PubMed İndeksli Yayınlar Koleksiyonu

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Citation - WoS: 1
Citation - Scopus: 1
Cinnamomum Zeylanicum Extract Incorporated Electrospun Poly(Lactic Acid)/ Gelatin Membrane as a New Wound Dressing
(Elsevier, 2025) Tarhan, Seray Zora; Pepe, Nihan Aktas; Sen, Alaattin; Isoglu, Ismail Alper
In this study, we fabricated poly(lactic acid)/gelatin electrospun membranes containing various concentrations of Cinnamomum zeylanicum extract and evaluated them as a novel wound dressing. The electrospun membranes were chemically, morphologically, and mechanically characterized, and the results were discussed in comparison with the literature. Electrospun membranes' biodegradability, swelling, and release properties were evaluated, with the CE7.5 membrane having values of 29.60 f 7.20 and 542.1 f 48.3 % and 66.9 %, respectively. Antibacterial activity was observed in CE7.5 and CE10 membranes against E. coli and S. aureus strains. At the highest concentration (CE10), 111.7 f 5.6 % and 96 f 12.375 % cell viability were detected in fibroblasts and differentiated LPS-induced THP-1 cells. Cell viability was further evaluated by Annexin-V/PI staining, revealing that 97.95 f 1.63 % of the cells remained viable in the CE7.5-treated membranes, while only 1.85 f 1.49 % of necrotic cells were detected in the treated cell population. Fibroblasts treated with the CE7.5 membrane showed a 42 % improvement in wound closure compared to non-treated cells. The anti-inflammatory properties of the electrospun membranes were also investigated. Treatment with the conditioned CE7.5 membrane downregulated Tba1 and tau proteins by 45.1 and 51.055 %, respectively. This study concluded that the newly developed Cinnamomum zeylanicum extract incorporated poly(lactic acid)/gelatin electrospun membranes could be a promising wound dressing material.
High Carbohydrate Diet Decreases Microbial Diversity and Increases Il-1β Levels in Mice Colon
(Korean Society Food Science & Technology-kosfost, 2024) Ulutas, Mehmet Sefa; Aydin, Erkin; Cebeci, Aysun
Western diet is known to contribute to intestinal dysbiosis and the progression of inflammation. Although the Turkish diet has different macronutrient contents, the intestinal inflammatory disease incidences in T & uuml;rkiye are comparable to Western countries. Thus, we hypothesized that high carbohydrate diets also contribute to inflammation of the colon. We compared diets with different macronutrient compositions and investigated their effects on colonic microbiota, cytokine, histology, and tight junction protein levels. High carbohydrate diet caused the lowest microbial diversity and is accompanied by the highest expression of interleukin-1 beta and claudin-1. A low carbohydrate diet with zero fiber resulted in the lowest inflammatory markers as well as the lowest occludin and claudin levels. Overall, our results indicate that carbohydrate and fiber contents of the diets are important contributors to colon health.
Citation - WoS: 29
Citation - Scopus: 41
Optimisation of the Reaction Conditions for the Production of Cross-Linked Starch With High Resistant Starch Content
(Elsevier Sci Ltd, 2015) Kahraman, Kevser; Koksel, Hamit; Ng, Perry K. W.
The optimum reaction conditions (temperature and pH) for the preparation of cross-linked (CL) corn and wheat starches with maximum resistant starch (RS) content were investigated by using response surface methodology (RSM). According to the preliminary results, five levels were selected for reaction temperature (38-70 degrees C) and pH (10-12) in the main study. RS contents of the CL corn and wheat starch samples increased with increasing temperature and pH, and pH had a greater influence on RS content than had temperature. The maximum RS content (with a maximum p value of 0.4%) was obtained in wheat starch cross-linked at 38 degrees C and pH 12. In the case of CL corn starch, the optimum condition was 70 degrees C and pH 12. CL corn and wheat starch samples were also produced separately under the optimum conditions and their RS contents were 80.4% and 83.9%, respectively. These results were also in agreement with the values predicted by RSM. (C) 2014 Elsevier Ltd. All rights reserved.
