PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Trna Wobble Base Modifications and Boric Acid Resistance in Yeast: Boron-Resistant Deletion Mutants Induce the General Amino Acid Control Mechanism and Activate Boron Efflux(NLM (Medline), 2020) Uluisik, I.; С Karakaya, H.; Koc, A.Boric acid is essential for plants and has many vital roles in animals and microorganisms. However, its high doses are toxic to all organisms. We previously screened yeast deletion collections to identify boric acid-resistant and susceptible mutants to identify genes that play a role in boron tolerance. Here, we analyzed boron resistant mutants (elplΔ, elp3Δ, elp6Δ, ncs2Δ, ncs6Δ and ktil2Δ) for their abilities to modulate the general amino acid control system (GAAC) and to induce boron efflux pump ATR1. The mutants analyzed in this study lack the genes that play roles in tRNA Wobble base modifications. We found that all of the boron resistant mutants activated Gcn4-dependent reporter gene activity and increased the transcript level of the ATR1 gene. Additionally, boron resistant cells accumulated less boric acid in their cytoplasm compared to the wild type cells upon boron exposure. Thus, our findings suggested that loss of wobble base modifications in tRNA leads to GAAC activation and ATR1 induction, which in turn reduced intracellular boron levels and caused boron resistance.Article Citation - WoS: 5Citation - Scopus: 5Multiorgan-On for Cancer Drug Pharmacokinetics-Pharmacodynamics (pk-Pd) Modeling and Simulations(Springer/plenum Publishers, 2025) Mohammed, Abdurehman Eshete; Kurucaovali, Filiz; Okvur, Devrim PesenCancer is one of the most common and fatal diseases worldwide and kills millions of people every year. Cancer drug resistance, lack of efficacy, and safety are significant problems in cancer patients. A multiorgan-on-a-chip (MOC) device consisting of breast and liver compartments was designed with AutoCAD software. The MOC molds were printed by a Formlabs Form 2 3D printer. MDA-MB-231, HepG2, and MCF-10 A cells were used for the MOC experiments. The cell lines were cultured at 37 degrees C with 5% CO2, and cell viability was assessed via Alamar blue dye to generate pharmacodynamics (PD) data. Drug concentrations from the cell culture media were analyzed via Agilent 1260 Infinity II HPLC with a Waters Symmetry C18 column and used to generate pharmacokinetics (PK) data. The PK and PD data were modeled and simulated by Monolix and Simulix software, respectively. The safety and efficacy of drug dosing regimens were compared, and the best dosing regimens were selected. This research designed and fabricated a unique MOC consisting of liver and breast compartments that overcomes the need for sealing or assembling. It was used for PK-PD modeling and simulations, and its functionality was proven experimentally. The new MOC will be helpful in preclinical trials to evaluate the efficacy and safety of drugs.Article Citation - WoS: 4Citation - Scopus: 3An Investigation of Rna Methylations With Biophysical Approaches in a Cervical Cancer Cell Model(Mdpi, 2024) Saglam, Buket; Akkus, Onur; Akcaoz-Alasar, Azime; Ceylan, Cagatay; Guler, Gunnur; Akgul, BunyaminRNA methylation adds a second layer of genetic information that dictates the post-transcriptional fate of RNAs. Although various methods exist that enable the analysis of RNA methylation in a site-specific or transcriptome-wide manner, whether biophysical approaches can be employed to such analyses is unexplored. In this study, Fourier-transform infrared (FT-IR) and circular dichroism (CD) spectroscopy are employed to examine the methylation status of both synthetic and cellular RNAs. The results show that FT-IR spectroscopy is perfectly capable of quantitatively distinguishing synthetic m(6)A-methylated RNAs from un-methylated ones. Subsequently, FT-IR spectroscopy is successfully employed to assess the changes in the extent of total RNA methylation upon the knockdown of the m(6)A writer, METTL3, in HeLa cells. In addition, the same approach is shown to accurately detect reduction in total RNA methylation upon the treatment of HeLa cells with tumor necrosis factor alpha (TNF-alpha). It is also demonstrated that m(1)A and m(6)A methylation induce quite a distinct secondary structure on RNAs, as evident from CD spectra. These results strongly suggest that both FT-IR and CD spectroscopy methods can be exploited to uncover biophysical properties impinged on RNAs by methyl moieties, providing a fast, convenient and cheap alternative to the existing methods.Article Citation - WoS: 2Citation - Scopus: 3Development of Mg-Alginate Based Self Disassociative Bio-Ink for Magnetic Bio-Patterning of 3d Tumor Models(Wiley-v C H verlag Gmbh, 2024) Coban, Basak; Baskurt, Mehmet; Sahin, Hasan; Arslan-Yildiz, AhuAlginate forms a hydrogel via physical cross-linking with divalent cations. In literature, Ca2+ is mostly utilized due to strong interactions but additional procedures are required to disassociate Ca-alginate hydrogels. On the other hand, Mg-alginate hydrogels disassociate spontaneously, which might benefit certain applications. This study introduces Mg-alginate as the main component of a bio-ink for the first time to obtain 3D tumor models by magnetic bio-patterning technique. The bio-ink contains magnetic nanoparticles (MNPs) for magnetic