Biyomühendislik / Bioengineering

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/208

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3-Sulfopropyl methacrylate based cryogels as potential tissue engineering scaffolds
(TAYLOR & FRANCIS LTD, 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND, 2019) Durukan, Adile Yuruk; Isoglu, Ismail Alper; 0000-0001-6428-4207; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
In this study, we developed cryogels containing 3-sulfopropyl methacrylate (SPMA) and 4-vinyl pyridine (4-VP) as a potential scaffold for tissue engineering applications. Cryogels with varying monomer ratios were synthesised by chemical cross-linking under cryogelation conditions. Effect of initiators and cross-linker amount (0.025-0.15 g MBA; 0.012-0.05 g APS; 2.5-12.5 mu l TEMED) and also freezing temperature (-20 and -80oC) were investigated, and the conditions were optimised according to the morphological structures examined by SEM. The functional groups of the materials were characterised by FT-IR. Compression test and swelling were applied to investigate mechanical properties and water absorption ability, respectively. As a preliminary study, selected materials were tested for cell cytotoxicity with MTT. According to our results, the ionic and biocompatible cryogels prepared in this study possessing a highly porous and interconnective structure with good mechanical characteristics and swelling properties can be suitable as tissue scaffolds for many applications.
Advances in Micelle-based Drug Delivery: Cross-linked Systems
(BENTHAM SCIENCE PUBL LTDEXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES, 2017) Isoglu, Ismail Alper; Ozsoy, Yildiz; Isoglu, Sevil Dincer; 0000-0002-6887-6549; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
There are several barriers that drug molecules encounter in body beginning from kidney filtration and reticulo-endothelial system (RES) clearance to cellular trafficking. Multifunctional nanocarriers have a great potential for the delivery of drugs by enhancing therapeutic activity of existing methodologies. A variety of nanocarriers are constructed by different material types, which have unique physicochemical properties for drug delivery applications. Micelles formed by amphiphilic polymers are one of the most important drug/nanocarrier formulation products, in which the core part is suitable for encapsulation of hydrophobic agent whereas the outer shell can be utilized for targeting the drug to the disease area. Micelles as self-assembled nanostructures may encounter difficulties in biodistribution of encapsulated drugs because they have a tendency to be dissociated in dilution or high ionic strength. Therefore, therapeutic efficiency is decreased and it requires high amount of drug to be administered to achieve more efficient result. To overcome this problem, covalently stabilized structures produced by cross-linking in core or shell part, which can prevent the micelle dissociation and regulate drug release, have been proposed. These systems can be designed as responsive systems in which cross-links are degradable or hydrolysable under specific conditions such as low pH or reductive environment. These are enhancing characteristics in drug delivery because their cleavage allows the release of bioactive agent encapsulated in the carrier at a certain site or time. This review describes the chemical methodologies for the preparation of cross-linked micelles, and reports an update of latest studies in literature.
Alantolactone ameliorates graft versus host disease in mice
(ELSEVIER, 2024) Odabas, Gul Pelin; Aslan, Kubra; Suna, Pinar Alisan; Kendirli, Perihan Kader; Erdem, Şerife; Çakır, Mustafa; Özcan, Alper; Yılmaz, Ebru; Karakukcu, Musa; Donmez-Altuntas, Hamiyet; Yay, Arzu Hanim; Deniz, Kemal; Altay, Derya; Arslan, Duran; Canatan, Halit; Eken, Ahmet; Unal, Ekrem; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Kendirli, Perihan Kader
The anti-inflammatory and immunosuppressive drugs which are used in the treatment of Graft-versus-Host Disease (GVHD) have limited effects in controlling the severity of the disease. In this study, we aimed to investigate the prophylactic effect of Alantolactone (ALT) in a murine model of experimental GVHD. The study included 4 BALB/c groups as hosts: Naïve (n = 7), Control GVHD (n = 16), ALT-GVHD (n = 16), and Syngeneic transplantation (n = 10). Busulfan (20 mg/kg/day) for 4 days followed by cyclophosphamide (100 mg/kg/day) were administered for conditioning. Allogeneic transplantation was performed with cells collected from mismatched female C57BL/6, and GVHD development was monitored by histological and flow cytometric assays. Additionally, liver biopsies were taken from GVHD patient volunteers between ages 2–18 (n = 4) and non-GVHD patients between ages 2–50 (n = 5) and cultured ex vivo with ALT, and the supernatants were used for ELISA. ALT significantly ameliorated histopathological scores of the GVHD and improved GVHD clinical scores. CD8+ T cells were shown to be reduced after ALT treatment. More importantly, ALT treatment skewed T cells to a more naïve phenotype (CD62L+ CD44− ). ALT did not alter Treg cell number or frequency. ALT treatment appears to suppress myeloid cell lineage (CD11c+). Consistent with reduced myeloid lineage, liver and small intestine levels of GM-CSF were reduced in ALT-treated mice. IL-6 gene expression was significantly reduced in the intestinal tissue. Ex vivo ALT-treated liver biopsy samples from GVHD patients showed a trend of decrease in proinflammatory cytokines but there was no statistical significance. Collectively, the data indicated that ALT may have immunomodulatory actions in a preclinical murine GVHD model.
