PubMed İndeksli Yayınlar Koleksiyonu

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

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Citation - WoS: 9
Citation - Scopus: 10
An Answer to Colon Cancer Treatment by Mesenchymal Stem Cell Originated from Adipose Tissue
(Mashhad Univ Med Sciences, 2018) Iplik, Elif Sinem; Ertugrul, Baris; Kozanoglu, Ilknur; Baran, Yusuf; Cakmakoglu, Bedia
Objective(s): Colon cancer is risen up with its complex mechanism that directly impacts on its treatment as well as its common prevalence. Mesenchymal stem cells (MSCs) have been considered as a therapeutic candidate for conventional disease including cancer. In this research, we have focused on apoptotic effects of adipose tissue-derived MSCs in colon cancer. Materials and Methods: MSCs were obtained from adipose tissue and characterized by Flowcytometer using suitable antibodies. MSCs, HT-29, HCT-116, RKO and healthy cell line MRC5 were cultured by different seeding procedure. After cell viability assay, changes in caspase 3 enzyme activity and the level of phosphatidylserine were measured. Results: For cell viability assay, a 48 hr incubation period was chosen to seed all cells together. There was a 1.36-fold decrease in caspase 3 enzyme activity by co-treatment of RKO and MSCs in addition to 2.02-fold decrease in HT-29 and MSCs co-treatment, and 1.103-fold increase in HCT-116 and MSCs. The results demonstrated that HCT-116 led to the highest rate of apoptotic cell death (7.5%) compared with other cells. Conclusion: We suggest that MSCs might remain a new treatment option for cancer by its differentiation and repair capacity.
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
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.
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
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: 12
Citation - Scopus: 14
4D-QSAR Investigation and Pharmacophore Identification of Pyrrolo[2,1-C][1,4]Benzodiazepines Using Electron Conformational-Genetic Algorithm Method
(Taylor & Francis Ltd, 2016) Ozalp, A.; Yavuz, S. C.; Sabanci, N.; Copur, F.; Kokbudak, Z.; Saripinar, E.
In this paper, we present the results of pharmacophore identification and bioactivity prediction for pyrrolo[2,1-c][1,4]benzodiazepine derivatives using the electron conformational-genetic algorithm (EC-GA) method as 4D-QSAR analysis. Using the data obtained from quantum chemical calculations at PM3/HF level, the electron conformational matrices of congruity (ECMC) were constructed by EMRE software. The ECMC of the lowest energy conformer of the compound with the highest activity was chosen as the template and compared with the ECMCs of the lowest energy conformer of the other compounds within given tolerances to reveal the electron conformational submatrix of activity (ECSA, i.e. pharmacophore) by ECSP software. A descriptor pool was generated taking into account the obtained pharmacophore. To predict the theoretical activity and select the best subset of variables affecting bioactivities, the nonlinear least square regression method and genetic algorithm were performed. For four types of activity including the GI(50), TGI, LC50 and IC50 of the pyrrolo[2,1-c][1,4] benzodiazepine series, the r(train)(2), r(test)(2) and q(2) values were 0.858, 0.810, 0.771; 0.853, 0.848, 0.787; 0.703, 0.787, 0.600; and 0.776, 0.722, 0.687, respectively.
Citation - WoS: 2
Citation - Scopus: 2
Possible Boron-Rich Amorphous Silicon Borides From Ab Initio Simulations
(Springer, 2023) Karacaoglan, Aysegul Ozlem Cetin; Durandurdu, Murat
ContextBy means of ab initio molecular dynamics simulations, possible boron-rich amorphous silicon borides (BnSi1-n, 0.5 <= n <= 0.95) are generated and their microstructure, electrical properties and mechanical characters are scrutinized in details. As expected, the mean coordination number of each species increases progressively and more closed packed structures form with increasing B concentration. In all amorphous models, pentagonal pyramid-like configurations are observed and some of which lead to the development of B-12 and B11Si icosahedrons. It should be noted that the B11Si icosahedron does not form in any crystalline silicon borides. Due to the affinity of B atoms to form cage-like clusters, phase separations (Si:B) are perceived in the most models. All simulated amorphous configurations are a semiconducting material on the basis of GGA+U calculations. The bulk modulus of the computer-generated amorphous compounds is in the range of 90 GPa to 182 GPa. As predictable, the Vickers hardness increases with increasing B content and reaches values of 25-33 GPa at 95% B concentration. Due to their electrical and mechanical properties, these materials might offer some practical applications in semiconductor technologies.MethodThe density functional theory (DFT) based ab initio molecular dynamics (AIMD) simulations were used to generate B-rich amorphous configurations.
