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EgeUn###, Neurodegenerative diseases affect millions of people. Major reasons behind the onset and progression of these diseases are still under investigation. Therefore, any approach that would treat/prevent progression is important. In this study, we aimed to investigate the potential protective effects of Psephellus pyrrhoblepharus (Boiss.) Wagenitz extracts in MPP+-induced dopaminergic cell damage and compare the effectiveness of different extracts (methanol:water (1:1), chloroform and n-hexane). The cells were pretreated with four different concentrations (10, 50, 100, and 200 mu g/ml) of methanol:water (1:1), chloroform and n-hexane extracts of P. pyrrhoblepharus following MPP+ treatment for 12 or 24 h. The changes in cell viability were determined using the MTT assay. Additionally, antioxidant activities and total phenolic/flavonoid contents of the extracts were determined with radical scavenging capacity, Folin-Ciocalteu and aluminum chloride assays, respectively. The extracts at selected concentrations were found to be protective in a dose-dependent manner at 12 and 24 h. Nevertheless, the methanol extract of the plant showed the highest protection both at 100 and 200 mu g/ml (115.13%+/- 3.98, 121.87%+/- 1.66; p < 0.05) against dopaminergic damage at 24 h. The results showed that selected concentrations were not toxic and did not affect cell proliferation rate. Besides, the chloroform extract was found to have higher antioxidant activity than the other extracts (p < 0.05). The total phenolic and total flavonoid contents were found consistent with antioxidant activities. Our findings support the neuroprotective and antioxidant potential of P. pyrrhoblepharus. However, further studies on identifying the presence of chemicals in P. pyrrhoblepharus extracts which are responsible for protection should be carried out to confirm their therapeutic potential.

Purpose: The present study was conducted to determine oxidative stress and cell viability after contact with resin composites polymerized for different times. Methods: Disk-shaped specimens of Admira Fusion. Ceram X One Universal. Solare x and Filtek Z550 (n = 12) were prepared, and two subgroups with polymerization times of 20 and 40 s were employed. The specimens were incubated with mouse fibroblast cells for 48 and 72 h, and changes in reactive oxygen species (ROS) production and cellular viability were determined by an assay with a cell-permeable fluorescent dye, 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA), and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, respectively. Results: At 72 h, ROS production in the presence of Admira Fusion polymerized for 40 s was reduced relative to that in the presence of Admira Fusion polymerized for 20 s (P < 0.05). Cell viability was maximal in the Admira Fusion and Solare x groups and there was no difference relative to the control group at 48 h. Cell viability was higher in the Admira Fusion and Solare x groups polymerized for 40 s than for the same materials polymerized for 20 sat 72 h (P < 0.05). Conclusion: Extension of the polymerizaton lime has a material-specific effect and may be used as a strategy to increase the biocompability of resin composites.

WOS: 000474396700008, PubMed: 30415440, ObjectiveThe aim of this in vitro study is to evaluate the effects of resveratrol (RES) addition on the cytotoxicity and microtensile bond strength (mu TBS) of different adhesives.Materials and methodsFive self-etching adhesives (G-aenial Bond-GC, Optibond All in One-Kerr, Gluma Self Etch-Kulzer, Clearfil S-3 Bond-Kuraray, and Nova Compo-B Plus-Imicryl) were tested. They were applied to L-929 cell culture by the extract method. In the test groups, 0.5 mu M RES (Sigma-Aldrich) was added into the medium. Cell viability was assessed by MTT assay after 24h. Human extracted third molars were used for mu TBS test (n=7). The adhesives with or without 0.5 mu M RES addition were applied on dentin surfaces. A composite build-up was constructed. Then, the specimens were sectioned into multiple beams with the non-trimming version of the microtensile test and subjected to microtensile forces. Statistical analysis was performed using ANOVA and post hoc Tukey test (p?0.05).ResultsThe extracts of all adhesives decreased the cell viability. However, RES addition increased the cell viability in all groups (p?0.05). RES addition did not cause any decrease in mu TBS values of the adhesives compared to baseline. Optibond All in One showed the highest mu TBS after RES addition. It was followed by Clerafil S-3 Bond and Nova Compo-B Plus. No difference was determined between the Optibond All in One and Clearfil S-3 Bond. There was difference between Optibond All in One and Nova Compo-B Plus (p?0.05).ConclusionRES addition may improve the biocompatibility without causing negative influence on mu TBS of the adhesives.Clinical relevanceRES addition has clinical applicable potential to overcome the adverse biocompatibility of adhesives.