Antibacterial Bilayered Skin Patches Made of HPMA and Quaternary Poly(4-vinyl pyridine)
(KOREAN FIBER SOC, KOREA SCIENCE TECHNOLOGY CTR #501 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA, 2018) Isoglu, I. Alper; Demirkan, Cemre; Seker, Mine Gul; uzlakoglu, Kadriye; Isoglu, Sevil Dincer; 0000-0002-6887-6549; 0000-0002-6226-7507; 0000-0002-7564-9213; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
This study aimed to produce poly(4-vinyl pyridine) and hydroxypropyl methacrylamide (HPMA)-based bilayer wound dressings materials enhancing healing mechanism for the wounds which have self-healing problem and high infection risk. These materials were designed to protect wound from secondary traumas caused microorganism invasion and do not have toxic substance release problem. Synthesis of quaternary poly(4-vinyl pyridine) (poly(Q4-VP)) which is the antibacterial layer of wound dressing material was carried out in two stages. At first stage, poly(4-vinyl pyridine) polymer was synthesized from 4-vinyl pyridine monomer by free radical polymerization. Then, poly(Q4-VP) was synthesized from poly(4-VP) by alkylation reaction with 6-bromocaproic acid. Resulted polymer was structurally characterized by FT-IR. The macroporous spongy structure, as the lower layer of wound dressing material, was prepared by cryogelation of HPMA. Then, the antibacterial polymer was electrospun onto the cryogel structure and bilayered material was obtained. Cryogel structure, fiber morphology and layer integration was examined by SEM. In order to enhance wound healing process, ascorbic acid (vitamin C) was loaded to cryogel layer and release was followed by spectrophotometrically. The antimicrobial properties of the materials were examined against Escherichia coli, Staphylococcus aureus and Candida albicans, respectively. According to the results, bilayered, antibacterial and antifungal against Staphylococcus aureus and Candida albicans, temporary wound dressings which can stimulate wound healing and have high swelling capacity were obtained successfully.
Bovine serum albumin (BSA)-Loaded polyvinyl alcohol (PVA) / chitosan (CH) / hydroxyapatite (HA) electrospun nanofibers for bone tissue regeneration
(ELSEVIER, 2025) Bozdag, Mehmet; Urek, Ferhat; Cesur, Sumeyye; Sahin, Ali; Gunduz, Oguzhan; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Urek, Ferhat
The natural bone structure consists of three different nanocomposite layers; a porous polymer ceramic part, a lamellar, and a fiber-matrix composition gives the bone its unique physical and biological properties. During bone tissue regeneration bioactivity, and osteoinductivity are especially important with other parameters such as porosity, degradation rate, and cell adhesion. In this study, hydroxyapatite (HA) and bovine serum albumin (BSA) protein-loaded, polyvinyl alcohol (PVA) and chitosan (CH) nanofibers were fabricated via the electrospinning method. The mean diameters of PVA/CH/HA/BSA-5, PVA/CH/HA/BSA-10, and PVA/CH/HA/BSA-15 nanofibers were measured as 325.39 +/- 77.512 nm, 332.45 +/- 82.251 nm, 447.03 +/- 101.382 nm respectively, required porosity and properties for bone tissue engineering were considered achieved. BSA release profiles of BSA-5, BSA-10, and BSA-15 nanofibers were similar in terms of burst release which continued until the 12th hour, 58 %, 78 %, and 73 % of the BSA were released, respectively. After 72 h 100 % of BSA were released from all nanofibers. Cell viability tests showed that PVA/CH/HA/BSA nanofibers exceeded the control group in terms of cell viability by 119.9 %. In future bone injury treatment, PVA/CH/HA/BSA nanofibers can assist the healing process of cracks and fractures, and decrease the recovery time of bone as an alternative bone healing nanofiber.
