PubMed İndeksli Yayınlar Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397

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Citation - WoS: 6
Citation - Scopus: 6
Absorption Enhancement by Semi-Cylindrical Structures for an Organic Solar Cell Application
(Optical Soc Amer, 2020) Hah, Dooyoung; 01. Abdullah Gül University; 02. Mühendislik Fakültesi; 02.05. Elektrik & Elektronik Mühendisliği
Organic solar cells are attractive for various applications with their flexibility and low-cost manufacturability. In order to increase their attractiveness in practice, it is essential to improve their energy conversion efficiency. In this work, semi-cylindrical-shell-shaped structures are proposed as one of the approaches, aiming at absorption enhancement in an organic solar cell. Poly(3-hexylthiophene-2,5-diyl) blended with indene-C60 bisadduct (P3HT:ICBA) is considered as the active layer. Light coupling to the guided modes and a geometrical advantage are attributed to this absorption enhancement. Finite-difference time-domain methods and finite element analysis are used to examine the absorption spectra for two types of devices, i.e., a debossed type and an embossed type. It is shown that absorption enhancement increases as the radius of the cylinder increases, but reaches a saturation at about 4-mu m radius. The average absorption enhancement with an active layer thickness of 200 nm and radius of 4 mu m, and for incidence angles between 0 degrees and 70 degrees, is found as 51%-52% for TE-polarized input and as 30%-33% for TM-polarized input when compared to a flat structure. Another merit of the proposed structures is that the range of incidence angles where the integrated absorption is at the level of the normal incidence is significantly broadened, reaching 70 degrees-80 degrees. This feature can be highly useful especially when organic solar cells are to be placed around a round object. The study results also exhibit that the proposed devices bear broadband absorption characteristics. (C) 2020 Optical Society of America
Citation - WoS: 34
Citation - Scopus: 38
Advances in Micelle-Based Drug Delivery: Cross-Linked Systems
(Bentham Science Publ Ltd, 2017) Isoglu, Ismail Alper; Ozsoy, Yildiz; Isoglu, Sevil Dincer; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
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.
Citation - WoS: 6
Citation - Scopus: 8
Anhedonia in Relation to Reward and Effort Learning in Young People With Depression Symptoms
(MDPI, 2023) Frey, Anna-Lena; Kaya, M. Siyabend; Adeniyi, Irina; McCabe, Ciara; 01. Abdullah Gül University; 06. İnsan ve Toplum Bilimleri Fakültesi; 06.02. Psikoloji
Anhedonia, a central depression symptom, is associated with impairments in reward processing. However, it is not well understood which sub-components of reward processing (anticipation, motivation, consummation, and learning) are impaired in association with anhedonia in depression. In particular, it is unclear how learning about different rewards and the effort needed to obtain them might be associated with anhedonia and depression symptoms. Therefore, we examined learning in young people (N = 132, mean age 20, range 17-25 yrs.) with a range of depression and anhedonia symptoms using a probabilistic instrumental learning task. The task required participants to learn which options to choose to maximize their reward outcomes across three conditions (chocolate taste, puppy images, or money) and to minimize the physical effort required to obtain the rewards. Additionally, we collected questionnaire measures of anticipatory and consummatory anhedonia, as well as subjective reports of "liking", "wanting" and "willingness to exert effort" for the rewards used in the task. We found that as anticipatory anhedonia increased, subjective liking and wanting of rewards decreased. Moreover, higher anticipatory anhedonia was significantly associated with lower reward learning accuracy, and participants demonstrated significantly higher reward learning than effort learning accuracy. To our knowledge, this is the first study observing an association of anhedonia with reward liking, wanting, and learning when reward and effort learning are measured simultaneously. Our findings suggest an impaired ability to learn from rewarding outcomes could contribute to anhedonia in young people. Future longitudinal research is needed to confirm this and reveal the specific aspects of reward learning that predict anhedonia. These aspects could then be targeted by novel anhedonia interventions.