manipulation, Mg-alginate hydrogel as a sacrificial material, and cells. The applicability of the methodology is tested for the formation of 3D tumor models using HeLa, SaOS-2, and SH-SY5Y cells. Long-term cultures are examined by Live/dead and MTT analysis and revealed high cell viability. Subsequently, Collagen and F-actin expressions are observed successfully in 3D tumor models. Finally, the anti-cancer drug Doxorubicin (DOX) effect is investigated on 3D tumor models, and IC50 values is calculated to assess the drug response. As a result, significantly higher drug resistance is observed for bio-patterned 3D tumor models up to tenfold compared to 2D control. Overall, Mg-alginate hydrogel is successfully used to form bio-patterned 3D tumor models, and the applicability of the model is shown effectively, especially as a drug screening platform.Article Citation - WoS: 4Citation - Scopus: 4Tailored Bodipy-Based Fluorogenic Probes for Phosgene Detection: a Comparative Evaluation of Recognition Sites(Royal Soc Chemistry, 2024) Dartar, Suay; Kaya, Beraat Umur; Yayak, Yanki Oncu; Vural, Ezgi; Emrullahoglu, MustafaWe constructed two novel boron-dipyrromethene (BODIPY)-based fluorescent probes, BOPD and BOBA, each equipped with the phosgene specific recognition units o-phenylenediamine (OPD) and o-aminobenzylamine (OBA) at the 2-position of the BODIPY core. BOPD and BOBA represent rare examples of BODIPY-based probes that operate by modulating an intramolecular charge transfer process (ICT), as validated by computational studies. We systematically compared the analytic performance of those recognition units while focusing on selectivity, fluorescence turn-on ratios and response times. Probe BOBA, equipped with OBA as the recognition unit, demonstrated a remarkably low detection limit (i.e., 1.40 nM) and a rapid response time (<10 s) for triphosgene. By comparison, BOPD, featuring an OPD unit, showed superior selectivity towards triphosgene, with a detection limit of 93 nM and a response time of up to 30 s. A portable sensing platform was developed by loading BOPD onto test strips made of TLC plates, nonwoven materials and small-headed cotton swabs, which were assessed for their effectiveness in detecting phosgene. We additionally performed the first successful application of a fluorescent probe, namely BOPD, for monitoring the accumulation of phosgene in plants.Article Citation - WoS: 2Citation - Scopus: 2Mapk Pathway and Nis in B-Cpap Human Papillary Thyroid Carcinoma Cells Treated With Resveratrol(Elsevier Gmbh, 2024) Kocabas, Gokcen Unal; Blatti, Asli Kisim; Berdeli, Afig; Ozgen, Ahmet Gokhan; Yurekli, Banu SarerBackground: Resveratrol, a herbal phytoalexin, is known to have anti-tumor effects in several tumors including thyroid cancer cells. Aim: The aim of this study was to determine the effects of resveratrol on the expression of BRAF, ERK and NIS mRNA levels and protein expression in B-CPAP human thyroid papillary cancer cell line. Methods: B-CPAP cells were treated with resveratrol at concentrations of 10-100 mu M for 24-48-72 h. Cell viability was assessed by XTT Cell Proliferation Assay. BRAF, ERK and NIS mRNA levels were evaluated by rtPCR method. Protein expressions were evaluated by Western Blot method. Results: Resveratrol was found to inhibit cell proliferation in a time and dose dependent manner. The IC50 values of resveratrol were 18.7 mu M and 56.8 mu M after 48 h and 72 h respectively. Resveratrol treatment of B-CPAP cells resulted in up to 1.5-fold reduction in BRAF mRNA and up to 5.5 fold reduction in ERK mRNA levels. NIS mRNA levels showed up to 3-fold increase. Western Blot studies confirmed the rt- PCR results with a decrease in BRAF and ERK, and increase in NIS protein expressions. Conclusion: This study demonstrated that resveratrol inhibits thyroid papillary carcinoma cell proliferation and reduces poor prognostic BRAF and ERK mRNA and protein expressions, while increasing NIS mRNA and protein expression suggesting a redifferentiating effect. More studies are needed to evaluate resveratrol as a novel therapeutic agent in the treatment of papillary thyroid cancer.Article Citation - WoS: 2Citation - Scopus: 1A Safe Fiber-Optic-Sensor-Assisted Industrial Microwave-Heating System(Mdpi, 2024) Yuksel, Kivilcim; Merdin, Oguz Deniz; Kinet, Damien; Merdin, Murat; Guyot, Corentin; Caucheteur, ChristopheIndustrial microwave-heating systems are pivotal in various sectors, including food processing and materials manufacturing, where precise temperature control and safety are critical. Conventional systems often struggle with uneven heat distribution and high fire risks due to the intrinsic properties of microwave heating. In this work, a fiber-optic-sensor-assisted monitoring system is presented to tackle the pressing challenges associated with uneven heating and fire hazards in industrial microwave systems. The core innovation lies in the development of a sophisticated fiber-optic 2D temperature distribution sensor and a dedicated fire detector, both designed to significantly mitigate risks and optimize the heating process. Experimental results set the stage for future innovations that could transform the landscape of industrial heating technologies toward better process quality.Article Citation - WoS: 1Citation - Scopus: 1Altitude Shapes Gut Microbiome Composition Accounting