Can mesenchymal stem/stromal cells and their secretomes combat bacterial persisters?
(SPRINGER, 2023) Bicer-Çalışkan, Mesude; Fidan, Ozkan; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Bicer-Çalışkan, Mesude; Fidan, Ozkan
The increasing number of life-threatening infections caused by persister bacteria is associated with various issues, including antimicrobial resistance and biofilm formation. Infections due to persister cells are often difficult to suppress without the use of last-resort antibiotics. Throughout the world, bacterial persistence and resistance create an unmet clinical demand for the exploration of newly introduced therapeutic approaches. Mesenchymal stem / stromal cells (MSCs) have an antimicrobial activity to protect against bacterial infections, including those caused by bacterial persisters. MSCs have substantial potential to secrete antimicrobial peptides (AMPs), including cathelicidin, beta-defensins, lipocalin-2, hepcidin, indoleamine 2,3-dioxygenase (IDO), cysteine proteases, and inducible nitric oxide synthases (iNOS). MSCs possess the potential to contribute to innate immunity by regulating the immune response. Recently, MSCs and their secreted components have been reported to improve antimicrobial activity. Bactericidal activity by MSCs and their secretomes has been shown to be mediated in part by the secretion of AMPs. Even though they were discovered more than 80 years ago, therapeutic options for persisters are restricted, and there is an urgent need for alternative treatment regimens. Hence, this review intends to critically assess the current literature on the effects of MSCs and their secretomes on persister bacteria. MSCs and their secretome-based therapies could be preferred as an up-and-coming approach to reinforce the antimicrobial efficiency in persister infections.
CC2D1A AS A NOVEL CILIOPATHY GENE
(SPRINGERNATURE, CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND, 2020) Sakin, I.; Tuncel, G.; Sag, S. Ozemri; Kaplan, O. I.; Khokha, M. K.; Ergoren, M. C.; Deniz, E.; Temel, S. G.; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
Özet bulunamamıştır
Centella AsiaticaExtract Containing Bilayered Electrospun Wound Dressing
(KOREAN FIBER SOC, KOREA SCIENCE TECHNOLOGY CTR #501 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA, 2020) Isoglu, Ismail Alper; Koc, Nuray; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
Innovative and bioactive wound dressings prepared by electrospinning mimicking the native structure of the extracellular matrix (ECM) have gained significant interest as an alternative to conventional wound care applications. In this study, bilayered wound dressing material was produced by sequential electrospinning of quaternized poly(4-vinyl pyridine) (upper layer) on theCentella Asiatica(CA) extract containing electrospun poly(D, L-lactide-co-glycolide) (PLGA)/poly(3-hydroxybutyrate-co-3-hydroxy valerate) (PHBV) blend membrane (lower layer). Scanning electron microscopy (SEM) was utilized to show a uniform and bead-free fiber structure of electrospun membranes. The average diameter of CA extract containing electrospun PLGA/PHBV blend membrane was calculated 0.471 +/- 0.11 mu m, whereas the average fiber diameter of electrospun poly(Q-VP) membranes was in the range of 0.460 +/- 0.057 mu m. Chemical, thermal, mechanical properties, and adsorption capacity of electrospun membranes, as well as the cumulative release of CA from the electrospun PLGA/PHBV membrane, were investigated. Viability, adhesion, and attachment of human fibroblast cells on the electrospun membranes on pre-set days were evaluated by the colorimetric CellTiter 96 (R) Aqueous One Solution Cell Proliferation Assay (MTS assay) and SEM. Results revealed that CA loaded bilayered electrospun wound dressing showed promoted attachment and proliferation of fibroblasts. Hence, it can be concluded that CA extract containing bilayered electrospun wound dressing prepared in this study has a promising potential for wound healing applications.
