Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Review Citation - WoS: 17Citation - Scopus: 16Engineering Periodontal Tissue Interfaces Using Multiphasic Scaffolds and Membranes for Guided Bone and Tissue Regeneration(Elsevier, 2024) Özkendir, Özge; Karaca, İlayda; Çullu, Selin; Yaşar, Hüsniye Nur,; Erdoğan, Oğulcan; Dikici, Serkan; Dikici, Betul AldemirPeriodontal diseases are one of the greatest healthcare burdens worldwide. The periodontal tissue compartment is an anatomical tissue interface formed from the periodontal ligament, gingiva, cementum, and bone. This multifaceted composition makes tissue engineering strategies challenging to develop due to the interface of hard and soft tissues requiring multiphase scaffolds to recreate the native tissue architecture. Multilayer constructs can better mimic tissue interfaces due to the individually tuneable layers. They have different characteristics in each layer, with modulation of mechanical properties, material type, porosity, pore size, morphology, degradation properties, and drug-releasing profile all possible. The greatest challenge of multilayer constructs is to mechanically integrate consecutive layers to avoid delamination, especially when using multiple manufacturing processes. Here, we review the development of multilayer scaffolds that aim to recapitulate native periodontal tissue interfaces in terms of physical, chemical, and biological characteristics. Important properties of multiphasic biodegradable scaffolds are highlighted and summarised, with design requirements, biomaterials, and fabrication methods, as well as post-treatment and drug/growth factor incorporation discussed.Article Citation - WoS: 14Citation - Scopus: 14Comparative Membrane Lipidomics of Hepatocellular Carcinoma Cells Reveals Diacylglycerol and Ceramide as Key Regulators of Wnt/Β-catenin Signaling and Tumor Growth(Wiley, 2023) Heger, Guillaume; Azbazdar, Yağmur; Demirci, Yeliz; İpekgil, Doğaç; Karabiçici, Mustafa; Özhan, GüneşHepatocellular carcinoma (HCC) is largely associated with aberrant activation of Wnt/beta-catenin signaling. Nevertheless, how membrane lipid composition is altered in HCC cells with abnormal Wnt signaling remains elusive. Here, by exploiting comprehensive lipidome profiling, we unravel the membrane lipid composition of six different HCC cell lines with mutations in components of Wnt/beta-catenin signaling, leading to differences in their endogenous signaling activity. Among the differentially regulated lipids are diacylglycerol (DAG) and ceramide, which were downregulated at the membrane of HCC cells after Wnt3a treatment. DAG and ceramide enhanced Wnt/b-catenin signaling by inducing caveolin-mediated endocytosis of the canonical Wnt-receptor complex, while their depletion suppressed the signaling activity along with a reduction of caveolin-mediated endocytosis in SNU475 and HepG2 cells. Moreover, depletion of DAG and ceramide significantly impeded the proliferation, tumor growth, and in vivo migration capacity of SNU475 and HepG2 cells. This study, by pioneering plasma membrane lipidome profiling in HCC cells, exhibits the remarkable potential of lipids to correct dysregulated signaling pathways in cancer and stop abnormal tumor growth.Letter Citation - WoS: 1Citation - Scopus: 2C-Met Activation Promotes Extravasation of Hepatocellular Carcinoma Cells Into 3d-Cultured Hepatocyte Cells in Lab-On Device(Elsevier, 2023) Solmaz, Gülhas; Bağcı, Gülsün; Çömez, Dehan; Topel, Hande; Yılmaz, Yeliz; Bağırsakçı, Ezgi; Güneş, Aysim; Batı Ayaz, Gizem; Tahmaz, İsmail; Bilgen, Müge; Pesen Okvur, DevrimActivation of c-Met signaling is associated with an aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC); however, its contribution to organ preference in metastasis remains unclear. In this study, using a Lab on a Chip device, we defined the role of aberrant c-Met activation in regulating the extravasation and homing capacity of HCC cells. Our studies showed that (i) c-Met overexpression and activation direct HCC cells preferentially towards the hepatocytes-enriched microenvironment, and (ii) blockage of c-Met phosphorylation by a small molecule inhibitor attenuated extravasation and homing capacity of HCC cells. These results, thus, demonstrate the role of c-Met signaling in regulating the colonization of HCC cells preferentially in the liver. © 2023 Elsevier B.V.Review Citation - WoS: 6Citation - Scopus: 8Molecular Trojan Horses for Treating Lysosomal Storage Diseases(Academic Press, 2023) Leal, Andres Felipe; Rintz, Estera; Çelik, Betül; Ago, Yasuhiko; León, Daniel; İnci, Orhan Kerim; Seyrantepe, VolkanLysosomal storage diseases (LSDs) are caused by monogenic mutations in genes encoding for proteins related to the lysosomal function. Lysosome plays critical roles in molecule degradation and cell signaling through interplay with many other cell organelles, such as mitochondria, endoplasmic reticulum, and peroxisomes. Even though several strategies (i.e., protein replacement and gene therapy) have been attempted for LSDs with promising results, there are still some challenges when hard-to-treat tissues such as bone (i.e., cartilages, ligaments, meniscus, etc.), the central nervous system (mostly neurons), and the eye (i.e., cornea, retina) are affected. Consistently, searching for