detection in Olive Oil(Elsevier Ltd., 2017) Uncu, Ali Tevfik; Uncu, Ayşe Özgür; Frary, Anne; Doğanlar, SamiThe aim of this study was to compare the performance of a DNA-barcode assay with fatty acid profile analysis to authenticate the botanical origin of olive oil. To achieve this aim, we performed a PCR-capillary electrophoresis (PCR-CE) approach on olive oil: seed oil blends using the plastid . trnL (UAA) intron barcode. In parallel to genomic analysis, we subjected the samples to gas chromatography analysis of fatty acid composition. While the PCR-CE assay proved equally efficient as gas chromatography analysis in detecting adulteration with soybean, palm, rapeseed, sunflower, sesame, cottonseed and peanut oils, it was superior to the widely utilized analytical chemistry approach in revealing the adulterant species and detecting small quantities of corn and safflower oils in olive oil. Moreover, the DNA-based test correctly identified all tested olive oil: hazelnut oil blends whereas it was not feasible to detect hazelnut oil adulteration through fatty acid profile analysis. Thus, the present research has shown the feasibility of a PCR-CE barcode assay to detect adulteration in olive oil.Article Citation - Scopus: 35Computational Prediction of Micrornas From Toxoplasma Gondii Potentially Regulating the Hosts' Gene Expression(Elsevier Ltd., 2014) Saçar, Müşerref Duygu; Bağcı, Caner; Allmer, JensMicroRNAs (miRNAs) were discovered two decades ago, yet there is still a great need for further studies elucidating their genesis and targeting in different phyla. Since experimental discovery and validation of miRNAs is difficult, computational predictions are indispensable and today most computational approaches employ machine learning. Toxoplasma gondii, a parasite residing within the cells of its hosts like human, uses miRNAs for its post-transcriptional gene regulation. It may also regulate its hosts' gene expression, which has been shown in brain cancer. Since previous studies have shown that overexpressed miRNAs within the host are causal for disease onset, we hypothesized that T. gondii could export miRNAs into its host cell. We computationally predicted all hairpins from the genome of T. gondii and used mouse and human models to filter possible candidates. These were then further compared to known miRNAs in human and rodents and their expression was examined for T. gondii grown in mouse and human hosts, respectively. We found that among the millions of potential hairpins in T. gondii, only a few thousand pass filtering using a human or mouse model and that even fewer of those are expressed. Since they are expressed and differentially expressed in rodents and human, we suggest that there is a chance that T. gondii may export miRNAs into its hosts for direct regulation.Article Citation - WoS: 56Citation - Scopus: 66Molecular Mechanisms of Quercitrin-Induced Apoptosis in Non-Small Cell Lung Cancer(Elsevier Ltd., 2014) Çinçin, Zeynep Birsu; Ünlü, Miray; Kıran, Bayram; Bireller, Elif Sinem; Baran, Yusuf; Çakmakoğlu, BediaBackground and Aims: Quercitrin (QR; quercetin-3-O-rhamnoside) has been used previously as an antibacterial agent and has been shown to inhibit the oxidation of low-density lipoproteins and prevent an allergic reaction. Furthermore, it was demonstrated that quercitrin exerts protective effects against H2O2-induced dysfunction in lung fibroblast cells. However, the mechanisms of quercitrin effects on cancer cell proliferation and apoptosis is not well understood. The aim of this study is to investigate the cytotoxic and apoptotic effects of quercitrin and the molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer (NSCLC) cell lines. Methods: Time- and dose-dependent antiproliferative and apoptotic effects of quercitrin determined by WST-1cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, determination of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine in the plasma membrane. Changes in whole genome gene expression levels were examined by Illumina Human HT-12v4 beadchip microarrays. Results: There were significant increases in caspase-3 activity, loss of MMP, and increases in apoptotic cell population in response to quercitrin in A549 and NCI-H358 NSCLC cells in a time- and dose-dependent manner. Conclusion: Our results demonstrated that genes involved in leukocyte transendothelial migration, cell adhesion and phosphatidylinositol signaling system pathways were the most statistically significant pathways in NCI-H358 and A549cells. These results revealed that quercitrin has antiproliferative and apoptotic effects on lung cancer cells by modulating the immune response. After confirming its anticarcinogenic effects invivo, quercitrin could be a novel and strong anticancer agent against NSCLC.
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