Combination of the Simple Additive (SAW) Approach and Mixture Design to Determine Optimum Cocoa Combination of the Hot Chocolate Beverage
(TAYLOR & FRANCIS INC, 2015) DOGAN, Mahmut; Aktar, Tugba; Toker, Omer Said; Tatlisu, Nevruz Berna; 0000-0001-8417-868X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Aktar, Tugba
Physicochemical (pH, brix, and color), sensory (color, taste, odor, mouthfeeling, consistency, bitter flavor, and general acceptability), and rheological properties of the hot chocolate beverages including different cocoa combinations were investigated in the present study. Cocoa type significantly affected all of the properties. Simple additive weighting approach was applied to obtain one score from seven different sensory parameters and simple additive weighting score was used in mixture design to determine optimum cocoa type or cocoa combination. Ostwald de Waele model described the flow behavior of the hot chocolate beverage samples with R2 values ranged between 0.818 and 0.999. The consistency coefficient (K) and apparent viscosity at shear rate 50 s−1 (η50) were significantly affected by cocoa type found in the formulation of the beverage. The mixture design approach was performed in order to determine variation of the responses (physicochemical, sensory, and rheological parameters) as a function of cocoa concentration. Simple additive weighting scores were satisfactorily described by established equation as a function of cocoa concentration to be used in the formulation of the hot chocolate beverage (R2 = 0.8645).
Computational Detection of Pre-microRNAs
(Humana Press Inc., 2022) Saçar Demirci, Müşerref Duygu; 0000-0003-2012-0598; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Saçar Demirci, Müşerref Duygu
MicroRNA (miRNA) studies have been one of the most popular research areas in recent years. Although thousands of miRNAs have been detected in several species, the majority remains unidentified. Thus, finding novel miRNAs is a vital element for investigating miRNA mediated posttranscriptional gene regulation machineries. Furthermore, experimental methods have challenging inadequacies in their capability to detect rare miRNAs, and are also limited to the state of the organism under examination (e.g., tissue type, developmental stage, stress-disease conditions). These issues have initiated the creation of high-level computational methodologies endeavoring to distinguish potential miRNAs in silico. On the other hand, most of these tools suffer from high numbers of false positives and/or false negatives and as a result they do not provide enough confidence for validating all their predictions experimentally. In this chapter, computational difficulties in detection of pre-miRNAs are discussed and a machine learning based approach that has been designed to address these issues is reviewed.
Computational Prediction of Functional MicroRNA-mRNA Interactions
(HUMANA PRESS INC, 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA, 01.01.2019) Demirci, Muserref Duygu Sacar; Yousef, Malik; Allmer, Jens; 0000-0003-2012-0598; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
Proteins have a strong influence on the phenotype and their aberrant expression leads to diseases. MicroRNAs (miRNAs) are short RNA sequences which posttranscriptionally regulate protein expression. This regulation is driven by miRNAs acting as recognition sequences for their target mRNAs within a larger regulatory machinery. A miRNA can have many target mRNAs and an mRNA can be targeted by many miRNAs which makes it difficult to experimentally discover all miRNA-mRNA interactions. Therefore, computational methods have been developed for miRNA detection and miRNA target prediction. An abundance of available computational tools makes selection difficult. Additionally, interactions are not currently the focus of investigation although they more accurately define the regulation than pre-miRNA detection or target prediction could perform alone. We define an interaction including the miRNA source and the mRNA target. We present computational methods allowing the investigation of these interactions as well as how they can be used to extend regulatory pathways. Finally, we present a list of points that should be taken into account when investigating miRNA-mRNA interactions. In the future, this may lead to better understanding of functional interactions which may pave the way for disease marker discovery and design of miRNA-based drugs.
