Araştırma Çıktıları | WoS | Scopus | TR-Dizin | PubMed
Permanent URI for this communityhttps://hdl.handle.net/20.500.14719/1741
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Publication Metadata only In vitro Chondrogenic Induction Promotes the Expression Level of IL-10 via the TGF-β/SMAD and Canonical Wnt/β-catenin Signaling Pathways in Exosomes Secreted by Human Adipose Tissue-derived Mesenchymal Stem Cells (vol 82, pg 3741, 2024)(HUMANA PRESS INC, 2025) Sevimli, Tugba Semerci; Inan, Ulukan; Mantar, Dilara; Guler, Kubra; Ahmadova, Zarifa; Gulec, Kadri; Topal, Ahmet Emin; Eskisehir Osmangazi University; Eskisehir Osmangazi University; Erzurum Technical University; Bahcesehir University; Ruprecht Karls University Heidelberg; Anadolu UniversityPublication Metadata only Niraparib Demonstrates Therapeutic Potential in Multiple Sclerosis through Inhibition of IL-17A Receptor Interaction and Promotion of Remyelination(AMER CHEMICAL SOC, 2025) Orhan, Muge Didem; Oktay, Lalehan; Cinar, Ayse Irem; Yesil, Aybek Kagan; Tunc, Huseyin; Eren, Fatih; Durdagi, Serdar; Avsar, Timucin; Bahcesehir University; Bahcesehir University; Bahcesehir University; Bahcesehir University; Bahcesehir University; University of Bonn; Bahcesehir University; Marmara University; Recep Tayyip Erdogan University; Marmara University; Bahcesehir UniversityIL-17A is a pro-inflammatory cytokine that significantly contributes to the pathogenesis of autoimmune diseases, including multiple sclerosis (MS). Previous studies have suggested that PARP-1 inhibitors can modulate IL-17A-mediated inflammation, prompting the investigation of Niraparib, an FDA-approved PARP-1 inhibitor, as a potential therapeutic agent for MS. In this study, we hypothesized that Niraparib could disrupt the interaction between IL-17A and its receptor, IL-17RA. To evaluate this, we employed a binary quantitative structure-activity relationship (QSAR) model against anti-inflammatory diseases, which indicated Niraparib's potential efficacy against MS. In silico analyses were conducted to identify key interaction sites and critical amino acid residues involved in the IL-17A/IL-17RA binding. Molecular docking simulations demonstrated Niraparib's capability to interfere with these interactions. It has demonstrated significant efficacy in inhibiting the interaction between the IL-17A ligand and its receptor via reporter assay. In vivo assessments were performed using a cuprizone-induced demyelination model. Immune profiling revealed modulation of various T cell subsets and B cells, while cytokine analysis indicated a shift in inflammatory responses. Histological evaluations confirmed reduced demyelination and enhanced remyelination in affected brain regions. These findings support Niraparib's potential as a therapeutic option for MS, warranting further exploration of its mechanisms and clinical relevance.Publication Metadata only The Values of Potentially Toxic Elements (PTEs) in Prescription and Non-prescription Dry Cat and Dog Diets in Turkey(SPRINGERNATURE, 2025) Bilgic, Bengu; Tarhan, Duygu; Ates, Fatma; Dhamo, Gerta; Koenhemsi, Lora; Dokuzeylul, Banu; Or, M. Erman; Istanbul University - Cerrahpasa; Bahcesehir University; Bezmialem Vakif UniversityProlonged exposure to high doses of certain toxic metals can cause cytotoxic, genotoxic, and carcinogenic effects in cats and dogs. This study aimed to determine the levels of potentially toxic elements in various prescription and non-prescription commercial diets for cats and dogs. A total of 84 dry cat diets and 152 dry dog diets were analyzed. Prescription cat diets were subgrouped into digestive (n = 24) and urinary (n = 20), while prescription dog diets were categorized as digestive (n = 28), urinary (n = 16), hypoallergenic (n = 20), and joint (n = 12). Additionally, non-prescription diets from various brands and flavors were included for dogs (n = 76) and cats (n = 40). Chromium (Cr), arsenic (As), boron (B), aluminum (Al), and cobalt (Co) concentrations were determined using inductively coupled plasma with optical emission spectrometry (ICP OES) (Thermo iCAP 6000 series) at appropriate wavelengths. No significant differences were found in mean As, B, and Co levels between total dog and cat diets (p > 0.05). However, mean Cr and Al levels were significantly higher in dog diets compared to cat diets (p < 0.001). Among cat diets, no significant differences were observed for Cr, As, B, Al, or Co (p > 0.05). In non-prescription dog diets, mean Cr was significantly higher than in urinary group (p < 0.001). Mean Al levels in digestive, joint, and non-prescription groups were higher than in urinary group (p < 0.001). The levels of Cr, As, B, Al, and Co in both prescription and non-prescription