Person: BİNGÖL ÖZAKPINAR, ÖZLEM
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BİNGÖL ÖZAKPINAR
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ÖZLEM
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Publication Metadata only Investigation of the protective effect of gel incorporating Eugenia jambolana leaf extract on 5-fluorouracil-induced oral mucositis: an animal study(2022-08-01) BİNGÖL ÖZAKPINAR, ÖZLEM; ARICIOĞLU, FEYZA; AKSOY N., Sen E., Sukmasari S., BİNGÖL ÖZAKPINAR Ö., ARICIOĞLU F., YÜCEL Y. Y., Dumlu M. R., Doolaanea A. A., AbdulRahman M. N., OLGAÇ N. V., et al.Purpose The study aimed to evaluate the possible preventive effect of two concentrations (3 and 5% w/w) of Eugenia jambolana (EJ) extract against 5-FU-induced mucositis. Method Sixteen adult rats were separated into four groups: two control and two preventive groups. Animals in Groups 1, 2, and 3 were injected intraperitoneally with 60 mg/kg/day of 5-FU on Day 1 followed by 150 mg/kg/day on Day 5. The rats in Group 4 (negative control) were given physiological saline at the same times and doses. Furthermore, on the fifth day of the study, the cheek and sublingual mucosa were irritated by external superficial scratches using the tip of an 18-G needle, followed by the application 15 mu L of 20% acetic acid, after which 3 and 5% EJ w/w gels were applied topically for animals in Groups 2 and 3, respectively. Results The weight and the mucositis scores were recorded. Antioxidant and anti-inflammatory markers and biochemical tests were analyzed. Significant differences were found between the study groups in weight loss, clinical mucositis scores, mortality rates, and antioxidant and anti-inflammatory parameters. Conclusion The preventive effect of 3% gel was significant, with no mortality rate, making it an option for preventive strategies.Publication Open Access Novel 1,2,4-triazoles derived from Ibuprofen: synthesis and in vitro evaluation of their mPGES-1 inhibitory and antiproliferative activity(2022-11-01) BİNGÖL ÖZAKPINAR, ÖZLEM; KULABAŞ, NECLA; TATAR, ESRA; KÜÇÜKGÜZEL, İLKAY; Bulbul B., Ding K., Zhan C., Ciftci G., YELEKÇİ K., Gurboga M., BİNGÖL ÖZAKPINAR Ö., Aydemir E., Baybag D., ŞAHİN F., et al.Some novel triazole-bearing ketone and oxime derivatives were synthesized from Ibuprofen. In vitro cytotoxic activities of all synthesized molecules against five cancer lines (human breast cancer MCF-7, human lung cancer A549, human prostate cancer PC-3, human cervix cancer HeLa, and human chronic myelogenous leukemia K562 cell lines) were evaluated by MTT assay. In addition, mouse embryonic fibroblast cells (NIH/3T3) were also evaluated to determine the selectivity. Compounds 18, 36, and 45 were found to be the most cytotoxic, and their IC50 values were in the range of 17.46-68.76 mu M, against the tested cancer cells. According to the results, compounds 7 and 13 demonstrated good anti-inflammatory activity against the microsomal enzyme prostaglandin E2 synthase-1 (mPGES-1) enzyme at IC50 values of 13.6 and 4.95 mu M. The low cytotoxicity and non-mutagenity of these compounds were found interesting. Also, these compounds significantly prevented tube formation in angiogenesis studies. In conclusion, the anti-inflammatory and angiogenesis inhibitory activities of these compounds without toxicity suggested that they may be promising agents in anti-inflammatory treatment and they may be supportive agents for the cancer treatment.Publication Metadata only Morphological and biochemical investigation of the healing effects of exercise on high fat diet induced kidney and bladder damage(2022-10-01) BİNGÖL ÖZAKPINAR, ÖZLEM; ERCAN, FERİHA; Açıkel Elmas M., Bingöl Özakpınar Ö., Kolgazi M., Şener G., Ercan F.Objective: The aim of this study was to evaluate the ameliorative effects of swimming training on renal and bladder damage caused by a highfatdiet (HFD) using morphological and biochemical measurements.Methods: Sprague Dawley rats were fed either standard chow (CONT, 6% fat) or HFD (45% fat) for 18 weeks, these rats were divided into twosubgroups at the last 6 weeks of the experiment. The exercise groups (CONT+EXC, HFD+EXC) were trained daily swimming sessions (1 h per dayfor 5 days/week) during the last 6 weeks. Kidney and bladder samples were prepared for light and electron microscopic examination at the endof experiment. Malondialdehyde, glutathione, interleukin-6, and tumor necrosis factor-α were measured by biochemically.Results: Regular morphology of the renal cortex and bladder mucosa was observed in the CONT and CONT +EXC groups. Degenerated renalcorpuscles and proximal tubules in the kidney and degenerated