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    Alternations in interleukin-1? and nuclear factor kappa beta activity (NF-kB) in rat liver due to the co-exposure of Cadmium and Arsenic: Protective role of curcumin
    (Elsevier, 2023) Cengiz, Mustafa; Gur, Bahri; Sezer, Canan Vejselova; Cengiz, Betuel Peker; Gur, Fatma; Bayrakdar, Alpaslan; Ayhanci, Adnan
    Cadmium chloride (Cd) and sodium arsenite (As) are two prominent examples of non-biodegradable substances that accumulate in ecosystems, pose a serious risk to human health and are not biodegradable. Although the toxicity caused by individual use of Cd and As is known, the toxicity of combined use (Cd+As) to mammals is poorly understood. The present study aims to investigate the hepatoprotective effect of curcumin (CUR), a naturally occurring bioactive component isolated from the root stem of Curcuma longa Linn., in preventing liver damage caused by a Cd+As mixture. A group of 30 Sprague-Dawley rats were subjected to intraperitoneal administration of Cd+As (0.44 mg/kg+5.55 mg/kg i.p.) and CUR (100 or 200 mg/kg) for a period of 14 days. The experimental results showed that the animals treated with Cd+As exhibited changes in liver biochemical parameters, inflammation and oxidative stress at the end of the experiment. Administration of CUR significantly reduced inflammation, oxidative stress and lipid peroxidation in the Cd+As plus CUR groups compared to the Cd+As group. Furthermore, histological examination of the liver tissue showed that administration of CUR had led to a significant reduction in the liver damage observed in the Cd+As group. The present study provides scientific evidence for the protective effects of CUR against lipid peroxidation, inflammation, oxidative stress and liver damage induced by Cd+As in the liver of rats. The results of our in vivo experiments were confirmed by those of our molecular modelling studies, which showed that CUR can enhance the diminished antioxidant capacity caused by Cd+As.
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    Alternations in nuclear factor kappa beta activity (NF-kB) in the rat brain due to long-term use of atomoxetine for treating ADHD: In vivo and in silico studies
    (Academic Press Inc Elsevier Science, 2021) Gur, Fatma; Cengiz, Mustafa; Gur, Bahri
    Attention Deficit Hyperactivity Disorder (ADHD) is the most common psychiatric disorder reported particularly in children. Long-term use of antipsychotic drugs used in the treatment of ADHD has been shown to exert toxic effects on the brain. However, not enough research has been carried out on the neurotoxic effects of these drugs on the brain tissue. Atomoxetine (ATX) is the most widely used antipsychotic drug that has gained approval for ADHD treatment. The present study aims to determine the damage induced by long-term use of three different doses of ATX in the brain tissue of experimental rats. 24 rats were divided into Control group (0.5 mL saline), Group 2 (0.5 mg/mL ATX), Group 3 (1.0 mg/mL ATX), and Group 4 (2.0 mg/mL ATX), each group having 6 members. Their brain tissues were taken for stereological, histological, and nuclear factor kappa-B (NF-kB) protein expression analysis. ATX was determined to have caused a few alterations in the brain tissue, such as disruption in the endothelial epithelium of capillaries, a couple of large astrocyte nuclei, and mitotic astrocytes. Moreover, a significant difference was observed in Group 4 compared to Control Group in terms of astrocyte counts in the brain sections. As for Groups 3 and 4, there were differences in terms of oligodendrocyte counts in the incisions cultivated from the brain tissues of the animals. On the other hand, NF-kB positive astrocytes of Groups 3 and 4 differed significantly from those of Control and Group 2. The results of molecular dockings of the present study are in line with the in-vivo results. Therefore, it was concluded that the higher the dose of ATX was, the more damage the brain tissue sustained. (c) 2020 Elsevier Inc. All rights reserved.
