Fen Edebiyat Fakültesi / Faculty of Letters and Sciences

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    The Comparison of Differentially Expressed microRNAs in Bag-1 Deficient and Wild Type MCF-7 Breast Cancer Cells by Small RNA Sequencing
    (TUBITAK Scientific & Technical Research Council Turkey, 2022) KILBAŞ, PELİN ÖZFİLİZ; Alkurt, Gizem; Çoker Gürkan, Ajda; DİNLER DOĞANAY, GİZEM; ARISAN, ELİF DAMLA; YERLİKAYA, PINAR OBAKAN
    The multifunctional BAG-1 (Bcl-2 athanogene-1) protein promotes breast cancer survival through direct or indirect interaction partners. The number of the interacting partners determines its cellular role in different conditions. As well as interaction partner variability, the amount of BAG-1 protein in the cells could cause dramatic alterations. According to previous studies, while the transient silencing of Bag-1 enhanced drug-induced apoptosis, deletion of BAG-1 could induce stemness properties and Akt-mediated actin remodeling in MCF-7 breast cancer cells. Considering the heterogeneity of breast cancer and the variability of BAG-1-mediated cell response, it has become essential to determine microRNA (miRNA) functions in breast cancer depending on Bag-1 expression level. This study aims to compare microRNA expression levels in wt and Bag-1 knockout (KO) MCF-7 breast cancer cells. hsa-miR-429 was selected as a potential miRNA in BAG-1KO MCF-7 cells because of the downregulation both in bioinformatics and validation qRT-PCR assay. According to predicted mRNA targets and functional enrichment analysis the ten hub proteins that are phosphatidylinositol4,5-biphosphate 3-kinase catalytic subunit alpha (PIK3CA), kinase insert domain receptor (KDR), GRB2 associated binding protein 1 (GAB1), Rac family small GTPase1 (RAC1), vascular endothelial growth factor A (VEGFA), Cbl proto-oncogene (CBL), syndecan 2 (SDC2), phospholipase C gamma 1 (PLCG1), E1A binding protein p300 (EP300), and CRK like proto-oncogene, adaptor protein (CRKL) were identified as targets of hsa-miR-429. The functional enrichment analysis showed that the most significant proteins were enriched in PI3K/Akt, focal adhesion, cytoskeleton regulation, proteoglycans in cancer, and Ras signaling pathways. It was determined that hsa-miR-429 targeted these pathways in Bag-1 deficient conditions and could be used as a potential therapeutic target in future studies.
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    CRISPR/Cas9-Mediated Bag-1 Knockout Increased Mesenchymal Characteristics of MCF-7 Cells Via Akt Hyperactivation-Mediated Actin Cytoskeleton Remodeling
    (Public Library of Science, 2022) KILBAŞ, PELİN ÖZFİLİZ; Can, Nisan Denizce; Kızılboğa, Tuğba; Ezberci, Fikret; Doğanay, Hamdi Levent; Doğanay, Gizem Dinler; ARISAN, ELİF DAMLA
    Bag-1 protein is a crucial target in cancer to increase the survival and proliferation of cells. The Bag-1 expression is significantly upregulated in primary and metastatic cancer patients compared to normal breast tissue. Overexpression of Bag-1 decreases the efficiency of conventional chemotherapeutic drugs, whereas Bag-1 silencing enhances the apoptotic efficiency of therapeutics, mostly in hormone-positive breast cancer subtypes. In this study, we generated stable Bag-1 knockout (KO) MCF-7 breast cancer cells to monitor stress-mediated cellular alterations in comparison to wild type (wt) and Bag-1 overexpressing (Bag-1 OE) MCF-7 cells. Validation and characterization studies of Bag-1 KO cells showed different cellular morphology with hyperactive Akt signaling, which caused stress-mediated actin reorganization, focal adhesion decrease and led to mesenchymal characteristics in MCF-7 cells. A potent Akt inhibitor, MK-2206, suppressed mesenchymal transition in Bag-1 KO cells. Similar results were obtained following the recovery of Bag-1 isoforms (Bag-1S, M, or L) in Bag-1 KO cells. The findings of this study emphasized that Bag-1 is a mediator of actin-mediated cytoskeleton organization through regulating Akt activation. © 2022 Kilbas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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    Minimal Generators of Annihilators of Even Neat Elements in the Exterior Algebra
    (Scientific Technical Research Council Turkey-TUBITAK, 2022) ESİN, SONGÜL
    This paper deals with an exterior algebra of a vector space whose base field is of positive characteristic. In this work, a minimal set of generators forming the annihilator of even neat elements of such an exterior algebra is exhibited. The annihilator of some special type of even neat elements is determined to prove the conjecture established in [3]. Moreover, a vector space basis for the annihilators under consideration is calculated.
