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: 2Fabrication of Bioactive Helix Aspersa Extract-Loaded Chitosan-Based Bilayer Wound Dressings for Skin Tissue Regeneration(Amer Chemical Soc, 2024) Perpelek, Merve; Tıhmınlıoğlu, Funda; Tamburaci, Sedef; Karakasli, Ahmet; Tihminlioglu, FundaIn recent years, there has been a notable shift toward exploring plant and animal extracts for the fabrication of tissue engineering structures that seamlessly integrate with the human body, providing both biological compatibility and physical reinforcement. In this particular investigation, we synthesized bilayer wound dressings by incorporating snail (Helix aspersa) secretions, comprising mucus and slime, into chitosan matrices via lyophilization and electrospinning methodologies. A nanofiber layer was integrated on top of the porous structure to mimic the epidermal layer for keratinocyte activity as well as acting as an antibacterial barrier against possible infection, whereas a porous structure was designed to mimic the dermal microenvironment for fibroblast activity. Comprehensive assessments encompassing physical characterization, antimicrobial efficacy, in vitro bioactivity, and wound healing potential were conducted on these bilayer dressings. Our findings revealed that the mucus and slime extract loading significantly altered the morphology in terms of nanofiber diameter and average pore size. Snail extracts loaded on a nanofiber layer of bilayer dressings showed slight antimicrobial activity against Staphylococcus epidermidis and Escherichia coli. An in vitro release study of slime extract loaded in the nanofiber layer indicated that both groups 1 and 2 showed a burst release up to 6 h, and a sustained release was observed up to 96 h for group 1, whereas slime extract release from group 2 continued up to 72 h. In vitro bioactivity assays unveiled the favorable impact of mucus and slime extracts on NIH/3T3 fibroblast and HS2 keratinocyte cell attachment, proliferation, and glycosaminoglycan synthesis. Furthermore, our investigations utilizing the in vitro scratch assay showcased the proliferative and migratory effects of mucus and slime extracts on skin cells. Collectively, our results underscore the promising prospects of bioactive snail secretion-loaded chitosan constructs for facilitating skin regeneration and advancing wound healing therapies.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: 1Comparison of Cell-Penetrating and Fusogenic Tat-Ha2 Peptide Performance in Peptideplex, Multicomponent, and Conjugate Sirna Delivery Systems(Amer Chemical Soc, 2024) Uz, Metin; Bulmus, Volga; Altinkaya, Sacide AlsoyIn this study, the performance of the cell-penetrating and fusogenic peptide, TAT-HA2, which consists of a cell-permeable HIV trans-activator of transcription (TAT) protein transduction domain and a pH-responsive influenza A virus hemagglutinin protein (HA2) domain, was comparatively evaluated for the first time in peptideplex, multicomponent, and conjugate siRNA delivery systems. TAT-HA2 in all three systems protected siRNA from degradation, except in the conjugate system with a low Peptide/siRNA ratio. The synergistic effect of different peptide domains enhanced the transfection efficiency of multicomponent and conjugate systems compared to that of peptideplexes, which was attributed to the surface configuration of TAT-HA2 peptides depending on the nature of attachment. Particularly, the multicomponent system showed better cellular uptake and endosomal escape than the peptideplexes, resulting in enhanced siRNA delivery in the cytoplasm. In addition, the presence of cleavable disulfide bonds in multicomponent and conjugate systems promoted the effective siRNA delivery in the cytoplasm, resulting in improved gene silencing activity. The multicomponent system reduced the level of luciferase expression in SKOV3 cells to 45% (+/- 4). In contrast, the conjugate system and the commercially available siRNA transfection agent, Lipofectamine RNAiMax, caused luciferase suppression down to 55% (+/- 2) at a siRNA dose of 100 nM. For the same dose, the peptideplex system could only reduce the luciferase expression to 65% (+/- 5). None of the developed systems showed significant toxicity at any dose. Overall, the TAT-HA2 peptide is promising as a siRNA delivery vector; however, its performance depends on the nature of attachment and, as a result, its surface configuration on the developed delivery system.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: 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.