Citation - WoS: 35
Citation - Scopus: 35
Glucose-Dependent Anaplerosis in Cancer Cells Is Required for Cellular Redox Balance in the Absence of Glutamine
(Nature Portfolio, 2016) Cetinbas, Naniye Malli; Sudderth, Jessica; Harris, Robert C.; Cebeci, Aysun; Negri, Gian L.; Yilmaz, Oemer H.; Sorensen, Poul H.
Cancer cells have altered metabolism compared to normal cells, including dependence on glutamine (GLN) for survival, known as GLN addiction. However, some cancer cell lines do not require GLN for survival and the basis for this discrepancy is not well understood. GLN is a precursor for antioxidants such as glutathione (GSH) and NADPH, and GLN deprivation is therefore predicted to deplete antioxidants and increase reactive oxygen species (ROS). Using diverse human cancer cell lines we show that this occurs only in cells that rely on GLN for survival. Thus, the preference for GLN as a dominant antioxidant source defines GLN addiction. We show that despite increased glucose uptake, GLN addicted cells do not metabolize glucose via the TCA cycle when GLN is depleted, as revealed by C-13-glucose labeling. In contrast, GLN independent cells can compensate by diverting glucose-derived pyruvate into the TCA cycle. GLN addicted cells exhibit reduced PDH activity, increased PDK1 expression, and PDK inhibition partially rescues GLN starvation-induced ROS and cell death. Finally, we show that combining GLN starvation with pro-oxidants selectively kills GLN addicted cells. These data highlight a major role for GLN in maintaining redox balance in cancer cells that lack glucose-dependent anaplerosis.
Citation - WoS: 53
Citation - Scopus: 59
Thickness-Tunable Self-Assembled Colloidal Nanoplatelet Films Enable Ultrathin Optical Gain Media
(Amer Chemical Soc, 2020) Erdem, Onur; Foroutan, Sina; Gheshlaghi, Negar; Guzelturk, Burak; Altintas, Yemliha; Demir, Hilmi Volkan
We propose and demonstrate construction of highly uniform, multilayered superstructures of CdSe/CdZnS core/shell colloidal nanoplatelets (NPLs) using liquid interface self-assembly. These NPLs are sequentially deposited onto a solid substrate into slabs having monolayer-precise thickness across tens of cm(2) areas. Because of near-unity surface coverage and excellent uniformity, amplified spontaneous emission (ASE) is observed from an uncharacteristically thin film having 6 NPL layers, corresponding to a mere 42 nm thickness. Furthermore, systematic studies on optical gain of these NPL superstructures having thicknesses ranging from 6 to 15 layers revealed the gradual reduction in gain threshold with increasing number of layers, along with a continuous spectral shift of the ASE peak (similar to 18 nm). These observations can be explained by the change in the optical mode confinement factor with the NPL waveguide thickness and propagation wavelength. This bottom-up construction technique for thickness-tunable, three-dimensional NPL superstructures can be used for large-area device fabrication.
Citation - WoS: 8
Citation - Scopus: 8
Involvement of Sphingolipid Metabolism Enzymes in Resveratrol-Mediated Cytotoxicity in Philadelphia-Positive Acute Lymphoblastic Leukemia
(Routledge Journals, Taylor & Francis Ltd, 2022) Oguz, Osman; Adan, Aysun
Targeting the key enzymes of sphingolipid metabolism including serine palmitoyltransferase (SPT), sphingosine kinase (SK) and glucosylceramide synthase (GCS) has a therapeutic importance. However, sphingolipid metabolism-mediated anti-leukemic actions of resveratrol in Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) remain unknown. Therefore, we explored potential mechanisms behind resveratrol-mediated cytotoxicity in SD1 and SUP-B15 Ph + ALL cells in the context of sphingolipid metabolism and apoptosis induction. The anti-proliferative and apoptotic effects of resveratrol alone and in combination with SPT inhibitor (myriocin), SK inhibitor (SKI II), GCS inhibitor (PDMP) were determined by MTT cell proliferation assay and flow cytometry, respectively. The effects of resveratrol on PARP cleavage, SPT, SK and GCS protein levels were investigated by Western blot. Resveratrol inhibited proliferation and triggered apoptosis via PARP activation and externalization of phosphatidylserine (PS). Resveratrol increased the expression of SPT whereas it downregulated SK and GCS. Resveratrol's combinations with SKI II and PDMP intensified its anti-leukemic activity by increasing the relocalization of PS while its combination with myriocin suppressed apoptosis. Therefore, resveratrol inhibited cell proliferation and induced apoptosis through modulating SK, GCS and SPT expression, which may be considered as novel biomarkers of resveratrol-induced cytotoxicity in Ph + ALL.