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    Biogenic Synthesized Bare and Boron-Doped Copper Oxide Nanoparticles from Thymbra spicat ssp. spicata: In Silico and In Vitro Studies
    (Springer/Plenum Publishers, 2024) Cengiz, Mustafa; Baytar, Orhan; Sahin, Omer; Kutlu, Hatice Mehtap; Ayhanci, Adnan; Sezer, Canan Vejselova; Gur, Bahri
    The biosynthesis technique and biogenic copper oxide nanoparticles (CuONPs) are commonly used in a variety of applications including medicine. Bare (CuONPs) and boron-doped copper oxide nanoparticles (B/CuONPs) were produced via the green synthesis method using Thymbra spicat ssp. spicata due to their nontoxic, coast effective and facile properties. The nanoparticles were characterized by using X-ray diffraction, fourier transform infrared, UV-visible spectroscopy, transmission electron microscopy, and Scanning electron microscopy with Energy Dispersive X-ray spectroscopy analysis. The produced nanoparticles performed antibacterial activity against human pathogenic organisms of both Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria by using the microdilution technique. B/CuONPs showed high activity on Gram-positive bacteria, while CuONPs showed high activity on Gram-negative bacteria. The cytotoxic effect synthesized CuONPs and B/CuONPs were evaluated against human hepatocarcinoma (HepG2) cells by using MTT, Annexin-V, Caspase-3/7, and confocal microscopic evaluations. Moreover, the in-silico results have shown for the first time that the active role in the Caspase-3/7 step of the triggered apoptosis pathway is due to the activity of Caspase-7. The results indicated that the biogenic CuONPs and B/CuONPs exerted potential anti-cancer and anti-bacterial activity on HepG2 and S. aureus and E. coli that imply to remarkable biological activity. The green synthesized nanoparticles have clearly proposed promising biogenic nanomaterials for biomedical treatments.
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    Cilomilast, a PDE4 Inhibitor, Suppresses CD4++ and CD8++ T Cell Proliferation in the Thymus and Spleen of Rats: Mechanism of Glutathione Reduction
    (Univ Agriculture, Fac Veterinary Science, 2024) Gezer, Arzu; Baygutalp, Nurcan Kilic; Cengiz, Mustafa; Gur, Bahri; Ozkaraca, Mustafa
    Cilomilast is an oral phosphodiesterase-4 (PDE4) inhibitor recommended for treating COPD. However, its side effects and low therapeutic index remain an unresolved problem in clinical practice. This study aimed to evaluate the effects of cilomilast on the spleen and thymus tissues of rats. For experimental studies, 24 male Sprague-Dawley rats weighing 200-220g were randomly divided into three experimental groups: The procedures were repeated for 7 days for the control, sham, and cilomilast groups. Blood and tissue samples were collected from the rats under anesthesia on day 8 of the experiment for analysis. p<0.05 at a 95% confidence level was considered to indicate statistical significance. Severe tissue damage in the thymus and spleen was observed in the cilomilast group. In the thymus and spleen tissues of the control and sham groups, CD4+ + and CD8+ + cell immunopositivity were more intense, while the density of these cells was significantly reduced in the cilomilast group. In addition, glutathione (GSH) levels decreased, and nitric oxide levels increased in both tissues of the cilomilast group. However, in-silico results showed that the decrease in GSH levels is due to the enzymes gamma-glutamylcysteine synthase and glutathione synthase, which act as catalysts in the two-step GSH biosynthesis mechanism. Suppression of the immune system targets both harmful and compensatory pathways so that both beneficial mechanisms and pathological changes can be blocked. To eliminate these cilomilast-induced side effects and enable more effective clinical application, it may be recommended to develop formulations such as lipid-based inhaled forms or nano-drug delivery systems including dendrimers, reverse micelle systems, polymeric or lipid-based carriers as an alternative to conventional application.