Recently, nuclear translocation and stability of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) have gained increasing attention in the prevention of oxidative stress. The present study was aimed to evaluate the regulatory role of glycogen synthase kinase-3&beta, (GSK-3&beta, ) inhibition by tideglusib through the Nrf2 pathway in a cellular damage model. Gene silencing (siRNA-mediated) was performed to examine the responses of Nrf2-target genes (i.e., heme oxygenase-1, NAD(P)H:quinone oxidoreductase1) to siRNA depletion of Nrf2 in MPP+-induced dopaminergic cell death. Nrf2 and its downstream regulated genes/proteins were analyzed using Real-time PCR and Western Blotting techniques, respectively. Moreover, free radical production, the changes in mitochondrial membrane potential, total glutathione, and glutathione-S-transferase were examined. The possible contribution of peroxisome proliferator-activated receptor gamma (PPAR&gamma, ) to tideglusib-mediated neuroprotection was evaluated. The number of viable cells and mitochondrial membrane potential were increased following GSK-3&beta, enzyme inhibition against MPP+. HO-1, NQO1 mRNA/protein expressions and Nrf2 nuclear translocation significantly triggered by tideglusib. Moreover, the neuroprotection by tideglusib was not observed in the presence of siRNA Nrf2. Our study supports the idea that GSK-3&beta, enzyme inhibition may modulate the Nrf2/ARE pathway in cellular damage and the inhibitory role of tideglusib on GSK-3&beta, along with PPAR&gamma, activation may be responsible for neuroprotection.

Objective: In Psephellus and Centaurea genuses a lot of species have important pharmacological activities like antipyretic, antiinflamatory, diuretic, cytotoxic etc. In Psephellus genus the endemic plant Psephellus pyrrhoblepharus (Boiss.) Wagenitz (Centaurea pyrrhoblephara) was collected from Elazığ, Turkey. Recently interest in use of plant-derived compounds for therapeutic purposes in cancer is increasing day by day. Liver cancer which is one of the cancer types is affecting millions of people all over the world. So any approach to treat liver cancer is extremely valuable. Materials and methods: We have purposed to determine the cytotoxic activity of methanol:water (1:1), n-hexane and chloroform extracts of the aerial parts of P. pyrrhoblepharus using human liver cancer cell (HepG2) by utilizing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay in different concentrations (50, 100 ,200 µg/ml) and time points (6, 12, 24 h). Results: Regarding the cytotoxicity, cell viability was seen as decreased following extract exposures at three different time points. The highest cytotoxic activity was observed in 100 µg/ml concentrations of chloroform extract at 24 h. At 12 h chloroform extract of plant showed the highest cytotoxic activity in 200 µg/ml concentrations when compared to methanol:water and n-hexane extracts. Conclusion: It can be suggested that extracts of P. pyrrhoblepharus show dose-dependent and time-dependent cytotoxic effects in HepG2 carsinoma cells. In general, the results provide information about the threshold concentrations of P. pyrrhoblepharus extracts that might be used in different applications without the risk of toxicity., Amaç: Birçok Psephellus ve Centaurea türü antipiretik, antiinflamatuar, diüretik ve sitotoksik gibi önemli farmakolojik aktivitelere sahiptir. Endemik bir bitki olan Psephellus pyrrhoblepharus (Boiss.) Wagenitz, Elazığ, Türkiye’den toplanmıştır. Son günlerde kanserde terapötik amaçlar için bitki kaynaklı bileşiklerin kullanımına olan ilgi artmaktadır. Bir kanser türü olan karaciğer kanseri de tüm dünyada milyonlarca insanı etkilemekteyken, karaciğer kanserini tedavi etmek için herhangi bir yaklaşım son derece değerlidir. Bu çalışmada, insan karaciğer kanseri hücresi (HepG2) kullanılarak P. pyrrhoblepharus bitkisinin topraküstü kısımlarından hazırlanmış olan metanol:su (1:1), kloroform ve n-hekzan ekstrelerinin sitotoksik potansiyelini değerlendirilmesi amaçlanmıştır. Gereç ve yöntemler: 3-(4,5-dimetiltiyazol-2-il)-2,5-difenltetrazolyumbromit (MTT) metodu kullanılarak, insan karaciğer kanser hücre hatlarında (HepG2) farklı konsantrasyonlarda (50, 100, 200 ug/ml) MTT, farklı zaman noktalarında (6, 12, 24 s) çalışmalar gerçekleştirildi. Bulgular: Sitotoksisite ile ilgili olarak, farklı zaman noktalarında ekstrelerin maruziyetlerinin ardından hücre canlılığının azaldığı gözlenmiştir. Bununla birlikte, en yüksek sitotoksik aktivite, 24 saatte 100 ug/ml konsantrasyondaki kloroform ekstresinde gözlenmiştir. Bitkinin kloroform ekstresi, metanol:su ve n-hekzan ekstreleri ile karşılaştırıldığında 12 saatte 200 ug/ml konsantrasyonda en yüksek sitotoksik etkinliği göstermiştir. Sonuç: P. pyrrhoblepharus ekstrelerinin HepG2 karsinoma hücrelerinde doza ve zamana bağlı bir şekilde sitotoksik etki gösterdiği ileri sürülebilir. Genel olarak elde edilen sonuçlar, toksisite tehlikesi olmadan farklı uygulamalarda kullanılabilecek P. pyrhoblepharus ekstrelerinin eşik konsantrasyonları hakkında bilgi sağlamıştır.

