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: 2Citation - Scopus: 2Exploring the Use of Water-Extracted Flaxseed Hydrocolloids in Three-Dimensional Cell Culture(Mary Ann Liebert, inc, 2024) Yildirim-Semerci, Ozum; Bilginer-Kartal, Rumeysa; Arslan-Yildiz, AhuPlant-derived hydrocolloids offer promising prospects in biomedical applications. Among these, Flaxseed hydrocolloid (FSH) can form a soft, elastic, and biocompatible hydrocolloid with tunable viscosity and superior swelling capacity, making it an attractive scaffold. This study introduces a green extraction method for FSH, employing a single-step aqueous extraction process and fabrication of FSH scaffold. Despite growing interest, the pristine form of FSH has not been investigated for sustainable long-term three-dimensional (3D) cell culture. Here, FSH scaffolds were thoroughly characterized for their morphological, chemical, mechanical, and biological properties. 3D cell culture experiments were conducted using NIH-3T3 mouse fibroblast cells, and cell viability was assessed using live/dead and Alamar Blue assays. High cell viability was sustained for long term compared with 2D cell culture. Cell adhesion and 3D cellular morphology on FSH scaffold for 30 days were monitored by scanning electron microscopy analysis. Also, collagen type-I and F-actin expressions were analyzed by immunostaining after 30 days of culture, resulting in 5- and 4-fold increments of fluorescence intensity, respectively. Results indicate sustained cell viability in the long term and favorable cell-material interaction, demonstrating the potential of FSH as a scaffold. This study emphasizes the importance of the green extraction approach, improving the biocompatibility and functionality of FSH tissue engineering applications. Impact Statement Flaxseed hydrocolloid (FSH) is a promising scaffold for biomedical applications due to its biocompatibility and tunable properties. This study introduces a green extraction method for FSH and evaluates its use in 3D cell culture with NIH-3T3 mouse fibroblast cells. The findings indicate high cell viability and enhanced cell-material interactions over 30 days, highlighting the potential of FSH for tissue engineering.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: 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: 1Gliflozins, Sucrose and Flavonoids Are Allosteric Activators of Lecithin-Cholesterol Acyltransferase(Nature Portfolio, 2024) Niemela, Akseli; Giorgi, Laura; Nouri, Sirine; Yurttas, Betul; Rauniyar, Khushbu; Jeltsch, Michael; Koivuniemi, ArtturiLecithin-cholesterol acyltransferase (LCAT) serves as a pivotal enzyme in preserving cholesterol homeostasis via reverse cholesterol transport, a process closely associated with the onset of atherosclerosis. Impaired LCAT function can lead to severe LCAT deficiency disorders for which no pharmacological treatment exists. LCAT-based therapies, such as small molecule positive allosteric modulators (PAMs), against LCAT deficiencies and atherosclerosis hold promise, although their efficacy against atherosclerosis remains challenging. Herein we utilized a quantitative in silico metric to predict the activity of novel PAMs and tested their potencies with in vitro enzymatic assays. As predicted, sodium-glucose cotransporter 2 (SGLT2) inhibitors (gliflozins), sucrose and flavonoids activate LCAT. This has intriguing implications for the mechanism of action of gliflozins, which are commonly used in the treatment of type 2 diabetes, and for the endogenous activation of LCAT. Our results underscore the potential of molecular dynamics simulations in rational drug design.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: 1Citation - Scopus: 1Abnormally Accumulated Gm2 Ganglioside Contributes To Skeletal Deformity in Tay-Sachs Mice(Springer Heidelberg, 2024) Demir, Secil Akyildiz; Seyrantepe, VolkanTay-Sachs Disease is a rare lysosomal storage disorder caused by mutations in the HEXA gene, responsible for the degradation of ganglioside GM2. In addition to progressive neurodegeneration, Tay-Sachs patients display bone anomalies, including kyphosis. Tay-Sachs disease mouse model (Hexa-/-Neu3-/-) shows both neuropathological and clinical abnormalities of the infantile-onset disease phenotype. In this study, we investigated the effects of GM2 accumulation on bone remodeling activity. Here, we evaluated the bone phenotype of 5-month-old Hexa-/-Neu3-/- mice with age-matched control groups using gene expression analysis, bone plasma biomarker analysis, and micro-computed tomography. We demonstrated lower plasma alkaline phosphatase activity and calcium levels with increased tartrate-resistant acid phosphatase levels, indicating reduced