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
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.
Citation - WoS: 26
Citation - Scopus: 31
miRcorrNet: Machine Learning-Based Integration of miRNA and mRNA Expression Profiles, Combined with Feature Grouping and Ranking
(PeerJ Inc., 2021) Yousef, M.; Göy, G.; Mitra, R.; Eischen, C.M.; Jabeer, A.; Bakir-Güngör, B.
A better understanding of disease development and progression mechanisms at the molecular level is critical both for the diagnosis of a disease and for the development of therapeutic approaches. The advancements in high throughput technologies allowed to generate mRNA and microRNA (miRNA) expression profiles; and the integrative analysis of these profiles allowed to uncover the functional effects of RNA expression in complex diseases, such as cancer. Several researches attempt to integrate miRNA and mRNA expression profiles using statistical methods such as Pearson correlation, and then combine it with enrichment analysis. In this study, we developed a novel tool called miRcorrNet, which performs machine learning-based integration to analyze miRNA and mRNA gene expression profiles. miRcorrNet groups mRNAs based on their correlation to miRNA expression levels and hence it generates groups of target genes associated with each miRNA. Then, these groups are subject to a rank function for classification. We have evaluated our tool using miRNA and mRNA expression profiling data downloaded from The Cancer Genome Atlas (TCGA), and performed comparative evaluation with existing tools. In our experiments we show that miRcorrNet performs as good as other tools in terms of accuracy (reaching more than 95% AUC value). Additionally, miRcorrNet includes ranking steps to separate two classes, namely case and control, which is not available in other tools. We have also evaluated the performance of miRcorrNet using a completely independent dataset. Moreover, we conducted a comprehensive literature search to explore the biological functions of the identified miRNAs. We have validated our significantly identified miRNA groups against known databases, which yielded about 90% accuracy. Our results suggest that miRcorrNet is able to accurately prioritize pan-cancer regulating high-confidence miRNAs. miRcorrNet tool and all other supplementary files are available at https://github.com/ malikyousef/miRcorrNet. © 2021 Elsevier B.V., All rights reserved.
Citation - WoS: 3
Citation - Scopus: 4
Matching Variants for Functional Characterization of Genetic Variants
(Oxford Univ Press inc, 2023) Cevik, Sebiha; Zhao, Pei; Zorluer, Atiyye; Pir, Mustafa S.; Bian, Wenyin; Kaplan, Oktay, I
Rapid and low-cost sequencing, as well as computer analysis, have facilitated the diagnosis of many genetic diseases, resulting in a substantial rise in the number of disease-associated genes. However, genetic diagnosis of many disorders remains problematic due to the lack of interpretation for many genetic variants, especially missenses, the infeasibility of high-throughput experiments on mammals, and the shortcomings of computational prediction technologies. Additionally, the available mutant databases are not well-utilized. Toward this end, we used Caenorhabditis elegans mutant resources to delineate the functions of eight missense variants (V444I, V517D, E610K, L732F, E817K, H873P, R1105K, and G1205E) and two stop codons (W937stop and Q1434stop), including several matching variants (MatchVar) with human in ciliopathy associated IFT-140 (also called CHE-11)//IFT140 (intraflagellar transport protein 140). Moreover, MatchVars carrying C. elegans mutants, including IFT-140(G680S) and IFT-140(P702A) for the human (G704S) (dbSNP: rs150745099) and P726A (dbSNP: rs1057518064 and a conflicting variation) were created using CRISPR/Cas9. IFT140 is a key component of IFT complex A (IFT-A), which is involved in the retrograde transport of IFT along cilia and the entrance of G protein-coupled receptors into cilia. Functional analysis of all 10 variants revealed that P702A and W937stop, but not others phenocopied the ciliary phenotypes (short cilia, IFT accumulations, mislocalization of membrane proteins, and cilia entry of nonciliary proteins) of the IFT-140 null mutant, indicating that both P702A and W937stop are phenotypic in C. elegans. Our functional data offered experimental support for interpreting human variants, by using ready-to-use mutants carrying MatchVars and generating MatchVars with CRISPR/Cas9.