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    The Protective Impact of Growth Hormone Against Rotenone-Induced Apoptotic Cell Death via Acting on Endoplasmic Reticulum Stress and Autophagy Axis
    (Scientific and Technological Research Council Turkey, 2023) RENCÜZOĞULLARI, ÖZGE; TORNACI, SELAY; ÇELİK, YAĞMUR; TAŞ, NAYAT NAROT; YERLİKAYA, PINAR OBAKAN; Arısan, Elif Damla; Gürkan, Ajda Çoker
    Human growth hormone (GH) is crucial modulator of cellular metabolisms, including cell proliferation and organ development, by stimulating insulin-like growth factor-1 (IGF-1), which has various functions such as cell proliferation, tissue growth, survival, or neuroprotection. Therefore, GH is implicated as a critical player in the cell and can enhance neurogenesis and provide neuroprotection during the treatment of neurological diseases such as Parkinson's disease (PD). In this study, the neuroprotective role of GH was investigated in rotenone-induced PD models for the first time. Both SH-SY5Y and SK-N-AS neuroblastoma cells were exposed to rotenone to mimic PD pathogenesis as stated in previous studies. Our data demonstrated that overexpression of GH led to the resistance of the SH-SY5Y and SK-N-AS cell lines to rotenone treatment. The levels of ER stress markers, CHOP, PERK, XBP-1, and ATF6, were higher in wt cells than GH+ SH-SY5Y cells. However, the level of autophagy markers LC3 increased and the levels of reactive oxygen species (ROS) decreased with the overexpression of GH. Furthermore, while rotenone significantly increased the SubG1 population in the cell cycle of SH-SY5Y wt cells, there was a minor alteration in GH+ cell population. Concomitantly, the levels of the proapoptotic marker, cleaved-PARP, and positive staining of Annexin V in SH-SY5Y wt cells were higher after rotenone treatment. Together, these results revealed that overexpression of GH enhanced the autophagy response by triggering the ER stress of SH-SY5Y cells to rotenone exposure and showed a neuroprotective effect in vitro PD models.
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    A Randomized-Controlled Trial of EMDR Flash Technique on Traumatic Symptoms, Depression, Anxiety, Stress, and Life of Quality With Individuals Who Have Experienced a Traffic Accident
    (Frontiers Media SA, 2022) Yaşar, Alişan Burak; Konuk, Emre; KAVAKCI, ÖNDER; Uygun, Ersin; Gündoğmuş, İbrahim; Taygar, Afra Selma; Uludağ, Esra
    The Flash Technique of Eye Movement Desensitization and Reprocessing (EMDR) is widely recognized for its effectiveness in reducing the effects of emotional responses associated with traumatic memories. Using a randomized-controlled trial methodology, this study attempts to establish the efficacy of the EMDR Flash Technique. This study's sample includes volunteers who were involved in traffic accidents and were given the randomized EMDR Flash Technique and Improving Mental Health Training for Primary Care Residents (mhGAP) Stress management module. The participants were given a socio-demographic data form, the Depression-Anxiety-Stress 21 scale (DASS-21), the Impact of Event Scale-Revised (IES-R), and the WHOQOL Quality of Life scale. Participants were evaluated using measurements taken before and after the application, as well as a one-month follow-up. The mean age of the participants was 36.20 (11.41) years and 82.1% (n = 32) were female. The DASS-21 Anxiety (eta(2) = 0.085), IES-R Intrusion (eta(2) = 0.101), Avoidance (eta(2) = 0.124), Total (eta(2) = 0.147), and WHOQOL-BREF Psychological (eta(2) = 0.106) score improvements of the EMDR Flash Technique group were shown to be statistically significant when compared to the mhGAP group. However, no statistically significant difference in the DASS-21 Depression, Stress, Impact of Event Scale-Revised Hyperarousal WHOQOL-BREF General Health, Physical, Social Relationships, and Environment component scores was reported between the two groups. The present study's findings clearly demonstrate that the EMDR Flash technique, when applied to persons involved in traffic accidents, is successful in improving anxiety, intrusion, avoidance, total traumatic stress, and mental quality of life symptoms for at least 1 month. We believe that these findings will improve the reliability and applicability of the EMDR Flash Technique, which was tested for the first time in a clinical randomized-controlled trial (RCT).