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    Decreased Na+/K+ pump activity in the erythrocyte membrane due to malondialdehyde in rheumatoid arthritis: an in vivo and in silico study
    (Canadian Science Publishing, 2022) Ogul, Yasemin; Gur, Fatma; Gur, Bahri; Cengiz, Mustafa; Sari, Refik Ali; Kiziltunc, Ahmet
    Apart from demonstrating the interaction behavior of malondialdehyde (MDA) with Na+/K+-ATPase using in silico, the current study aims to investigate the effect of rheumatoid arthritis-related oxidative stress on Na+/K+-ATPase activity that is present in the erythrocyte cell membrane, which is rich in proteins vulnerable to damage from MDA and other free radicals. The target population of this study consists of 28 rheumatoid arthritis patients and 20 healthy volunteers whose MDA levels and Na+/K+-ATPase activity were determined. It was shown that MDA levels of rheumatoid arthritis patients increased (p < 0.001) and their Na+/K+-ATPase activity noticeably decreased when compared to those of healthy individuals. Also, according to this in silico modeling, MDA decreased Na+/K+-ATPase activity in line with the correlation analyses. Consequently, while elevated levels of MDA in the rheumatoid arthritis group were suggestive of oxidative stress, a decreased Na+/K+-ATPase-activity led us to speculate that the cellular membrane had sustained injury. Therefore, our results could be useful in explaining how MDA affects Na+/K+-ATPase activity in the interior of a specific molecular pathway.
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    Evaluation of oxidant and intracellular anti-oxidant activity in rheumatoid arthritis patients: In vivo and in silico studies
    (Elsevier, 2021) Ogul, Yasemin; Gur, Fatma; Cengiz, Mustafa; Gur, Bahri; Sari, Refik Ali; Kiziltunc, Ahmet
    Rheumatoid Arthritis (RA) is the most prevalent cause of the systematic inflammatory arthritis that destroys the joints. While the pathogenesis of RA remains to be clarified, the imbalance in the oxidant and anti-oxidant defense system plays a crucial role. This study aims to evaluate oxidant and anti-oxidant levels of RA patients and their impacts on the activity of the disease via in silico studies. 28 patients who had not previously received any treatment for RA and 20 healthy controls were included. Their oxidative stress markers, antioxidant markers, and inflammatory factors were investigated via in silico studies. Compared to the Control Group, serum CRP levels, MDA levels, and XO activities were higher in RA Group. Cu/ZnSOD and GPx activities decreased while CAT activities remained unchanged. Besides, there was a positive correlation between MDA-serum CRP levels but a negative correlation between MDA levels-Cu/ZnSOD activities. Furthermore, we observed a negative correlation between CRP levels and Cu/ZnSOD activities. Based on these results, it was concluded that oxidative stress had increased, the defense system had weakened, and ROS production had increased. Finally, our study results with SOD and CAT activity were confirmed by molecular docking studies.
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    Green biosynthesis of selenium and zinc oxide nanoparticles using whole plant extract of Rheum ribes: Characterization, anticancer, and antimicrobial activity
    (Elsevier, 2024) Cengiz, Mustafa; Gur, Bahri; Sezer, Canan Vejselova; Baytar, Orhan; Sahin, Omer; Ayhanci, Adnan; Kutlu, Hatice Mehtap
    Scientists are becoming interested in nanomedicine as a potential new approach to cancer detection and therapy in the twenty-first century. This paper presents the first investigation of the anticancer and antibacterial properties of selenium (Se) and zinc oxide (ZnO) nanoparticles obtained from Rheum ribes plant extract by a green synthesis method. Morphological and spectroscopic characterization of the synthesized nanoparticles was performed using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible (UV-Vis), which is a useful and straightforward technique for the preliminary characterisation of nanoparticles, dynamic light scattering (DLS) and X-ray diffraction (XRD) analysis. The size of the nanoparticles was determined to be 33 nm for Se-Nps and 32.8 nm for ZnO-Nps. The anticancer activity was assessed by the use of MTT, annexin V, caspase 3/7, and confocal microscopy imaging techniques. ZnO-Nps and Se-Nps were found to have significant antibacterial activity with MIC values for Escherichia coli (0.7 mu g/mL, 0.63 mu g/mL), and Staphylococcus aureus (1.56 mu g/mL and 1.1 mu g/mL). Furthermore, the antibacterial activity and the mechanism of action of the nanoparticles on E. coli and S. aureus bacteria were evaluated using microdilution and disc diffusion methods. In addition, the antiproliferative properties of ZnO-Np and Se-Np significantly suppressed the growth of A549 cells during a 24-hour incubation period (IC50 18.89 mu g/mL ve 23.88 mu g/mL). The results of the anti-cancer and anti-bacterial activity of the present study suggest that certain concentrations of Se-Np and ZnO-Np could be useful for pharmacological applications in cancer treatment and for coating surfaces for sterilization of medical equipment in healthcare settings, particularly in intensive care units.
