PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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Article Citation - WoS: 2Citation - Scopus: 2Pangenome Analysis and Genome-Guided Probiotic Evaluation of Cyclic Dipeptides Producing Levilactobacillus Brevis DY55bre Strain From a Lactic Acid Fermented Shalgam to Assess Its Metabolic, Probiotic Potentials, and Cytotoxic Effects on Colorectal Cancer Cells(Springer, 2025-10-01) Yetiman, Ahmet E.; Horzum, Mehmet; Kanbur, Ertan; Cadir, Mehmet; Bahar, Dilek; Gurbuz, Serife; Akbulut, MikailThis study investigates the genetic, metabolic, and probiotic characteristics of Levilactobacillus brevis DY55bre, a strain isolated from the traditional Turkish fermented beverage, shalgam. Whole-genome sequencing revealed a circular genome of 2.485 Mb with a GC content of 45.72%, predicted 2791 genes, and multiple CRISPR-Cas systems. Pangenome analysis demonstrated an open structure, with 18.9% core genes and 103 strain-specific genes, highlighting its genetic diversity. The DY55bre exhibits heterofermentative carbohydrate metabolism due to the presence of the araBAD operon and the lack of 1-phosphofructokinase (pfK) and fructose-1,6-bisphosphate aldolase enzymes. Probiotic evaluation revealed firm survival under simulated gastrointestinal conditions, including resistance to acidic pH (as low as 3.0) and bile salts (up to 1%), along with significant adhesion to intestinal epithelial cell lines (HT29;59.3%, Caco-2;87%, and DLD-1;60.8%). The strain exhibited high auto-aggregation (84.55%) and cell surface hydrophobicity (56.69%), essential for gut colonization. Safety assessments confirmed its non-hemolytic nature and absence of horizontally acquired antibiotic resistance genes. Notably, GC-MS analysis identified bioactive cyclic dipeptides, Cyclo(D-Phe-L-Pro) and Cyclo(L-Leu-L-Pro), which demonstrated cytotoxic effects against colorectal cancer cell lines, with IC50 values of 7.71 mg/mL for HT29 and 3.19 mg/mL for DLD-1. The cell-free supernatant exhibited antimicrobial activity against pathogens, likely due to the synergistic effects of cyclic dipeptides, organic acids, and other metabolites. Antioxidant assays revealed significant ABTS+ (76.63%) and DPPH (34.25%) radical scavenging activities, while cholesterol assimilation tests showed a 27.29% reduction. These findings position the DY55bre as a promising candidate for functional foods, nutraceuticals, and therapeutic applications, warranting further in vivo validation.Article Citation - WoS: 6Citation - Scopus: 6Sleep-Aware Wavelength and Bandwidth Assignment Scheme for TWDM PON(Springer, 2021-06) Butt, Rizwan Aslam; Faheem, Muhammad; Ashraf, M. Waqar; Arfeen, Asad; Memon, Kamran Ali; Khawaja, AttaullahThe energy efficiency and delay performance of PON are two inversely related phenomena. Higher sleep time of the Optical Network Units (ONUs) results in higher upstream (US) delays due to increased traffic queues during the ONU Asleep state. Although an efficient dynamic bandwidth and wavelength assignment (DWBA) scheme can decrease US delays by minimizing the bandwidth waste and improving the fairness of bandwidth distribution among the ONUs. However, the conventional DWBA schemes are not designed to work with cyclic sleep mode (CSM) and they keep on assigning bandwidth to ONUs even if the ONU is in Asleep state leading to wastage of bandwidth and degraded CSM performance. Therefore, in this work a sleep aware DWBA scheme for TWDM PON is presented to coordinate with CSM mode. It only assign bandwidth to Active ONUs during the guaranteed phase, surplus phase and excess phase allocation phases which minimizes the bandwidth waste and the bandwidth lost at the ONU end. The wavelength switching process is also improved by only considering the Active state ONUs to balance the traffic load on all the wavelengths. The simulation results support our claim as the SA-DWBA scheme on average achieves DWBA schemes due to up to 50% to 65% higher energy savings compared to other due to longer ONU Asleep times. However, the increased upstream delays of all