Person: ÖZKAN YENAL, NAZİYE
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ÖZKAN YENAL
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NAZİYE
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Publication Metadata only Investigation of the Therapeutic Efficacy of Codelivery of psiRNA-Vascular Endothelial Growth Factor and pIL-4 into Chitosan Nanoparticles in the Breast Tumor Model(ELSEVIER SCIENCE INC, 2014) EREN, FATİH; Salva, Emine; Turan, Suna O.; Kabasakal, Levent; Alan, Saadet; Ozkan, Naziye; Eren, Fatih; Akbuga, JulideAngiogenesis has been known to increase tumor growth and for its metastatic potential in human tumors. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and is a promising therapeutic target for breast cancer. VEGF is an essential target for RNAi-based gene therapy of breast cancer. Interleukin-4 (IL-4) may act as an anti-angiogenic molecule that inhibits tumor growth and migration in rats. The purpose of the present study was to improve therapeutic efficacy in breast cancer with the codelivery of siRNA-expressing plasmid targeting VEGF and IL-4-expressing plasmid encapsulating into chitosan nanoparticles (NPs). The codelivery of psiVEGF and pIL-4 plasmids greatly enhanced in vitro and in vivo gene-silencing efficiency. For the in vitro study, when psiVEGF and pIL-4 into chitosan NPs were combined (81%), the gene-silencing effect was higher than psiVEGF and pIL-4 NPs alone. The in vivo study breast tumor model demonstrated that the administration of coencapsulation of psiVEGF and pIL-4 into chitosan NPs caused an additive effect on breast tumor growth inhibition (97%), compared with containing NPs psiVEGF or pIL-4 alone. These results indicate that chitosan NPs can be effectively used for the codelivery of pIL-4 and siVEGF-expressing plasmid in a combination therapy against breast cancer. (c) 2013 Wiley Periodicals, Inc.Publication Metadata only Repair of critical size defects using bioactive glass seeded with adipose-derived mesenchymal stem cells(WILEY, 2017) YILMAZ, BETÜL; Sacak, Bulent; Certel, Furkan; Akdeniz, Zeynep D.; Karademir, Betul; Ercan, Feriha; Ozkan, Naziye; Akpinar, Ihsan Nuri; Celebiler, OzhanBioactive glass has been demonstrated as a biocompatible bone substitute. However bone healing process can be prolonged due to late resorption of the material. Adipose derived stem cells (ASC) have osteogenic differentiation potential and hence can be a cell source for bone regeneration. The aim of this study was to test whether combination of bioactive glass with ASCs would enhance bone regeneration. Following creation of critical sized defects on the calvaria of 32 Wistar rats, the animals were randomly divided into four groups: Group C (control): Defects were left untreated; Group G: Defects were covered with autologous bone graft; Group BG: Defects were filled with bioactive glass; Group BG/ASC: Defects were filled with bioactive glass seeded with ASCs. The defect size was significantly greater in Group compared to all other groups. Bone density was significantly lower in Group C compared to Group G and Group BG/ASC. Bone regeneration score of Group C was significantly lower than other groups. Group BG/ASC demonstrated lamellar bone and havers canal formation. The results of this study demonstrated that bioactive glass implanted with ASC is a biocompatible construct stimulating radiologically and histologically evident bone regeneration similar to autologous bone grafting. (C) 2016 Wiley Periodicals, Inc.Publication Metadata only The antifibrotic drug halofuginone reduces ischemia/reperfusion-induced oxidative renal damage in rats(ELSEVIER SCI LTD, 2013) YEGEN, BERRAK; Cerit, Kivilcim Karadeniz; Karakoyun, Berna; Yuksel, Meral; Ozkan, Naziye; Cetinel, Sule; Dagli, E. Tolga; Yegen, Berrak C.; Tugtepe, HalilAim: The objective of the present study was to evaluate the protective effects of halofuginone against renal ischemia/reperfusion (I/R) injury. Materials and methods: Male Wistar albino rats were unilaterally nephrectomized and the left renal pedicles were occluded for 45 min to induce ischemia and then reperfused for 6 h (early) or for 72 h (late). The rats were treated intraperitoneally with either halofuginone (100 mu g/kg/day) or saline 30 min prior to ischemia and the dose was repeated in the late reperfusion groups. In the sham groups, rats underwent unilateral nephrectomy and were treated at similar time points. The