Citation - WoS: 5
Citation - Scopus: 6
Capturing B Type Acute Lymphoblastic Leukemia Cells Using Two Types of Antibodies
(Wiley, 2019) Icoz, Kutay; Gercek, Tayyibe; Murat, Ayseguel; Ozcan, Servet; Unal, Ekrem; 01. Abdullah Gül University
One way to monitor minimal residual disease (MRD) is to screen cells for multiple surface markers using flow cytometry. In order to develop an alternative microfluidic based method, isolation of B type acute lymphoblastic cells using two types of antibodies should be investigated. The immunomagnetic beads coated with various antibodies are used to capture the B type acute lymphoblastic cells. Single beads, two types of beads and surface immobilized antibody were used to measure the capture efficiency. Both micro and nanosize immunomagnetic beads can be used to capture B type acute lymphoblastic cells with a minimum efficiency of 94% and maximum efficiency of 98%. Development of a microfluidic based biochip incorporating immunomagnetic beads and surface immobilized antibodies for monitoring MRD can be an alternative to current cost and time inefficient laboratory methods. (c) 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2737, 2019
Citation - WoS: 417
Citation - Scopus: 462
Cell Proliferation and Cytotoxicity Assays
(Bentham Science Publ Ltd, 2016) Adan, Aysun; Kiraz, Yagmur; Baran, Yusuf; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.02. Moleküler Biyoloji ve Genetik
Cell viability is defined as the number of healthy cells in a sample and proliferation of cells is a vital indicator for understanding the mechanisms in action of certain genes, proteins and pathways involved cell survival or death after exposing to toxic agents. Generally, methods used to determine viability are also common for the detection of cell proliferation. Cell cytotoxicity and proliferation assays are generally used for drug screening to detect whether the test molecules have effects on cell proliferation or display direct cytotoxic effects. Regardless of the type of cell-based assay being used, it is important to know how many viable cells are remaining at the end of the experiment. There are a variety of assay methods based on various cell functions such as enzyme activity, cell membrane permeability, cell adherence, ATP production, co-enzyme production, and nucleotide uptake activity. These methods could be basically classified into different categories: (I) dye exclusion methods such as trypan blue dye exclusion assay, (II) methods based on metabolic activity, (III) ATP assay, (IV) sulforhodamine B assay, (V) protease viability marker assay, (VI) clonogenic cell survival assay, (VII) DNA synthesis cell proliferation assays and (V) raman micro-spectroscopy. In order to choose the optimal viability assay, the cell type, applied culture conditions, and the specific questions being asked should be considered in detail. This particular review aims to provide an overview of common cell proliferation and cytotoxicity assays together with their own advantages and disadvantages, their methodologies, comparisons and intended purposes.
Citation - Scopus: 7
Cerium Oxide Nanoparticles Biosynthesized Using Fresh Green Walnut Shell in Microwave Environment and Their Anticancer Effect on Breast Cancer Cells
(John Wiley and Sons Inc, 2022) Sulak, Mine; Turgut, Gurbet Çelik; Sen, Alaattin; 01. Abdullah Gül University
In this study, cerium oxide nanoparticles (CONPs) were synthesized using fresh green walnut shell extract in microwave environment. The morphology and structure of the CONPs were determined using ultraviolet-visible (UV/VIS), attenuated total reflection-Fourier transform infrared (ATR-FT-IR), X-ray diffraction (XRD), energy-dispersive X-ray (EDX) spectroscopy, and scanning electron microscopy (SEM). Crystal purple staining, Annexin V-FITC detection, RT-PCR, P53, and NF-κB luciferase reporter assays were performed to evaluate the mechanism of action of CONPs in breast cancer cell lines (MCF7). The biosynthesized CONPs showed cytotoxic effects and induced apoptosis in MCF7 cells. Furthermore, CONPs induced P53 expression and suppressed NF-κB gene expression, both of which were confirmed using reporter assays. Based on the present results, it was concluded that CONPs can induce apoptosis by acting on P53 at the transcriptional level and may cause cell death by suppressing NF-κB-mediated transcription. © 2022 Elsevier B.V., All rights reserved.