the traffic classes in SA-DWBA scheme remain within the set delay limit of 50 ms.Article Citation - WoS: 24Citation - Scopus: 27In Silico Analysis of Bacteriocins From Lactic Acid Bacteria Against SARS-CoV(Springer, 2021-11-27) Erol, Ismail; Kotil, Seyfullah Enes; Fidan, Ozkan; Yetiman, Ahmet E.; Durdagi, Serdar; Ortakci, FatihThe COVID-19 pandemic caused by a novel coronavirus (SARS-CoV-2) is a serious health concern in the twenty-first century for scientists, health workers, and all humans. The absence of specific biotherapeutics requires new strategies to prevent the spread and prophylaxis of the novel virus and its variants. The SARS-CoV-2 virus shows pathogenesis by entering the host cells via spike protein and Angiotensin-Converting Enzyme 2 receptor protein. Thus, the present study aims to compute the binding energies between a wide range of bacteriocins with receptor-binding domain (RBD) on spike proteins of wild type (WT) and beta variant (lineage B.1.351). Molecular docking analyses were performed to evaluate binding energies. Upon achieving the best bio-peptides with the highest docking scores, further molecular dynamics (MD) simulations were performed to validate the structure and interaction stability. Protein-protein docking of the chosen 22 biopeptides with WT-RBD showed docking scores lower than -7.9 kcal/mol. Pediocin PA-1 and salivaricin P showed the lowest (best) docking scores of - 12 kcal/mol. Pediocin PA-1, salivaricin B, and salivaricin P showed a remarkable increase in the double mutant's predicted binding affinity with -13.8 kcal/mol, -13.0 kcal/mol, and -12.5 kcal/mol, respectively. Also, a better predicted binding affinity of pediocin PA-1 and salivaricin B against triple mutant was observed compared to the WT. Thus, pediocin PA-1 binds stronger to mutants of the RBD, particularly to double and triple mutants. Salivaricin B showed a better predicted binding affinity towards triple mutant compared to WT, showing that it might be another bacteriocin with potential activity against the SARS-CoV-2 beta variant. Overall, pediocin PA-1, salivaricin P, and salivaricin B are the most promising candidates for inhibiting SARS-CoV-2 (including lineage B.1.351) entrance into the human cells. These bacteriocins derived from lactic acid bacteria hold promising potential for paving an alternative way for treatment and prophylaxis of WT and beta variants.Article Citation - WoS: 8Citation - Scopus: 9Emerging DNA Methylome Targets in FLT3-ITD Acute Myeloid Leukemia: Combination Therapy With Clinically Approved FLT3 Inhibitors(Springer, 2024-05-02) Tecik, Melisa; Adan, AysunThe internal tandem duplication (ITD) mutation of the FMS-like receptor tyrosine kinase 3 (FLT3-ITD) is the most common mutation observed in approximately 30% of acute myeloid leukemia (AML) patients. It represents poor prognosis due to continuous activation of downstream growth-promoting signaling pathways such as STAT5 and PI3K/AKT. Hence, FLT3 is considered an attractive druggable target; selective small FLT3 inhibitors (FLT3Is), such as midostaurin and quizartinib, have been clinically approved. However, patients possess generally poor remission rates and acquired resistance when FLT3I used alone. Various factors in patients could cause these adverse effects including altered epigenetic regulation, causing mainly abnormal gene expression patterns. Epigenetic modifications are required for hematopoietic stem cell (HSC) self-renewal and differentiation; however, critical driver mutations have been identified in genes controlling DNA methylation (such as DNMT3A, TET2, IDH1/2). These regulators cause leukemia pathogenesis and affect disease diagnosis and prognosis when they co-occur with FLT3-ITD mutation. Therefore, understanding the role of different epigenetic alterations in FLT3-ITD AML pathogenesis and how they modulate FLT3I's activity is important to rationalize combinational treatment approaches including FLT3Is and modulators of methylation regulators or pathways. Data from ongoing pre-clinical and clinical studies will further precisely