TR-Dizin İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/396
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Article Citation - WoS: 1Comprehensive Prediction of FBN1 Targeting Mirnas: A Systems Biology Approach for Marfan Syndrome(Galenos Publishing House, 2025-09-22) Orhan, M.E.; Demirci, Y.M.; Saçar Demirci, M.D.S.; Demirci, Muserref Duygu SacarObjective: Marfan syndrome (MFS) is a genetic connective tissue disorder primarily caused by mutations in the FBN1 gene. Emerging evidence highlights the regulatory role of microRNAs (miRNAs) in modulating gene expression in MFS, but a systematic investigation into miRNAs targeting FBN1 is lacking. This study aimed to comprehensively identify miRNAs interacting with the FBN1 transcript to reveal potential molecular regulators and therapeutic targets. Methods: Human miRNA sequences were retrieved from miRBase (Release 22.1), and the canonical FBN1 transcript (RefSeq: NM_000138.5) was used for target prediction. Computational interaction analysis was conducted using the psRNATarget server with stringent parameters to detect potential miRNA binding sites. Expression profiles and disease associations of the top candidate miRNAs were further investigated through database integration and literature review. Results: Out of 2656 human mature miRNAs analyzed, 251 were predicted to bind FBN1, with the hsa-miR-181 family exhibiting the highest number of predicted interactions. Evidence from the literature highlighted dysregulation of hsa-miR-181 expression in MFS patients, suggesting a functional role in disease pathophysiology. Conclusion: This study identifies key members of the hsa-miR-181 family as post-transcriptional regulators of FBN1, offering new insights into miRNA-driven mechanisms in MFS. These findings support the potential of RNA-based diagnostics and therapeutic strategies targeting miRNA-FBN1 interactions. ©Copyright 2025 The Author.Article Citation - WoS: 2Citation - Scopus: 2The Nexus of Leadership, Political Empowerment, and Social Mobilization: The Case of the July 15 Coup Attempt in Turkey(Seta Foundation, 2020-06-30) Donmez, Rasim Ozgur; Timur, Kasim; Lloyd, Fatma Armagan TekeThis study analyzes the mutually empowering relations between Turkish President Recep Tayyip Erdogan and his followers, and how Erdogan's charismatic leadership and image functioned to galvanize his followers on the night of July 15, 2016, when large numbers of them mobilized against the attempted coup. The article has three sections. The first is a theoretical discussion which sheds light on the concept and the underlying mechanisms of political empowerment and its effects on the relationships between leaders and followers. The second section evaluates Erdogan's characteristics and ruling style, which was instrumental in motivating resistance to the abortive coup. Finally, the third section analyzes the various means by which Erdogan was able to inspire the masses to mobilize against the armed junta through interviews and observations.Article Citation - WoS: 1Citation - Scopus: 1The Comparison of Fragility Curves of Moment-Resisting and Braced Frames Used in Steel Structures Under Varying Wind Load(Turkish Chamber Civil Engineers, 2025-03-01) Ozalp, Abdulkadir; Gokdemir, Hande; Ciftci, CihanIn this study, the performance of two different steel structure types (moment-resisting frame and braced frame) under wind loading was compared by addressing the fragility curves of these structure types. To perform this comparison, the dimensions of the members of these structural systems were first determined. Then, nonlinear static pushover analyses were conducted to assess the performance levels of each frame type. After applying these analyses, time-history analyses were performed with 100 different wind loads for each varying equivalent mean wind speed. Afterwards, the probability of exceeding the predetermined structural performance limits of the structure types was determined using Monte Carlo simulation method. Finally, the results of the simulation method were used to adapt the maximum likelihood estimation method to obtain the fragility curves of the structures. To conclude, it has been revealed that the material cost of the structure doubles when diagonal elements are used, but the wind speed required for a 100% collapse probability to occur in the braced frame is twice as high compared to the moment-resisting