Bir dental implant tedavisinin başarısında cerrahi teknik, implant materyali ve implant dizaynı gibi faktörlerin yanı sıra, implant materyalinin yüzey özelliklerinin de önemli olduğu bilinmektedir. Son yıllarda yapılan çalışmalar iyon implantasyonunun dental implantların yüzey modifikasyonu açısından iyi bir aday olduğunu göstermiştir._Bu çalışmada, MEVVA iyon implantasyon teknolojisi kullanılarak, metal+gaz hibrit iyon implantasyonu yapılmış yüzeylerin osteoblast hücre tutunmasına etkisi incelenmiştir. Bu amaçla, iyon implante edilecek materyal olarak son yıllarda dental implant materyali olarak en çok kullanılan titanyum (ISO 5832-2 Grade 4) seçilmiştir. Titanyum yüzeylere implante edilecek metal element olarak yüksek biyouyumluluğu ile bilinen zirkonyum ve zirkonyum ile eş zamanlı implante edilen gaz elementi olarakta titanyum yüzeylerin pasivasyonunu arttırmak için oksijen kullanılmıştır. Osteoblast hücre tutunmaları in vitro ortamda gerçekleştirilerek yüzey pürüzlülüğünün ve iyon implantasyon işleminin osteoblast hücre tutunmaları üzerine etkisi karşılaştırılmalı olarak incelenmiştir. Sonuç olarak pürüzlü ve iyon implante edilmiş yüzeylerde hücrelerin daha iyi tutunduğu görülmüştür, Achivement of a dental implant treatment depend on also surface properties of implant material as well as surgical method, implant material and implant desing, Studies have shown that ion implantation is a good candidate for modifying of dental implant surface._In this thesis, it was observed the effects on osteoblast attachment on modified surfaces with metal+gas hybrid ion implantation by using MEVVA ion implantation technology. For this aim, the material for ion implantation was chosen as titanium (ISO 5832-2 Grade 4) which is the most common material used in dentistry. Zirconium element known as biocompatible and oxygen to increase the passivation of titanium surfaces were used for creating ions simultaneously._ Attachment of osteoblast on samples was investigated in vitro for comparing the effects of the rougnesses and ion implantation surface modification on attachment of osteoblast. It is observed at the end of the in vitro osteoblast cell attachment is better on rough and ion implanted surfaces

Results of electrophysiological studies suggest a significant role of the lateral spinal nucleus (LSpN) in the transmission of nociceptive signals. In our study, the presence of Fos immunoreactivity and NADPH-diaphorase positivity was observed in the rat LSpN following noxious peripheral subcutaneous stimulation. Formalin-induced unilateral hindpaw stimulation in the rat caused bilateral NADPH-d reactivity and ipsilateral Fos expression in this nucleus. In the LSpN of the L3-L5 segments of stimulated rats, on average, 4.1 +/- 1.2 NADPH-d-positive, NADPH-d(+), 5.1+1.8 Fos-immunoreactive, Fos(+), and 3.0 +/- 1.1 double-labeled neurons per 25-mu m-thick section were found unilaterally. A close anatomical relationship between NADPH-d(+) processes and Fos(+) cell nuclei in the LSpN was also observed following noxious peripheral stimulation. These neuroanatomical findings support the hypothesis that the LSpN is involved in pain processing and suggest an important role of nitric oxide-mediated signal transduction in this nucleus.

