Bioengineering / Biyomühendislik

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Citation - WoS: 7
Citation - Scopus: 10
Adjuvant Potency of Astragaloside Vii Embedded Cholesterol Nanoparticles for H3n2 Influenza Vaccine
(TÜBİTAK, 2020) Genç, Rukan; Yakuboğulları, Nilgün; Nalbantsoy, Ayşe; Coven, Fethiye; Bedir, Erdal; 01.01. Units Affiliated to the Rectorate; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03. Faculty of Engineering
Adjuvants are substances that increase the immune response to a given antigen. In the development of novel vaccine adjuvants/systems, saponins are one of the most attractive molecules due to their altered immunomodulatory activities. In this study, we tried to develop PEG (polyethylene glycol)/cholesterol-based lipid nanoparticles (LNPs) to deliver the Astragaloside VII (AST-VII) and potentiate adjuvant properties of AST-VII for the influenza vaccine. In the formation of PEG/cholesterol/AST-VII-based LNPs (PEG300: Chol-AST-VII LNPs), 3 different primary solvents (acetone, ethanol, and chloroform) were evaluated, employing their effects on hydrodynamic particle size, distribution, surface chemistry, and colloidal stability. Prepared nanoparticles were simply admixtured with inactivated influenza antigen (H3N2) and applied to PMA (phorbol 12-myristate 13-acetate)-ionomycin treated human whole blood to evaluate their cytokine release profile. PEG300: Chol-AST-VII LNPs (80.2 +/- 7.7 nm) were obtained using chloroform as a desolvation agent. Co-treatment of PMA-ionomycin with AST-VII and PEG300: Chol-AST-VII LNPs significantly increased the levels of IL-2 and IFN-gamma, compared to PMA-ionomycin alone. In the presence of H3N2, AST-VII was able to augment IL-17A, while PEG300: Chol-AST-VII LNPs stimulated the production of IFN-gamma. Hemolysis was only observed in PEG300: Chol-AST-VII LNPs (250 mu g/mL) treatment. AST-VII and AST-VII-integrated LNPs could be used as efficacious adjuvants for an inactivated H3N2 vaccine in vitro, and cytokine response through Th1/Th17 route was reported.
Citation - WoS: 4
Citation - Scopus: 5
Adsorption/Desorption and Biofunctional Properties of Oleuropein Loaded on Different Types of Silk Fibroin Matrices
(The Society of Chemists and Techonogists of Macedonia, 2017) Bayraktar, Oğuz; Balta, Ali Bora; Başal Bayraktar, Güldemet; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
The objective of this study was to investigate the adsorption/desorption behavior of oleuropein on different types of silk fibroin matrices including silk fibroin microfibers (MF), regenerated silk fibroin (RSF), and silk fibroin nanofibers (NF). Nanofibers with an average diameter of ranging between 24 and 326 nm were successfully prepared using the electrospinning technique. The effects of the silk fibroin concentration, the voltage applied and the distance between needle tip and collector plate on the morphol-ogy of the NF were investigated. The adsorption capacities of MF, RSF and NF were determined as 104.92, 163.07 and 228.34 mg oleuropein per gram of material, respectively. The percentage of initially adsorbed oleuropein that was desorbed was 86.08, 91.29 and 96.67% for MF, RSF and NF, respectively. NF and RSF discs loaded with oleuropein were subjected to disc diffusion assays to determine their antibacterial activity against test microorganisms Staphylococcus epidermidis (Gram +) and Esche-richia coli (Gram -). The results showed that both biomaterials possessed antibacterial properties after loading with oleuropein. Wound scratch assays using oleuropein released from NF revealed an enhance-ment of cell migration, indicating a wound healing property of the material. In conclusion, the NF can be utilized as a biofunctional polymeric material with better perfor-mance for the adsorption and desorption of oleuropein compared with MF and RSF.