urothelium with leaky tight junctions and mast cell increase in the bladdermucosa were observed in the HFD group. Ameliorated renal cortex and bladder mucosa were observed in the HFD+EXC group. In addition,malondialdehyde, glutathione, interleukin-6, and tumor necrosis factor-α levels were also consistent with the histological findings.Conclusion: HFD-induced renal and bladder damage may be related to increased oxidative damage. It was observed that the histologicaldamage and altered oxidative stress parameters could be reversed by swimming training, and it is thought that moderate swimming exercisemay play a role in regulating oxidative stress.Publication Open Access Synthesis, in vitro and in silico studies on novel 3-aryloxymethyl-5-[(2-oxo-2-arylethyl)sulfanyl]-1,2,4-triazoles and their oxime derivatives as potent inhibitors of mPGES-1(2023-01-01) KULABAŞ, NECLA; TATAR, ESRA; KÜÇÜKGÜZEL, İLKAY; BİNGÖL ÖZAKPINAR, ÖZLEM; Erensoy G., Ding K., Zhan C., Çiftçi G., Yelekçi K., Duracık M., Bingöl Özakpınar Ö., Aydemir E., Yılmaz Z. N. , Şahin F., et al.Human microsomal prostaglandin E synthase (mPGES)-1 is a glutathione-dependent membrane-bound enzyme which is involved in the terminal stage of prostaglandin E2 (PGE2) synthesis. It has been well reported as a key target for the discovery of new anti-inflammatory and anti-cancer drugs. Specific inhibitors of mPGES-1 are anticipated to selectively restrain the generation of PGE2 induced by the inflammatory stimuli, without obstructing of the regular biosynthesis of other homeostatic prostanoids. Therefore, the design of mPGES-1 inhibitors can represent a better choice to take control of PGE2 associated diseases, compared with conventional non-steroidal anti-inflammatory drugs and cyclooxygenase (COX) inhibitors, which are known for their serious side effects. Although there is an intensive effort for the identification of mPGES-1 inhibitors, none of the unveiled molecules so far have reached the clinical market. Therefore, the development of novel mPGES-1 inhibitors with proper drug-like properties is still an unmet medical need. As a continuation of our research for the identification of new chemotypes which might inhibit this enzyme, we now report the design and synthesis of 3-aryloxymethyl-5-[(2-oxo2-arylethyl)sulfanyl]-1,2,4-triazoles and their oxime derivatives as inhibitors of human mPGES-1. All synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR (for compounds 12, 14, 15, 26, 27), HMBC (for compounds 6, 7, 8, 16, 19, 23, 28), and MS data. Twenty-four target compounds 7–30 were screened for their mPGES-1/COX-2 inhibitory activities as well as their cytotoxicity. Of these compounds, 20 and 24 showed potent mPGES-1 inhibition by IC50 values of 0.224±0.070 μM and 1.08±0.35 μM, respectively. These two compounds have also been observed to inhibit angiogenesis in matrigel tube formation assay with no toxicity toward HUVEC cells. In silico studies were also held to understand inhibition mechanisms of the most active compounds using molecular docking, molecular dynamics calculations and ADMET predictions.Publication Open Access Determination of the Plasma Levels of Growth Arrest Specific 6 in Colon Cancer Patients(2023-06-01) BİNGÖL ÖZAKPINAR, ÖZLEM; Tezcan S., İzzettin F., Özakpınar Ö., Attaallah V., Yumuk P., Uras F.Objective: Growth arrest-specific 6 (GAS 6) has a role in cell proliferation and was detected in different cancer types. The aim of this study was to evaluate the plasma GAS 6 levels in colon cancer patients. Methods: This was a prospective study and conducted in a research and training hospital in Turkey. Thirty-three healthy volunteers were enrolled in the control group, thirty-three colon cancer patients who were diagnosed with colon cancer for the first time. Sociodemographic characteristics of participants were recorded. Blood samples of the control group were taken once a time. Patients’ blood samples were taken before and one month after surgery. Results: There were no statistically significant differences between the sociodemographic characteristics of the two groups. The mean plasma GAS 6 levels in control were significantly higher than that of colon cancer patients (p<.0001). There is a statistically significant increase in GAS 6 values after surgery (p<.0001). Conclusion: It was observed that plasma GAS 6 levels of the patients were lower than the control group and were elevated after surgery. We think that our study will contribute to the literature in addition to studies showing that GAS 6 levels may be associated with survival and prognosis in different cancer types. Keywords: Colon cancer, growth arrest-specific 