Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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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.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: 4Citation - Scopus: 4Autophagic Flux Is Impaired in the Brain Tissue of Tay-Sachs Disease Mouse Model(Public Library of Science, 2023) Şengül, Tuğçe; Can, Melike; Ateş, Nurselin; Seyrantepe, VolkanTay-Sachs disease is a lethal lysosomal storage disorder caused by mutations in the HexA gene encoding the α subunit of the lysosomal β-hexosaminidase enzyme (HEXA). Abnormal GM2 ganglioside accumulation causes progressive deterioration in the central nervous system in Tay-Sachs patients. Hexa-/-mouse model failed to display abnormal phenotype. Recently, our group generated Hexa-/-Neu3-/-mouse showed severe neuropathological indications similar to Tay-Sachs patients. Despite excessive GM2 ganglioside accumulation in the brain and visceral organs, the regulation of autophagy has not been clarified yet in the Tay-Sachs disease mouse model. Therefore, we investigated distinct steps of autophagic flux using markers including LC3 and p62 in four different brain regions from the Hexa-/-Neu3-/-mice model of Tay-Sachs disease. Our data revealed accumulated autophagosomes and autophagolysosomes indicating impairment in autophagic flux in the brain. We suggest that autophagy might be a new therapeutic target for the treatment of devastating Tay-Sachs disease. © 2023 Sengul et al.Review Citation - WoS: 96Citation - Scopus: 112Therapeutic Potential of Luteolin on Cancer(MDPI, 2023) Çetinkaya, Melisa; Baran, YusufCancer is a global concern, as the rate of incidence is increasing each year. The challenges related to the current chemotherapy drugs, such as the concerns related to toxicity, turn to cancer therapeutic research to discover alternative therapy strategies that are less toxic to normal cells. Among those studies, the use of flavonoids-natural compounds produced by plants as secondary metabolites for cancer therapy-has been a hot topic in cancer treatment. Luteolin, a flavonoid that has been present in many fruits, vegetables, and herbs, has been identified to exhibit numerous biological activities, including anti-inflammatory, antidiabetic, and anticancer properties. The anticancer property of Luteolin has been extensively researched in many cancer types and has been related to its ability to inhibit tumor growth by targeting cellular processes such as apoptosis, angiogenesis, migration, and cell cycle progression. It achieves this by interacting with various signaling pathways and proteins. In the current review, the molecular targets of Luteolin as it exerts its anticancer properties, the combination therapy that includes Luteolin with other flavonoids or chemotherapeutic drugs, and the nanodelivery strategies for Luteolin are described for several cancer types.Article Citation - WoS: 20Citation - Scopus: 21Progression of Irradiated Mesenchymal Stromal Cells From Early To Late Senescence: Changes in Sasp Composition and Anti-Tumour Properties(Wiley, 2023) Alessio, Nicola; Acar, Mustafa Burak; Squillaro, Tiziana; Aprile, Domenico; Ayaz Güner, Şerife; Di Bernardo, Giovanni; Özcan, ServetGenotoxic injuries converge on senescence-executive program that promotes production of a senescence-specific secretome (SASP). The study of SASP is particularly intriguing, since through it a senescence process, triggered in a few cells, can spread to many other cells and produce either beneficial or negative consequences for health. We analysed the SASP of quiescent mesenchymal stromal cells (MSCs) following stress induced premature senescence (SIPS) by ionizing radiation exposure. We performed a proteome analysis of SASP content obtained from early and late senescent cells. The bioinformatics studies evidenced that early and late SASPs, besides some common ontologies and signalling pathways, contain specific factors. In spite of these differences, we evidenced that SASPs can block in vitro proliferation of cancer cells and promote senescence/apoptosis. It is possible to imagine that SASP always contains core components that have an anti-tumour