animals were decapitated at either 6 h or 72 h of reperfusion and trunk blood and kidney samples were obtained. Results: I/R injury increased renal malondialdehyde levels, myeloperoxidase activity and reactive oxygen radical levels, and decreased the renal glutathione content. Halofuginone treatment was found to reduce oxidative I/R injury and improve renal function in the rat kidney, as evidenced by reduced generation of reactive oxygen species, depressed lipid peroxidation and myeloperoxidase activity, and increased glutathione levels. Conclusions: The present findings demonstrate the anti-inflammatory and antioxidant effects of halofuginone in renal I/R injury, supporting its potential use where renal I/R injury is inevitable. (C) 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.Publication Metadata only Chitosan/Short Hairpin RNA Complexes for Vascular Endothelial Growth Factor Suppression Invasive Breast Carcinoma(MARY ANN LIEBERT, INC, 2010) EREN, FATİH; Salva, Emine; Kabasakal, Levent; Eren, Fatih; Cakalagaoglu, Fulya; Ozkan, Naziye; Akburga, JuelideVascular endothelial growth factor (VEGF) plays a critical role in angiogenesis. The aim of this study was to use chitosan/short hairpin VEGF (shVEGF) [short hairpin RNA (shRNA)-expressing pDNA targeting VEGF-A] complexes in the treatment of rat breast cancer model. Therefore, chitosan/shVEGF complexes were prepared in (2/1) ratio and injected to the breast-tumor bearing Sprague-Dawley rats. Intratumoral and intraperitoneal injections were applied and compared. Tumor volumes were measured during the 36 days. To investigate the effect of complexes on the VEGF expression, VEGF were analyzed by immunohistochemistry and western blotting. The mRNA levels of VEGF were determined by real-time polymerase chain reaction. Tumor volume decreased at the end of experiments after shRNA treatment. The highest suppression in the tumor volume was observed after intratumoral complex injection to rats (96%). Compared with intratumoral and intraperitoneal injection, higher tumor inhibition was obtained with intratumoral injection. Free shRNA injection indicated lower tumor suppression. The immunohistochemistry and western blotting results correlated with the real-time polymerase chain reaction and tumor volume measurements. The data suggest that chitosan/shVEGF complexes can be used to inhibit tumor growth in breast carcinoma model of rats.Publication Metadata only Local Delivery of Chitosan/VEGF siRNA Nanoplexes Reduces Angiogenesis and Growth of Breast Cancer In Vivo(MARY ANN LIEBERT, INC, 2012) EREN, FATİH; Salva, Emine; Kabasakal, Levent; Eren, Fatih; Ozkan, Naziye; Cakalagaoglu, Fulya; Akbuga, JulideVascular endothelial growth factor (VEGF) is the important angiogenic factor associated with tumor growth and metastasis in a wide variety of solid tumors. The aim of this study is to investigate the tumor suppressive effect of chitosan/small interfering RNA (siRNA)-VEGF nanoplexes in the rat breast cancer model. Chitosan/siRNA nanoplexes (siVEGF-A, siVEGFR-1, siVEGFR-2) and NRP-1 were prepared in a 15 to1 ratio and injected (intratumorally) into the breast-tumor-bearing Sprague-Dawley rats. Tumor volumes were measured during 21 days. To investigate the effect of chitosan/siRNA nanoplexes on VEGF expression in tumors, VEGF was analyzed with immunohistochemistry and western blotting. The mRNA levels of VEGF in tumor samples were determined with real-time PCR (RT-PCR). After siRNA treatment, a marked reduction in tumor volumes was measured in complex-injected rats (97%). Free siRNA injection showed lower tumor inhibition. Reduction of VEGF protein was also shown with western blotting and immunohistochemistry. Similar results were obtained with RT-PCR also. These results indicate that the chitosan/siRNA targeting to VEGF nanoplexes have a remarkably suppressive effect on VEGF expression and tumor volume in breast cancer model of rats.Publication Metadata only Sıçanlarda parkinson hastalığına bağlı oluşan bellek disfonksiyonuna farklı egzersiz uygulamalarının etkileri(2022-05-12) KOYUNCUOĞLU, TÜRKAN; ÖZKAN YENAL, NAZİYE; KASIMAY ÇAKIR, ÖZGÜR; GÜLHAN, REZZAN; YÜKSEL, MERAL; Koyuncuoğlu T., Erol G., Çulpan Y., Gülhan R., Yüksel M., Özkan Yenal N., Kasımay Çakır Ö.Giriş: Parkinson hastalığı (PH) Alzheimer hastalığından sonra en yaygın görülennörodejeneratif hastalıktır.1 PH’da motor semptomların yanı sıra bellek disfonksiyonugörülmektedir. Yüksek