Anthraquinones and Macrocyclic Lactones From Endophytic Fungus Penicillium Roseopurpureum and Their Bioactivities
(ACG Publications, 2024) Dizmen,B.; Üner,G.; Küçüksolak,M.; Gören,A.C.; Kırmızıbayrak,P.B.; Bedir,E.; 01. Izmir Institute of Technology
Endophytic fungi colonize the internal and distinct tissues of the host plants. In recent years, there has been growing interest in endophytic fungi as valuable sources for drug discovery based on their rich metabolic profiles consisting of novel and bioactive compounds. Accordingly, our preliminary study demonstrated that an endophyte, namely Penicillium roseopurpureum isolated from Astragalus angustifolius, had high chemical diversity with an antiproliferative effect. Herein, fermentation of P. roseopurpureum resulted in the production of five new anthraquinone-type compounds (2, 4, 6, 7, 8) together with several known compounds [11-methoxycurvularin (1: epimeric mixture of 1a and 1b), carviolin (3), 11-hydroxycurvularin (5: diastereoisomeric mixture of 5a and 5b) and 1-O-methylemodin (9)]. The structures of the new compounds were established by NMR spectroscopy and HR-MS analysis. Cytotoxicity studies demonstrated that none of the compounds except for 1 and 5 had antiproliferative activity against prostate cancer cell lines. Interestingly, 1 was found as cytotoxic, whereas 5 exhibited cytostatic properties. Also, 7-AAD/Annexin V staining supported these results by showing that 1 caused cellular death, while 5 did not show any increase in dead cell content in comparison to the control. Lastly, cell cycle analysis showed that compounds had distinctive cell cycle arrest patterns. © 2024 ACG Publications.
Citation - WoS: 4
Antioxidant, Antimicrobial and Cytotoxic Activities of Extracts From Some Selected Mediterranean Shrub Species (maquis)
(Biointerface Research Applied Chemistry, 2016) Bayraktar, Oğuz; Altıok, Evren; Yılmazer, Özgür; Rusçuklu, Dane; Büyüköz, Melda; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
In this study in vitro antioxidant, antimicrobial and cytotoxic activities of ethanol extracts of some plants from Urla region in Turkey were investigated. Plant material samples of Pistacia lentiscus, Vitex agnus-castus, Cistus creticus and Nerium oleander were collected in October, November and December. The harvesting time significantly affected their antioxidant, antimicrobial and cytotoxic activities of these plant extracts. The highest biological activities in terms of antioxidant, antimicrobial and cytotoxic activities were observed for the leaf extract of C. creticus. The applied doses of leaf extracts of C. creticus, P. lentiscus, and N. oleander resulted in higher Bax and GAPDH expressions than those for control cells. These plant extracts may trigger apoptosis and may be a promising natural source for prostate cancer treatment.
Citation - WoS: 8
Citation - Scopus: 11
Application of Low Intensity Mechanical Vibrations for Bone Tissue Maintenance and Regeneration
(TÜBİTAK, 2016) Ölçüm, Melis; Baskan, Öznur; Karadaş, Özge; Özçivici, Engin; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03. Faculty of Engineering
Physical exercise is beneficial for bone tissue health, yet its usage is limited for preventing osteoporosis. Even though natural for the bone tissue from development to homeostasis, mechanical loads present with a multitude of physical parameters, including amplitude, duration, frequency, and distribution. Utilizing the most beneficial parameters of mechanical loads may potentiate a nonpharmaceutical tool for biotechnology to prevent and treat bone loss related to aging, bedrest, sedentary lifestyles, weightlessness, and other diseases. Low intensity vibrations (LIVs) consist of mechanical loads with amplitudes smaller than loads prescribed by habitual activity, with a higher frequency. In this review, literature covering LIV signal application on bone tissue and cellular and molecular level is presented. Studies indicate that LIV signals are safe, anabolic, and anticatabolic for skeletal tissue and are of great significance in regenerative medicine applications.
Citation - WoS: 5
Citation - Scopus: 7
Ascorbic Acid Enhances the Metabolic Activity, Growth and Collagen Production of Human Dermal Fibroblasts Growing in Three-Dimensional (3D) Culture
(Gazi Üniversitesi, 2023) Dikici, Serkan; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
Tissue engineering (TE) enables the development of functional synthetic substitutes to be replaced with damaged tissues and organs instead of the use of auto or allografts. A wide range of biomaterials is currently in use as TE scaffolds. Among these materials, naturally sourced ones are favorable due to being highly biocompatible and supporting cell growth and function, whereas synthetic ones are advantageous because of the high tunability on mechanical and physical properties as well as being easy to process. Alongside the advantages of synthetic polymers, they mostly show hydrophobic behavior that limits biomaterial-cell interaction and, consequently, the functioning of the developed TE constructs. In this study, we assessed the impact of L-Ascorbic acid 2-phosphate (AA2P) on improving the culture conditions of human dermal fibroblasts (HDFs) growing on a three-dimensional (3D) scaffold made of polycaprolactone (PCL) using emulsion templating. Our results demonstrated that AA2P enhances the metabolic activity and growth of HDFs as well as collagen deposition by them when supplemented in their growth medium at 50 µg/mL concentration. It showed a great potential to be used as a growth medium supplement to circumvent the disadvantages of culturing human cells on a synthetic biomaterial that is not favored in default. AA2P's potential to improve cell growth and collagen deposition may prove an effective way to culture human cells on 3D PCL PolyHIPE scaffolds for various TE applications.