Citation - WoS: 1
Citation - Scopus: 2
Complementary Medicines Used in Ulcerative Colitis and Unintended Interactions With Cytochrome P450-Dependent Drug-Metabolizing Enzymes
(Tubitak Scientific & Technological Research Council Turkey, 2022) Sen, Alaattin; 01. Abdullah Gül University
Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease with multiple genetic and a variety of environmental risk factors. Although current drugs significantly aid in controlling the disease, many people have led to the application of complementary therapies due to the common belief that they are natural and safe, as well as due to the consideration of the side effect of current drugs. Curcumin, cannabinoids, wheatgrass, Boswellia, wormwood and Aloe vera are among the most commonly used complementary medicines in UC. However, these treatments may have adverse and toxic effects due to unintended interactions with drugs or drug-metabolizing enzymes such as cytochrome P450s; thus, being ignorant of these interactions might cause deleterious effects with severe consequences. In addition, the lack of complete and controlled long-term studies with the use of these complementary medicines regarding drug metabolism pose additional risk and unsafety. Thus, this review aims to give an overview of the potential interactions of drug-metabolizing enzymes with the complementary botanical medicines used in UC, drawing attention to possible adverse effects.
A Comprehensive MicroRNA-seq Transcriptomic Analysis of Tay-Sachs Disease Mice Revealed Distinct miRNA Profiles in Neuroglial Cells
(Springernature, 2025) Kaya, Beyza; Orhan, Mehmet Emin; Yanbul, Selman; Demirci, Muserref Duygu Sacar; Demir, Secil Akyildiz; Seyrantepe, Volkan; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
Tay-Sachs disease (TSD) is a rare lysosomal storage disorder marked by the progressive buildup of GM2 in the central nervous system (CNS). This condition arises from mutations in the HEXA gene, which encodes the alpha subunit of the enzyme beta-hexosaminidase A. A newly developed mouse model for early-onset TSD (Hexa-/-Neu3-/-) exhibited signs of neurodegeneration and neuroinflammation, evidenced by elevated levels of pro-inflammatory cytokines and chemokines, as well as significant astrogliosis and microgliosis. Identifying disease-specific MicroRNAs (miRNAs) may aid the development of targeted therapies. Although previous small-scale studies have investigated miRNA expression in some regions of GM2 gangliosidosis mouse models, thorough profiling of miRNAs in this innovative TSD model remains to be done. In this study, we employed next-generation sequencing to analyze the complete miRNA profile of neuroglial cells from Hexa-/-Neu3-/- mice. By comparing KEGG and Reactome pathways associated with neurodegeneration, neuroinflammation, and sphingolipid metabolism in Hexa-/-Neu3-/- neuroglial cells, we discovered new MicroRNAs and their targets related to the pathophysiology of GM2 gangliosidosis. For the first time, our findings showed that miR-708-5p, miR-672-5p, miR-204-5p, miR-335-5p, and miR-296-3p were upregulated, while miR-10 b-5p, miR-615-3p, miR-196a-5p, miR-214-5p, and miR-199a-5p were downregulated in Hexa-/-Neu3-/- neuroglial cells in comparison to age-matched wild-type (WT). These specific changes in miRNA expression deepen our understanding of the disease's neuropathological characteristics in Hexa-/-Neu3-/- mice. Our study suggests that miRNA-based therapeutic strategies may improve clinical outcomes for TSD patients.
