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Öğe Adjuvant effects of chemotherapeutics and Metformin on MFE-319 endometrial carcinoma cell line(Editura Acad Romane, 2020) Aydemir, Isil; Uluer, Elgin Turkoz; Korkmaz, Oya; Tuglu, Mehmet Ibrahim; Inan, SevincWe aimed to investigate the cytotoxicity of Metformin, Cisplatin, and Paclitaxel on MFE-319 endometrial carcinoma cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and immunocytochemistry assays. Half maximal inhibitory concentration (IC50) doses of three drugs alone and in the dual combinations were applied to the cells. Immunocytochemical method was performed for the cell survival and for phosphatidylinositol 3-kinase (PI3K), phosphorylated extracellular regulated kinases (pErk)-1/2, Akt-1, phosphorylated Akt (pAkt)-1/2/3 cell growth markers and angiogenic vascular endothelial growth factor (VEGF). Immunoreactivities were evaluated using H-score and analyzed using the one-way analysis of variance (ANOVA) test for statistics. It was found that these drugs caused a decrease in the immunoreactivities of these markers. Particularly, dual combination of Paclitaxel and Cisplatin decreased the immunoreactivities of PI3K, pErk-1/2, Akt-1, and pAkt-1/2/3. Cisplatin and Paclitaxel were more effective than Metformin; on the other hand, Metformin has been shown to enhance the efficacy of these two drugs. In vitro or in vivo further studies are needed to investigate the efficacy of these three drugs via PI3K/Akt signal pathway.Öğe Apoptotic and cytotoxic effect of origanum minutiflorum on NB2A neuroblastoma cells(University of Ankara, 2020) Sari, Ismail; Donmez Arat, Gonca; Ozkan, Oktay; Aydemir, Isil; Ozbey, Caner; Tu?lu, M. IbrahimObjective: The aim of the present study is to investigate the cytotoxic and apoptotic effects of oregano oil from Origanum minutiflorum, which is an endemic medicinal plant in Turkey, on NB2a neuroblastoma cells. Material and Method: Cell proliferation, apoptosis, and expression of inducible and endothelial nitric oxide synthase have been determined by MTT, TUNEL, and immunohistochemistry, respectively. Result and Discussion: The cell viability was significantly decreased gradually in NB2a cells when the concentrations of both oregano oil and doxorubicin were increased. IC50doses were found to be10.75 ?l/ml for oregano oil and 5?M for doxorubicin. Furthermore, expression of inducible and endothelial nitric oxide synthase, also the number of apoptotic cells was significantly enhanced in NB2a cells after treatment with oregano oil and doxorubicin. There was a remarkable increase in inducible and endothelial nitric oxide synthase expression levels and in the number of apoptotic cells by the dual application of these agents. In addition, oregano oil enhanced the apoptotic effect of doxorubicin. In conclusion, our results indicated that oregano oil of O. minutiflorum has a cytotoxic and apoptotic effect on NB2a cells and these effects may be related to its enhancing effects on inducible and endothelial nitric oxide synthase levels. © 2020 University of Ankara. All rights reserved.Öğe Effects of ?-lactalbumin and sulindac on primary and metastatic human colon cancer cell lines(Walter De Gruyter Gmbh, 2019) Aydemir, Isil; Vatansever, Seda; Ozbilgin, KemalBackground: HAMLET (human alpha-lactalbumin made lethal to tumor cells) and sulindac are active ingredients which are used in the treatment of cancers. Under both in vivo and in vitro conditions, HAMLET binds to the surface of tumor cells and enters the cells. Sulindac is one of nonsteroidal anti-inflammatory drugs. It inhibits the growth of tumor cells by inducing the apoptosis. In our study, we aimed to investigate effects of alpha-lactalbumin and sulindac on COLO-320 primary and COLO-741 metastatic human colon carcinoma cell lines via mitochondrial apoptotic pathway by indirect immunocytochemistry and TUNEL assays. Materials and methods: The effects of alpha-lactalbumin and sulindac were assessed by using MTT assay at 24, 48 and 72 h and apoptosis markers caspase-3, caspase-9 and cytochrome-c were detected using immunocytochemistry and TUNEL methods. Results: It was appeared that alpha-lactalbumin and sulindac may triggger mechanisms of apoptosis in both primary and metastatic colon carcinoma cell lines and the primary colon carcinoma cell line was affected more than the metastatic cells. Conclusion: It is proposed that alpha-lactalbumin and sulindac can be used in cancer treatments and future in vivo experiments.