Computational prediction of microRNAs in Histoplasma capsulatum
(ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND, 2020) Demirci, Mueserref Duygu Sagar; 0000-0003-2012-0598; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
MicroRNAs (miRNAs) are small and non-coding RNAs that regulate gene expression through post-transcriptional regulation. Although, the standard miRNA repository, MiRBase, lists more than 200 organisms having miRNA mediated regulation mechanism and thousands of miRNAs, there is not enough information about miRNAs of fungal species. Considering that there are various fungal pathogens causing disease phenotypes, it is important to search for miRNAs of those organisms. The leading cause of endemic mycosis in the USA is a fungal disease known as histoplasmosis, which is resulted by infection with a fungal intracellular parasite, Histoplasma capsulatum (H. capsulatum). In this work, genomes of H. capsulatum strains NAm1 and G217B were explored for potential miRNA like sequences and structures. Through a complex workflow involving miRNA detection and target prediction, several miRNA candidates of H. capsulatum and their possible targets in human were identified. The results presented here indicate that H. capsulatum might be one of the fungal pathogens having a miRNA based post-transcriptional gene regulation mechanism and it might have a miRNA mediated host - parasite interaction with human.
Computer-Aided Classification of Breast Cancer Histopathological Images
(IEEE345 E 47TH ST, NEW YORK, NY 10017 USA, 2017) Aksebzeci, Bekir Hakan; Kayaalti, Omer; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
Nowadays, one of the most common types of cancer is breast cancer. The early and accurate diagnosis of breast cancer has great importance in the treatment of the disease. In the diagnosis of breast cancer, histopathological analysis of cell and tissue specimens taken by biopsy is considered as the gold standard. Histopathological analysis is a tedious process that is highly dependent on the knowledge and experience of the pathologists. In this study; it is aimed to develop a computer-aided system that can reduce the workload of pathologists and help them in their diagnosis. An image set containing benign and malignant tumor images of breast cancer has been studied. To perform texture analysis on tumor images; first order statistics, Gabor and gray-level co-occurrence matrix (GLCM) feature extraction methods have been applied. Then, various classifiers were applied to the obtained feature matrices and their performances were compared. The highest classification accuracy was achieved 82.06% by Random Forests classifier with feature combination of Gabor and GLCM methods. The results presented here show that computer-assisted diagnosis of breast cancer is a promising field.
Core-crosslinking as a pathway to develop inherently antibacterial polymeric micelles
(WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, 2019) Kadayifci, Melike Seyma; Gokkaya, Damla; Topuzogullari, Murat; Isoglu, Sevil Dincer; Atabey, Tugba; Arasoglu, Tulin; Ozmen, Mehmet Murat; 0000-0002-6887-6549; 0000-0002-9330-5107; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
Positively charged polymeric materials have been an alternative to combat bacteria as they exhibit inherently antibacterial potency via bacteria membrane disruption. In this study, we report facile preparation of positively charged core-crosslinked polymeric micelles with inherent antibacterial properties. Spherical micelles were prepared by self-assembling of poly(4-vinylpyridine)-b-(oligoethylene glycol methyl ether methacrylate) copolymer in aqueous solution. Herein, quaternization reaction was utilized for the first time to core crosslink the micelles through the pyridine rings utilizing their hydrophobic core and thus resulting positively charged nanostructures. Dynamic light scattering (DLS) results identified that the micelles have an average hydrodynamic diameter of 114 nm with a polydispersity index ranging between 0.105 and 0.114. The electrophoretic light scattering (ELS) measurements demonstrated that the micelles have zeta potential values ranging from +38 to +63 mV. It was evident from both ELS and DLS results that the micelles in solution exhibit long-term stability as the samples were able to maintain their size and charge even after a year of storage. Further, the micelles exhibited inherently antibacterial activity against Escherichia coli and furthermore, this antibacterial efficacy was sustained over a period of 1 year. These stable core-crosslinked micelles are proposed to have great potential as antibacterial materials for long-term applications. (c) 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48393.