diets were below the maximum tolerable limits established by FEDIAF, AAFCO, and FDA, indicating no risk of diet-related toxicosis in cats and dogs.Publication Metadata only The Impact of Liraglutide, a GLP-1 Receptor Agonist, on High Glucose-Induced Inflammation, Apoptosis, Oxidative Stress, and NLRP3 Signaling(HUMANA PRESS INC, 2025) Gokce, Mustafa; Civelek, Dilek Ozturk; Vidin Sen, Aylin; Guler, Eray Metin; Civelek, Erkan; Dogan, Birsel Sonmez Uydes; Yildirim, F. Ilkay Alp; Istanbul University; Bezmialem Vakif University; Bahcesehir University; University of Health Sciences Turkey; University of Health Sciences TurkeyDiabetes-related endothelial dysfunction, alteration in cell signaling, increased oxidative stress and activation of pro-inflammatory processes are the main causes of diabetes-related vascular complications. Glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) play a crucial role in regulating glucose homeostasis, insulin secretion, and reducing inflammation. GLP-1R agonists have been explored for their potential in mitigating diabetes-related vascular dysfunction. The NOD-like receptor protein 3 (NLRP3) inflammasome, a key protein complex in immune response, activates caspase-1 and promotes proinflammatory cytokine secretion. High glucose levels activate NLRP3 in macrophages via reactive oxygen species and mitochondrial dysfunction. This study aims to investigate the effects of GLP-1 receptor agonist, Liraglutide, on cell proliferation, inflammation, oxidative stress and NLRP3-related signaling pathways in human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cell (HCAEC) cultures. HUVEC and HCAEC were incubated with Liraglutide (10 and 100 nM, 48 h) either in normoglycemic (5.5 mM) or hyperglycemic (25 mM) condition. Cell proliferation, oxidative stress, mRNA and protein expressions of ASC, caspase-1, NLRP3 which are. components of NLRP3 inflammasome, were determined. Our results showed that, Liraglutide significantly reduced hyperglycemia-induced oxidative stress, mRNA and protein expressions of NLRP3 inflammasome and proinflammatory cytokine levels, as well as cell membrane damage in HUVEC and HCAEC. Our results indicate that Liraglutide may have the potential on preventing hyperglycemia-induced cellular damage by reducing inflammation and immune response activation both in human venous and arterial endothelial cells.Publication Metadata only Synthesis, characterization, cytotoxic activity, and molecular docking of 3,4-diaminobenzophenone-CuhNFs and its major components-based nanoflowers(TAYLOR & FRANCIS INC, 2024) Somturk-Yilmaz, Burcu; Altiparmak, Aysegul; Turkmenoglu, Burcin; Akkoc, Senem; Erciyes University; Erzincan Binali Yildirim University; Suleyman Demirel University; Bahcesehir UniversityIn this study, organic-inorganic hybrid nanoflower (hNFs) synthesis was realized using 3,4-diaminobenzophenone and Cu(II) metal ions as organic and inorganic ingredients, respectively. The characterization of the synthesized hNFs was carried out using SEM, EDX, FT-IR, XRD, and elemental mapping. The cytotoxic effect of hNFs was investigated against A549 (lung) and MCF-7 (breast) cancer cell lines. Interactions of 3,4-diaminobenzophenone were also investigated via molecular docking studies at the binding site of the human estrogen receptor (PDB ID:3ERT) and epidermal growth factor receptor tyrosine kinase (PDB ID: 1M17). Physicochemical and pharmacokinetic parameters for ligands that could be potential anticancer drug candidates were determined by ADME prediction calculations from in silico approaches. In vitro results showed an increase in cell death when the synthesized hybrid nanoflowers were applied against both cell lines, depending on the concentrations tested. Additionally, it was determined that the synthesized nanoflower was more effective on the MCF-7 cell line.Publication Metadata only Solvent-mediated dynamics of diphtheria toxin and NAD interaction(TAYLOR & FRANCIS INC, 2025) Dinc, Bircan; Ustunsoy, Recep; Ertas, Tahsin; Bektas, Muhammet; Bahcesehir University; Istanbul Atlas University; Istanbul University; Adiyaman UniversityThe interaction between diphtheria toxin (DT) and nicotinamide adenine dinucleotide (NAD) is central to DT's enzymatic activity, which involves ADP-ribosylation of eukaryotic elongation factors. This study aims to elucidate how solvent environments influence the thermodynamic and structural properties of the DT-NAD interaction. Using Raman Spectroscopy, and complementary techniques, we analyzed two different DTs, and by using Differential Scanning Calorimetry (DSC) we try to understand DT-NAD binding under varying solvent conditions, including distilled water, phosphate-buffered saline (PBS), and different