Citation - WoS: 1
Citation - Scopus: 1
Concurrent Inhibition of FLT3 and Sphingosine Kinase-1 Triggers Synergistic Cytotoxicity in Midostaurin Resistant FLT3-ITD Positive Acute Myeloid Leukemia Cells via Blocking FLT3/TAT5A Signaling to Induce Apoptosis
(Taylor & Francis Ltd, 2025) Tecik, Melisa; Adan, Aysun; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.02. Moleküler Biyoloji ve Genetik
The FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is one of the most frequent mutations observed in acute myeloid leukemia (AML) which contributes to disease progression and unfavorable prognosis. Midostaurin, a small FLT3 inhibitor (FLT3I), is clinically approved. However, patients generally possess acquired resistance when midostaurin used alone. Shifting the balance in the sphingolipid rheostat toward anti-apoptotic sphingosine kinase-1 (SK-1) or glucosylceramide synthase (GCS) is related to therapy resistance in cancer, however, their role in midostaurin resistant FLT3-ITD positive AML has not been previously investigated. We generated midostaurin resistant MV4-11 and MOLM-13 cell lines which showed increased IC50 values compared to their sensitive partner cells. SK-1 is overexpressed in resistant cells while GCS remains unchanged. Subsequent pharmacological targeting of SK-1 in resistant cells decreased SK-1 protein level, inhibited cell proliferation and showed additive or synergistic effect on cell growth, as confirmed by the Chou-Talalay combination index, and induced G0/G1 arrest (PI staining by flow cytometry). Cotreatment (SKI-II plus midostaurin) triggered apoptosis via phosphatidylserine exposure (annexin V/PI double staining). Mechanistically, induction of the intrinsic pathway of apoptosis was confirmed as increased activating cleavages of caspase-3 and PARP and increased Bax/Bcl-2 ratios. Activating phosphorylations of FLT3 (at tyrosine residue 591) and STAT5A (at tyrosine residue 694) dramatically inhibited in resistant cells treated with the combination. In conclusion, midostaurin resistance could be reversed by dual SK-1 and FLT3 inhibition in midostaurin resistant AML cell lines, providing the first evidence of a novel treatment approach to re-sensitize FLT3-ITD positive AML.
A Decision Support System for the Prediction of Mortality in Patients With Acute Kidney Injury Admitted in Intensive Care Unit
(Univ South Bohemia, 2020) Kayaalti, Selda; Kayaalti, Omer; Aksebzeci, Bekir Hakan; 01. Abdullah Gül University
Intensive care unit (ICU) is a very special unit of a hospital, where healthcare professionals provide treatment and, later, close followup to the patients. It is crucial to estimate mortality in ICU patients from many viewpoints. The purpose of this study is to classify the status of patients with acute kidney injury (AKI) in ICU as early mortality, late mortality, and survival by the application of Classification and Regression Trees (CART) algorithm to the patients' attributes such as blood urea nitrogen, creatinine, serum and urine neutrophil gelatinase-associated lipocalin (NGAL), alkaline phosphatase, lactate dehydrogenase (LDH), gamma-glutamyl transferase, laboratory electrolytes, blood gas, mean arterial pressure, central venous pressure and demographic details of patients. This study was conducted 50 patients with AKI who were followed up in the ICU. The study also aims to determine the significance of relationship between the attributes used in the prediction of mortality in CART and patients' status by employing the Kruskal-Wallis H test. The classification accuracy, sensitivity, and specificity of CART for the tested attributes for the prediction of early mortality, late mortality, and survival of patients were 90.00%, 83.33%, and 91.67%, respectively. The values of both urine NGAL and LDH on day 7 showed a considerable difference according to the patients' status after being examined by the Kruskal-Wallis H test.