Öğe Effects of oxidative stress and apoptosis on vascularity and viability of perforator flaps(Taylor & Francis Ltd, 2021) Bali, Ulas; Aydemir, Isil; Kececi, Yavuz; Yoleri, Levent; Tuglu, Mehmet IbrahimWe investigated lateral thoracic and posterior thigh perforator flaps for viability, vascularization, perfusion and apoptosis in a rat model. Wistar albino rats were divided into six groups: lateral thoracic artery perforator flap (LTPF) sham, 3 x 2 cm(2) LTPF, 3 x 6 cm(2) LTPF, posterior thigh perforator flap (PTPF) sham, 3 x 2 cm(2) PTPF, and 3 x 6 cm(2) PTPF. Flap viability was determined on postoperative days 1 and 7. On day 7, flaps were photographed and their viability was measured using two-dimensional planimeter paper. Tissue samples were harvested for examination by histology and immunohistochemistry. Viability differences were statistically significant. Epithelial thickness, vascularity and number of fibroblasts were reduced in the 3 x 6 cm(2) groups. Neovascularization and apoptosis based on molecular tests were not significantly different among groups. Flap size and location are important factors for closure of surgical or traumatic defects. We suggest that for clinical application, wound complications will occur less frequently with perforators that nourish large areas of flaps.Öğe Histological and immunohistochemical studies of the proximal caecum and caecal tonsils of quail (Coturnix coturnix japonica)(Wiley, 2019) Yildiz, Mustafa; Aydemir, Isil; Kum, Sadiye; Eren, UlkerThe proximal caecum in quails consists of lymphoid and non-lymphoid structures. The caecal tonsils in the proximal part of the caecum are units of gut-associated lymphoid tissue in poultry. This study aimed to examine the histological characteristics of the proximal caecum, as well as compositions of dendritic cells (DCs) and antigen-presenting cells (APCs) in the caecal tonsil of quails. Tissue sections were stained with Crossman's triple, periodic acid-Schiff, Gordon and Sweet's silver, Congo red and methyl green-pyronin dyes, as well as immunohistochemically by the streptavidin-biotin-peroxidase complex method. Caecal lymphoid tissue was located in the lamina propria and submucosa. Germinative centres were observed within the lymphoid tissue. Reticular fibres were mainly distributed in the border area of the germinal centre with only a few fibres scattered in the centre. Plasma cells were observed in the subepithelial region and germinal centres. Eosinophil granulocytes were prevalent in the lymphoid tissue. Additionally, CD83-immunoreactive DCs and MHC class II immunoreactive APCs were present in the subepithelial area and diffuse lymphoid tissue. While DCs were seen in the germinal centres of tonsillar units, APCs were rarely present in the germinal centres, but they were noticed around the germinal centres. In conclusion, the histological structure of the proximal caecum in quails and the distributions of some immunological cells in the caecal tonsils were revealed. Therefore, the defensive role of the caecal tonsils in the digestive system may be better understood, and comparative studies may be carried out.Öğe IN VIVO HEPATOPROTECTIVE EFFECTS OF Hypericum crenulatum BOISS ON NIMESULIDE-INDUCED TOXICITY IN MICE(Parlar Scientific Publications (P S P), 2022) Ozkan, Oktay; Ozbey, Caner; Arat, Gonca Donmez; Kart, Asim; Sari, Ismail; Aydemir, IsilPlants of Hypericaceae family including many species have been used for the treatment of various dieases such as melancholia, abdominal pain, wound, tumor and oxidative stress in folk medicine. Hypericum crenulatum Boiss is a member of this family and is found throughout Bolkar mount from Meydan Yayla to San Tepe. It is an endemic herbaceous perennial plant. It is aimed to investigate in this study whether this plant specie have a hepatoprotective properties against nimesulide-induced liver injury in mice. According to the results of the study, methanolic extract of Hypericum crenulatum Boiss showed significant differences on serum ALP and liver histopathology. However, serum AST and ALT values, TAS, TOS and OSI were not altered. Hypericum crenulatum Boiss significant improvement Boiss extract at low dose provided a in nimesulide-induced acute liver toxicity. The data indicate that methanolic extract of Hypericum crenulatum Boiss is considered to be effective against liver toxicity.