anksiyete seviyeleri bellek fonksiyonlarını olumsuz etkilemektedir.2Amaç: İstemli tekerlek çevirme egzersizi, direnç egzersizi ve kombine egzersizuygulamalarının anksiyete düzeyleri ile bellek üzerindeki etkilerinin araştırılması ve alttayatan mekanizmaların ortaya konulması amaçlanmıştır.Yöntem: Çalışmada Wistar Albino erkek sıçanlarda (n=50) taklit cerrahi ve Parkinsongrupları oluşturulduktan sonra sedanter ve 3 farklı egzersiz protokolünün uygulandığı istemli(İE), rezistans (RE) ve kombine (KE: İE+RE) grupları oluşturuldu. Egzersizler 6 haftaboyunca (3 gün/hafta) uygulandı. PH modeli oluşturmak için sıçanlarda sağ mediyal önbeyine 6-OHDA (0.5 μl/dk) enjeksiyonu yapıldı. Taklit cerrahili gruplara 6-OHDA’nınçözücüsü verildi. Apomorfin uygulamaları sonrası rotasyon hareketi ile Parkinson modelideğerlendirildi. Obje tanıma testi ve delikli levha testleri sıçanlarda bellek fonksiyonlarını veanksiyete düzeylerini değerlendirmek için yaptırıldı. Beyin dokusunda antioksidan glutatyon(GSH) ve lipid peroksidasyonu belirteci malondialdehit (MDA) ve nötrofil infiltrasyonugöstergeci miyeloperoksidaz (MPO) aktivitesi, oksidan radikallerin belirteci luminol velusigenin ölçüldü. Verilerin analizinde tek yönlü ANOVA ardından Tukey-Kramer testi ilestudent’s t testi kullanıldı. Bulgular: Her 3 egzersiz ile Parkinsona bağlı gerileyen bellek fonksiyonu düzelmiştir(p<0.05-0.01). Sedantere kıyasla PH oluşturulmuş KE grubunda rotasyon hareketi azalırken,İE grubunda arttı (p<0.05-0.01). PH oluşturulmasıyla luminol ve lusigenin düzeyleri artarken,İE ile luminol azalmıştır (p<0.05-0.001). MPO aktivitesinin PH oluşturulmasıyla sedantergrubunda yükseldiği, ancak İE ve RE gruplarında baskılandığı gözlenmiştir (p<0.01-0.001).Her 3 egzersiz ile GSH düzeylerinin arttığı (p<0.05-0.01), KE ile MDA düzeylerinin düştüğübulundu (p<0.05). PH oluşturulmasıyla sedanter grupta azalmış bulunan bakılan delik sayısıve şahlanma sayısı (p<0.01-0.001), RE ve KE gruplarında artmıştır (p<0.05-0.01). Sedanterve İE gruplarında artan donma süresi, KE ile azalmıştır (p<0.05-0.001).Tartışma ve Sonuç: KE lipid peroksidasyonunu baskılamış, İE ve RE nötrofilinfiltrasyonunu azaltmıştır. RE ve KE anksiyeteyi hafifletmiştir. PH’da oluşan bellekdisfonksiyonunda farklı egzersiz uygulamalarının koruyucu etki gösterdikleri ortayakonmuştur.Anahtar Sözcükler: Egzersiz, Parkinson, Anksiyete, Bellek, AntioksidanPublication Open Access BRAFV600E Immunohistochemistry in Papillary Thyroid Carcinomas: Relationship Between Clinical and Morphological Parameters(FEDERATION TURKISH PATHOLOGY SOC, 2019) UĞURLU, MUSTAFA ÜMİT; Kombak, Faruk Erdem; Ozkan, Naziye; Ugurlu, Mustafa Umit; Kaya, HandanObjective: To investigate the association of the BRAFV600E mutation with papillary thyroid carcinoma using clinical, morphological and prognostic parameters. We also intend to assess the utility of the BRAFV600E immunohistochemistry and compare it with BRAF polymerase chain reaction (RT-PCR). Material and Method: We applied BRAFV600E immunohistochemistry in a cohort of 107 papillary carcinomas, 19 adenomas and 13 normal thyroid tissues that was chosen retrospectively between 2011 and 2015. Statistical analysis was based on semiquantitative immunohistochemistry findings. We also applied BRAF RT-PCR in a subgroup of 14 papillary carcinomas, 13 metastatic lymph nodes and 4 adenomas that was chosen randomly. Results: In regard to the comparison of BRAFV600E immunohistochemistry and BRAF RT-PCR, a 3+ nuclear and cytoplasmic immunoexpression was considered 'positive The BRAFV600E mutation was most frequently observed in classic variant cases. No mutation was detected in follicular variant cases. The mutational status of the primary tumour and the lymph node metastasis was consistent. A significant relationship of the BRAFV600E mutation was found with prognostic factors such as higher pT stage, classic variant, lymphatic invasion, perineural invasion, lower mitotic index, lack of tumour capsule, intrathyroidal spread and extrathyroidal extension. Conclusion: Immunohistochemistry, using the VE1 clone, is a reliable technique for detection of the BRAFV600E mutation. Our results with immunohistochemistry are consistent with a previous effort. In our study, despite the correlation between some pathological prognostic parameters and the BRAFV600E mutation; poor prognosis was found to be irrelevant overall. Morphological parameters seem to be keener than the