Developing a Label Propagation Approach for Cancer Subtype Classification Problem
(Tubitak Scientific & Technological Research Council Turkey, 2022) Guner, Pinar; Bakir-Gungor, Burcu; Coskun, Mustafa; 02. 04. Bilgisayar Mühendisliği; 01. Abdullah Gül University; 02. Mühendislik Fakültesi
Cancer is a disease in which abnormal cells grow uncontrollably and invade other tissues. Several types of cancer have various subtypes with different clinical and biological implications. Based on these differences, treatment methods need to be customized. The identification of distinct cancer subtypes is an important problem in bioinformatics, since it can guide future precision medicine applications. In order to design targeted treatments, bioinformatics methods attempt to discover common molecular pathology of different cancer subtypes. Along this line, several computational methods have been proposed to discover cancer subtypes or to stratify cancer into informative subtypes. However, existing works do not consider the sparseness of data (genes having low degrees) and result in an ill-conditioned solution. To address this shortcoming, in this paper, we propose an alternative unsupervised method to stratify cancer patients into subtypes using applied numerical algebra techniques. More specifically, we applied a label propagation based approach to stratify somatic mutation profiles of colon, head and neck, uterine, bladder, and breast tumors. We evaluated the performance of our method by comparing it to the baseline methods. Extensive experiments demonstrate that our approach highly renders tumor classification tasks by largely outperforming the state-of-the-art unsupervised and supervised approaches.
Citation - WoS: 1
Citation - Scopus: 2
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, 2025) Fidan, Ozkan; Karipcin, Ayse Doga; Kose, Ayse Hamide; Anaz, Ayse; Demirsoy, Beyza Nur; Arslansoy, Nuriye; Mujwar, Somdutt; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
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.
Citation - WoS: 10
Citation - Scopus: 12
The Effect of Seed Sludge Type on Aerobic Granulation via Anoxic-Aerobic Operation
(Taylor & Francis Ltd, 2014) Ersan, Yusuf Cagatay; Erguder, Tuba Hande; 01. Abdullah Gül University
The effects of two seed sludge types, namely conventional activated sludge (CAS) and membrane bioreactor sludge (MBS), on aerobic granulation were investigated. The treatment performances of the reactors were monitored during and after the granulation. Operational period of 37 days was described in three phases; Phase 1 corresponds to Days 1-10, Phase 2 (overloading conditions) to Days 11-27 and Phase 3 (recovery) to Days 28-37. Aerobic granules of 0.56 +/- 0.23 to 2.48 +/- 1.28mm were successfully developed from both MBS and CAS. First granules appeared on Day 9 in both reactors, indicating that there was no difference between two seed sludge types in terms of the time period for granulation initiation. The results revealed that the granules developed from MBS performed better than CAS in terms of settleability, stability, biomass retention, adaptation, protection of granular structure at high loading rates (0.86 gN/L d and 3.92 gCOD/Ld) and low COD/TAN ratio (5). Granules of MBS were also found to be capable of providing better protection for nitrifiers at toxic free-ammonia concentrations (38-46 mg/L NH3-N), thus showing better treatment recovery than those of CAS.
Citation - WoS: 10
Citation - Scopus: 11
Effect of the Shell Material and Confinement Type on the Conversion Efficiency of Core/Shell Quantum Dot Nanocrystal Solar Cells
(IOP Publishing Ltd, 2018) Sahin, Mehmet; 01. Abdullah Gül University; 02.02. Endüstri Mühendisliği; 02. Mühendislik Fakültesi
In this study, the effects of the shell material and confinement type on the conversion efficiency of core/shell quantum dot nanocrystal (QDNC) solar cells have been investigated in detail. For this purpose, the conventional, i.e. original, detailed balance model, developed by Shockley and Queisser to calculate an upper limit for the conversion efficiency of silicon p-n junction solar cells, is modified in a simple and effective way to calculate the conversion efficiency of core/shell QDNC solar cells. Since the existing model relies on the gap energy (E-g) of the solar cell, it does not make an estimation about the effect of QDNC materials on the efficiency of the solar cells, and gives the same efficiency values for several QDNC solar cells with the same E-g. The proposed modification, however, estimates a conversion efficiency in relation to the material properties and also the confinement type of the QDNCs. The results of the modified model show that, in contrast to the original one, the conversion efficiencies of different QDNC solar cells, even if they have the same E-g, become different depending upon the confinement type and shell material of the core/shell QDNCs, and this is crucial in the design and fabrication of the new generation solar cells to predict the confinement type and also appropriate QDNC materials for better efficiency.