Citation - Scopus: 1
Possible Drug-Drug Interactions Between Mesalamine and Tricyclic Antidepressants Through CYP2D6 Metabolism - in Silico and in Vitro Analyses
(Georg Thieme Verlag, 2025) Ozen, Melek B.; Gazioğlu, Işil; Ozgun-Acar, Özden; Guner, Hüseyin; Semiz, Gürkan; Sen, Alaattin
Mesalamine (mesalazine, 5-aminosalicylic acid, 5-ASA) is an essential anti-inflammatory agent both used for therapy and as a remission control in patients with inflammatory bowel diseases (IBD) such as ulcerative colitis (UC). Tricyclic antidepressants (TCAs) are used to alleviate remaining symptoms in patients already receiving IBD therapy or with quiescent inflammation. The cytochrome P4502D6 enzyme is involved in the metabolism of TCAs. Hence, it is crucial to investigate the role of CYP2D6 in 5-ASA metabolism. Initially, in silico analysis involving the docking of 5-ASA to CYP2D6 and molecular dynamics simulations was conducted. Next, the rate of O-demethylation of a nonfluorescent probe 3-[2-(N,N-diethyl-N-methylammonium)-ethyl]-7-methoxy-4-methylcoumarin (AMMC) into a fluorescent metabolite AMHC (3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-hydroxy-4-methylcoumarin) was optimized with baculosomes co-expressing human CYP2D6 and human P450 oxidoreductase (hCPR) to monitor CYP2D6 activity in a microtiter plate assay. The apparent Km and Vmax were found to be 1.30 μM and 32.68 pmol/min/mg of protein for the O-demethylation of AMMC to AMHC, and the reaction was linear for 40 min. Then, nonselective inhibition of CYP2D6 activity with various concentrations of 5-ASA was detected. Finally, the conversion of AMMC to metabolites was analyzed by HPLC-ESI-MS/MS spectrometry, and none were identified. Thus, this study suggests that concurrent use of mesalamine with TCA may lead to adverse effects, and CYP2D6 genotyping should be routinely performed on these patients to eliminate possible threats. © 2025 Elsevier B.V., All rights reserved.
Citation - WoS: 2
Citation - Scopus: 3
Multi Fragment Melting Analysis System (MFMAS) for One-Step Identification of Lactobacilli
(Elsevier, 2020) Kesmen, Zulal; Kilic, Ozge; Gormez, Yasin; Celik, Mete; Bakir-Gungor, Burcu
The accurate identification of lactobacilli is essential for the effective management of industrial practices associated with lactobacilli strains, such as the production of fermented foods or probiotic supplements. For this reason, in this study, we proposed the Multi Fragment Melting Analysis System (MFMAS)-lactobacilli based on high resolution melting (HRM) analysis of multiple DNA regions that have high interspecies heterogeneity for fast and reliable identification and characterization of lactobacilli. The MFMAS-lactobacilli is a new and customized version of the MFMAS, which was developed by our research group. MFMAS-lactobacilli is a combined system that consists of i) a ready-to-use plate, which is designed for multiple HRM analysis, and ii) a data analysis software, which is used to characterize lactobacilli species via incorporating machine learning techniques. Simultaneous HRM analysis of multiple DNA fragments yields a fingerprint for each tested strain and the identification is performed by comparing the fingerprints of unknown strains with those of known lactobacilli species registered in the MFMAS. In this study, a total of 254 isolates, which were recovered from fermented foods and probiotic supplements, were subjected to MFMAS analysis, and the results were confirmed by a combination of different molecular techniques. All of the analyzed isolates were exactly differentiated and accurately identified by applying the single-step procedure of MFMAS, and it was determined that all of the tested isolates belonged to 18 different lactobacilli species. The individual analysis of each target DNA region provided identification with an accuracy range from 59% to 90% for all tested isolates. However, when each target DNA region was analyzed simultaneously, perfect discrimination and 100% accurate identification were obtained even in closely related species. As a result, it was concluded that MFMAS-lactobacilli is a multi-purpose method that can be used to differentiate, classify, and identify lactobacilli species. Hence, our proposed system could be a potential alternative to overcome the inconsistencies and difficulties of the current methods.
Citation - WoS: 5
Citation - Scopus: 5
Linear Variable Optical Attenuators With Shaped-Finger Comb-Drive Actuators
(Optical Soc Amer, 2020) Hah, Dooyoung
A design method is proposed for variable optical attenuators (VOAs), aiming at linear attenuation-voltage characteristics, and verified by finite element analysis. Devices of interest are planar VOAs based on microelectromechanical systems technology, with either a knife-edge shutter or a reflector. The proposed method calculates the shape of the fingers of the comb-drive actuators that are used to move the optical component (shutter or reflector) to change the attenuation level. The calculation is, in effect, tantamount to solving a differential equation that encompasses the optical model of the device, electromechanical behavior of the actuators, and the objective of the design, i.e., linear attenuation-voltage characteristics. The design method is almost all-analytical with minimum usage of numerical analysis. The obtained designs are further examined by three-dimensional finite element analysis to understand their effectiveness and to probe the validity of the approximations used. The best linearity factor (defined as % deviation from the ideal case) obtained is 1.34% for both shutter- and reflection-type devices when the conditions are set as 1-dB insertion loss and 50-dB maximum attenuation. (C) 2020 Optical Society of America
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
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.