Citation - WoS: 50
Citation - Scopus: 149
An Investigation on the Determinants of Carbon Emissions for OECD Countries: Empirical Evidence From Panel Models Robust to Heterogeneity and Cross-Sectional Dependence
(Springer Heidelberg, 2016) Dogan, Eyup; Seker, Fahri
This empirical study analyzes the impacts of real income, energy consumption, financial development and trade openness on CO2 emissions for the OECD countries in the Environmental Kuznets Curve (EKC) model by using panel econometric approaches that consider issues of heterogeneity and cross-sectional dependence. Results from the Pesaran CD test, the Pesaran-Yamagata's homogeneity test, the CADF and the CIPS unit root tests, the LM bootstrap cointegration test, the DSUR estimator, and the Emirmahmutoglu-Kose Granger causality test indicate that (i) the panel time-series data are heterogeneous and cross-sectionally dependent; (ii) CO2 emissions, real income, the quadratic income, energy consumption, financial development and openness are integrated of order one; (iii) the analyzed data are cointegrated; (iv) the EKC hypothesis is validated for the OECD countries; (v) increases in openness and financial development mitigate the level of emissions whereas energy consumption contributes to carbon emissions; (vi) a variety of Granger causal relationship is detected among the analyzed variables; and (vii) empirical results and policy recommendations are accurate and efficient since panel econometric models used in this study account for heterogeneity and cross-sectional dependence in their estimation procedures.
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
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.
Citation - WoS: 27
Citation - Scopus: 22
Quantum Dot and Electron Acceptor Nano-Heterojunction for Photo-Induced Capacitive Charge-Transfer
(Nature Portfolio, 2021) Karatum, Onuralp; Eren, Guncem Ozgun; Melikov, Rustamzhon; Onal, Asim; Ow-Yang, Cleva W.; Sahin, Mehmet; Nizamoglu, Sedat
Capacitive charge transfer at the electrode/electrolyte interface is a biocompatible mechanism for the stimulation of neurons. Although quantum dots showed their potential for photostimulation device architectures, dominant photoelectrochemical charge transfer combined with heavy-metal content in such architectures hinders their safe use. In this study, we demonstrate heavy-metal-free quantum dot-based nano-heterojunction devices that generate capacitive photoresponse. For that, we formed a novel form of nano-heterojunctions using type-II InP/ZnO/ZnS core/shell/shell quantum dot as the donor and a fullerene derivative of PCBM as the electron acceptor. The reduced electron-hole wavefunction overlap of 0.52 due to type-II band alignment of the quantum dot and the passivation of the trap states indicated by the high photoluminescence quantum yield of 70% led to the domination of photoinduced capacitive charge transfer at an optimum donor-acceptor ratio. This study paves the way toward safe and efficient nanoengineered quantum dot-based next-generation photostimulation devices.
Citation - WoS: 35
Citation - Scopus: 39
Advances in Micelle-Based Drug Delivery: Cross-Linked Systems
(Bentham Science Publ Ltd, 2017) Isoglu, Ismail Alper; Ozsoy, Yildiz; Isoglu, Sevil Dincer
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: 134
Citation - Scopus: 136
The Impacts of Different Proxies for Financialization on Carbon Emissions in Top-Ten Emitter Countries
(Elsevier, 2020) Amin, Azka; Dogan, Eyup; Khan, Zeeshan
The nexus of financialization and carbon emissions has been widely discussed in the literature. A vast body of literature that estimates the impact of financialization on carbon emissions proxies financialization with either domestic credit or market capitalization. However, these representatives do not fully respond to the complicated nature of financial development. To till the gaps in the existing literature, nine different proxies for financial development are used in the links with carbon emissions in the framework of EKC theory for the years 1980-2014. This study exposes reliable and robust empirical results due to the use of a number of proxies for financialization and second-generation econometric approaches in the empirical analysis. The quantile regression approach deals with unobserved heterogeneity for each cross-section and estimates different slope parameters at varying quantiles. Because non-normality and heterogeneity are detected in datasek quantile regression provides more robust and reliable estimates than conventional econometric techniques. Results from quantile regression estimator support mixed effects of financial development on carbon emissions over quantiles: in addition, the impact of financial development on carbon emissions is varying not only for each quantile but also for different proxies of financial development. The EKC hypothesis is validated for the top-ten emitter economies. Interpretations and policy suggestions are further discussed in the present study. (C) 2020 Elsevier B.V. All rights reserved.