6, patient, plasma levelsPublication Open Access Determination of in vitro genotoxic effects of pine resin and Aronia melonacarpa on prostate and breast cancer cell lines by using comet assay technique(2022-11-05) BECEREN, AYFER; BİNGÖL ÖZAKPINAR, ÖZLEM; Beceren A., Bingöl Özakpınar Ö.The cancer burden continues to grow globally and places extraordinary physical, emotional and financial pressures on individuals, communities and health systems. Studies continue without slowing down to establish new targets and treatment strategies for cancer, which still remains an important problem in the clinic and does not have a definitive cure yet. Natural compounds obtained from different sources stand out as new therapeutic agents in cancer due to their more effective and selective properties and lower toxic effects. Thus, we aimed to clarify the possible anticancer effects of Aronia melonacarpa on human breast cancer cell line (MCF-7) and pine resinon prostate cancer cell line (PC-3).Our target plants, pine resin and Aronia melonacarpa were collected from different locations from Aegean and Blacksea region of Türkiye, respectively. The genotoxic effect of the methanol extracts was determined by alkaline comet assay. 100, 200 and 400 μg/ml extract concentrations, which have the high cytotoxic effect, were used. The examined groups were control negative, plant extract and positive control groups. Comparison of the anti-cancer and genotoxic effect of different concentrations on MCF-7 of Aronia melonacarpa and pine resin on PC-3 was evaluated by SPSS 20.0 program. Comet assay results showed that the both Aronia melonacarpa and pine resin extract exhibited genotoxic effects against MCF-7 and PC-3 cell lines in a dose-dependent manner by increasing the mean percentage of DNA damage after 24hrs of treatment (p<0.001).However, the observed toxicity of this two plant extract needs to be confirmed by additional studies. Based on our results, further examination of the potential anticancer properties of two plant species and the identification of the active ingredients of these extracts is warranted. This preliminary study is important for future studies and we anticipate that it will contribute to the development of a new drug in cancer treatment.Publication Open Access Carbon nanofiber—sodium alginate composite aerogels loaded with vitamin D: The cytotoxic and apoptotic effects on colon cancer cells(2023-07-01) BİNGÖL ÖZAKPINAR, ÖZLEM; Bingol Ozakpinar Ö., Dastan H., Gurboga M., Sayin F. S., Ozsavci D., Caliskan Salihi E.Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide. A substantial body of literature supports the crucial role of vitamin D (VD) in the etiology, progression, prognosis, and treatment of cancer. Recent clinical studies have found an inverse correlation between CRC incidence and serum VD levels. However, the low water solubility of VD and its anticarcinogenic activity at supraphysiological plasma levels, which causes hypercalcemia, required carrier systems. Carbon-based nanomaterials are excellent eco-friendly candidates, with exceptional chemical resistance, efficient mechanical properties, and negligible weight. Furthermore, composite aerogels manufactured from these nanomaterials have gained interest due to their extensive surface areas and porous structures, which make them suitable for delivering drugs. Our research aimed to study the development of composite aerogels loaded with VD by utilizing carbon nanofibers (CNFs) in an aerogel matrix provided to colon cancer cells. For this purpose, Aero1 as a drug delivery system was first prepared and characterized using XRD, FTIR, and SEM methods. Biochemical methods were employed to evaluate the antiproliferative, apoptotic, and anti-migratory effects on colon cancer cells. FTIR and XRD measurements confirmed the production of aerogels. SEM analysis revealed that aerogels have a non-uniform surface. The findings showed that aerogels can effectively deliver VD to the colon cancer cells, while also inhibiting cancer cell proliferation and migration. This research suggests that the Aero1 drug delivery system could be a valuable tool in the fight against colon cancer and other health issues.Publication Open Access Effects of apocynin against monosodium glutamate-induced oxidative damage in rat kidney(2022-01-01) BİNGÖL ÖZAKPINAR, ÖZLEM; AÇIKEL ELMAS M., Ozgun G., Ozakpinar Ö., Guleken Z., ARBAK S.Objective: Monosodium glutamate causes oxidative stress that affects a variety of organ systems, along with the kidney. The aim of this study was to evaluate the protective role of apocynin in kidney degeneration caused by monosodium