Citation - WoS: 6
Citation - Scopus: 6
Benzodiazepine Derivatives From Marine-Derived Streptomyces Cacaoi 14cm034
(ACG Publications, 2021) Çetinel Aksoy, Semiha; Küçüksolak, Melis; Uzel, Ataç; Bedir, Erdal; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
7-methoxy-8-hydroxy cycloanthranilylproline (2), a new natural product with pyrrolobenzodiazepine (PBD) framework, was isolated from marine-derived actinobacterium Streptomyces cacaoi 14CM034, together with cycloanthranilylproline (1). Structural elucidation of the compounds was based on FTIR, 1D-(H-1 and C-13 NMR), 2D-NMR (COSY, HMBC and NOESY) and HR-MS analyses. Compounds 1 and 2 exhibited notable antimicrobial activity. The presence of PBD derivatives in S. cacaoi was first demonstrated with this study.
Bioassay Guided Isolation of Naphthoquinones From Onosma Aksoyii, Investigation of Their Cytotoxic Properties
(Georg Thieme Verlag, 2019) Kul, Demet; Karakoyun, Çiğdem; Yılmaz, Sinem; Pirhan, Ademi Fahri; Bedir, Erdal; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
The genus Onosma L. (Boraginaceae) includes about 230 species, distributed mainly in the Mediterranean region and Central Asia. Major constituents of Onosma species are alkaloids, naphthoquinones, polyphenols, phytosterols, terpenoids and fatty acids [1], [2]. Naphthoquinones are naturally widespread secondary metabolites deriving from some higher plants, fungi and bacteria. They exhibit significant biological activities such as cytotoxicity, antimalarial, antibacterial, antifungal and wound healing [2], [3]. Recently naphthoquinone derivatives have also been recognized as potent topoisomerase inhibitors [4].
Citation - WoS: 5
Citation - Scopus: 7
A Biodesign Approach To Obtain High Yields of Biosimilars by Anti-Apoptotic Cell Engineering: A Case Study To Increase the Production Yield of Anti-Tnf Alpha Producing Recombinant Cho Cells
(Humana Press, 2018-01) Gülce İz, Sultan; Anıl İnevi, Müge; Sağlam Metiner, Pelin; Ayyıldız Tamiş, Duygu; Kisbet, Nazlı; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
Recent developments in medical biotechnology have facilitated to enhance the production of monoclonal antibodies (mAbs) and recombinant proteins in mammalian cells. Human mAbs for clinical applications have focused on three areas, particularly cancer, immunological disorders, and infectious diseases. Tumor necrosis factor alpha (TNF-α), which has both proinflammatory and immunoregulatory functions, is an important target in biopharmaceutical industry. In this study, a humanized anti-TNF-α mAb producing stable CHO cell line which produces a biosimilar of Humira (adalimumab) was used. Adalimumab is a fully human anti-TNF mAb among the top-selling mAb products in recent years as a biosimilar. Products from mammalian cell bioprocesses are a derivative of cell viability and metabolism, which is mainly disrupted by cell death in bioreactors. Thus, different strategies are used to increase the product yield. Suppression of apoptosis, also called anti-apoptotic cell engineering, is the most remarkable strategy to enhance lifetime of cells for a longer production period. In fact, using anti-apoptotic cell engineering as a BioDesign approach was inspired by nature; nature gives prolonged life span to some cells like stem cells, tumor cells, and memory B and T cells, and researchers have been using this strategy for different purposes. In this study, as a biomimicry approach, anti-apoptotic cell engineering was used to increase the anti-TNF-α mAb production from the humanized anti-TNF-α mAb producing stable CHO cell line by Bcl-xL anti-apoptotic protein. It was shown that transient transfection of CHO cells by the Bcl-xL anti-apoptotic protein expressing plasmid prolonged the cell survival rate and protected cells from apoptosis. The transient expression of Bcl-xL using CHO cells enhanced the anti-TNF-α production. The production of anti-TNF-α in CHO cells was increased up to 215 mg/L with an increase of 160% after cells were transfected with Bcl-xL expressing plasmid with polyethylenimine (PEI) reagent at the ratio of 1:6 (DNA:PEI). In conclusion, the anti-apoptotic efficacy of the Bcl-xL expressing plasmid in humanized anti-TNF-α MAb producing stable CHO cells is compatible with curative effect for high efficiency recombinant protein production. Thus, this model can be used for large-scale production of biosimilars through transient Bcl-xL gene expression as a cost-effective method.