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.
Citation - WoS: 1
Citation - Scopus: 1
ConVarT: Search Engine for Missense Variants Between Humans and Other Organisms
(Wiley, 2022) Pir, Mustafa S.; Cevik, Sebiha; Kaplan, Oktay I.
ConVarT (https://convart.org/) is a search engine for searching for conjugate variants between humans and other species. The search engine is based on matching conjugate variants called MatchVars between species. Matching equivalent variants requires correct alignment of orthologous proteins with the use of multiple sequence alignments (MSA). Indeed, the ConVarT pipeline has performed over a million MSAs and integrated variants and variant-specific annotations (pathogenicity, phenotypic variants; etc.) into the corresponding positions on MSAs. When a clinically relevant variant is discovered whose functional relevance is unknown, ConVarT offers clinician scientists the possibility to search for a MatchVar in other species and to look for functional data on that variant. Fortunately, ConVarT enables users to paste a protein sequence in FASTA format to search for human orthologous proteins. A pairwise sequence alignment (PSA) is then performed between the provided protein sequence and the human orthologous protein, allowing users to visualize human variants on the PSA. Here, we describe the step-by-step usage of ConVarT.
Citation - WoS: 21
Citation - Scopus: 23
Photonic-Lantern Coherent LIDAR System
(Optical Soc Amer, 2015) Ozdur, Ibrahim; Toliver, Paul; Woodward, T. K.
In this work, a photonic-lantern-based coherent LIDAR system is experimentally demonstrated and the voltage signal-to-noise ratio improvement is analyzed. A voltage signal-to-noise ratio (SNRV) improvement of 2.8 is demonstrated experimentally for photonic-lantern-based coherent receivers relative to single-mode coherent receivers. The voltage signal-to-noise ratio improvement is obtained when other parameters are kept constant. We have also analyzed the effect of random optical power distribution among the single-mode fibers. We found that the distribution does not significantly impact the SNRV improvement. The mean value of voltage signal-to-noise ratio improvement is found to be similar to 2.4. (C) 2015 Optical Society of America
Citation - WoS: 17
Citation - Scopus: 24
Quality, Nutritional Properties, and Glycemic Index of Colored Whole Wheat Breads
(MDPI, 2023) Koksel, Hamit; Cetiner, Buket; Shamanin, Vladimir P.; Tekin-Cakmak, Z. Hazal; Pototskaya, Inna V.; Kahraman, Kevser; Morgounov, Alexey I.
The main aim of this study was to investigate the quality and nutritional properties (dietary fiber, phenolic, antioxidant contents, and glycemic index) of breads made from whole wheat flours of colored wheats. White (cultivar Agronomicheskaya 5), red (Element 22), purple (EF 22 and Purple 8), and blue (Blue 10) colored wheats were used in the study. The whole wheat flours of Blue 10 and Purple 8 had higher farinograph stability, lower softening degree, and higher quality numbers indicating that they had better rheological properties. Bread produced from whole wheat flour of blue-colored grain had significantly higher loaf volume and better symmetry, crust color, crumb cell structure, and softness values among others (p < 0.05). The whole wheat bread produced using Element 22 had the highest crust and crumb L* color values, while Purple 8 and EF 22 had the lowest crust and crumb L* color values, suggesting that purple-colored grains have a tendency to make whole wheat bread with darker crust and crumb color. Bread produced from cultivar Blue 10 had the lowest firmness values while Element 22 had the highest firmness values. The highest total phenolic content and antioxidant capacity values were obtained from the whole wheat bread sample from purple-colored wheat (Purple 8). The whole wheat flour of Element 22 had the highest total dietary fiber content among all samples (p < 0.05). The differences between whole wheat bread samples in terms of total dietary fiber and glycemic index were not statistically significant. The results of the present study indicated that colored wheats can be used to produce whole wheat breads with higher nutritional properties and acceptable quality characteristics.
