Background/Objectives: Glioblastoma, the most common primary tumor of the central nervous system, is characterized by high malignancy and poor prognosis. One of the main challenges in neurological disorders is to develop an effective treatment modality that can cross the blood–brain barrier. Nanoparticles are revolutionary for neurodegenerative diseases due to their targeted delivery and ability to overcome biological barriers. Cerium oxide (Ce₂O₃) nanoparticles are suitable for use as drug delivery systems. Methods: In our study, we investigated the anticancer mechanism using SN-38, lithium, and Ce₂O₃, a powerful agent used in GBM treatment. We evaluated their anticancer activities separately and in combination with U373 cell lines. GBM cell line U373 cells were cultured. Then, all groups except the control group were treated with different doses of SN-38 and lithium combination therapy with SN-38, lithium, and Ce₂O₃ combination therapy. The results were evaluated using MTT and ELISA tests. Results: When the results were examined, anticancer activity was detected at PTEN, AKT, mTOR, and BAX/Bcl-2 levels in the SN-38 + NPs 25 µg/mL + Lithium 50 µg/mL and SN-38 + NPs 50 µg/mL + Lithium 50 µg/mL dose groups. In addition, findings that inflammation markers were correlated with the apoptosis mechanism were obtained. Conclusion: This study is the first to report that combining lithium with SN-38 and NPs increased oxidative stress more than lithium with SN-38, leading glioblastoma cells to apoptosis and its potential anticancer activity. These results provide a basis for further investigation of its clinical application in cancer treatment.

Amygdalin (Vitamin B17) Effect on Glioblastoma: Focus on Oxidant Capacity and Antioxidant Status Running Title: Amygdalin anticancer effect on GBM TR Title: Glioblastoma Üzerindeki Amigdalin (B17 Vitamini) Etkisi: Oksidan Kapasite ve Antioksidan Durumuna Odaklanma Objective: Amygdalin (Vitamin B-17) is a type of vitamin, naturally found in many fruits and plants. The aim of the study is the evaluation of Amygdalin effect on the oxidant capacity and oxidant status of the T98G cancer cells. A T98G cell line was used in the study. Cell viability and oxidative stress evaluation were done. Methods: Amygdalin 1, 4, and 8 µgr/mL doses were used. TAC and TOS values were measured. Results: According to the result, amygdalin 8 µgr/mL shows the highest anticancer effects. TAC level was 3.2 Trolox Equiv/L-1 and TOS was 3.6 H2O2 Equiv/L-1. Conclusion: Vit B17 can increase oxidative stress in T98G cells and decrease cell viability. Keywords: Amygdalin, TAC, TOS, MTT, T98G Özet: Amaç: Amigdalin (Vitamin B-17), birçok meyve ve bitkide doğal olarak bulunan bir vitamin türüdür. Çalışmanın amacı, Amigdalin'in T98G kanser hücrelerinin oksidan kapasitesi ve oksidan durumu üzerindeki etkisinin değerlendirilmesidir. Çalışmada bir T98G hücre hattı kullanıldı. Hücre canlılığı ve oksidatif stres değerlendirmesi yapıldı. Yöntemler: Amigdalin 1, 4 ve 8 µgr/mL dozları kullanıldı. TAC ve TOS değerleri ölçüldü. Sonuçlar: Sonuçlara göre, amigdalin 8 µgr/mL en yüksek antikanser etkisini göstermektedir. TAC seviyesi 3.,2 Trolox Equiv/L-1 ve TOS ise 3.6 H2O2 Equiv/L-1 idi. Sonuç: Vit B17, T98G hücrelerinde oksidatif stresi artırabilir ve hücre canlılığını azaltabilir. Anahtar kelimeler: Amigdalin, TAC, TOS, MTT, T98G