frame.Article Citation - WoS: 4Citation - Scopus: 5Noise-Assisted Multivariate Empirical Mode Decomposition Based Emotion Recognition(Istanbul Univ-Cerrahapasa, 2018-08-03) Ozel, Pinar; Akan, Aydin; Yilmaz, BulentEmotion state detection or emotion recognition cuts across different disciplines because of the many parameters that embrace the brain's complex neural structure, signal processing methods, and pattern recognition algorithms. Currently, in addition to classical time-frequency methods, emotional state data have been processed via data-driven methods such as empirical mode decomposition (EMD). Despite its various benefits, EMD has several drawbacks: it is intended for univariate data; it is prone to mode mixing; and the number of local extrema must be enough before the EMD process can begin. To overcome these problems, this study employs a multivariate EMD and its noise-assisted version in the emotional state classification of electroencephalogram signals. Emotion state detection or emotion recognition cuts across different disciplines because of the many parameters that embrace the brain's complex neural structure, signal processing methods, and pattern recognition algorithms. Currently, in addition to classical time-frequency methods, emotional state data have been processed via data-driven methods such as empirical mode decomposition (EMD). Despite its various benefits, EMD has several drawbacks: it is intended for univariate data; it is prone to mode mixing; and the number of local extrema must be enough before the EMD process can begin. To overcome these problems, this study employs a multivariate EMD and its noise-assisted version in the emotional state classification of electroencephalogram signals.Article Cytotoxic and Cytostatic Effects of Targeting mTOR and Hedgehog Pathways in Acute Myeloid Leukemia(Istanbul Univ, 2022-12-29) Cicek, Enes; Kucuktas, Fulya Mina; Yenigul, Munevver; Akcok, Emel Basak GencerObjectives: Acute myeloid leukemia (AML) is a highly aggressive heterogeneous hematopoietic malignancy characterized by a rapid and abnormal proliferation of immature myeloid leukemia cells in the bone marrow and peripheral blood. Aberrant alterations in signal transduction pathways are strongly associated with the progression of AML. This study aimed to investigate cell viability and the cell cycle in AML cells by targeting the Hedgehog and mTOR signaling pathways with rapamycin and GANT61. Materials and Method: The antiproliferative effect of rapamycin and GANT61 was assessed by the MTT cell viability assay in two AML cell lines: CMK and MOLM-13. The effect of the inhibitors on cell-cycle distribution was determined using propidium iodide staining and measured with flow cytometry. Results: Rapamycin, an mTOR inhibitor, and GANT61, a Gli-1 inhibitor, decreased the cell proliferation of CMK and MOLM-13 cells. The IC20 values, which is the drug concentration that inhibits cell growth by 20%, were combined and administered to the cells. The results show the drugs to have a combinatorial inhibitory effect on CMK cells but not on MOLM-13 cells. In addition, the combination of drugs arrested the cells during the G0/G1 phase. Conclusion: This study suggests a novel combination therapy approach for AML via mTOR and Hedgehog signaling pathway inhibition using rapamycin and GANT61, respectively. It also suggest further studies be performed to reveal the mechanism of action.Article Citation - Scopus: 1Correlation of PAPP-A Values With Maternal Characteristics, Biochemical and Ultrasonographic Markers of Pregnancy(Marmara Univ, Fac Medicine, 2021-01-29) Kaymakcalan, Hande; Uzut, Ommu Gulsum; Harkonen, Juho; Bakir Gungor, Burcu; Bakir-gungor, Burcu; Söylemez, Ümmü GülsümObjective: Our aim is to investigate whether there is a correlation of pregnancy-associated plasma protein A (PAPP-A) values with other variables in pregnancy and maternal characteristics. Materials and Methods: We retrospectively analyzed the relation between the PAPP-A levels, demographics, biochemical and ultrasonographic markers of the first trimester screening of 11,842 pregnant women seen at a tertiary hospital between November 2002 and November 2008. Results: A significant difference between PAPP-A values of the diabetic and non-diabetic pregnant women were observed (p=0.0005, Mann-Whitney U test). In terms of weight, crown-rump length, Beta-hCG values, significant differences were observed between low and medium level PAPP-A subgroups and between low and high level PAPP-A subgroups. PAPP-A levels were found to differ significantly between the pregnant women of Caucasian origin and other racial origins. Conclusions: Pregnant women with different ethnic and medical backgrounds have different PAPP-A values and other markers of the aneuploidy screening. 