Blank Frame and Intensity Variation Distortion Detection and Restoration Pipeline for Phase-Contrast Microscopy Time-Lapse Images
(Aves, 2024) Ucar, Mahmut; Iheme, Leonardo O.; Onal, Sevgi; Pesen-Okvur, Devrim; Yalcin-Ozuysal, Ozden; Toreyin, Behcet U.; Unay, Devrim; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
In this study, we propose a preprocessing pipeline for the detection and correction of distorted frames in time-lapse images obtained from phase-contrast microscopy. The proposed pipeline employs the average intensities of frames as a foundational element for the analysis. In order to evaluate the degree of correction required for intensity variance, a normalization technique is applied to the difference between the average intensity of a specific frame and the median average intensity of all frames within the study. Our restoration method increases the histogram similarity between the distorted and non-distorted frames, preserves trans-passing pixels in regions of interest, and mitigates the development of additional distortions. The efficacy of the proposed method was evaluated using 15 395 time-lapse image frames from 27 experiments using our own dataset and 830 time-lapse images from four different experiments obtained from the cell tracking challenge. The results of the validation demonstrate a high degree of numerical and visual accuracy of the proposed pipeline.
Citation - WoS: 2
Citation - Scopus: 2
Cloning, Expression, and Characterization of a Novel Sericin-Like Protein
(Wiley, 2022) Bostan, Fatmanur; Sürmeli, Nur Başak; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
Silk consists of two proteins called fibroin and sericin. While fibroin is used in the textile industry and has various biomaterial applications, sericin has been considered as waste material until recently. Sericin is a multicomponent protein and it has important properties such as biocompatibility, biodegradability, cryoprotectivity, and antioxidant. Sericin from silkworm cocoons can be obtained by chemical, enzymatic, and heat treatment methods. However, sericin obtained with these treatment methods is not of consistent and high quality. Moreover, the exposure of sericin to harsh conditions during extraction leads to inconsistencies in the composition and structure of the sericin obtained. The inconsistencies in sericin structure and composition decrease application of sericin as a biomaterial. Here, we produce a sericin-like protein (Ser4mer) with native sequence of sericin encoding four repeats of the conserved 38 amino acid motif recombinantly in Escherichia coli and characterize its structural properties. Ser4mer protein shows similar structure to native sericin and higher solubility than previously obtained recombinant sericin-like proteins. Recombinant production of a soluble sericin-like protein will significantly expand its applications as a biomaterial. In addition, recombinant production of silk proteins will allow us to understand sequence-structure relationships in these proteins.
Citation - WoS: 6
Citation - Scopus: 7
Connexin 32 Overexpression Increases Proliferation, Reduces Gap Junctional Intercellular Communication, Motility and Epithelial-To Transition in Hs578t Breast Cancer Cells
(Springer, 2022-07) Uğur, Deniz; Güngül, Taha Buğra; Yücel, Simge; Özçivici, Engin; Yalçın Özuysal, Özden; Meşe Özçivici, Gülistan; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 04.03. Department of Molecular Biology and Genetics; 03. Faculty of Engineering; 04. Faculty of Science
Connexins (Cx) are primary components of gap junctions that selectively allow molecules to be exchanged between adjacent cells, regulating multiple cellular functions. Along with their channel forming functions, connexins play a variety of roles in different stages of tumorigenesis and their roles in tumor initiation and progression is isoform- and tissue-specific. While Cx26 and Cx43 were downregulated during breast tumorigenesis, Cx32 was accumulated in the cytoplasm of the cells in lymph node metastasis of breast cancers and Cx32 was further upregulated in metastasis. Cx32's effect on cell proliferation, gap junctional communication, hemichannel activity, cellular motility and epithelial-to-mesenchymal transition (EMT) were investigated by overexpressing Cx32 in Hs578T and MCF7 breast cancer cells. Additionally, the expression and localization of Cx26 and Cx43 upon Cx32 overexpression were examined by Western blot and immunostaining experiments, respectively. We observed that MCF7 cells had endogenous Cx32 while Hs578T cells did not and when Cx32 was overexpressed in these cells, it caused a significant increase in the percentages of Hs578T cells at the S phase in addition to increasing their proliferation. Further, while Cx32 overexpression did not induce hemichannel activity in either cell, it decreased gap junctional communication between Hs578T cells. Additionally, Cx32 was mainly observed in the cytoplasm in both cells, where it did not form gap junction plaques but Cx32 overexpression reduced Cx43 levels without affecting Cx26. Moreover, migration and invasion potentials of Hs578T and migration in MCF7 were reduced upon Cx32 overexpression. Finally, the protein level of mesenchymal marker N-cadherin decreased while epithelial marker ZO-1 and E-cadherin increased in Hs578T cells. We observed that Cx32 overexpression altered cell proliferation, communication, migration and EMT in Hs578T, suggesting a tumor suppressor role in these cells while it had minor effects on MCF7 cells.