concentrations of dimethyl sulfoxide (DMSO). Our findings reveal that solvent composition significantly alters the thermal stability and binding dynamics of DT. Notably, DSC data showed distinct shifts in melting temperatures (Tm) and enthalpy changes (Delta H) across solvents, with 100% DMSO disrupting the interaction and causing structural denaturation. This study underscores the critical role of solvent selection in modulating protein-ligand interactions and offers valuable insights into the molecular dynamics of DT. These findings have broad implications for biochemical research and therapeutic applications involving protein stability in diverse environments.Publication Metadata only Molecular modeling and cytotoxic activity studies of oxirane-2-carboxylate derivatives(TAYLOR & FRANCIS INC, 2024) Muhammed, Muhammed Tilahun; Er, Mustafa; Akkoc, Senem; Suleyman Demirel University; Suleyman Demirel University; Bahcesehir UniversityIn this study, five 3-aryloxirane-2-carboxylate derivatives were prepared, and the antiproliferative activities of molecules were screened in lung and colon cancer cell lines. The results showed that molecules had antiproliferative activity on cancerous cells with IC50 values under 100 mu M. Furthermore, all of the molecules were found to have a much higher cytotoxic effect than cisplatin in colon cancer cells. The interactions of the relatively active compounds to the crucial enzyme in cancer cell proliferation, cyclin-dependent kinase 1 (CDK1), were investigated using molecular docking. The stability of the resulting CDK1-compound complexes procured from the docking was also assessed through molecular dynamics (MD) simulations. Then, the binding affinity of compounds 2-3a and 2-3c to the target enzyme was computed by MMPBSA. The molecular docking study demonstrated that the two most active compounds could bind to the enzyme. The binding potential of 2-3a is anticipated to be higher as it had one more conventional hydrogen bond and a slightly lower binding energy than compound 2-3c. The MD simulation study exhibited that the two compounds formed a stable complex with the enzyme. On the other hand, the MMPBSA energy computation implicated a slightly higher binding affinity for compound 2-3c toward the enzyme. Furthermore, electrical and frontier molecular orbital analysis of all of the tested compounds was conducted by density functional theory (DFT) studies. Compound 2-3a is anticipated to be the most chemically stable as it gave the highest energy gap value in the DFT analysis.Publication Metadata only Computational Analysis of CC2D1A Missense Mutations: Insight into Protein Structure and Interaction Dynamics(AMER CHEMICAL SOC, 2025) Abuelrub, Anwar; Erol, Ismail; Bingol, Nurdeniz Nalbant; Sag, Sebnem Ozemri; Temel, Sehime G.; Durdagi, Serdar; Bahcesehir University; Bahcesehir University; Bahcesehir University; Bahcesehir University; Uludag University; Uludag University; Uludag University; Bahcesehir UniversityCC2D1A is implicated in a range of conditions, including autism spectrum disorder, intellectual disability, seizures, autosomal recessive nonsyndromic intellectual disability, heterotaxy, and ciliary dysfunction. In order to understand the molecular mechanisms underlying these conditions, we focused on the structural and dynamic activity consequences of mutations within this gene. In this study, whole exome sequencing identified the c.1552G > A (GLU518LYS) missense mutation in the CC2D1A in an 18-year-old male, linking it to intellectual disability and autism. In addition to the GLU518LYS mutation, we conducted a comprehensive analysis of other predefined missense mutations (i.e., PRO192LEU, GLN506ARG, PRO532LEU, GLY781VAL, and GLY781GLU) found within the CC2D1A. Utilizing all-atom molecular dynamics (MD) simulations and neighborhood interaction analyses, we delve into the impact of these mutations on protein structure and function at an atomic level, aiming to shed light on their contribution to the pathogenesis of related diseases. The results suggest that GLU518LYS, GLY781VAL, and GLY781GLU mutations did not significantly alter overall global protein structure compared to the wild type, while PRO192LEU, GLN506ARG, and PRO532LEU exhibited slightly higher protein root-mean-square deviation (RMSD) values, which may indicate potential impacts on whole protein stability. Moreover, neighborhood interaction analysis indicated that ASP85 emerges as a unique interaction partner specifically associated with the GLU518LYS mutation, whereas LYS75, which interacts with the ASP85 in the mutated form, is absent in the wild type. This alteration signifies a crucial reconfiguration in the local interaction network at the site of the mutation.