WOS: 000378324000020, PubMed ID: 26981753, The aim of this study was to evaluate whether medium modification improves the odontogenic differentiation of human dental pulp stem cells (DPSC) in vitro and in vivo. DPSC isolated from human impacted third molar teeth were analysed for clusters of differentiation with flow cytometry. Odontogenic differentiation was stimulated by medium modification with the addition of bone morphogenetic protein 2 (BMP2). The expression of dentin sialophosphoprotein, dentin matrix protein 1, enamelysin/matrix metalloproteinase 20 and the phosphate-regulating gene with homologies to endopeptidases on the X chromosome of the cells were analysed with RT-PCR at 7, 14 and 21 days. Then, DPSC were transplanted on the back of immunocompromised mice via a hydroxyapatite tricalcium phosphate scaffold, and the structure of the formed tissue was investigated. The cells were identified as mesenchymal stem cells with a 98.3% CD73 and CD90 double-positive cell rate. The increase in mineralization capacity and expression of human enamel-dentin specific transcripts proportional to the culture period were determined after differentiation. Six weeks after transplantation, an osteo-dentin matrix was formed in the group in which odontogenic differentiation was stimulated, and the odontogenic characteristics of the matrix were confirmed by histological examination and RT-PCR analysis. Odontogenic differentiation of the isolated and characterized human DPSC was improved with medium modification by the addition of BMP2 in vitro and in vivo. The defined medium and applied technique have a potential use for forming reparative dentin in the future, but the effects of the method should be investigated in long-term studies., Ege University's Scientific Research FoundationEge University [2009-Dis-036]; Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK), This study was supported by Ege University's Scientific Research Foundation (2009-Dis-036). We also acknowledge The Scientific and Technological Research Council of Turkey (TUBITAK) for its PhD scholarship support.

WOS: 000404458100052, PubMed ID: 27901202, This study was designed to determine the in vivo performance of three different materials as scaffolds for dental pulp stem cells (DPSC) undergoing induced odontogenic differentiation. An odontogenic medium modified by the addition of recombinant human bone morphogenetic protein 2 was used in the experimental groups to induce differentiation. Mesenchymal stem cell medium was used in the control groups. DPSC were transplanted onto the backs of mice via three scaffolds: copolymer of L-lactide and DL-lactide (PLDL), copolymer of DL-lactide (PDL) and hydroxyapatite tricalcium phosphate (HA/TCP). The expression levels of dentin sialo-phosphoprotein (DSPP), dentin matrix protein-1 (DMP1), enamelysin/matrix metalloproteinase 20 (MMP20) and phosphate-regulating gene with homologies to endopeptidases on X chromosome (PHEX) were analysed using RT-PCR. The expressions in the experimental groups were compared to those in the control groups. The transcript expressions at 6 and 12 weeks were significantly different for all scaffolds (p < 0.05), except for the expression of DSPP in the PLDL group with regard to the time variable. Although there was a decrease in the expression of enamelysin/MMP20 in PLDL and HA/TCP at 12 weeks, all other expressions increased and reached their highest level at 12 weeks. The highest DSPP expression was in the PDL group (p < 0.05). The highest expression of DMP1 was detected in the HA/TCP group (p < 0.05). The highest expression of PHEX was in the PLDL group (p < 0.05). Consequently, PLDL and PDL seemed to be promising scaffold candidates for odontogenic regeneration at least as HA-TCP, when they were applied with the DPSC induced for odontogenic differentiation., Ege University's Scientific Research FoundationEge University [2010-Dis-006], This study was supported by Ege University's Scientific Research Foundation (2010-Dis-006). The authors sincerely thank Gul KAYRAK for her help in language editing.

WOS: 000368755700005, PubMed ID: 26510940, This study was designed to evaluate the cytotoxicity of four dentin bonding agents and the effects of an antioxidant addition. Group A: G-aerial Bond, Group B: Optibond All in One, Group C: Gluma Self Etch and Group D: Clearfil S-3 Bond were added to the medium using extract method. The cells were cultured with or without resveratrol (RES) addition. MTT, reactive oxygen species (ROS), DCF, Comet and 8-OHdG measurements were performed. The agents had a dose-dependent (1:1>1:10>1:20) cytotoxic effect. Considering 1:10 concentration; Group D at 1 h (p, Ege University's Scientific Research FoundationEge University [2012-Dis-022], This study was supported by Ege University's Scientific Research Foundation (2012-Dis-022). The authors would also like to thank Prof. S. Ismet Deliloglu Gurhan and Mehmet Ozgun Ozen for their kind help in providing cells.

