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.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: 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: 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.Article Citation - WoS: 25Citation - Scopus: 38Biodiversity: the Overlooked Source of Human Health(Elsevier, 2023) Linhares, Yuliya; Kaganski, Alexander; Agyare, Christian; Aksan Kurnaz, Işıl; Neergheen, Vidushi; Kolodziejczyk, Bartlomiej; Baran, YusufBiodiversity is the measure of the variation of lifeforms in a given ecological system. Biodiversity provides ecosystems with the robustness, stability, and resilience that sustains them. This is ultimately essential for our survival because we depend on the services that natural ecosystems provide (food, fresh water, air, climate, and medicine). Despite this, human activity is driving an unprecedented rate of biodiversity decline, which may jeopardize the life-support systems of the planet if no urgent action is taken. In this article we show why biodiversity is essential for human health. We raise our case and focus on the biomedicine services that are enabled by biodiversity, and we present known and novel approaches to promote biodiversity conservation.Article Citation - WoS: 27Citation - Scopus: 27Epithelial-Myeloid Exchange of Mhc Class Ii Constrains Immunity and Microbiota Composition(Elsevier, 2021) Stephens, W. Zac; Kubinak, Jason L.; Ghazaryan, Arevik; Bauer, Kaylyn M.; Buhrke, Kate; Round, June L.; Ekiz, Hüseyin AtakanIntestinal epithelial cells (IECs) have long been understood to express high levels of major histocompatibility complex class II (MHC class II) molecules but are not considered canonical antigen-presenting cells, and the impact of IEC-MHC class II signaling on gut homeostasis remains enigmatic. As IECs serve as the primary barrier between underlying host immune cells, we reasoned that IEC-intrinsic antigen presentation may play a role in responses toward the microbiota. Mice with an IEC-intrinsic deletion of MHC class II (IECΔMHC class II) are healthy but have fewer microbial-bound IgA, regulatory T cells (Tregs), and immune repertoire selection. This was associated with increased interindividual microbiota variation and altered proportions of two taxa in the ileum where MHC class II on IECs is highest. Intestinal mononuclear phagocytes (MNPs) have similar MHC class II transcription but less surface MHC class II and are capable of acquiring MHC class II from IECs. Thus, epithelial-myeloid interactions mediate development of adaptive responses to microbial antigens within the gastrointestinal tract.Article Citation - WoS: 16Citation - Scopus: 18Connexin 32 Induces Pro-Tumorigenic Features in Mcf10a Normal Breast Cells and Mda-Mb Metastatic Breast Cancer Cells(Elsevier, 2020) Yalçın Özuysal, Özden; Adak, Aslı; Ünal, Yağmur Ceren; Yücel, Simge; Vural, Zehra; Turan, Fatma Başak; Meşe, GülistanConnexins (Cx), the basic subunit of gap junctions, play important roles in cell homeostasis, and their abnormal expression and function are associated with human hereditary diseases and cancers. In tumorigenesis, connexins were observed to have both anti-tumorigenic and pro-tumorigenic roles in a context- and stage-dependent manner. Initially, Cx26 and Cx43 were thought to be the only connexins involved in normal breast homeostasis and breast cancer. Later on, association of Cx32 expression with lymph node metastasis of breast cancer and subsequent demonstration of its expression in normal breast tissue suggested that Cx32 contributes to breast tissue homeostasis. Here, we aimed to determine the effects of Cx32 on normal breast cells, MCF10A, and on breast cancer cells, MDA-MB-231. Cx32 overexpression had profound effects on MCF10A cells, decreasing cell proliferation by increasing the doubling time of MCF10A. Furthermore, MCF10A cells acquired mesenchymal-like appearance upon Cx32 expression and had increased migration capacity and expression of both E-cadherin and vimentin. In contrast, Cx32 overexpression altered the EMT markers of MDA-MB-231 by increasing the expression of mesenchymal markers, such as slug and vimentin, and decreasing E-cadherin expression without affecting their proliferation and morphology. Our results indicate, for the first time in the literature, that Cx32 has tumor-promoting roles in MCF10A and MDA-MB-231 cells.Article Citation - WoS: 10Citation - Scopus: 11A New Drug Testing Platform Based on 3d Tri-Culture in Lab-On Devices(Elsevier, 2020) Gökçe, Begüm; Akçok, İsmail; Çağır, Ali; Pesen Okvur, DevrimDrug discovery has a 90% rate of failure because preclinical platforms for drug testing do not mimic