Citation - WoS: 16
Citation - Scopus: 18
Cycloartane-Type Glycosides From Astragalus Brachycalyx Fischer and Their Effects on Cytokine Release and Hemolysis
(Elsevier Ltd., 2017-09) Aslanipour, Behnaz; Gülcemal, Derya; Nalbantsoy, Ayşe; Yusufoğlu, Hasan; Bedir, Erdal; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
Two new tridesmosidic cycloartane-type triterpene glycosides (1 and 2) were isolated from the methanolic extract of the roots of Astragalus brachycalyx FISCHER (A. brachycalyx) along with ten (3–12) known cycloartane-type triterpene glycosides. Structures of the new compounds were established as 3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosyl-16-O-β-D-glucopyranosyl-3β,6α,16β,24(S)-25-pentahydroxycycloartane (1), 3-O-[α-L-arabinopyranosyl-(1→2)-β-D-xylopyranosyl]-6-O-β-D-glucopyranosyl-16-O-β-D-glucopyranosyl-3β,6α,16β,24(S)-25-pentahydroxycycloartane (2), by using 1D and 2D-NMR techniques and mass spectrometry. In vitro immunomodulatory effects and hemolytic activities of the new saponins (1 and 2) and acetylated form of 1 (1a) were studied together with the BuOH and MeOH extracts of Astragalus brachycalyx. The results have proven that tridesmosidic Astragalus cycloartanes are noteworthy immunomodulatory compounds via induction of cytokine production, namely IL-2 and IFN-γ. The test compounds also resulted slight hemolysis at very high doses substantiating a safer profile compared to the positive control QS-21.
Citation - WoS: 11
Citation - Scopus: 11
Cycloartane-Type Sapogenol Derivatives Inhibit Nf?b Activation as Chemopreventive Strategy for Inflammation-Induced Prostate Carcinogenesis
(Elsevier Ltd., 2018-07) Debeleç Bütüner, Bilge; Öztürk, Mert Burak; Tağ, Özgür; Akgün, İsmail Hakkı; Yetik Anacak, Günay; Bedir, Erdal; Korkmaz, Kemal Sami; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
Chronic inflammation is associated to 25% of cancer cases according to epidemiological data. Therefore, inhibition of inflammation-induced carcinogenesis can be an efficient therapeutic approach for cancer chemoprevention in drug development studies. It is also determined that anti-inflammatory drugs reduce cancer incidence. Cell culture-based in vitro screening methods are used as a fast and efficient method to investigate the biological activities of the biomolecules. In addition, saponins are molecules that are isolated from natural sources and are known to have potential for tumor inhibition. Studies on the preparation of analogues of cycloartane-type sapogenols (9,19-cyclolanostanes) have so far been limited. Therefore we have decided to direct our efforts toward the exploration of new anti-tumor agents prepared from cycloastragenol and its production artifact astragenol. The semi-synthetic derivatives were prepared mainly by oxidation, condensation, alkylation, acylation, and elimination reactions. After preliminary studies, five sapogenol analogues, two of which were new compounds (2 and 3), were selected and screened for their inhibitory activity on cell viability and NFκB signaling pathway activity in LNCaP prostate cancer cells. We found that the astragenol derivatives 1 and 2 as well as cycloastragenol derivatives 3, 4, and 5 exhibited strong inhibitory activity on NFκB signaling leading the repression of NFκB transcriptional activation and suppressed cell proliferation. The results suggested that these molecules might have significant potential for chemoprevention of prostate carcinogenesis induced by inflammatory NFκB signaling pathway.