glutamate using biochemical and histological methods. Materials and Methods: Sprague-Dawley rats (n=32) were used for this study. Four experimental groups were randomly formed: the Control (Cont), Apocynin (APO), Monosodium Glutamate (MSG), and MSG+APO groups. The MSG group received oral administration of MSG (120 mg/kg) for 28 days. The MSG+APO and APO groups received apocynin (25 mg/kg) during the last 5 days of the experiment. Kidney tissue was processed for biochemical and microscopic analyses. Biochemical methods were used to examine the levels of malondialdehyde (MDA) and glutathione (GSH) in the tissue and the activities of myeloperoxidase (MPO) and superoxide dismutase (SOD). Light and electron microscopy were also used to examine for histological changes in kidney tissue. Results: The MSG group was compared with the Cont and APO groups; it was found that MDA and MPO levels were elevated, whereas GSH and SOD activity were decreased. In contrast to the Cont and APO groups, the MSG+APO group showed higher GSH levels, lower MPO activities and increased MDA levels. While apocynin treatment improved renal tissue histology, MSG-induction led to deterioration of renal morphology. Conclusion: The study revealed that MSG increased oxidative damage and renal tissue degeneration. Moreover, apocynin reduced renal damage by modulating the ratio of antioxidants to oxidants.Publication Open Access Effects of SPARC and possible receptors on colon cancer cell line(2023-06-01) BİNGÖL ÖZAKPINAR, ÖZLEM; Mısırlı D., Bingöl Özakpınar Ö., Şekerler T., Aru B., Demirel G. Y., Tunoğlu S., Ozsavci D.Objective: The aim of this study was to observe the apoptotic/cytotoxic effects of exogenous SPARC on colon cancer cell line HT-29, then to investigate the function of stabilin-1 and integrin αvβ3, which are possible receptors for SPARC in colon cancer cells and to determine the quantitation of their receptor numbers. Methods: Appropriate doses of exogenous SPARC and it’s inhibitor, cilengitide added to HT-29 cell line were determined by xCELLigence RealTime Cell Analysis system, SPARC-mediated caspase 3 expressions were measured. Using the RT-PCR system, gene expression levels of SPARC, stabilin-1 and integrin αvβ3 receptors (silenced/nonsilenced with cilengitide) were detected then the numbers of receptors per cell were quantitated by flow cytometry. Results: IC50 value of SPARC was determined as 4.57 µg/mL and IC50 value of cilengitide was determined as 50 nM. 5 µg/mL exogenous SPARC caused increased apoptosis in the HT-29 line. Significant increase in gene expression of integrin αvβ3 receptor was observed in the group incubated with 5 µg/mL SPARC, contrarily, the addition of cilengitide decreased gene expressions. The integrin αvβ3 receptor numbers increased approximately 2-fold with SPARC compared to the control. No significant changes were observed in the gene expression and receptor numbers of stabilin-1. Conclusion: Exogenous SPARC was shown to reduce proliferation and induce apoptosis in colon cancer cells. Integrin αvβ3 is thought to be the possible receptor mediating SPARC in colon cancer cells. Quantification of surface receptors per cell, which we think we have done first, can be considered as a marker in the follow-up of anticancer treatments.Publication Metadata only Synthesis, molecular modeling, anti-cancer and COX-1/2 inhibitory activities of novel thiazolidinones containing benzothiazole core(2024-01-01) KULABAŞ, NECLA; BİNGÖL ÖZAKPINAR, ÖZLEM; KÜÇÜKGÜZEL, İLKAY; KULABAŞ N., Guven C. T., Duracik M., BİNGÖL ÖZAKPINAR Ö., Kucukguzel I.In this study, new 1,3-thiazolidin-4-one derivatives containing arylmethylene groups in the 5-position were obtained from 6-(trifluoromethoxy)-1,3-benzo-thiazol-2-amine (riluzole). Synthesized compounds were characterized by spectral data and elemental analysis. In vitro, cytotoxic activities of the synthesized molecules were evaluated against the human lung cancer (A549) and human prostate cancer (PC-3) cell lines. Compounds were also tested on mouse embryonic fibroblast cells (NIH/3T3) to determine selectivity. Ten target compounds 3-12 were also screened for their COX-1 and COX-2 inhibitory activities. Of these compounds, 4 showed the highest COX-2 inhibition at 10 μM. Molecular docking calculations were performed to understand the binding interactions of compounds with COX-1 and COX-2 proteins. In silico studies of the tested compounds represented important binding modes that may be responsible for their anti-cancer activity via selective inhibition of the COX-2 enzyme. ADMET predictions were conducted to assess the drug-like properties of the novel compounds.