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    Changes in arginine metabolism in advanced Alzheimer?s patients: Experimental and theoretical analyses
    (Elsevier, 2023) Saria, Ismail; Ersan, Serpil; Ozmen, Esma; Ayan, Durmus; Ersan, Erdal; Berisha, Avni; Kayae, Savas
    Limited data obtained in studies conducted in recent years suggest that changes in arginine metabolism may be associated with the pathogenesis of Alzheimer's disease (AD). However, the underlying mecha-nisms of this pathway's effects on the disease are not clear and there are conflicting data. Therefore, in this study, we aimed to determine the levels of L-arginine and its important metabolites and enzymes involved in the pathway in advanced AD patients to examine the change in L-arginine metabolism as inclusively as possible.Serum and plasma samples were obtained from 51 patients diagnosed with advanced AD and 30 volunteer controls. Arginase, Ornithine Decarboxylase (ODC), Arginine Decarboxylase (ADC), and Agmati-nase levels in serum samples were determined by enzyme-linked immunosorbent assay (ELISA) and, L- arginine, Ornithine and nitric oxide (NO) levels were determined by colorimetric method. Agmatine levels were measured by high-performance liquid chromatography in the plasma samples of the study groups. Furthermore, in silico molecular docking studies were performed to get preliminary knowledge about the binding interactions of the agmatine with various targets such as AChE, butyrylcholinesterase (BuChE), BACE-1 and tau protein kinase 1 which play an important role in AD pathogenesis.Agmatine and L-arginine levels were found to be significantly lower in the patient group than in the control group. Milder but not statistically significant reductions were observed in all other param-eters we measured involved in L-arginine metabolism. Furthermore, NO levels were found to be sig-nificantly lower in men with advanced AD patients than in control men. It has been analyzed that agmatine ligand interacts effectively with the studied proteins which play an important role in AD pathogenesis; these interactions were significant and, based on the docking score, occurred in the fol-lowing order: butyrylcholinesterase (PDB id: 1P0I) > Human acetylcholinesterase > Human tau-protein kinase I.In conclusion, in advanced AD patients, the activity of the L-arginine pathway decreased in gen-eral, especially agmatine formation, and this may be due to the decrease in L-arginine levels. Therefore, arginine de novo synthesis may be decreased in advanced AD patients. Furthermore, according to the MolDock binding score, agmatine ligand has a high binding affinity for proteins involved in AD manage-ment and/or pathogenesis. Therefore, agmatine may play a role in the pathogenesis of AD by inhibit-ing the activity of these proteins. However, additional comprehensive studies are needed to clarify these thoughts.(c) 2023 Elsevier B.V. All rights reserved.
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    PEGylated Titanium Dioxide Nanoparticle-bound Doxorubicin and Paclitaxel Drugs Affect Prostate Cancer Cells and Alter the Expression of DUSP Family Genes
    (Bentham Science Publ Ltd, 2025) Tuncbilek, Zuhal; Cakmak, Nese Keklikcioglu; Tas, Ayca; Ayan, Durmus; Silig, Yavuz
    Background PC is among the cancer types with high incidence and mortality. New and effective strategies are being sought for the treatment of deadly cancers, such as PC. In this context, the use of nanocarrier systems containing titanium dioxide can improve treatment outcomes and increase the effectiveness of anticancer drugs.Objective This study aimed to evaluate the cytotoxic activity of doxorubicin (DOX) and paclitaxel (PTX) drugs on the prostate cancer (PC) cell line by attaching them to pegylated titanium dioxide nanoparticles and to examine their effect on the expression levels of dual-specificity phosphatase (DUSP) genes.Methods Free DOX and PTX drugs, DOX and PTX compounds bound to the pegylated titanium dioxide system were applied to DU-145 cells, a PC cell line, under in vitro conditions, and MTT analysis was performed. Additionally, the IC50 values of these compounds were analyzed. In addition, the expression levels of DUSP1, DUSP2, DUSP4, DUSP6, and DUSP10 genes were measured using RT-PCR. Additionally, bioinformatics and molecular docking analyses were performed on DUSP proteins.Results The cytotoxic activity of PTX compound bound to PEGylated TiO2 was found to be higher than that of DOX compound bound to PEGylated TiO2. Additionally, when the expression levels were compared to the control group, the expression levels of DUSPs were found to be lower in the drugs of the drug carrier systems.Conclusion Accordingly, it was predicted that the pegylated titanium dioxide nano-based carrier could be effective in PC.