Citation - WoS: 31
Citation - Scopus: 33
Discovery of Adapalene and Dihydrotachysterol as Antiviral Agents for the Omicron Variant of SARS-CoV-2 Through Computational Drug Repurposing
(Springer, 2023) Fidan, Ozkan; Mujwar, Somdutt; Kciuk, Mateusz
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been significantly paralyzing the societies, economies and health care systems around the globe. The mutations on the genome of SARS-CoV-2 led to the emergence of new variants, some of which are classified as "variant of concern" due to their increased transmissibility and better viral fitness. The Omicron variant, as the latest variant of concern, dominated the current COVID-19 cases all around the world. Unlike the previous variants of concern, the Omicron variant has 15 mutations on the receptor-binding domain of spike protein and the changes in the key amino acid residues of S protein can enhance the binding ability of the virus to hACE2, resulting in a significant increase in the infectivity of the Omicron variant. Therefore, there is still an urgent need for treatment and prevention of variants of concern, particularly for the Omicron variant. In this study, an in silico drug repurposing was conducted through the molecular docking of 2890 FDA-approved drugs against the mutant S protein of SARS-CoV-2 for Omicron variant. We discovered promising drug candidates for the inhibition of alarming Omicron variant such as quinestrol, adapalene, tamibarotene, and dihydrotachysterol. The stability of ligands complexed with the mutant S protein was confirmed using MD simulations. The lead compounds were further evaluated for their potential use and side effects based on the current literature. Particularly, adapalene, dihydrotachysterol, levocabastine and bexarotene came into prominence due to their non-interference with the normal physiological processes. Therefore, this study suggests that these approved drugs can be considered as drug candidates for further in vitro and in vivo studies to develop new treatment options for the Omicron variant of SARS-CoV-2. [GRAPHICS] .
Citation - WoS: 18
Citation - Scopus: 20
Optimization Study on Surface Roughness and Tribological Behavior of Recycled Cast Iron Reinforced Bronze MMCs Produced by Hot Pressing
(MDPI, 2021) Gunes, Aydin; Sahin, Omer Sinan; Duzcukoglu, Hayrettin; Salur, Emin; Aslan, Abdullah; Kuntoglu, Mustafa; Pimenov, Danil Yurievich
Surface roughness reflects the quality of many operational parameters, namely service life, wear characteristics, working performance and tribological behavior of the produced part. Therefore, tribological performance is critical for the components used as tandem parts, especially for the MMCs (Metal Matrix Composites) which are a unique class of materials having extensive application areas such as aerospace, aeronautics, marine engineering and the defense industry. Current work covers the optimization study of production parameters for surface roughness and tribological indicators of newly produced cast iron reinforced bronze MMCs. In this context, two levels of temperature (400 and 450 degrees C), three levels of pressure (480, 640 and 820 MPa) and seven levels of reinforcement ratios (60/40, 70/30, 80/20, 90/10, 100/0 of GGG40/CuSn10, pure bronze-as received and pure cast iron-as received) are considered. According to the findings obtained by Taguchi's signal-to-noise ratios, the reinforcement ratio has a dominant effect on surface roughness parameters (Ra and Rz), the coefficient of friction and the weight loss in different levels. In addition, 100/0 reinforced GGG40/CuSn10 gives minimum surface roughness, pure cast iron provides the best weight loss and pure bronze offers the desired coefficient of friction. The results showed the importance of material ingredients on mechanical properties by comparing a wide range of samples from starting the production phase, which provides a perspective for manufacturers to meet the market supply as per human requirements.
Citation - WoS: 2
Citation - Scopus: 1
Computational Prediction of MicroRNAs in Histoplasma Capsulatum
(Academic Press Ltd- Elsevier Science Ltd, 2020) Demirci, Mueserref Duygu Sagar
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.