Deep learning based semantic segmentation and quantification for MRD biochip images
(ELSEVIER SCI LTD, 2022) Çelebi, Fatma; Tasdemir, Kasim; Icoz, Kutay; 0000-0002-0947-6166; AGÜ, Mühendislik Fakültesi, Bilgisayar Mühendisliği Bölümü; Çelebi, Fatma; Tasdemir, Kasim; Icoz, Kutay
Microfluidic platforms offer prominent advantages for the early detection of cancer and monitoring the patient response to therapy. Numerous microfluidic platforms have been developed for capturing and quantifying the tumor cells integrating several readout methods. Earlier, we have developed a microfluidic platform (MRD Biochip) to capture and quantify leukemia cells. This is the first study which employs a deep learning-based segmentation to the MRD Biochip images consisting of leukemic cells, immunomagnetic beads and micropads. Implementing deep learning algorithms has two main contributions; firstly, the quantification performance of the readout method is improved for the unbalanced dataset. Secondly, unlike the previous classical computer visionbased method, it does not require any manual tuning of the parameters which resulted in a more generalized model against variations of objects in the image in terms of size, color, and noise. As a result of these benefits, the proposed system is promising for providing real time analysis for microfluidic systems. Moreover, we compare different deep learning based semantic segmentation algorithms on the image dataset which are acquired from the real patient samples using a bright-field microscopy. Without cell staining, hyper-parameter optimized, and modified U-Net semantic segmentation algorithm yields 98.7% global accuracy, 86.1% mean IoU, 92.2% mean precision, 92.2% mean recall and 92.2% mean F-1 score measure on the patient dataset. After segmentation, quantification result yields 89% average precision, 97% average recall on test images. By applying the deep learning algorithms, we are able to improve our previous results that employed conventional computer vision methods.
Differential in vitro anti-leukemic activity of resveratrol combined with serine palmitoyltransferase inhibitor myriocin in FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) carrying AML cells
(SPRINGER, 2022) Ersoz, Nur Sebnem; Adan, Aysun; 0000-0003-3343-9936; 0000-0002-3747-8580; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Ersoz, Nur Sebnem; Adan, Aysun
Treatment of FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) AML is restricted due to toxicity, drug resistance and relapse eventhough targeted therapies are clinically available. Resveratrol with its multi-targeted nature is a promising chemopreventive remaining limitedly studied in FLT3-ITD AML regarding to ceramide metabolism. Here, its cytotoxic, cytostatic and apoptotic effects are investigated in combination with serine palmitoyltransferase (SPT), the first enzyme of de novo pathway of ceramide production, inhibitor myriocin on MOLM-13 and MV4-11 cells. We assessed dose-dependent cell viability, flow cytometric cell death and cell cycle profiles of resveratrol in combination with myriocin by MTT assay, annexin-V/PI staining and PI staining respectively. Resveratrol's dose-dependent effect on SPT protein expression was also checked by western blot. Resveratrol decreased cell viability in a dose- dependent manner whereas myriocin did not affect cell proliferation effectively in both cell lines after 48h treatments. Although resveratrol induced both apoptosis and a significant S phase arrest in MV4-11 cells, it triggered apoptosis and non-significant S phase accumulation in MOLM-13 cells. Co-administrations reduced cell viability. Increased cytotoxic effect of co-treatments was further proved mechanistically through induction of apoptosis via phosphatidylserine relocalization. The cell cycle alteration in co-treatment was significant with an S phase arrest in MV4-11 cells, however, it was not effective on cell cycle progression of MOLM-13 cells. Resveratrol also increased SPT expression. Overall, modulation of SPT together with resveratrol might be the possible explanation for resveratrol's action. It could be an integrative medicine for FLT3-ITD AML after investigating its detailed mechanism of action in relation to de novo pathway of ceramide production.