novel strategies to reach those tissues remains a priority. Molecular Trojan Horses have been well-recognized as a potential alternative in several pathological scenarios for drug delivery, including LSDs. Even though molecular Trojan Horses refer to genetically engineered proteins to overcome the blood-brain barrier, such strategy can be extended to strategies able to transport and deliver drugs to specific tissues or cells using cell-penetrating peptides, monoclonal antibodies, vesicles, extracellular vesicles, and patient-derived cells. Only some of those platforms have been attempted in LSDs. In this paper, we review the most recent efforts to develop molecular Trojan Horses and discuss how this strategy could be implemented to enhance the current efficacy of strategies such as protein replacement and gene therapy in the context of LSDs. © 2023Article Citation - WoS: 4Citation - Scopus: 4Mitigation Potential of Zingerone and Rutin on Toxicity Mechanisms of Nickel To Zebrafish Based on Morphological, Dna Damage and Apoptosis Outcome Analysis(Elsevier, 2023) Köktürk, Mine; Yıldırım, Serkan; Atamanalp, Muhammed; Kılıçoğlu, Metin; Uçar, Arzu; Özhan, Güneş; Alak, GoncaAlthough nickel (Ni) is an important cofactor for various enzymes in biological systems, it can cause serious problems when insufficient or excessive in an organism. Therefore, it is very important to investigate Ni in biological systems, especially in cells with its related pathogenic mechanism. This study was carried out to demonstrate the effects of zingerone (ZO) and rutin (RN) administration against nickel chloride (NiCl2) toxicity on neurobehavioral performance and brain oxidative status in zebrafish (Danio rerio) embryos/larvae on histological perspective. The experimental design of the study, which included twenty groups of fish, each containing 10 embryos, was prepared as semi-static and the trial continued for 96 hpf. In the obtained findings, it was determined that ZO and RN had a mitigating effect in this toxicity table where Ni caused oxidative stress in zebrafish larvae, induced DNA damage and apoptosis. A similar picture is valid for malformation processes as well as survival and hatching rates. These results showed that nickel is toxic to developing embryos via acting different mechanisms. In conclusion, we observed that ZO and RN have a greater effect on physiology, DNA damage and apoptosis than gross morphology, with a significant ameliorative effect.Article Citation - WoS: 12Citation - Scopus: 13Lc-esi-ms/Ms Analysis of Secondary Metabolites of Different St. John's Wort (hypericum Perforatum) Extracts Used as Food Supplements and Evaluation of Developmental Toxicity on Zebrafish (danio Rerio) Embryos and Larvae(Elsevier, 2023) Atalar, Mehmet Nuri; Köktürk, Mine; Altındağ, Fikret; Özhan, Güneş; Özen, Tevfik; Demirtaş, İbrahim; Gülçin, İlhamiHypericum perforatum (St. John's wort) belongs to the Hypericaceae family and is one of the best known Hypericum species worldwide. It is a very popular and valuable medicinal plant widely distributed in Anatolia. Hypericum perforatum contains many bioactive components that play a role in activities has been used as a food supplement. The extracts are used within safe dose range that are harmless and effective for health. When the SJW1, SJW2 and SJW3 fractions of St. John's Wort extracts were exposed to zebrafish embryos and larvae at different concentrations (5, 10, 100, and 300 µg/mL), the survival rates at 96th hour were determined as 83.3, 27.5 and 2.5%, respectively. No significant changes were found in the malformation rates, and the larval emergence was found to be above 80% at 96th hour for all extracts. No caspase-3 expression was found at the 96th hour in the larvae. Similar secondary components of extracts were observed except quantitative differences. The use of samples in doses of 10 µg/mL and below as food supplement may be harmless, however, threshold dose values of H. perforatum extracts lower toxic doses may be due to the different amounts of secondary metabolites. © 2023Article Citation - WoS: 21Citation - Scopus: 22High-Dose Exposure To Polymer-Coated Iron Oxide Nanoparticles Elicits Autophagy-Dependent Ferroptosis in Susceptible Cancer Cells(MDPI, 2023) Lomphithak, Thanpisit; Helvacıoğlu, Selin; Armenia, Ilaria; Keshavan, Sandeep; Ovejero, Jesus G.; Baldi, Giovanni; Ravagli, Costanza; Grazú, Valeria; Fadeel, BengtFerroptosis, a form of iron-dependent, lipid peroxidation-driven cell death, has been extensively investigated in recent years, and several studies have suggested that the ferroptosis-inducing properties of iron-containing nanomaterials could be harnessed for cancer treatment. Here we evaluated the potential cytotoxicity of iron oxide nanoparticles, with and without cobalt functionalization (Fe2O3 and Fe2O3@Co-PEG), using an established, ferroptosis-sensitive fibrosarcoma cell line (HT1080) and a normal fibroblast cell line (BJ). In addition, we evaluated poly (ethylene glycol) (PEG)-poly(lactic-co-glycolic acid) (PLGA)-coated iron oxide nanoparticles (Fe3O4-PEG-PLGA). Our results showed that all the nanoparticles tested were essentially non-cytotoxic at concentrations up to 100 mu g/mL. However, when the cells were exposed to higher concentrations (200-400 mu g/mL), cell death with