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    The role of ceranib-2 and its nanoform on the decrease of telomerase levels in human non-small cell cancer
    (Springer, 2024) Cengiz, Mustafa; Sezer, Canan Vejselova; Gur, Bahri; Bayrakdar, Alpaslan; Izgordu, Hueseyin; Alanyali, Filiz; Ozic, Cem
    BackgroundCeranib-2, an acid ceramidase (AC) inhibitor, can inhibit cancer cell proliferation and tumor development. However, poor water solubility and low cellular bioavailability limit its efficacy in cancer treatment.Methods and resultsThis study aimed to investigate the cell death induced by ceranib-2 and its solid lipid nanoformulation (ceranib-2-SLN) produced by the hot homogenization technique and the synergistic relationship between ceramide and telomerase in vitro and in silico. Furthermore, this study proved the possible mechanism of ceranib-2-induced AC inhibition by in silico studies. The effective cytotoxic concentrations of ceranib-2, telomerase level, and changes in ceramide levels were measured by MTT colorimetric cytotoxicity assay, ELISA, and LC/MS/MS methods, respectively. TEM results showed that ceranib-2-SLN was 13-fold smaller than the size of ceranib-2. Ceranib-2 and ceranib-2-SLN had IC50 concentrations of 31.62 (+/- 2.1) and 27.69 (+/- 1.75) mu M in A549, and 48.79 (+/- 1.56) and 67.98 (+/- 2.33) in Beas-2B cells. These compounds simultaneously increased ceramide levels and decreased telomerase levels in A549 cells. Ceranib-2 increased telomerase levels while decreasing ceramide levels in Beas-2B cells. It was shown how the synergistic impact of ceranib-2-induced ceramide production and ceramide-induced telomerase level reduction on cytotoxicity in A549 cells.ConclusionsCeranib-2-SLN was discovered to be more cytotoxic on cancer cells than ceranib-2, suggesting that it could be a promising option for the development of a new anti-cancer agent.
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    Therapeutic role of boron on acrylamide-induced nephrotoxicity, cardiotoxicity, neurotoxicity, and testicular toxicity in rats: Effects on Nrf2/Keap-1 signaling pathway and oxidative stress
    (Elsevier Gmbh, 2023) Gur, Fatma; Cengiz, Mustafa; Gur, Bahri; Cengiz, Osman; Saricicek, Osman; Ayhanci, Adnan
    Background: Acrylamide (ACR) is a heat-related carcinogen used in cooking some foods as well as in other thermal treatments. The present study aims to investigate the possible protective effect of boron (BA) against ACR-induced toxicity of kidney, brain, heart, testis, and bladder tissues in rats. Methods: Rats have been divided into 5 equal groups: Control (saline), ACR (38.27 mg/kg), BA (20 mg/kg), BA+ ACR (10 mg/kg + ACR), and BA+ ACR (20 mg/kg BA+ACR). Kidney tissue from rats was collected and the levels of malondialdehyde (MDA), glutathione (GSH), and the activity of superoxide dismutase (SOD) were measured. In addition, the kidneys of these animals, as well as the brain, heart, testes, and bladder tissues were examined for possible histological changes. Total Nrf2 and Keap-1 protein expression in kidney, heart, and testis tissues was examined by immunohistochemistry. Results: While significant increases in MDA levels were observed in the kidneys of rats receiving ACR alone, significant decreases in antioxidant markers (SOD and GSH) were observed. Besides, kidney, brain, heart, and testicular tissues were analyzed and damage was observed in the groups receiving ACR. However, no significant histologic changes were noted in the bladder tissue. Both dosages of BA in combination with ACR improved the changes in ACR-induced antioxidant tissue parameters. Despite the fact that MDA levels were decreased with these two dosages, histological structural abnormalities were found to be greatly improved. Conclusion: Our results show that BA has a strong protective effect on ACR-induced multi-organ toxicity. The study results show that BA could be a potential element to reduce ACR toxicity to which we are often exposed.