Citation - Scopus: 25
Recursive Cluster Elimination Based Rank Function (SVM-RCE-R) Implemented in KNIME
(F1000 Research Ltd, 2021) Yousef, Malik; Bakir-Güngör, Burcu; Jabeer, Amhar; Göy, Gökhan; Qureshi, Rehman A.; C Showe, Louise
In our earlier study, we proposed a novel feature selection approach, Recursive Cluster Elimination with Support Vector Machines (SVM-RCE) and implemented this approach in Matlab. Interest in this approach has grown over time and several researchers have incorporated SVM-RCE into their studies, resulting in a substantial number of scientific publications. This increased interest encouraged us to reconsider how feature selection, particularly in biological datasets, can benefit from considering the relationships of those genes in the selection process, this led to our development of SVM-RCE-R. SVM-RCE-R, further enhances the capabilities of SVM-RCE by the addition of a novel user specified ranking function. This ranking function enables the user to stipulate the weights of the accuracy, sensitivity, specificity, f-measure, area under the curve and the precision in the ranking function This flexibility allows the user to select for greater sensitivity or greater specificity as needed for a specific project. The usefulness of SVM-RCE-R is further supported by development of the maTE tool which uses a similar approach to identify MicroRNA (miRNA) targets. We have also now implemented the SVM-RCE-R algorithm in Knime in order to make it easier to applyThe use of SVM-RCE-R in Knime is simple and intuitive and allows researchers to immediately begin their analysis without having to consult an information technology specialist. The input for the Knime implemented tool is an EXCEL file (or text or CSV) with a simple structure and the output is also an EXCEL file. The Knime version also incorporates new features not available in SVM-RCE. The results show that the inclusion of the ranking function has a significant impact on the performance of SVM-RCE-R. Some of the clusters that achieve high scores for a specified ranking can also have high scores in other metrics. © 2021 Elsevier B.V., All rights reserved.
Citation - WoS: 20
Citation - Scopus: 23
Apoptotic Effects of Non-Edible Parts of Punica Granatum on Human Multiple Myeloma Cells
(Sage Publications Ltd, 2016) Kiraz, Yagmur; Neergheen-Bhujun, Vidushi S.; Rummun, Nawraj; Baran, Yusuf
Multiple myeloma is of great concern since existing therapies are unable to cure this clinical condition. Alternative therapeutic approaches are mandatory, and the use of plant extracts is considered interesting. Punica granatum and its derived products were suggested as potential anticancer agents due to the presence of bioactive compounds. Thus, polypenolic-rich extracts of the non-edible parts of P. granatum were investigated for their antiproliferative and apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were dose-dependent decreases in the proliferation of U266 cells in response to P. granatum extracts. Also, exposure to the extracts triggered apoptosis with significant increases in loss of mitochondrial membrane potential in U266 cells exposed to the leaves and stem extracts, while the flower extract resulted in slight increases in loss of MMP. These results were confirmed by Annexin-V analysis. These results documented the cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells via disruption of mitochondrial membrane potential and increasing cell cycle arrest. The data suggest that the extracts can be envisaged in cancer chemoprevention and call for further exploration into the potential application of these plant parts.
Citation - Scopus: 8
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
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: 1
Prediction of Biomechanical Properties of Ex Vivo Human Femoral Cortical Bone Using Raman Spectroscopy and Machine Learning Algorithms
(Elsevier, 2025) Unal, Mustafa; Unlu, Ramazan; Uppuganti, Sasidhar; Nyman, Jeffry S.
This study applied Raman spectroscopy (RS) to ex vivo human cadaveric femoral mid-diaphysis cortical bone specimens (n = 118 donors; age range 21-101 years) to predict fracture toughness properties via machine learning (ML) models. Spectral features, together with demographic variables (age, sex) and structural parameters (cortical porosity, volumetric bone mineral density), were fed into support vector regression (SVR), extreme tree regression (ETR), extreme gradient boosting (XGB), and ensemble models to predict fracture-toughness metrics such as crack-initiation toughness (Kinit) and energy-to-fracture (J-integral). Feature selection was based on Raman-derived mineral and organic matrix parameters, such as nu 1Phosphate (PO4)/CH2-wag, nu 1PO4/ Amide I, and others, to capture the complex composition of bone. Our results indicate that ensemble models consistently outperformed individual models, with the best performance for crack initiation toughness (Kinit) prediction being achieved using the ensemble approach. This yielded a coefficient of determination (R2) of 0.623, root-mean squared error (RMSE) of 1.320, mean absolute error (MAE) of 1.015, and mean percentage absolute error (MAPE) of 0.134. For prediction of the overall energy to propagate a crack (J-integral), the XGB model achieved an R2 of 0.737, RMSE of 2.634, MAE of 2.283, and MAPE of 0.240. This study highlights the importance of incorporating mineral quality properties (MP) and organic matrix properties (OMP) for enhanced prediction accuracy. This work represents the first-ever study combining Raman spectroscopy with other clinical and structural features to predict fracture toughness of human cortical bone, demonstrating the potential of artificial intelligence (AI) and ML in advancing bone research. Future studies could focus on larger datasets and more advanced modeling techniques to further improve predictive capabilities.