Öğe Inhibiting effect of oleocanthal on neuroblastoma cancer cell proliferation in culture(Taylor & Francis Ltd, 2020) Unsal, Ulkun Unlu; Mete, Mesut; Aydemir, Isil; Duransoy, Yusuf Kurtulus; Umur, Ahmet Sukru; Tuglu, Mehmet IbrahimWe investigated the potential anticancer effects of oleocanthal (OC) on neuroblastoma cells. Cells were divided into four groups: group 1, neuroblastoma cells were treated with OC; group 2, neurons that differentiated from neuroblastoma cells were treated with phosphate-buffered saline(PBS); group 3, bone marrow derived neuronal (BMDN) cells that were differentiated from bone marrow derived mesenchymal stem cells (BMSCs) were treated with OC; group 4, BMDN cells that were differentiated from BMSCs were treated with PBS. Groups 2 and 4 were control groups. The effects of OC on cell viability, oxidative stress, neurite inhibition and apoptosis at IC50 dose were investigated using MTT analysis, i-NOS and e-NOS measurement, neurotoxicity screening test (NST) and TUNEL staining, respectively. MTT analysis demonstrated that cells were significantly less viable in group 1 than in group 3. i-NOS and e-NOS staining intensity was significantly greater in group 1 than in group 3. NST revealed that OC inhibited neurite growth in both neuroblastoma and BMND cells; inhibition was significantly less in group 3 than in group 1. Significantly more TUNEL labeled cells were found in group 1 than in group 3. We found that OC prevented growth and proliferation of neuroblastoma cells in culture by increasing oxidative stress and apoptosis. We also found that the cytotoxicity of OC is negligible in BMDN cells.Öğe Inhibitory Effect of Valsartan on Pterygium Fibroblasts(Lippincott Williams & Wilkins, 2020) Kucuk, Erkut; Aydemir, Isil; Zor, Kursad Ramazan; Ozkan, OktayPurpose: Angiotensin receptor blockers (ARBs) were shown to have antifibrotic properties in ocular and systemic diseases. In this study, our aim was to investigate the effect of an angiotensin receptor blocker, valsartan, on pterygium fibroblasts and compare this effect with that of mitomycin C (MMC). Methods: Pterygium tissue samples were obtained from 3 patients during surgical excision. Primary cultured pterygium fibroblasts and L929 cell cultures were treated with different concentrations of MMC and valsartan. Results: The cell viability decreased with increasing concentrations of valsartan at 48 hours for both cell types. MMC inhibited the proliferation of both cell types at 48 hours. Both agents significantly decreased the cell migration of the 2 cell types, although it was more prominent in the MMC-treated group. Conclusions: Valsartan inhibited the proliferation and migration of pterygium fibroblasts. The known favorable safety profile of these drugs and the results of this study showing inhibitory effect on pterygium fibroblasts make valsartan a potential therapeutic agent for pterygium treatment.Öğe Investigation of distribution of GSK-3ß signal pathway by age groups in cases of ulcerative colitis(Editura Acad Romane, 2023) Ozbey, Caner; Aydemir, IsilUlcerative colitis (UC), one of the inflammatory bowel diseases, has been reported to increase in recent years. Although the exact cause is unknown, disruptions in the molecular pathways are thought to trigger UC. We aimed to examine the distributions of glycogen synthase kinase-3beta (GSK-3 ss), nuclear factor-kappa B (NF-kappa B) and wingless/int-1 (Wnt-1) in different age groups diagnosed with UC. Patients diagnosed with UC were divided into four groups according to their ages: Group 1, aged 18-30 (n=20); Group 2, aged 31-45 (n=20); Group 3, aged 46-60 (n=20); Group 4, aged 61-75 ( n=20). Tissue sections were histochemically stained to examine the parameters of epithelial cell height, length of crypt, thickness of muscularis mucosa and extent of submucosal fibrosis. The immunohistochemistry assay was performed using cell survival and for GSK-3 ss, NF-.B and Wnt-1 cell growth markers. Immunoreactivities were evaluated using H-score and analyzed using the one-way analysis of variance (ANOVA) test for statistics. It was detected a decrease in the histopathological parameters whereas the immunoreactivities of GSK-3 ss, NF-kappa B and Wnt-1 were increased with increasing age. The levels of GSK-3 ss immunoreactivity were similar in both epithelium and submucosa in all groups. NF-.B immunoreactivity was higher in submucosa of Groups 1, 2 and 3, while Wnt-1 was enhanced in Groups 1 and 3. The results of histopathology showed that the integrity of the epithelial tissue in the colon deteriorated with increasing age. The expressions of GSK-3 ss, NF-kappa B and Wnt-1 were detected in all age groups. We thought that there was a synergistic activation between these three markers. Nevertheless, studies are needed to investigate this molecular pathway.