Discovery of a C-S lyase inhibitor for the prevention of human body malodor formation: tannic acid inhibits the thioalcohol production in Staphylococcus hominis
(SPRINGER NATURE LINK, 2025) Fidan, Ozkan; Karipcin, Ayse Doga; Kose, Ayse Hamide; Anaz, Ayse; Demirsoy, Beyza Nur; Arslansoy, Nuriye; Sun, Lei; Mujwar, Somdutt; 0000-0001-5312-4742; 0009-0005-7132-842X; 0009-0008-5514-8711; 0000-0003-4037-5475; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Ozkan; Karipcin, Ayse Doga; Kose, Ayse Hamide; Anaz, Ayse; Demirsoy, Beyza Nur; Arslansoy, Nuriye
Human body odor is a result of the bacterial biotransformation of odorless precursor molecules secreted by the underarm sweat glands. In the human axilla, Staphylococcus hominis is the predominant bacterial species responsible for the biotransformation process of the odorless precursor molecule into the malodorous 3M3SH by two enzymes, a dipeptidase and a specific C-S lyase. The current solutions for malodor, such as deodorants and antiperspirants are known to block the apocrine glands or disrupt the skin microbiota. Additionally, these chemicals endanger both the environment and human health, and their long-term use can influence the function of sweat glands. Therefore, there is a need for the development of alternative, environmentally friendly, and natural solutions for the prevention of human body malodor. In this study, a library of secondary metabolites from various plants was screened to inhibit the C-S lyase, which metabolizes the odorless precursor sweat molecules, through molecular docking and molecular dynamics (MD) simulation. In silico studies revealed that tannic acid had the strongest affinity towards C-S lyase and was stably maintained in the binding pocket of the enzyme during 100-ns MD simulation. We found in the in vitro biotransformation assays that 1 mM tannic acid not only exhibited a significant reduction in malodor formation but also had quite low growth inhibition in S. hominis, indicating the minimum inhibitory effect of tannic acid on the skin microflora. This study paved the way for the development of a promising natural C-S lyase inhibitor to eliminate human body odor and can be used as a natural deodorizing molecule after further in vivo analysis.
Ethacrynic acid and cinnamic acid combination exhibits selective anticancer effects on K562 chronic myeloid leukemia cells
(SPRINGER, 2022) Yenigul, Munevver; Akcok, Ismail; Gencer Akcok, Emel Basak; 0000-0002-6559-9144; 0000-0002-5444-3929; 0000-0003-0468-721X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Yenigul, Munevver; Akcok, Ismail; Gencer Akcok, Emel Basak
Background Despite the recent advances in chemotherapy, the outcomes and the success of these treatments still remain insufficient. Novel combination treatments and treatment strategies need to be developed in order to achieve more effective treatment. This study was designed to investigate the combined effect of ethacrynic acid and cinnamic acid on cancer cell lines. Methods The anti-proliferative effect of ethacrynic acid and cinnamic acid was investigated by MTT cell viability assay in three different cancer cell lines. Combination indexes were calculated using CompuSyn software. Apoptosis was assessed by flow cytometric Annexin V-FITC/PI double-staining. The effect of the inhibitors on cell cycle distribution was measured by propidium iodide staining. Results The combination treatment of ethacrynic acid and cinnamic acid decreased cell proliferation significantly, by 63%, 75% and 70% for K562, HepG2 and TFK-1 cells, respectively. A 5.5-fold increase in the apoptotic cell population was observed after combination treatment of K562 cells. The population of apoptotic cells increased by 9.3 and 0.4% in HepG2 and TFK-1 cells, respectively. Furthermore, cell cycle analysis shows significant cell cycle arrest in S and G2/M phase for K562 cells and non-significant accumulation in G0/G1 phase for TFK-1 and HepG2 cells. Conclusions Although there is a need for further investigation, our results suggest that the inhibitors used in this study cause a decrease in cellular proliferation, induce apoptosis and cause cell cycle arrest.