BRAFV600E mutation. Nevertheless, different series display different results, possibly due to environmental factors. Considering this and the proven success of targeted therapies against the BRAFV600E mutation a thorough assessment would be important.Publication Metadata only The effect of carnitine against acrylamide-induced toxicity in rat lung and liver tissues(ELSEVIER IRELAND LTD, 2016) GÜÇLÜ, HÜLYA; Aydemir, S.; Guclu, H.; Ozkan, N.; Yuksel, M.; Erdogan, N.; Omurtag, G. Z.Publication Metadata only PROTECTIVE EFFECTS OF VORTIOXETINE IN PREDATOR SCENT STRESS MODEL OF POST-TRAUMATIC STRESS DISORDER IN RATS: ROLE ON NEUROPLASTICITY AND APOPTOSIS(POLISH PHYSIOLOGICAL SOC, 2019) YAVUZ, AYŞE NUR; Ozbeyli, D.; Aykac, A.; Alaca, N.; Hazar-Yavuz, A. N.; Ozkan, N.; Sener, G.Post-traumatic stress disorder (PTSD) can be observed after a traumatic event. The effect of an antidepressant vortioxetine (Vrx) against PTSD is unknown. The aim of this study was to investigate the possible protective effect of Vrx in the predator scent-induced PTSD rat model. The rats were exposed to dirty cat litter for 10 min and the protocol was repeated 1 week later with clean cat litter as a trauma reminder. The rats received Vrx (10 mg/kg/p.o.) or saline (1 ml/kg/p.o.) during 7 days between two exposure sessions. Novel object recognition test, hole board test, and elevated plus maze were performed. The b-cell lymphoma (bcl-2)/bcl-2-associated X protein (bax) ratio, brain-derived neurotrophic factor (BDNF), caspase-3 and -9 expressions were detected using Western blotting in the amygdaloid complex, hippocampus, and frontal cortex. Our results indicate that increased freezing time and anxiety index in the stress-induced group is decreased with Vrx application. Vrx treatment improved deteriorated recognition memory in the stress-induced group. Decreased bcl-2/bax ratio and BDNF level and increased caspase-3 and -9 expressions in the stress group, improved with Vrx in the amygdala, and hippocampus. Decreased bcl-2/bax ratio and increased casp-3 and -9 expressions in the stress group are ameliorated with Vrx in frontal cortex. The level of BDNF was increased with Vrx in the frontal cortex. Increased damage scores in the amygdaloid complex, hippocampal CA3, and frontal cortex in the stress group ameliorated with Vrx treatment. Our results show that if vortioxetine is administered immediately after trauma, it reduces anxiety, cognitive and neuronal impairment and may be protective against the development of PTSD.Publication Open Access The effects of resveratrol treatment on caveolin-3 expression and Na+/K+ ATPase activity in rats with isoproterenol-induced myocardial injury(KARE PUBL, 2020) YEGEN, BERRAK; Sehirli, Ahmet Ozer; Aykac, Asli; Tetik, Sermin; Yiginer, Omer; Cetinel, Sule; Ozkan, Naziye; Akkiprik, Mustafa; Kaya, Zehra; Yegen, Berrak Caglayan; Tezcan, Mehmet; Sener, GoekselOBJECTIVE: The present study aims to investigate the therapeutic effects of resveratrol (RES) on isoproterenol (ISO) induced myocardial injury rat model. METHODS: Catecholamine-induced heart damage was induced by ISO treatment for 30 days. The rats were divided into four groups as follows: the control group received saline, the ISO group received 5.0 mg/kg ISO, the RES group received 10 mg/kg RES, and the ISO-RES group received 10 mg/kg RES and 5 mg/kg ISO treatments for 30 days. Following echocardiographic measurements and body weight recorded, the rats were decapitated. Plasma and cardiac tissue samples obtained by decapitation were analyzed using biochemical, histopathological, molecular and immunohistochemical methods. RESULTS: In the ISO group, Na+/K+ ATPase activity and ATP content, GSH, and caveolin-3 levels were low. LDH, CK and lysosomal enzyme activities, MDA level, and MPO activity were found to be high. It was determined that GSH and MDA levels and MPO, Na+/K+ ATPase activity, ATP content caveolin-3 levels changes that arose from ISO treatment were suppressed by RES treatment. CONCLUSION: RES treatment has ameliorated all the functional and biochemical parameters. The results obtained in this study suggest that RES is a promising supplement against catecholamine exposure as it improves antioxidant defense mechanisms in the heart. In the light of above-mentioned data, RES can be assumed as a promising agent in ameliorating the oxidative injury of the myocardium.
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