Citation - WoS: 13
Citation - Scopus: 15
Cytotoxic Tolerance of Healthy and Cancerous Bone Cells To Anti-Microbial Phenolic Compounds Depend on Culture Conditions
(Humana Press, 2019) Karadaş, Özge; Meşe, Gülistan; Özçivici, Engin; 03.01. Department of Bioengineering; 04.03. Department of Molecular Biology and Genetics; 03. Faculty of Engineering; 04. Faculty of Science; 01. Izmir Institute of Technology
Carnosol and carnosic acid are polyphenolic compounds found in rosemary and sage with known anti-oxidant, anti-inflammatory, and anti-microbial properties. Here, we addressed the potential use of carnosol and carnosic acid for in vitro bone tissue engineering applications, specifically depending on their cytotoxic effects on bone marrow stromal and stem cells, and osteosarcoma cells in monolayer and 3D cultures. Carnosol and carnosic acid displayed a bacteriostatic effect on Gram-positive bacteria, especially on S. aureus. The viability results indicated that bone marrow stromal cells and bone marrow stem cells were more tolerant to the presence of carnosol compared to osteosarcoma cells. 3D culture conditions increased this tolerance further for healthy cells, while not affecting the cytotoxic potential of carnosol for osteosarcoma cells. Carnosic acid was found to be more cytotoxic for all cell types used in the study. Results suggest that phenolic compounds might have potential use as anti-microbial and anti-carcinogenic agents for bone tissue engineering with further optimization for controlled release.
Citation - WoS: 12
Citation - Scopus: 14
Development and Verification of a Three-Dimensional (3d) Breast Cancer Tumor Model Composed of Circulating Tumor Cell (ctc) Subsets
(Springer, 2020) Anıl İnevi, Müge; Sağlam Metiner, Pelin; Kabak, Evrim Ceren; Gülce İz, Sultan; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
Breast cancer is one of the most common cancer types among women in which early tumor invasion leads to metastases and death. EpCAM (epithelial cellular adhesion molecule) and HER2 (human epidermal growth factor receptor 2) are two main circulating tumor cell (CTC) subsets in HER2+ breast cancer patients. In this regard, the main aim of this study is to develop and characterize a three-dimensional (3D) breast cancer tumor model composed of CTC subsets to evaluate new therapeutic strategies and drugs. For this reason, EpCAM(+) and HER2(+) sub-populations were isolated from different cell lines to establish 3D tumor model that mimics in situ (in vivo) more closely than two-dimensional (2D) models. EpCAM(+)/HER2(+) cells had a high proliferation rate and low tendency to attach to the surface in comparison with parental MDA-MB-453 cells as CTC subsets. Aggressive breast cancer subpopulations cultured in 3D porous chitosan scaffold had enhanced cell-cell and cell-matrix interactions compared to 2D cultured cells and these 3D models showed more aggressive morphology and behavior, expressed higher levels of pluripotency marker genes, Nanog, Sox2 and Oct4. For the verification of the 3D model, the effects of doxorubicin which is a chemotherapeutic agent used in breast cancer treatment were examined and increased drug resistance was determined in 3D cultures. The 3D tumor model comprising EpCAM(+)/HER2(+) CTC subsets developed in this study has a promising potential to be used for investigation of an aggressive CTC microenvironment in vitro that mimics in vivo characteristics to test new drug candidates against CTCs.