for Diet, Thyroid Hormone Levels, and Host Genetics in a Subterranean Blind Mole Rat(Frontiers Media Sa, 2024) Solak, Halil Mert; Kreisinger, Jakub; Cizkova, Dagmar; Sezgin, Efe; Schmiedova, Lucie; Murtskhvaladze, Marine; Yanchukov, AlexeyThe animal gut microbiome acts as a crucial link between the host and its environment, playing a vital role in digestion, metabolism, physiology, and fitness. Using 16S rRNA metabarcoding, we investigated the effect of altitude on the microbiome composition of Anatolian Blind Mole Rats (Nannospalax xanthodon) across six locations and three altitudinal groups. We also factored in the host diet, as well as host microsatellite genotypes and thyroid hormone levels. The altitude had a major effect on microbiome composition, with notable differences in the relative abundance of several bacterial taxa across elevations. Contrary to prior research, we found no significant difference in strictly anaerobic bacteria abundance among altitudinal groups, though facultatively anaerobic bacteria were more prevalent at higher altitudes. Microbiome alpha diversity peaked at mid-altitude, comprising elements from both low and high elevations. The beta diversity showed significant association with the altitude. Altitude had a significant effect on the diet composition but not on its alpha diversity. No distinct altitude-related genetic structure was evident among the host populations, and no correlation was revealed between the host genetic relatedness and microbiome composition nor between the host microbiome and the diet. Free thyroxine (FT4) levels increased almost linearly with the altitude but none of the bacterial ASVs were found to be specifically associated with hormone levels. Total thyroxine (TT4) levels correlated positively with microbiome diversity. Although we detected correlation between certain components of the thyroid hormone levels and the microbiome beta diversity, the pattern of their relationship remains inconclusive.Review Citation - WoS: 1Citation - Scopus: 2Bergamot (<i>citrus Bergamia</I>), a (poly)phenol-Rich Source for Improving Osteosarcopenic Obesity: a Systematic Review(Mdpi, 2024) Mazzola, Giuseppe; Rondanelli, Mariangela; Baron, Giovanna; Zupo, Roberta; Castellana, Fabio; Clodoveo, Maria Lisa; Perna, SimoneThis systematic review investigates the potential of bergamot, a polyphenol-rich citrus fruit, in improving osteosarcopenic obesity, a condition characterized by the simultaneous presence of osteoporosis, obesity, and sarcopenia. Bergamot extracts have been suggested to possess several pharmacological properties, including anti-inflammatory and antioxidant effects, which could be useful in the management of age-related diseases and neuromuscular health. The review highlights the promising effects of bergamot extracts on skeletal muscle mass and function, particularly in the context of obesity, metabolic syndrome, osteosarcopenic obesity, and osteoporosis. Furthermore, some studies have shown that bergamot extracts can improve the metabolic balance, endothelial function, and maximal oxygen uptake in athletes, highlighting their potential benefits for skeletal muscle health. Taken together, these results suggest that bergamot extracts, especially those rich in polyphenols, may be a valuable adjunct in the management of osteosarcopenic obesity and other associated clinical conditions involving pro-inflammatory effects on organs and tissues.Article Citation - WoS: 2Citation - Scopus: 2Invasion/Chemotaxis- and Extravasation-Chip Models for Breast Cancer Bone Metastasis(Public Library Science, 2024) Firatligil-Yildirir, Burcu; Bati-Ayaz, Gizem; Nonappa, Devrim; Pesen-Okvur, Devrim; Yalcin-Ozuysal, OzdenBone is one of the most frequently targeted organs in metastatic cancers including the breast. Breast cancer bone metastasis often results in devastating outcomes as limited treatment options are currently available. Therefore, innovative methods are needed to provide earlier detection and thus better treatment and prognosis. Here, we present a new approach to model bone-like microenvironments to detect invasion and extravasation of breast cancer cells using invasion/chemotaxis (IC-) and extravasation (EX-) chips, respectively. Our results show that the behaviors of MDA-MB-231 breast cancer cells on IC- and EX-chip models correlate with their in vivo metastatic potential. Our culture model constitutes cell lines representing osteoblasts, bone marrow stromal cells, and monocytes embedded in three-dimensional (3D) collagen I-based extracellular matrices of varying composition and stiffness. We show that collagen I offers a better bone-like environment for bone cells and matrix composition and stiffness regulate the invasion of breast cancer cells. Using in situ contactless rheological measurements under cell culture conditions, we show that the presence of cells increased the stiffness values of the matrices up to 1200 Pa when monitored for five days. This suggests that the cellular composition has a significant effect on regulating matrix mechanical properties, which in turn contribute to the invasiveness. The platforms we present here enable the investigation of the underlying molecular mechanisms in breast cancer bone metastasis and provide the groundwork of developing preclinical tools for the prediction of bone metastasis risk.