bone remodeling activity in mice. Consistently, gene expression analysis confirmed osteoblast reduction and osteoclast induction in the femur of mice. Micro-computed tomography and analysis show reduced trabecular bone volume, mineral density, number, and thickness in Hexa-/-Neu3-/- mice. In conclusion, we demonstrated that abnormal GM2 ganglioside accumulation significantly triggers skeletal abnormality in Tay-Sachs mice. We suggest that further investigation of the molecular basis of bone structure anomalies is necessary to elucidate new therapeutic targets that prevent the progression of bone symptoms and improve the life standards of Tay-Sachs patients.Article Citation - WoS: 5Citation - Scopus: 6Beyond Lux: Methods for Species and Photoreceptor-Specific Quantification of Ambient Light for Mammals(Bmc, 2024) McDowell, Richard J.; Didikoğlu, Altuğ; Didikoglu, Altug; Woelders, Tom; Gatt, Mazie J.; Moffatt, Finn; Notash, Saba; Lucas, Robert J.BackgroundLight is a key environmental regulator of physiology and behaviour. Mistimed or insufficient light disrupts circadian rhythms and is associated with impaired health and well-being across mammals. Appropriate lighting is therefore crucial for indoor housed mammals. Light is commonly measured in lux. However, this employs a spectral weighting function for human luminance and is not suitable for 'non-visual' effects of light or use across species. In humans, a photoreceptor-specific (alpha-opic) metrology system has been proposed as a more appropriate way of measuring light.ResultsHere we establish technology to allow this alpha-opic measurement approach to be readily extended across mammalian species, accounting for differences in photoreceptor types, photopigment spectral sensitivities, and eye anatomy. We develop a high-throughput method to derive spectral sensitivities for recombinantly expressed mammalian opsins and use it to establish the spectral sensitivity of melanopsin from 13 non-human mammals. We further address the need for simple measurement strategies for species-specific alpha-opic measures by developing an accessible online toolbox for calculating these units and validating an open hardware multichannel light sensor for 'point and click' measurement. We finally demonstrate that species-specific alpha-opic measurements are superior to photopic lux as predictors of physiological responses to light in mice and allow ecologically relevant comparisons of photosensitivity between species.ConclusionsOur study presents methods for measuring light in species-specific alpha-opic units that are superior to the existing unit of photopic lux and holds the promise of improvements to the health and welfare of animals, scientific research reproducibility, agricultural productivity, and energy usage.Article Citation - WoS: 1Citation - Scopus: 1Studies on the Probiotic, Adhesion, and Induction Properties of Artisanal Lactic Acid Bacteria: To Customize a Gastrointestinal Niche To Trigger Anti-Obesity Functions(Springer, 2024) Kamber, A.; Albayrak, C. Bulut; Harsa, H. S.The primary goals of this work are to explore the potential of probiotic lactic acid bacteria's (LAB) mucin/mucus layer thickening properties and to identify anti-obesity candidate strains that improve appropriate habitat for use with the Akkermansia group population in the future. The HT-29 cell binding, antimicrobial properties, adhesion to the mucin/mucus layer, growth in the presence of mucin, stability during in vitro gastrointestinal (GI) conditions, biofilm formation, and mucin/mucus thickness increment abilities were all assessed for artisanal LAB strains. Sixteen LAB strains out of 40 were chosen for further analysis based on their ability to withstand GI conditions. Thirteen strains remained viable in simulated intestinal fluid, while most showed high viability in gastric juice simulation. Furthermore, 35.9-65.4% of those 16 bacteria adhered to the mucin layer. Besides, different lactate levels were produced, and Streptococcus thermophilus UIN9 exhibited the highest biofilm development. In the HT-29 cell culture, the highest mucin levels were 333.87 mu g/mL with O. AK8 at 50 mM lactate, 313.38 mu g/mL with Lactobacillus acidophilus NRRL-B 1910 with initial mucin, and 311.41 mu g/mL with Lacticaseibacillus casei NRRL-B 441 with initial mucin and 50 mM lactate. Nine LAB strains have been proposed as anti-obesity candidates, with olive isolates of Lactiplantibacillus plantarum being particularly important due to their ability to avoid mucin sugar consumption. Probiotic LAB's attachment to the colonic mucosa and its ability to stimulate HT-29 cells to secrete mucus are critical mechanisms that may support the development of Akkermansia.