the in vivo conditions. Doxorubicin (DOX) is a commonly used drug to treat breast cancer patients even though it has side effects. Lab-on-a-chip (LOC) devices provide spatial control at the micrometer scale and can thus emulate the cancer microenvironment. Here, using a multidisciplinary approach, a new drug testing platform based on 3D tri-culture in LOC devices was developed. Breast cancer cells alone or with normal mammary epithelial cells and macrophages were cultured in matrigel in LOC devices. The platform was used to test DOX and (R)-4'-methylklavuzon (KLA), which is a new anti-cancer drug candidate. Results showed that DOX and KLA were equally effective on breast cancer cells in 3D monoculture. KLA produced 26% less death for breast cancer cells than DOX in 3D tri-culture. More importantly, DOX was not selective between breast cancer cells and normal mammary epithelial cells in 3D tri- culture whereas KLA caused 56% less cell death than DOX for normal mammary epithelial cells. Results strongly recommend that 3D tri-culture in LOC devices be used for assessment of drug toxicity at the preclinical stage.Article Citation - WoS: 20Citation - Scopus: 21Breast Cancer Cells and Macrophages in a Paracrine-Juxtacrine Loop(Elsevier, 2021) Önal, Sevgi; Türker Burhan, Merve; Batı Ayaz, Gizem; Yanık, Hamdullah; Pesen Okvur, DevrimBreast cancer cells (BCC) and macrophages are known to interact via epidermal growth factor (EGF) produced by macrophages and colony stimulating factor-1 (CSF-1) produced by BCC. Despite contradictory findings, this interaction is perceived as a paracrine loop. Further, the underlying mechanism of interaction remains unclear. Here, we investigated interactions of BCC with macrophages in 2D and 3D. While both BCC and macrophages showed invasion/chemotaxis to fetal bovine serum, only macrophages showed chemotaxis to BCC in custom designed 3D cell-on-a-chip devices. These results were in agreement with gradient simulation results and ELISA results showing that macrophage-derived-EGF was not secreted into macrophage-conditioned-medium. Live cell imaging of BCC in the presence and absence of iressa showed that macrophages but not macrophage-derived-matrix modulated adhesion and motility of BCC in 2D. 3D co-culture experiments in collagen and matrigel showed that BCC changed their multicellular organization in the presence of macrophages. In custom designed 3D co-culture cell-on-a-chip devices, macrophages promoted and reduced migration of BCC in collagen and matrigel, respectively. Furthermore, adherent but not suspended BCC endocytosed EGFR when in contact with macrophages. Collectively, our data revealed that macrophages showed chemotaxis towards BCC whereas BCC required direct contact to interact with macrophage-derived-EGF. Therefore, we propose that the interaction between cancer cells and macrophages is a paracrine-juxtacrine loop of CSF-1 and EGF, respectively. © 2020 Elsevier LtdArticle Citation - WoS: 24Citation - Scopus: 23Polyethers Isolated From the Marine Actinobacterium Streptomyces Cacaoi Inhibit Autophagy and Induce Apoptosis in Cancer Cells(Elsevier, 2019) Khan, Nasar; Yılmaz, Sinem; Aksoy, Semiha; Uzel, Ataç; Tosun, Çiğdem; Ballar Kırmızıbayrak, Petek; Bedir, ErdalPolyether compounds, a large group of biologically active metabolites produced by Streptomyces species have been reported to show a variety of bioactivity such as antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Since some of these compounds target cancer stem cells and multi-drug resistant cancer cells, this family of compounds have become of high interest. In this study, three polyether-type metabolites (1-3), one of which was a new natural product (3), were isolated from the marine derived Streptomyces cacaoi via antimicrobial activity-guided fractionation studies. As several polyether compounds with structural similarity such as monensin have been linked with autophagy and cell death, we first assessed the cytotoxicity of these three compounds. Compounds 2 and 3, but not 1, were found to be cytotoxic in several cell lines with a higher potency towards cancer cells. Furthermore, 2 and 3 caused accumulation of both autophagy flux markers LC3-II and p62 along with cleavage of caspase-3, caspase-9 and poly (ADP-ribose) polymerase 1 (PARP-1). Interestingly, prolonged treatment of the compounds caused a dramatic downregulation of the proteins related to autophagasome formation in a dose dependent manner. Our findings provide insights on the molecular mechanisms of the polyether-type polyketides, and signify their potency as chemotherapeutic agents through inhibiting autophagy and inducing apoptosis.