Efficacy of Combinatorial Inhibition of Hedgehog and Autophagy Pathways on the Survival of AML Cell Lines
(Academic Press inc Elsevier Science, 2025) Sansacar, Merve; Pepe, Nihan Aktas; Akcok, Emel Basak Gencer; El Khatib, Mona; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik; 04.02. Moleküler Biyoloji ve Genetik
Acute myeloid leukemia (AML) is a common hematopoietic disease that results from diverse genetic abnormalities. Dysregulation of important signaling pathways, including the PI3K/AKT/mTOR, Wnt and Hedgehog pathways, plays crucial roles in the development of AML. Hedgehog pathway (Hh) is a conserved signaling pathway that is crucial throughout embryogenesis. Hh plays an important role in the regulation of autophagy, known as the cellular recycling process of organelles and unwanted proteins. Many studies have noted that the modulation of autophagy could act as a survival mechanism in AML. Considering the pivotal role of autophagy and Hh signaling in AML, understanding the relationship between these pathways is important for overcoming leukemia. Therefore, we examined the efficacy of Hh inhibition by GLI-ANTagonist 61 (GANT61) in MOLM-13 and CMK cells via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenil-2H-tetrazolium bromide (MTT) cell viability assays. GANT61 resulted in decreased cell viability in both cell lines. Therefore, we focused on the outcome of autophagy modulation in AML cells. We observed that the autophagy inhibitors ammonium chloride (NH4CI), chloroquine (CQ), and nocodazole led to a significant reduction in the proliferation of both cell lines. Cotreatment with autophagy pathway inhibitors and GANT61 synergistically affected both AML cell lines. Moreover, dual targeting of these pathways resulted in arrest at the G0/G1 phase in MOLM-13 cells but not in CMK cells. Furthermore, the combination of nocodazole and GANT61 increased the expression level of LC3B-II in both cell lines. Compared with that in the untreated control cells, the GLI1 gene expression level in both cell lines was significantly lower after GANT61 and autophagy cotreatment. In conclusion, targeting Hh and autophagy could be a favorable option to combat AML.
Enlightening the Molecular Mechanisms of Type 2 Diabetes With a Novel Pathway Clustering and Pathway Subnetwork Approach
(Tubitak Scientific & Technological Research Council Turkey, 2022) Bakir-Gungor, Burcu; Yazici, Miray Unlu; Goy, Gokhan; Temiz, Mustafa; 01. Abdullah Gül University; 02. 04. Bilgisayar Mühendisliği; 02. Mühendislik Fakültesi; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
Type 2 diabetes mellitus (T2D) constitutes 90% of the diabetes cases, and it is a complex multifactorial disease. In the last decade, genome-wide association studies (GWASs) for T2D successfully pinpointed the genetic variants (typically single nucleotide polymorphisms, SNPs) that associate with disease risk. In order to diminish the burden of multiple testing in GWAS, researchers attempted to evaluate the collective effects of interesting variants. In this regard, pathway-based analyses of GWAS became popular to discover novel multigenic functional associations. Still, to reveal the unaccounted 85 to 90% of T2D variation, which lies hidden in GWAS datasets, new post-GWAS strategies need to be developed. In this respect, here we reanalyze three metaanalysis data of GWAS in T2D, using the methodology that we have developed to identify disease-associated pathways by combining nominally significant evidence of genetic association with the known biochemical pathways, protein-protein interaction (PPI) networks, and the functional information of selected SNPs. In this research effort, to enlighten the molecular mechanisms underlying T2D development and progress, we integrated different in silico approaches that proceed in top-down manner and bottom-up manner, and presented a comprehensive analysis at protein subnetwork, pathway, and pathway subnetwork levels. Using the mutual information based on the shared genes, the identified protein subnetworks and the affected pathways of each dataset were compared. While most of the identified pathways recapitulate the pathophysiology of T2D, our results show that incorporating SNP functional properties, PPI networks into GWAS can dissect leading molecular pathways, and it could offer improvement over traditional enrichment strategies.