define the potential use of epigenetic therapy together with FLT3Is especially after characterized patients' mutational status in terms of FLT3 and DNA methlome regulators.Article Citation - WoS: 16Citation - Scopus: 17Can Laws Be a Potential PET Image Texture Analysis Approach for Evaluation of Tumor Heterogeneity and Histopathological Characteristics in NSCLC(Springer, 2017-07-06) Karacavus, Seyhan; Yilmaz, Bulent; Tasdemir, Arzu; Kayaalti, Omer; Kaya, Eser; Icer, Semra; Ayyildiz, OguzhanWe investigated the association between the textural features obtained from F-18-FDG images, metabolic parameters (SUVmax(,) SUVmean, MTV, TLG), and tumor histopathological characteristics (stage and Ki-67 proliferation index) in non-small cell lung cancer (NSCLC). The FDG-PET images of 67 patients with NSCLC were evaluated. MATLAB technical computing language was employed in the extraction of 137 features by using first order statistics (FOS), gray-level co-occurrence matrix (GLCM), gray-level run length matrix (GLRLM), and Laws' texture filters. Textural features and metabolic parameters were statistically analyzed in terms of good discrimination power between tumor stages, and selected features/parameters were used in the automatic classification by k-nearest neighbors (k-NN) and support vector machines (SVM). We showed that one textural feature (gray-level nonuniformity, GLN) obtained using GLRLM approach and nine textural features using Laws' approach were successful in discriminating all tumor stages, unlike metabolic parameters. There were significant correlations between Ki-67 index and some of the textural features computed using Laws' method (r = 0.6, p = 0.013). In terms of automatic classification of tumor stage, the accuracy was approximately 84% with k-NN classifier (k = 3) and SVM, using selected five features. Texture analysis of FDG-PET images has a potential to be an objective tool to assess tumor histopathological characteristics. The textural features obtained using Laws' approach could be useful in the discrimination of tumor stage.Article Citation - WoS: 6Citation - Scopus: 6An Integrative-Omics Analysis of an Industrial Clavulanic Acid-Overproducing Streptomyces Clavuligerus(Springer, 2022-08-10) Kurt-Kizildogan, Aslihan; Celik, Gozde; unsaldi, Eser; Ozcan, Servet; Ayaz-Guner, Serife; Ozcengiz, GulayClavulanic acid (CA) is a clinically important secondary metabolite used to treat infectious diseases. We aimed to decipher complex regulatory mechanisms acting in CA biosynthesis by analyzing transcriptome- and proteome-wide alterations in an industrial CA overproducer Streptomyces clavuligerus strain, namely DEPA and its wild-type counterpart NRRL3585. A total of 924 differentially expressed genes (DEGs) and 271 differentially produced proteins (DPPs) were obtained by RNA-seq and nanoLC-MS/MS analyses, respectively. In particular, CA biosynthetic genes, namely, car (cad), cast, oat2, pah, bls, ceas2, orf12, and claR, a cluster situated regulatory (CSR) gene, were significantly upregulated as shown by RNA-seq. Enzymes of clavam biosynthesis were downregulated considerably in the DEPA strain, while the genes involved in the arginine biosynthesis, one of the precursors of CA pathway, were overexpressed. However, the biosynthesis of the other CA precursor, glyceraldehyde-3-phosphate (G3P), was not affected. CA overproduction in the DEPA strain was correlated with BldD, BldG, BldM, and BldN (AdsA) overrepresentation. In addition, TetR, WhiB, and Xre family transcriptional regulators were shown to be significantly overrepresented. Several uncharacterized/unknown proteins differentially expressed in the DEPA strain await further studies for functional characterization. Correlation analysis indicated an acceptable degree of consistency between the transcriptome and proteome data. The study represents the first integrative-omics analysis in a CA overproducer S. clavuligerus strain, providing insights into the critical control points and potential rational engineering targets for a purposeful increase of CA yields in strain improvement.