'lb make patient specific risk predictions, understanding these interactions and differences is important. Future studies are needed to understand the pathopyhsiology behind these differences.Article Apatinib Sensitizes Human Breast Cancer Cells Against Navitoclax and Venetoclax Despite Up-Regulated Bcl-2 and Mcl-1 Gene Expressions(Kare Publ, 2021) Kavakcioglu Yardimci, Berna; Ozgun Acar, Ozden; Semiz, Asli; Sen, Alaattin; Acar, Ozden Ozgun; Yardımcı, Berna KavakcıoğluOBJECTIVE Defects in apoptotic cell death which restrict the success of conventional cytotoxic therapies have pivotal roles in a number of pathological conditions including cancer. However, a novel drug class targeting pro-survival Bcl-2 protein family members has been developed with the understanding of the structures and interactions of Bcl-2 proteins. Within this new class, Bcl-2/Bcl-xL inhibitor Navitoclax and Bcl-2 specific inhibitor Venetoclax have been shown to demonstrate strong anticancer activities on several types of cancers. But their low affinity to other anti-apoptotic proteins limits their clinical usage. Here, we investigated the cytotoxic and apoptotic effects of Navitoclax/Venetoclax and their combinations with specific tyrosine kinase inhibitor Apatinib on estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cell lines. METHODS MTT assay was used for the evaluation of the inhibition of cancer cell proliferation. ELISA test and Quantitative real-time PCR assay was performed to determine the role of caspase-3, Bak, Bax, Bcl-2, Bcl-xL and Mcl-1 proteins in the inhibition of cell proliferation triggered by the tested agents. RESULTS We found that aggressive MDA-MB-231 cell line was more sensitive to all tested agents. Apatinib significantly enhanced Navitoclax/Venetoclax mediated inhibition of cell viability in both cancer cell lines despite up-regulation in the expression levels of Bcl-2 and Mcl-1 genes. We further demonstrated significant Bak/Bax and caspase-3 expression in less aggressive MCF-7 cells. CONCLUSION Our findings have impacts on Navitoclax/Venetoclax plus Apatinib based therapy for breast adenocarcinoma. On the other hand, further studies should be conducted to elucidate the mechanisms underlying synergistic effects of Navitoclax/Venetoclax plus Apatinib combinations.Article Citation - Scopus: 1Glucosylceramide Synthase is a Novel Biomarker of Midostaurin-Induced Cytotoxicity in Non-Mutant FLT3 Positive Acute Myeloid Leukemia Cells(Istanbul University Press, 2021-12-03) Şahin, Hande Nur; Adan, AysunObjective: Glucosylceramide (GC) synthesized by glucosylce-ramide synthase (GCS) favors cell survival and proliferation in many cancers. However, it’s role in Fms-like tyrosine kinase 3 (FLT3) non-mutant Acute Myeloid Leukemia (AML) pathogenesis is not clarified. Midostaurin, a multi-kinase inhibitor, clinically benefits FLT3-mutated AML, however, its clinical efficacy is under-estimat-ed in FLT3 non-mutant AML. This study aimed to investigate the efficacy of combination of midostaurin with GCS inhibitor in FLT3 AML cell carrying wild-type FLT3 and the underlying molecular mechanisms. Material and Method: Cytotoxic and cytostatic effects of mido-staurin, PDMP (GCS inhibitor) alone and in combination on THP1 cells were determined by MTT assay and flow cytometric propidi-um iodide (PI) staining, respectively. Calcusyn software was used to calculate combination indexes (CIs). GCS expression was checked by western blot. Results: Midostaurin downregulated GCS. Simultaneous inhibition of FLT3 and GCS resulted in suppression of cell proliferation as compared to untreated control. Combinations showed synergistic cytotoxic effects (CI<1). Co-treatments increased cell cycle population at G2/M phase. Conclusion: Inhibition of GCS enhances the efficacy of midostau-rin in FLT3 non-mutant AML, which could be a novel therapeutic approach to increase midostaurin’s limited usage in the clinic after detailed mechanistic studies. © 2023 Elsevier B.V., All rights reserved.