EVALUATION OF THE SENSORY CORRELATION BETWEEN TOUCH SENSITIVITY AND THE CAPACITY TO DISCRIMINATE VISCOSITY
(WILEY, 2015) Aktar, Tugba; Chen, Jianshe; Ettelaie, Rammile; Holmes, Melvin; 0000-0001-8417-868X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
The capacity to discriminate the viscous nature of food materials is critically important in the sensory evaluation and subsequent perception of food texture and acceptability. It is generally assumed that this capability is closely linked to individual's tactile sensitivity, which in itself is a function of the individual's specific capabilities due to experience, age, lifestyle and health status for example. However, no experimental evidence is yet available to validate or disprove this assumption. By comparing the touch sensitivity and the capability of viscosity discrimination among individuals (using finger and tongue sensory perception), this work aims to establish if a correlation exists. Semmes-Weinstein monofilaments were used for touch sensitivity tests of the index fingers and tongue surfaces. A series of syrup solutions were prepared to give a wide range of viscosities with a viscosity scale factor of 1.20.009. A total of 30 healthy subjects (16 female and 14 male; mean age 29.9 +/- 9 years; mean body mass index 22.5 +/- 2.9kg/m(2)) participated in this study. A similar touch sensitivity threshold, 0.023 and 0.021g, was observed for the index fingertip and for the tongue, respectively. However, the tongue appears to be more sensitive to touch than the fingertips when the force range they cover was compared. The viscosity discrimination threshold was found to be approximately 53% for the index fingertip and around 47% for the tongue. By comparing individual capabilities of viscosity discrimination against touch sensitivity, no significant correlation was observed between the two factors. The results from this work suggest that the capability to discriminate viscosity differences is more likely attributed to experience and is little influenced by one's physiological capability of tactile sensation, e.g., the touch sensitivity. Practical ApplicationsThe capability to discriminate differences in viscosity and the subsequent perception is an important factor for food texture appreciation. Establishment of the underlying factors that characterize the variation in the ability for such discrimination across individuals is not only critically important for our fundamental understanding of the viscosity perception but is also hugely important for the food industry in development of new food products, and in particular for specific food design for individuals with special needs, e.g., elderly, dysphagia patients, etc. Differential threshold for certain tastes and aroma compounds has been investigated. However, little has been reported in the literature about the tactile interpretation of viscosity sensation and perception. Findings from this work could provide new insight for researchers in the food industry and in food development by giving them flexibility to redesign their ingredients especially the one that has thickening effect on the product viscosity. Methodologies used in this experiment could also be applied for general food sensory studies in establishing relationships between sensory psychology and sensory physiology and especially the threshold studies with a similar approach of finding just noticeable difference values of any stimuli. The method could also be applicable to sensory capability studies of some particular groups such as elderly people to assess how weakened physiology affects their sensory capability.
Exploring the binding capacity of lactic acid bacteria derived bacteriocins against RBD of SARS-CoV-2 Omicron variant by molecular simulations
(2023) Erol, Ismail; Kotil, Seyfullah Enes; Ortakci, Fatih; Durdagi, Serdar; 0000-0003-1319-0854; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Ortakci, Fatih
The changes in the SARS-CoV-2 genome have resulted in the emergence of new variants. Some of the variants have been classified as variants of concern (VOC). These strains have higher transmission rate and improved fitness. One of the prevalent were the Omicron variant. Unlike previous VOCs, the Omicron possesses fifteen mutations on the spike protein’s receptor binding domain (RBD). The modifications of spike protein’s key amino acid residues facilitate the virus’ binding capability against ACE2, resulting in an increase in the infectiousness of Omicron variant. Consequently, investigating the prevention and treatment of the Omicron variant is crucial. In the present study, we aim to explore the binding capacity of twenty-two bacteriocins derived from Lactic Acid Bacteria (LAB) against the Omicron variant by using protein-peptidedocking and molecular dynamics (MD) simulations. The Omicron variant RBD was prepared by introducing fifteen mutations using PyMol. The protein-peptide complexes were obtained using HADDOCK v2.4 docking webserver. Top scoring complexes obtained from HADDOCK webserver were retrieved and submitted to the PRODIGY server for the prediction of binding energies. RBD-bacteriocin complexes were subjected to MD simulations. We discovered promising peptide-based therapeutic candidates for the inhibition of Omicron variant for example Salivaricin B, Pediocin PA 1, Plantaricin W, Lactococcin mmfii and Enterocin A. The lead bacteriocins, except Enterocin A, are biosynthesized by food-grade lactic acid bacteria. Our study puts forth a preliminary information regarding potential utilization of food-grade LAB-derived bacteriocins, particularly Salivaricin B and Pediocin PA 1, for Covid-19 treatment and prophylaxis.

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