Öğe Investigation of the effects of bisphenol-A exposure on lymphoid system in prenatal stage(Sage Publications Inc, 2020) Aydemir, Isil; Ozbey, Caner; Ozkan, Oktay; Tuglu, Mehmet Ibrahim; Kum, SadiyeBisphenol-A (BPA) used in the production of plastic materials is a temperature-soluble agent. It also has a steroid hormone-like activity; therefore, it poses a danger to human health. In our study, we aimed to investigate the effects of BPA on lymph node and spleen in male rats exposed to this agent during prenatal stage. The pregnant female rats were divided into four groups: control, sham, low dose (300 mu g/kg BPA), and high dose (900 mu g/kg BPA). BPA was dissolved in 1 mL of corn oil and administered to the pregnant rats every day during pregnancy. On the 21st and 45th day after the birth, male rats' lymph node and spleen samples were taken and histopathological examination was performed. Samples were stained with hematoxylin and eosin to determine the general histological appearance, and with CD3 and CD20 immunohistochemically. The results of staining were evaluated by H-score, and statistical analysis was performed. In the samples, BPA applications were not found to cause significant tissue damage. But there was a significant decrease in the immunoreactivities of CD3 and CD20 after BPA applications in both 21st and 45th day samples. After high dose BPA administration, decreased CD3 immunoreactivity was statistically significant. It is thought that BPA does not cause histologically significant tissue damage, but it may impair organ function at cellular level. The investigation of molecules involved in organ function will be useful in revealing the mechanisms that will cause dysfunction.Öğe Neuroprotective Effects of Oleocanthal, a Compound in Virgin Olive Oil, in a Rat Model of Traumatic Brain Injury(Turkish Neurosurgical Soc, 2018) Mete, Mesut; Aydemir, Isil; Unsal, Ulkun Unlu; Collu, Fatih; Vatandas, Gokhan; Gurcu, Beyhan; Duransoy, Yusuf KurtulusAIM: To evaluate the neuroprotective effects of deocanthal OC in a rat model of traumatic brain injury (TBI). MATERIAL and METHODS: Twenty-six adult male, Wistar albino rats were used. The rats were divided into 4 groups. Group 1 was the sham group (n=5). Group 2 was the trauma group (n=5) where rats were treated with 10 mg/kg saline intraperitoneally (IP) twice a day. Groups 3 and 4, rats were treated with 10 (group 3, n=8) or 30 (group 4, n=8) mg/kg OC IP twice a day. For each group, brain samples were collected 72 hours after injury. Brain samples and blood were evaluated with histopathological and biochemical methods. RESULTS: Histopathological evaluation revealed a significant difference between Group 2 and Group 4. Biochemical findings demonstrated that the oxidative stress index was highest in Group 2 and lowest in Group 4. CONCLUSION: OC has a protective effect on neural cells after TBI. This effect is achieved by reducing oxidative stress and apoptosis.Öğe Punicic Acid Inhibits Glioblastoma Migration and Proliferation via the PI3K/AKT1/mTOR Signaling Pathway(Bentham Science Publ Ltd, 2019) Mete, Mesut; Unsal, Ulkun U.; Aydemir, Isil; Sonmez, Pinar K.; Tuglu, Mehmet, IBackground: Punicic Acid (PA) is a polyunsaturated fatty acid that accounts for approximately 70%-80% of Pomegranate Seed Oil (PSO). PA possesses strong antioxidant, anti-inflammatory, anti-atherogenic effects, and anti-tumorigenic properties. Pomegranate extracts have been shown to have anticancer activity in many studies. However, there is no evidence for the effect of PSO on T98 glioblastoma cells. Therefore, the present study was the first to investigate the mechanisms induced by PA on T98 cells, which is one of the major compounds extracted from PSO. Methods: The effects of PA on cell viability; oxidative stress; and migration, proliferation, and apoptosis at the IC50 close were studied. Results: The proliferation and migration were inhibited in the treated group compared to the non-treated group by 9.85 mu l/ml PA. The difference was statistically significant (***p<0.001). Furthermore, PA-induced apoptosis in the T98 glioblastoma cells compared to non-treated group and the difference was statistically significant (***p<0.001). Apoptosis was determined via immunocytochemistry staining of caspase-3, caspase-9 and TUNEL methods. Apoptosis was checked by flow cytometry (using caspase 3 methods) and Scanning Electron Microscopy Analysis. We also investigated the potential signaling pathway underlying this apoptotic effect. The immunocytochemical stainings of PI3K/ Akt-1/ mTOR-1 demonstrated that Akt-1 staining was increased with PA treatment similar to mTOR-1 and PI3K staining (***p<0.001). These increases were statistically significant compared to the non-treated group. Conclusion: PA exhibited exceptional abilities as an anticancer agent against GBM cells. The use of punicic acid in combination with other drugs used in the treatment of glioblastoma may increase the efficacy of the treatment. This study provided a basis for future investigation of its use in preclinical and clinical studies.