PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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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) Tıhmınlıoğlu, Funda; Tıhmınlıoğlu, Funda; Tamburaci, Sedef; Karakasli, Ahmet; Tihminlioglu, Funda; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyIn 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: 1Comparison of Cell-Penetrating and Fusogenic Tat-Ha2 Peptide Performance in Peptideplex, Multicomponent, and Conjugate Sirna Delivery Systems(Amer Chemical Soc, 2024) Alsoy Altınkaya, Sacide; Bulmuş Zareie, Volga; Altinkaya, Sacide Alsoy; 03.02. Department of Chemical Engineering; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyIn 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: 4Tailored Bodipy-Based Fluorogenic Probes for Phosgene Detection: a Comparative Evaluation of Recognition Sites(Royal Soc Chemistry, 2024) Dartar, Suay; Emrullahoğlu, Mustafa; Kaya, Beraat Umur; Kaya, Beraat Umur; Yayak, Yanki Oncu; Vural, Ezgi; Vural, Ezgi; Dartar, Suay; Emrullahoglu, Mustafa; 01. Izmir Institute of Technology; 04.01. Department of Chemistry; 04.04. Department of Photonics; 04. Faculty of ScienceWe 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, Artturi; 01. Izmir Institute of TechnologyLecithin-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: 2Invasion/Chemotaxis- and Extravasation-Chip Models for Breast Cancer Bone Metastasis(Public Library Science, 2024) Firatligil-Yildirir, Burcu; Yalçın Özuysal, Özden; Bati-Ayaz, Gizem; Pesen Okvur, Devrim; Nonappa, Devrim; Pesen-Okvur, Devrim; Yalcin-Ozuysal, Ozden; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyBone 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.Article Citation - WoS: 2Citation - Scopus: 2Investigation of the Biocompatibility of Various Pulp Capping Materials on Zebrafish Model(Public Library Science, 2024) Özhan, Güneş; Eliacik, Bahar Basak Kiziltan; Cagiral, Umut; Iscan, Evin; Ozhan, Gunes; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyTesting the biocompatibility of commercially available dental materials is a major challenge in dental material science. In the present study, the biocompatibility of four commercially available dental materials Mineral Trioxide Aggregate, Biodentine, Harvard BioCal-CAP and Oxford ActiveCal PC was investigated. The biocompatibility analysis was performed on zebrafish embryos and larvae using standard toxicity tests such as survivability and hatching rates. Comparative toxicity analysis of toxicity was performed by measuring apoptosis using acridine orange dye and whole mount immunofluorescence methods on zebrafish larvae exposed to the dental materials at different dilutions. Toxicity analysis showed a significant decrease in survival and hatching rates with increasing concentration of exposed materials. The results of the apoptosis assay with acridine orange showed greater biocompatibility of Biodentine, Oxford ActiveCal PC, Harvard BioCal-CAP and Biodentine compared to MTA, which was concentration dependent. Consequently, this study has shown that showed resin-modified calcium silicates are more biocompatible than traditional calcium silicates.Editorial Citation - WoS: 5Citation - Scopus: 5Rna M<sup>6</Sup>a Methylation at the Juxtaposition of Apoptosis and Rna Therapeutics(Cell Press, 2024) Akgül, Bünyamin; Akcaoez-Alasar, Azime; Saglam, Buket; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyTargeting RNA m(6)A marks in apoptosis-related transcripts holds promise for RNA therapeutics. However, pathway-specific RNA m(6)A sites on pro- or antiapoptotic transcripts have not been fully unveiled, let alone characterized. This article summarizes the current knowledge and gaps in the cellular response modulated by apoptotic stimulus-specific RNA m(6)A marks.Article Citation - WoS: 9Citation - Scopus: 6Fluorescence Lifetime Multiplexing With Fluorogen Activating Protein Fast Variants(Nature Portfolio, 2024) Bogdanova, Yulia A.; Solovyev, Ilya D.; Baleeva, Nadezhda S.; Myasnyanko, Ivan N.; Gorshkova, Anastasia A.; Gorbachev, Dmitriy A.; Baranov, Mikhail S.; 01. Izmir Institute of TechnologyIn this paper, we propose a fluorescence-lifetime imaging microscopy (FLIM) multiplexing system based on the fluorogen-activating protein FAST. This genetically encoded fluorescent labeling platform employs FAST mutants that activate the same fluorogen but provide different fluorescence lifetimes for each specific protein-dye pair. All the proposed probes with varying lifetimes possess nearly identical and the smallest-in-class size, along with quite similar steady-state optical properties. In live mammalian cells, we target these chemogenetic tags to two intracellular structures simultaneously, where their fluorescence signals are clearly distinguished by FLIM. Due to the unique structure of certain fluorogens under study, their complexes with FAST mutants display a monophasic fluorescence decay, which may facilitate enhanced multiplexing efficiency by reducing signal cross-talks and providing optimal prerequisites for signal separation upon co-localized and/or spatially overlapped labeling. A genetically encoded labeling system uses smallest-in-class fluorogen-activating protein tags for time-resolved fluorescence multiplexed cellular imaging, offering monoexponential decay and potential for sophisticated fluorescence lifetime analysis.Article Citation - WoS: 25Citation - Scopus: 25Topology Degree Results on a G-Abc Implicit Fractional Differential Equation Under Three-Point Boundary Conditions(Public Library Science, 2024) Aghazadeh, Nasser; Thabet, Sabri T. M.; Rafeeq, Ava Sh.; Kedim, Imed; Vivas-Cortez, Miguel; Aghazadeh, Nasser; 04.02. Department of Mathematics; 04. Faculty of Science; 01. Izmir Institute of TechnologyThis research manuscript aims to study a novel implicit differential equation in the non-singular fractional derivatives sense, namely Atangana-Baleanu-Caputo (A B C) of arbitrary orders belonging to the interval (2, 3] with respect to another positive and increasing function. The major results of the existence and uniqueness are investigated by utilizing the Banach and topology degree theorems. The stability of the Ulam-Hyers (U H) type is analyzed by employing the topics of nonlinear analysis. Finally, two examples are constructed and enhanced with some special cases as well as illustrative graphics for checking the influence of major outcomes.Article Citation - WoS: 6Citation - Scopus: 6Tumour-Intrinsic Endomembrane Trafficking by Arf6 Shapes an Immunosuppressive Microenvironment That Drives Melanomagenesis and Response To Checkpoint Blockade Therapy(Nature Portfolio, 2024) Wee, Yinshen; Wang, Junhua; Wilson, Emily C.; Rich, Coulson P.; Rogers, Aaron; Tong, Zongzhong; Grossmann, Allie H.; 01. Izmir Institute of TechnologyTumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development. This ARF6-dependent TME is vulnerable to immune checkpoint blockade therapy (ICB) but in murine melanoma, loss of Arf6 causes resistance to ICB. Likewise, downregulation of ARF6 in patient tumours correlates with inferior overall survival after ICB. Mechanistically, these phenotypes are at least partially explained by ARF6-dependent recycling, which controls plasma membrane density of the interferon-gamma receptor. Collectively, our findings reveal the importance of endomembrane trafficking in outfitting tumour cells with the ability to shape their immune microenvironment and respond to immunotherapy. The small GTPase ARF6 is known to regulate endocytosis and recycling of plasma membrane proteins. Here the authors show that tumourintrinsic ARF6 promotes an immunosuppressive microenvironment that accelerates melanoma progression but that is vulnerable to immune checkpoint blockade, mechanistically linked to ARF6-dependent recycling of interferon-gamma receptors in tumour cells.