To investigate nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and fos expression in spinal cord dorsal horn neurons following noxious peripheral stimulation.Expression of the immediate-early gene c-fos and nitric oxide containing neurons one hour after unilateral formalin injection to the dorsal hind paw was investigated in rat lumbar spinal cord, using fos immunohistochemistry and NADPH-d histochemical techniques. The experiments were performed in 2004 and 2006 at Ege University Center for Brain Research in Izmir, Turkey.In 10 adult male Sprague-Dawley rats, an increase in fos-immunoreactive neurons was observed ipsilateral, and NADPH-d positive neurons equally ipsi- and contralateral to the formalin injection site. Approximately 20% of fos-immunoreactive neurons were NADPH-d positive ipsilateral to the formalin injection, whereas no double labeling was observed in the contralateral side. Also, a close relation of NADPH-d positive processes with fos-immunoreactive nuclei were also observed.The results of this study support the hypothesis that nitric oxide synthase blocking agents may serve as a possible alternative in treatment of hyperalgesia following inflammation and peripheral nerve injury.

Aims The aim of this study is to determine the role of nitric oxide (NO) in neuropathic pain and the effect of embryonic neural stem cell (ENSC) transplantation on NO content in rat spinal cord neurons following spinal cord injury (SCI). Main methods Ninety adult male Sprague–Dawley rats were divided into 3 groups (n = 30, each): control (laminectomy), SCI (hemisection at T12–T13 segments) and SCI + ENSC. Each group was further divided into sub-groups (n = 5 each) based on the treatment substance (L-NAME, 75 mg/kg/i.p.; l -arginine, 225 mg/kg/i.p.; physiological saline, SF) and duration (2 h for acute and 28 days for chronic groups). Pain was assessed by tail flick and Randall–Selitto tests. Fos immunohistochemistry and NADPH-d histochemistry were performed in segments 2 cm rostral and caudal to SCI. Key findings Tail-flick latency time increased in both acute and chronic L-NAME groups and increased in acute and decreased in chronic l- arginine groups. The number of Fos (+) neurons decreased in acute and chronic L-NAME and decreased in acute l -arginine groups. Following ENSC, Fos (+) neurons did not change in acute L-NAME but decreased in the chronic L-NAME groups, and decreased in both acute and chronic l -arginine groups. NADPH-d (+) neurons decreased in acute L-NAME and increased in l -arginine groups with and without ENSC transplantation. Significance This study confirms the role of NO in neuropathic pain and shows an improvement following ENSC transplantation in the acute phase, observed as a decrease in Fos(+) and NADPH-d (+) neurons in spinal cord segments rostral and caudal to injury.

WOS: 000268125600014, PubMed ID: 18637713, The oxidative mechanisms of injury-induced damage of neurons within the spinal cord are not very well understood. We used a model of T8-T9 spinal cord injury (SCI) in the rat to induce neuronal degeneration. In this spinal cord injury model, unilateral avulsion of the spinal cord causes oxidative stress of neurons. We tested the hypothesis that apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1) regulates this neuronal oxidation mechanism in the spinal cord region caudal to the lesion, and that DNA damage is an early upstream signal. The embryonic neural stem cell therapy significantly decreased DNA-damage levels in both study groups-acutely (followed up to 7 days after SCI), and chronically (followed up to 28 days after SCI) injured animals. Meanwhile, mRNA levels of APE/Ref-1 significantly increased after embryonic neural stem cell therapy in acutely and chronically injured animals when compared to acute and chronic sham groups. Our data has demonstrated that an increase of APE/Ref-1 mRNA levels in the caudal region of spinal cord strongly correlated with DNA damage after traumatic spinal cord injury. We suggest that DNA damage can be observed both in lesional and caudal regions of the acutely and chronically injured groups, but DNA damage is reduced with embryonic neural stem cell therapy.

1. Glial cells are the most abundant cell population in the central nervous system. The aim of this study was to examine the effects of melatonin, 7-nitroindazole, and riluzole on glutamate toxicity in primary glial cell culture. 2. Glutamate toxicity was induced by addition of 100 microM glutamate to the cultures, and then 100 microM melatonin, 500 microM 7-nitroindazole, and 10 (M riluzole were administered in different groups. Lactate Dehydrogenase activity and nitrite levels were determined at the 1st, 6th, and 24th h. 3. Melatonin, 7-nitroindazole, and riluzole decrease Lactate Dehydrogenase activity at the 1st, 6th, and 24th h (at all hours, p0.05). Nitrite levels were decreased by melatonin and riluzole at the 1st, 6th, and 24th h. 4. In this study, we observed that melatonin, 7-nitroindazole, and riluzole are effective as protective agents on glutamate toxicity in mixed glial cells.