activity, the progression from early to late senescence enriches the SASP of factors that may promote SASP tumorigenic activity only by interacting and instructing cells of the immune system. Our results on Caco-2 cancer cells incubated with late SASP in presence of peripheral white blood cells strongly support this hypothesis. We evidenced that quiescent MSCs following SIPS produced SASP that, while progressively changed its composition, preserved the capacity to block cancer growth by inducing senescence and/or apoptosis only in an autonomous manner.Article Citation - WoS: 4Citation - Scopus: 5Development of Ab3-Type Novel Phthalocyanine and Porphyrin Photosensitizers Conjugated With Triphenylphosphonium for Higher Photodynamic Efficacy(American Chemical Society, 2022) Albakour, Mohamad; Önal, Emel; Tüncel, Özge; Erdoğan, İpek; Gümüşgöz Çelik, Gizem; Küçük, Tuǧba; Akgül, Bünyamin; Gürek, Ayşe Gül; Özçelik, SerdarThere are a number of lipophilic cations that can be chosen; the triphenylphosphonium (TPP) ion is particularly unique for mitochondrion targeting, mainly due to its simplicity in structure and ease to be linked to the target molecules. In this work, mitochondrion-targeted AB3-type novel phthalocyanine and porphyrin photosensitizers (PSs) were synthesized and their photophysical photochemical properties were defined. Fluorescence quantum yields (φF) are 0.009, 0.14, 0.13, and 0.13, and the singlet-oxygen quantum yields (φΔ) are 0.27, 0.75, 0.57, and 0.58 for LuPcPox(OAc), AB3TPP-Pc, AB3TPP-Por-C4, and AB3TPP-Por-C6, respectively. To evaluate the photodynamic efficacy of the TPP-conjugated PS cell viabilities of A549 and BEAS-2B lung cells were comparatively measured and IC-50 values were determined. AB3TPP-Por-C4, AB3TPP-Por-C6, and AB3TPP-Pc compounds compared to the reference molecules ZnPc and H2TPP were found to be highly cytotoxic (sub-micromolar concentration) under the light. LuPcPox(OAc) is the most effective molecule regarding cell killing (the activity). The cell killing of the TPP-conjugated porphyrin derivatives exhibits a similar response compared to LuPcPox(OAc) when the light absorbing factor of the PS is normalized at 660 nm: TPP-conjugated porphyrins absorb less light (lower extinction coefficient) but produce more radical species (higher singlet-oxygen quantum yield) and therefore effectively kill the cells. The singlet oxygen-producing capacity of AB3TPP-Pc is almost 3 times higher compared to LuPcPox(OAc) and 50% more efficient with respect to ZnPc, suggesting that TPP-conjugated phthalocyanine may serve as a good photosensitizer for photodynamic therapy (PDT). The high singlet oxygen generation capacity of these novel TPP-conjugated porphyrin and phthalocyanine PS suggests that they might be useful for PDT requiring lower photosensitizer concentration and reduced energy deposited through less light exposure.Article Citation - WoS: 11Citation - Scopus: 10Genomewide M6a Mapping Uncovers Dynamic Changes in the M6a Epitranscriptome of Cisplatin-Treated Apoptotic Hela Cells(MDPI, 2022) Akçaöz, Azime; Tüncel, Özge; Gelmez, Ayşe Bengisu; Sağlam, Buket; Erdoğan Vatansever, İpek; Akgül, BünyaminCisplatin (CP), which is a conventional cancer chemotherapeutic drug, induces apoptosis by modulating a diverse array of gene regulatory mechanisms. However, cisplatin-mediated changes in the m6A methylome are unknown. We employed an m6A miCLIP-seq approach to investigate the effect of m6A methylation marks under cisplatin-mediated apoptotic conditions on HeLa cells. Our high-resolution approach revealed numerous m6A marks on 972 target mRNAs with an enrichment on 132 apoptotic mRNAs. We tracked the fate of differentially methylated candidate mRNAs under METTL3 knockdown and cisplatin treatment conditions. Polysome profile analyses revealed perturbations in the translational efficiency of PMAIP1 and PHLDA1 transcripts. Congruently, PMAIP1 amounts were dependent on METTL3. Additionally, cisplatin-mediated apoptosis was sensitized by METTL3 knockdown. These results suggest that apoptotic pathways are modulated by m6A methylation events and that the METTL3–PMAIP1 axis modulates cisplatin-mediated apoptosis in HeLa cells.