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    Structure, Vibrational Spectra, and Cryogenic MatrixPhotochemistry of 6-Bromopyridine-2-Carbaldehyde: From the Single Molecule of the Compound to the Neat Crystalline Material
    (MDPI, 2023) Brito, Anna Luiza B.; Lopes, Susy; ILDIZ, GÜLCE ÖĞRÜÇ; Fausto, Rui
    6-Bromopyridine-2-carbaldehyde (abbreviated as BPCA) is used both as a building block in supramolecular chemistry and as a ligand for transition metal catalysts and luminescent complexes. In this study, the structure and vibrational spectra of BPCA were investigated in both the room temperature neat crystalline phase and for the compound isolated in cryogenic Ar, Kr and Xe matrices. The experimental studies were complemented by quantum chemical DFT(B3LYP)/6-311++G(d,p) calculations. For the crystalline compound, infrared and Raman spectra were obtained and interpreted. Comparison of the obtained infrared spectrum of the crystal with those obtained for the isolated molecules of BPCA in the studied cryomatrices helped to conclude that the intermolecular interactions in the crystal do not significantly perturb the intramolecular vibrational potential. Structural analysis further supports the existence of weak coupling between the intermolecular interactions and the structure of the constituting molecular units in crystalline state. The intermolecular interactions in the BPCA crystal were also evaluated by means of Hirshfeld analysis, which revealed that the most important interactions are weak and of the (HN)-N- horizontal ellipsis , (HO)-O- horizontal ellipsis , (HH)-H- horizontal ellipsis , (HBr)-Br- horizontal ellipsis and (BrBr)-Br- horizontal ellipsis types. The conformer of BPCA present in the crystal was found to correspond to the most stable form of the isolated molecule (trans), which bears stabilizing C-(HO)-O- horizontal ellipsis =C and C(=O)(HN)-N- horizontal ellipsis interactions. This conformer was shown to be the single conformer present in the as-deposited cryogenic matrices prepared from the room temperature gaseous compound. Broadband UV irradiation of matrix-isolated BPCA (lambda >= 235 nm) resulted in the conversion of the trans conformer into the higher-energy cis conformer, where repulsive C-(HH)-H- horizontal ellipsis -C(=O) and C=(OLPLPN)-N- horizontal ellipsis (where LP designates a lone electron pair) interactions are present, and decarbonylation of the compound with formation of 2-bromopyridine (plus CO). The decarbonylation reaction was found to be more efficient in the more polarizable Xe matrix, indicating stabilization of the radicals initially formed upon breaking of the C-C(HO) and C-H (aldehyde) bonds in this medium, and testifying the occurrence of the decarbonylation reaction with involvement of radical species. TD-DFT calculations were used to access the nature of the excited states associated with the observed UV-induced reactions. As a whole, this study provides fundamental data to understand the physicochemical behavior of the compound, bridging the properties of the isolated molecule to those of the neat crystalline com-pound. Such information is of fundamental importance for the understanding of the role of BPCA in supramolecular chemistry and to potentiate its applications in synthesis and as a ligand for transition metal catalysts and luminescent complexes.