features of ferroptosis was observed, and this was more pronounced for the Co-functionalized nanoparticles. Furthermore, evidence was provided that the cell death triggered by the nanoparticles was autophagy-dependent. Taken together, the exposure to high concentrations of polymer-coated iron oxide nanoparticles triggers ferroptosis in susceptible human cancer cells.Article Citation - WoS: 5Citation - Scopus: 5De-Sealing Reverses Habitat Decay More Than Increasing Groundcover Vegetation(MDPI, 2023) Couch, Virginia; Salata, Stefano; Saygın, Nicel; Frary, Anne; Arslan, BertanModeling ecosystem services is a growing trend in scientific research, and Nature-based Solutions (NbSs) are increasingly used by land-use planners and environmental designers to achieve improved adaptation to climate change and mitigation of the negative effects of climate change. Predictions of ecological benefits of NbSs are needed early in design to support decision making. In this study, we used ecological analysis to predict the benefits of two NbSs applied to a university masterplan and adjusted our preliminary design strategy according to the first modeling results. Our Area of Interest was the IZTECH campus, which is located in a rural area of the eastern Mediterranean region (Izmir/Turkey). A primary design goal was to improve habitat quality by revitalizing soil. Customized analysis of the Baseline Condition and two NbSs scenarios was achieved by using local values obtained from a high-resolution photogrammetric scan of the catchment to produce flow accumulation and habitat quality indexes. Results indicate that anthropogenic features are the primary cause of habitat decay and that decreasing imperviousness reduces habitat decay significantly more than adding vegetation. This study creates a method of supporting sustainability goals by quickly testing alternative NbSs. The main innovation is demonstrating that early approximation of the ecological benefits of NbSs can inform preliminary design strategy. The proposed model may be calibrated to address specific environmental challenges of a given location and test other forms of NbSs.Review Citation - WoS: 14Citation - Scopus: 14Recent Advances in Lab-On Systems for Breast Cancer Metastasis Research(Royal Society of Chemistry, 2023) Fıratlıgil Yıldırır, Burcu; Yalçın Özuysal, Özden; NonappaBreast cancer is the leading cause of cancer-related deaths in women. Multiple molecular subtypes, heterogeneity, and their ability to metastasize from the primary site to distant organs make breast cancer challenging to diagnose, treat, and obtain the desired therapeutic outcome. As the clinical importance of metastasis is dramatically increasing, there is a need to develop sustainable in vitro preclinical platforms to investigate complex cellular processes. Traditional in vitro and in vivo models cannot mimic the highly complex and multistep process of metastasis. Rapid progress in micro- and nanofabrication has contributed to soft lithography or three-dimensional printing-based lab-on-a-chip (LOC) systems. LOC platforms, which mimic in vivo conditions, offer a more profound understanding of cellular events and allow novel preclinical models for personalized treatments. Their low cost, scalability, and efficiency have resulted in on-demand design platforms for cell, tissue, and organ-on-a-chip platforms. Such models can overcome the limitations of two- and three-dimensional cell culture models and the ethical challenges involved in animal models. This review provides an overview of breast cancer subtypes, various steps and factors involved in metastases, existing preclinical models, and representative examples of LOC systems used to study and understand breast cancer metastasis and diagnosis and as a platform to evaluate advanced nanomedicine for breast cancer metastasis.Article Citation - WoS: 4Citation - Scopus: 3Boron Stress Signal Is Transmitted Through the Tor Pathway(Elsevier, 2023) Uluışık, İrem; Koç, AhmetAlthough boron is an essential element for many organisms, an excess amount of it can cause toxicity, and the mechanism behind this toxicity is not yet fully understood. The Gcn4 transcription factor plays a crucial role in the boron stress response by directly activating the expression of the boron efflux pump Atr1. More than a dozen transcription factors and multiple cell signaling pathways have roles in regulating the Gcn4 transcription factor under various circumstances. However, it is unknown which pathways or factors mediate boron signaling to Gcn4. Using the yeast Saccharomyces cerevisiae as a model, we analyzed the factors that converge on the Gcn4 transcription factor to assess their possible roles in boron stress signaling. Our findings show that the GCN system is activated by uncharged tRNA stress in response to boron treatment and that GCN1, which plays a role in transferring uncharged tRNAs to Gcn2, is necessary for the kinase activity of Gcn2. The SNF and PKA pathways were not involved in mediating boron stress, even though they interact with Gcn4. Mutations in TOR pathway genes, such as GLN3 and TOR1, abolished Gcn4 and ATR1 activation in response to boric acid treatment. Therefore, our study suggests that the TOR pathway must be functional to form a proper response against boric acid stress.