Citation - WoS: 14
Citation - Scopus: 14
Development of Biological Meniscus Scaffold: Decellularization Method and Recellularization With Meniscal Cell Population Derived From Mesenchymal Stem Cells
(SAGE Publications, 2021) Kara, Aylin; Koçtürk, Semra; Bilici, Gökçen; Havıtçıoğlu, Hasan; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
Tissue engineering approaches which include a combination of cells and scaffold materials provide an alternative treatment for meniscus regeneration. Decellularization and recellularization techniques are potential treatment options for transplantation. Maintenance of the ultrastructure composition of the extracellular matrix and repopulation with cells are important factors in constructing a biological scaffold and eliminating immunological reactions. The aim of the study is to develop a method to obtain biological functional meniscus scaffolds for meniscus regeneration. For this purpose, meniscus tissue was decellularized by our modified method, a combination of physical, chemical, and enzymatic methods and then recellularized with a meniscal cell population composed of fibroblasts, chondrocytes and fibrochondrocytes that obtained from mesenchymal stem cells. Decellularized and recellularized meniscus scaffolds were analysed biochemically, biomechanically and histologically. Our results revealed that cellular components of the meniscus were successfully removed by preserving collagen and GAG structures without any significant loss in biomechanical properties. Recellularization results showed that the meniscal cells were localized in the empty lacuna on the decellularized meniscus, and also well distributed and proliferated consistently during the cell culture period (p < 0.05). Furthermore, a high amount of DNA, collagen, and GAG contents (p < 0.05) were obtained with the meniscal cell population in recellularized meniscus tissue. The study demonstrates that our decellularization and recellularization methods were effective to develop a biological functional meniscus scaffold and can mimic the meniscus tissue with structural and biochemical features. We predict that the obtained biological meniscus scaffolds may provide avoidance of adverse immune reactions and an appropriate microenvironment for allogeneic or xenogeneic recipients in the transplantation process. Therefore, as a promising candidate, the obtained biological meniscus scaffolds might be verified with a transplantation experiment.
Citation - Scopus: 3
Development of Chrono-Spectral Gold Nanoparticle Growth Based Plasmonic Biosensor Platform
(Elsevier, 2024) Sözmen, Alper Baran; Elveren, Beste; Erdoğan, Duygu; Mezgil, Bahadır; Baştanlar, Yalın; Yıldız, Ümit Hakan; Arslan Yıldız, Ahu; 01. Izmir Institute of Technology; 04.01. Department of Chemistry; 03.04. Department of Computer Engineering; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 04. Faculty of Science
Plasmonic sensor platforms are designed for rapid, label-free, and real-time detection and they excel as the next generation biosensors. However, current methods such as Surface Plasmon Resonance require expertise and well-equipped laboratory facilities. Simpler methods such as Localized Surface Plasmon Resonance (LSPR) overcome those limitations, though they lack sensitivity. Hence, sensitivity enhancement plays a crucial role in the future of plasmonic sensor platforms. Herein, a refractive index (RI) sensitivity enhancement methodology is reported utilizing growth of gold nanoparticles (GNPs) on solid support and it is backed up with artificial neural network (ANN) analysis. Sensor platform fabrication was initiated with GNP immobilization onto solid support; immobilized GNPs were then used as seeds for chrono-spectral growth, which was carried out using NH2OH at varied incubation times. The response to RI change of the platform was investigated with varied concentrations of sucrose and ethanol. The detection of bacteria E.coli BL21 was carried out for validation as a model microorganism and results showed that detection was possible at 102 CFU/ml. The data acquired by spectrophotometric measurements were analyzed by ANN and bacteria classification with percentage error rates near 0% was achieved. The proposed LSPR-based, label-free sensor application proved that the developed methodology promises utile sensitivity enhancement potential for similar sensor platforms. © 2024 The Author(s)
Citation - WoS: 5
Citation - Scopus: 5
Diagnosis of Ruminant Viral Diseases With Loop-Mediated Isothermal Amplification
(Springer, 2023) Ayaz Kök, Sanem; Üstün, Selcen; Taşkent, Hümeyra; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
Infectious diseases in livestock industry are major problems for animal health, food safety, and the economy. Zoonotic diseases from farm animals are significant threat to human population as well. These are notifiable diseases listed by the World Organization for Animal Health (OIE). Rapid diagnostic methods can help keep infectious diseases under control in herds. Loop-mediated isothermal amplification (LAMP) is a simple and rapid nucleic acid amplification method that is studied widely for detection of many infectious diseases in the field. LAMP allows biosensing of target DNA or RNA under isothermal conditions with high specificity in a short period of time. An untrained user can analyze results based on color change or turbidity. Here we review LAMP assays to diagnose OIE notifiable ruminant viral diseases in literature highlighting properties of LAMP method considering what is expected from an efficient, field usable diagnostic test.
The Effects of Novel Telomerase Activators on Human Adipose-Derived Mesenchymal Stem Cell (had-Msc) Proliferation and Osteogenic Differentiation
(Georg Thieme Verlag Kg, 2022) Kuru, G.; Küçüksolak, Melis; Pulat, G.; Karaman, O.; Bedir, Erdal; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
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