Citation - Scopus: 4
CCPred: Global and Population-Specific Colorectal Cancer Prediction and Metagenomic Biomarker Identification at Different Molecular Levels Using Machine Learning Techniques
(Elsevier Ltd, 2024) Bakir-Güngör, Burcu; Temiz, Mustafa; Inal, Yasin; Cicekyurt, Emre; Yousef, Malik
Colorectal cancer (CRC) ranks as the third most common cancer globally and the second leading cause of cancer-related deaths. Recent research highlights the pivotal role of the gut microbiota in CRC development and progression. Understanding the complex interplay between disease development and metagenomic data is essential for CRC diagnosis and treatment. Current computational models employ machine learning to identify metagenomic biomarkers associated with CRC, yet there is a need to improve their accuracy through a holistic biological knowledge perspective. This study aims to evaluate CRC-associated metagenomic data at species, enzymes, and pathway levels via conducting global and population-specific analyses. These analyses utilize relative abundance values from human gut microbiome sequencing data and robust classification models are built for disease prediction and biomarker identification. For global CRC prediction and biomarker identification, the features that are identified by SelectKBest (SKB), Information Gain (IG), and Extreme Gradient Boosting (XGBoost) methods are combined. Population-based analysis includes within-population, leave-one-dataset-out (LODO) and cross-population approaches. Four classification algorithms are employed for CRC classification. Random Forest achieved an AUC of 0.83 for species data, 0.78 for enzyme data and 0.76 for pathway data globally. On the global scale, potential taxonomic biomarkers include ruthenibacterium lactatiformanas; enzyme biomarkers include RNA 2′ 3′ cyclic 3′ phosphodiesterase; and pathway biomarkers include pyruvate fermentation to acetone pathway. This study underscores the potential of machine learning models trained on metagenomic data for improved disease prediction and biomarker discovery. The proposed model and associated files are available at https://github.com/TemizMus/CCPRED. © 2024 Elsevier B.V., All rights reserved.
Citation - WoS: 26
Citation - Scopus: 25
Trail Promotes the Polarization of Human Macrophages Toward a Proinflammatory M1 Phenotype and Is Associated With Increased Survival in Cancer Patients With High Tumor Macrophage Content
(Frontiers Media S.A., 2023) Gunalp, Sinem; Helvaci, Derya Goksu; Oner, Aysenur; Bursali, Ahmet; Conforte, Alessandra; Guener, Hueseyin; Sag, Duygu
BackgroundTNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can either induce cell death or activate survival pathways after binding to death receptors (DRs) DR4 or DR5. TRAIL is investigated as a therapeutic agent in clinical trials due to its selective toxicity to transformed cells. Macrophages can be polarized into pro-inflammatory/tumor-fighting M1 macrophages or anti-inflammatory/tumor-supportive M2 macrophages and an imbalance between M1 and M2 macrophages can promote diseases. Therefore, identifying modulators that regulate macrophage polarization is important to design effective macrophage-targeted immunotherapies. The impact of TRAIL on macrophage polarization is not known.MethodsPrimary human monocyte-derived macrophages were pre-treated with either TRAIL or with DR4 or DR5-specific ligands and then polarized into M1, M2a, or M2c phenotypes in vitro. The expression of M1 and M2 markers in macrophage subtypes was analyzed by RNA sequencing, qPCR, ELISA, and flow cytometry. Furthermore, the cytotoxicity of the macrophages against U937 AML tumor targets was assessed by flow cytometry. TCGA datasets were also analyzed to correlate TRAIL with M1/M2 markers, and the overall survival of cancer patients.ResultsTRAIL increased the expression of M1 markers at both mRNA and protein levels while decreasing the expression of M2 markers at the mRNA level in human macrophages. TRAIL also shifted M2 macrophages towards an M1 phenotype. Our data showed that both DR4 and DR5 death receptors play a role in macrophage polarization. Furthermore, TRAIL enhanced the cytotoxicity of macrophages against the AML cancer cells in vitro. Finally, TRAIL expression was positively correlated with increased expression of M1 markers in the tumors from ovarian and sarcoma cancer patients and longer overall survival in cases with high, but not low, tumor macrophage content.ConclusionsTRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype via both DR4 and DR5. Our study defines TRAIL as a new regulator of macrophage polarization and suggests that targeting DRs can enhance the anti-tumorigenic response of macrophages in the tumor microenvironment by increasing M1 polarization.

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