Taner Dagci

Objectives: Dentin tissue can act as a reservoir for bioactive molecules that create signals for cellular proliferation and differentiation to initiate tissue regeneration. Therefore, the aim of this study is to compare the cell viability, inflammatory response, and antimicrobial activity of bovine dentin grain-added calcium-hydroxide (CH-BDG) with different pulp-capping materials. Methods: ProRoot MTA, Biodentine, Dycal, TheraCal-LC, and an experimental material, CH-BDG, were examined. Cell viability was determined via the WST-1 assay. The inflammatory response was analysed by the monocyte chemoattractant protein-1 (MCP-1/CCL2) and macrophage inflammatory protein-1α (MIP-1α/CCL3) levels. The antimicrobial activity was evaluated by agar-diffusion. Results: The cell viability of CH-BDG was analogous with Biodentine and control at 24 h. The cell viability of CH-BDG decreased at 48 h, but the rate was higher than ProRoot MTA and Dycal (p<0.05). For MCP-1 and MIP-1α values, there was no significant difference between the control and CH-BDG. The MCP-1 level of CH-BDG was lower compared to other pulp-capping materials (p<0.05). The MIP-1α level of CH-BDG was lower compared to ProRoot MTA, Biodentine, and TheraCal-LC (p<0.05). No inhibition zone was detected against oral microorganisms for CH-BDG. Conclusions: The experimentally developed CH-BDG showed competing properties and additional advantages compared to the existing pulp-capping materials.

Study Design: Pre‐clinical animal experiment.Objective: In this study, we investigated therapeutic effects of silibinin in a spinal cord injury (SCI) model. In SCI, loss of cells due to secondary damage mechanisms exceeds that caused by primary damage. Ferroptosis, which is iron‐dependent non‐apoptotic cell death, is shown to be influential in the pathogenesis of SCI.Methods: The study was conducted as an in vivo experiment using a total of 78 adult male/female Sprague Dawley rats. Groups were as follows: Sham, SCI, deferoxamine (DFO) treatment, and silibinin treatment. There were subgroups with follow‐up periods of 24 h, 72 h, and 6 weeks in all groups. Malondialdehyde (MDA), glutathione (GSH), and Fe²⁺ levels were measured by spectrophotometry. Glutathione peroxidase‐4 (GPX4), ferroportin (FPN), transferrin receptor (TfR1), and 4‐hydroxynonenal (4‐HNE)‐modified protein levels were assessed by Western blotting. Functional recovery was assessed using Basso–Beattie–Bresnahan test.Results: Silibinin achieved significant suppression in MDA and 4‐HNE levels compared to the SCI both in 72‐h and 6 weeks group (p < 0.05). GSH, GPX4, and FNP levels were found to be significantly higher in the silibinin 24 h, 72 h, and 6 weeks group compared to corresponding SCI groups (p < 0.05). Significant reduction in iron levels was observed in silibinin treated rats in 72 h and 6 weeks group (p < 0.05). Silibinin substantially suppressed TfR1 levels in 24 h and 72 h groups (p < 0.05). Significant difference among recovery capacities was observed as follows: Silibinin > DFO > SCI (p < 0.05).Conclusion: Impact of silibinin on iron metabolism and lipid peroxidation, both of which are features of ferroptosis, may contribute to therapeutic activity. Within this context, our findings posit silibinin as a potential therapeutic candidate possessing antiferroptotic properties in SCI model. Therapeutic agents capable of effectively and safely mitigating ferroptotic cell death hold the potential to be critical points of future clinical investigations.

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.

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 µg/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 µg/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.

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-3β (GSK-3β) 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 (PPARγ) to tideglusib-mediated neuroprotection was evaluated. The number of viable cells and mitochondrial membrane potential were increased following GSK-3β 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-3β enzyme inhibition may modulate the Nrf2/ARE pathway in cellular damage and the inhibitory role of tideglusib on GSK-3β along with PPARγ activation may be responsible for neuroprotection.

The aim of this in vitro study is to evaluate the effects of resveratrol (RES) addition on the cytotoxicity and microtensile bond strength (μTBS) of different adhesives.

Study Design.: Experimental animal study investigating the efficacy of C-terminal domain of tetanus toxin application as neuroprotective effects on rat brain in a model of spinal cord injury (SCI). Objective.: The aim of the present study was to investigate the possible role of C-terminal domain of tetanus toxin (Hc-TeTx) on cell death mechanisms including apoptosis and autophagy following SCI. Summary of Background Data.: Traumatic SCI can lead to posttraumatic inflammation, oxidative stress, motor neuron apoptosis, necrosis, and autophagy of tissue. To promote and enhance recovery after SCI, recent development of devices and therapeutic interventions are needed. Methods.: Twenty-eight adult rats were divided into four groups (n = 7 each) as follows: sham, trauma (SCI), SCI + Hc-TeTx, and SCI + methylprednisolone groups. The functional neurological deficits due to the SCI were assessed by behavioral analysis using the Basso, Beattie and Bresnahan (BBB) open-field locomotor test. The alterations in pro-/anti-apoptotic and autophagy related-protein levels were measured by Western blotting technique. Results.: In this study, Hc-TeTx promotes locomotor recovery and motor neuron survival of SCI rats. Hc-TeTx also decreased expression of bax, bad, bak, cleaved caspase-3, Ask1, and autophagy-related proteins including Atg5 and LC3II in brain. Our study provides an evidence that cell death mechanisms play critical roles in SCI and that the nontoxic peptides including Hc-TeTx may exert protective effect and decrease cell death following SCI. Conclusion.: Our preliminary findings suggest a possible therapeutic agent to improve survival after spinal cord trauma, but further analysis are still needed to evaluate the difference between acute and chronic injuries. Level of Evidence: N/A

Many species of Psephellus and Centaurea genuses have pharmacological activities including antiinflamatory, antipyretic, cytotoxic etc. Psephellus pyrrhoblepharus (Boiss.) Wagenitz (Centaurea pyrrhoblephara), an endemic plant, was collected from Elazığ, Turkey. Liver cancer is affecting millions of people all over the world. Recent days interest in use of plant-derived compounds for therapeutic purposes in cancer is increasing. So any approach to treat liver cancer is extremely valuable. We aimed to evaluate the cytotoxic potential of extracts (methanol:water 1:1, chloroform and n-hexane) of 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). Regarding the cytotoxicity, cell viability was decreased following extract exposures at different time points. However, the highest cytotoxic activity was observed in 100 µg/mL concentrations of chloroform extract at 24 h. Chloroform extract of plant showed the highest cytotoxic activity in 200 µg/mL concentrations when compared to methanol:water and n-hexane extracts at 12 h. It can be suggested that used extracts of P. pyrrhoblepharus exert cytotoxic effect in HepG2 carcinoma cells in a dose- and time-dependent manner. Generally, results provide information regarding the threshold concentrations of P. pyrrhoblepharus extracts that might be used in different applications without toxicity hazards.