Citation - WoS: 12
Citation - Scopus: 12
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; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik; 04.02. Moleküler Biyoloji ve Genetik
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.
Citation - WoS: 3
Citation - Scopus: 4
Evaluation of Anti-Alzheimer Activity of Synthetic Coumarins by Combination of in Vitro and in Silico Approaches
(Wiley-VCH Verlag GmbH, 2022) Orhan, Ilkay Erdogan; Deniz, F. Sezer Senol; Salmas, Ramin Ekhteiari; Irmak, Sule; Acar, Ozden Ozgun; Turgut, Gurbet Celik; Tataringa, Gabriela; 01. Abdullah Gül University
Series of synthetic coumarin derivatives (1-16) were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two enzymes linked to the pathology of Alzheimer's disease (AD). Compound 16 was the most active AChE inhibitor with IC50 32.23 +/- 2.91 mu M, while the reference (galantamine) had IC50=1.85 +/- 0.12 mu M. Compounds 9 (IC(50)75.14 +/- 1.82 mu M), 13 (IC50=16.14 +/- 0.43 mu M), were determined to be stronger BChE inhibitors than the reference galantamine (IC50=93.53 +/- 2.23 mu M). The IC50 value of compound 16 for BChE inhibition (IC50=126.56 +/- 11.96 mu M) was slightly higher than galantamine. The atomic interactions between the ligands and the key amino acids inside the binding cavities were simulated to determine their ligand-binding positions and free energies. The three inhibitory coumarins (9, 13, 16) were next tested for their effects on the genes associated with AD using human neuroblastoma (SH-SY5Y) cell lines. Our data indicate that they could be considered for further evaluation as new anti-Alzheimer drug candidates.
Citation - WoS: 5
Citation - Scopus: 6
Exploring the Binding Capacity of Lactic Acid Bacteria Derived Bacteriocins Against RBD of SARS-CoV Omicron Variant by Molecular Simulations
(Taylor & Francis inc, 2023) Erol, Ismail; Kotil, Seyfullah Enes; Ortakci, Fatih; Durdagi, Serdar; 01. Abdullah Gül University
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.Communicated by Ramaswamy H. Sarma
Citation - WoS: 3
Citation - Scopus: 3
Exploring Therapeutic Avenues: Mesenchymal Stem/Stromal Cells and Exosomes in Confronting Enigmatic Biofilm-Producing Fungi
(Springer, 2024) Bicer, Mesude; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
Fungal infections concomitant with biofilms can demonstrate an elevated capacity to withstand substantially higher concentrations of antifungal agents, contrasted with infectious diseases caused by planktonic cells. This inherent resilience intrinsic to biofilm-associated infections engenders a formidable impediment to effective therapeutic interventions. The different mechanisms that are associated with the intrinsic resistance of Candida species encompass drug sequestration by the matrix, drug efflux pumps, stress response cell density, and the presence of persister cells. These persisters, a subset of fungi capable of surviving hostile conditions, pose a remarkable challenge in clinical settings in virtue of their resistance to conventional antifungal therapies. Hence, an exigent imperative has arisen for the development of novel antifungal therapeutics with specific targeting capabilities focused on these pathogenic persisters. On a global scale, fungal persistence and their resistance within biofilms generate an urgent clinical need for investigating recently introduced therapeutic strategies. This review delves into the unique characteristics of Mesenchymal stem/stromal cells (MSCs) and their secreted exosomes, which notably exhibit immunomodulatory and regenerative properties. By comprehensively assessing the current literature and ongoing research in this field, this review sheds light on the plausible mechanisms by which MSCs and their exosomes can be harnessed to selectively target fungal persisters. Additionally, prospective approaches in the use of cell-based therapeutic modalities are examined, emphasizing the importance of further research to overcome the enigmatic fungal persistence.

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