Citation - WoS: 21
Citation - Scopus: 21
Polyethylenimine Modified and Non-Modified Polymeric Micelles Used for Nasal Administration of Carvedilol
(Amer Scientific Publishers, 2015) Kahraman, Emine; Karagoz, Ayse; Dincer, Sevil; Ozsoy, Yildiz
This study evaluates the ability of polyethylenimine-modified and non-modified polymeric micelles to enhance permeation through the nasal mucosa for a highly hydrophobic model drug. Carvedilol was loaded into polyethylenimine-modified and non-modified micelles by direct dissolution. Formulations were characterised by critical micelle concentration, micelle particle size and distribution, zeta potential, morphological structure and entrapment efficiency. The drug entrapment efficiency was determined to be as high as 77.14%, while micelle particle sizes and zeta potentials were within the range of 140.0-279.9 nm and (-40.6)-(+25.9) mV, respectively. In vitro studies showed 100% release of carvedilol from micelles in 120 hours. Ex vivo permeation studies showed that the drug in polyethylenimine non-modified micelles passed more efficiently than the drug in polyethylenimine modified micelles. These results demonstrated that polyethylenimine modified micelles did not significantly affect the permeation of the drug when compared to polyethylenimine non-modified micelles. On the contrary, the drug in poly(L-lactide)-block-methoxy poly(ethylene glycol) 5000 micelles, the polyethylenimine non-modified micelles, showed the highest permeation rate through bovine nasal mucosa. In conclusion, poly(L-lactide)-block-methoxy poly(ethylene glycol) 5000 polymeric micelles maybe useful as novel drug carriers that increase the permeation through the nasal mucosa.
Citation - WoS: 6
Citation - Scopus: 6
Absorption Enhancement by Semi-Cylindrical Structures for an Organic Solar Cell Application
(Optical Soc Amer, 2020) Hah, Dooyoung
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: 17
Citation - Scopus: 27
Blockchain for Genomics and Healthcare: A Literature Review, Current Status, Classification and Open Issues
(PeerJ Inc, 2021) Dedeturk, Beyhan Adanur; Soran, Ahmet; Bakir-Gungor, Burcu
The tremendous boost in the next generation sequencing technologies and in the "omics"technologies resulted in the generation of hundreds of gigabytes of data per day. Nowadays, via integrating -omics data with other data types, such as imaging and electronic health record (EHR) data, panomics studies attempt to identify novel and potentially actionable biomarkers for personalized medicine applications. In this respect, for the accurate analysis of -omics data and EHR, there is a need to establish secure and robust pipelines that take the ethical aspects into consideration, regulate privacy and ownership issues, and data sharing. These days, blockchain technology has picked up significant attention in diverse fields, including genomics, since it offers a new solution for these problems from a different perspective. Blockchain is an immutable transaction ledger, which offers secure and distributed system without a central authority. Within the system, each transaction can be expressed with cryptographically signed blocks, and the verification of transactions is performed by the users of the network. In this review, firstly, we aim to highlight the challenges of EHR and genomic data sharing. Secondly, we attempt to answer "Why"or "Why not"the blockchain technology is suitable for genomics and healthcare applications in detail. Thirdly, we elucidate the general blockchain structure based on the Ethereum, which is a more suitable technology for the genomic data sharing platforms. Fourthly, we review current blockchain-based EHR and genomic data sharing platforms, evaluate the advantages and disadvantages of these applications, and classify these applications using different metrics. Finally, we conclude by discussing the open issues and introducing our suggestion on the topic. In summary, to facilitate the diagnosis, monitoring and therapy of diseases with the effective analysis of -omics data with other available data types, through this review, we put forward the possible implications of the blockchain technology to life sciences and healthcare.
Citation - WoS: 13
Citation - Scopus: 13
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
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.

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