Öğe The Condylar Effects of Mesenchymal Stem Cells, Low-Level Laser Therapy and Grape Seed Extract on Functional Mandibular Advancement of the Rat Mandible(Galenos Publ House, 2023) Eglenen, Merve Nur; Tuglu, Mehmet Ibrahim; Aydemir, Isil; Gulec, AysegulObjective: Functional treatment of Class II malocclusion is expected to lead to adaptation in the condyle. This study aimed to evaluate the effects of adipose tissue-derived mesenchymal stem cells (ADMSCs), low-level laser therapy (LLLT), and grape-seed extract (GSE) on condylar growth after functional mandibular advancement. Methods: Forty-five rats were randomly divided into 8 groups. Functional appliances were applied to all groups (n=6) except the control group (n=3). One group was treated with appliances only; the other six groups received various combinations of ADMSCs, LLLT, and GSE. Analyses for new osteoblasts and new bone formation, vascular endothelial growth factor, and Type II collagen were performed on condylar tissues, after an experimental period of four weeks. The quantitative data obtained from the results of the experiments were evaluated by H-score and analyzed using One-Way ANOVA by Tukey-Kramer multiple comparisons test (p=0.05). Results: Levels of all investigated parameters increased in all groups (p <= 0.05). The highest increases were achieved by a combined application of functional appliance, ADMSCs, LLLT and GSE (p <= 0.05). Single LLLT administrations or single GSE applications did not create a statistical difference from appliance alone (p>0.05). A positive effect of ADMSCs or LLLT on osteoblast formation, neovascularization, and Type II collagen level was apparent (p <= 0.05), however, neither affected new bone formation (p>0.05). Conclusion: This study shows that ADMSCs with LLLT and GSE applications provide differing levels of new osteoblast and bone formation, new vascular formation, and Type II collagen formation in rat condyles after functional mandibular advancement.Öğe Therapeutic effects of Lacosamide in a rat model of traumatic brain injury: A histological, biochemical and electroencephalography monitoring study(Elsevier Sci Ltd, 2021) Mete, Mesut; Alpay, Suheda; Aydemir, Isil; Unsal, Ulkun Unlu; Collu, Fatih; Ozel, Hasan Fehmi; Duransoy, Yusuf KurtulusObjective: Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI can be classified based on severity, mechanism or other features. Inflammation, apoptosis, oxidative stress, and ischemia are some of the important pathophys-iological mechanisms underlying neuronal loss after TBI. Lacosamide (LCM) is an anticonvulsant compound approved for the adjunctive treatment of partial-onset seizures and neuropathic pain. This study aimed to investigate possible neuroprotective effects of LCM in a rat model of TBI. Material and methods: Twenty-eight adult male, Wistar albino rats were used. The rats were divided into 4 groups. Group 1 was the control group (n=7). Group 2 was the trauma group (n=7) where rats were treated with 100 mg/kg saline intraperitoneally (IP) twice a day. Groups 3 and 4, rats were treated with 6 (group 3, n=7) or 20 (group 4, n=7) mg/kg Lacosamide IP twice a day. For each group, brain samples were collected 72 hours after injury. Brain samples and blood were evaluated with histopathological and biochemical methods. In addition, electroencephalograpy monitoring results were compared. Results: The immunoreactivity of both iNOS and eNOS (oxidative stress markers) were decreased with LCM treatment compared to trauma group. The results were statistically significant (*** P<0.001). The treatments of low (56,17 +/- 9,69) and high-dose LCM (43,91 +/- 9,09) were decreased the distribution of HIF-1 alpha compared to trauma group (P<0.01). The number of apoptotic cells were decreased with LCM treatment the difference between the trauma group and 20mg/kg LCM treated group (9,55 +/- 1,02) was statistically significant (***P<0.001). Malondialdehyde level was reduced with LCM treatment. MDA level was significantly higher in trauma group compared to LCM treated groups (*** P<0.001). The level of Superoxide dismutase in the trauma group was 1,86 U/ml, whereas it was 36,85 U/ml in 20mg/kg LCM treated group (*** P<0.001). Delta strength of EEG in 20mg/kg LCM treated group were similar to control group values after LCM treatment. Conclusion: No existing study has produced results suggesting that different doses of LCM has therapeutic effect against TBI, using EEG recording in addition to histological and biochemical evaluations in rats. (C) 2021 Elsevier Ltd. All rights reserved.