Inflammation and increased cellular ROS levels caused by bee venom can increase formation of necrotic tissue and allergies. Many methods are used for bee venom induced toxicity. Two agents with therapeutic effects and pharmacological value have been included in these treatment options to decrease induced toxicity. L-tryptophan causes a decrease in the level of inflammation and the amount of ROS. Similarly, Amygdalin, which also targets the mTOR/AKT pathway and reduces inflammation, causes a decrease in FAK, ILK and β-catenin concentrations by inhibiting the expression of β1 and β4 integrins. Application of high doses of bee venom causes sensitization of nociceptors by activating TRPV1 via PLA2 cascade, which contains mellitin. This may result in pain and inflammation. We aimed to examine the toxic effects of bee venom by creating a wound model in the fibroblast cell line. After a linear wound was opened, the cells were exposed to bee venom (25 mg/ml) for 15 minutes. L-tryptophan and Vit B17 doses were applied at the end of 15 minutes. After 24 hours of incubation, wound healing was visualized and cell viability and oxidative damage tests were performed. The results showed that especially BV+ B17 + LT had a 60% effect on viability compared to the bee venom control group, resulting in wound closure. It was also determined that cellular ROS level decreased. All these results show that the combination of L-tryptophan and amygdalin has therapeutic efficacy on difficult-to-heal wounds.

Background/Objectives: Duchenne muscular dystrophy (DMD) is a genetic disorder caused by mutations in the dystrophin gene. DMD is characterized by exon deletions in about 76% of cases, with common deletions in exons 47, 48, 51, and 52. We evaluated the effectiveness of an mRNA-based therapy targeting these exon deletions, which are frequently seen in DMD patients. Methods: The current study involved two protocols: 1. applying the therapy to cells from patients diagnosed with DMD, and 2. applying the therapy to genetically modified transgenic mdx/d2 mice. After treatment, dystro-phin was detected in all experimental groups. Results: Our study showed that, both in vitro and in vivo analyses demonstrated that the mRNA-based therapy successfully restored dystrophin expression in dystrophic muscle cells and tissues. Gene expression analysis, together with protein-level assessments, including Western blot, immunoflu-orescence (IF), ELISA, and immunohistochemistry (IHC), confirmed a significant in-crease in dystrophin levels in the treated groups compared with the control group. In addition to dystrophin restoration, other key sarcolemmal proteins involved in main-taining muscle membrane stability, such as γ-sarcoglycan, β-dystroglycan, and β-actin, were also highly expressed. These findings suggest an overall improvement in muscle cell membrane integrity. Consistent with the molecular results, behavioral analyses performed in the animal model revealed significant functional improvements, includ-ing enhanced mobility, motor coordination, longer walking and resting durations, and a reduced risk of falls. Overall, the results indicate that mRNA-mediated dystrophin replacement improves both muscle structural integrity and functional performance. Conclusions: Our study proved that the mRNA complex successfully produced func-tional dystrophin in transgenic mdx/d2 mice without causing allergic reactions or damage to the kidney, intestines, muscles, or brain.

Background: Prolonged elevation of extracellular glutamate levels triggers intracellular events, increases glutamate excitotoxicity, and activates apoptotic pathways, causing Alzheimer's disease (AD). The literature has reported that vitamin B12 exhibits anti-inflammatory and anti-apoptotic activities in various diseases. Hydrocortisone (HC) therapy also substantially inhibits microglia and astrocyte hyperactivation, minimizing pro-inflammatory cytokines and reducing neuroinflammation. That is why our study aimed to evaluate the therapeutic effects of HC and B12 combination on oxidative stress and VIP and GAL levels in an in vitro Alzheimer's model. Method: To create the Alzheimer's model, the neuroblastoma cell line (SH-SY5Y) was cultured. Then, all cells except the control group were treated with different doses of HC and B12 combination for 24 hours by applying Glutamate (10-5 mM) to create excitotoxicity. The results were evaluated using MTT and ELISA tests. Results: When the results were examined, it was determined that exceptionally high-dose combination groups showed protective activity against glutamate excitotoxicity. HC+B12 25 µg/ml groups observed the most statistically significant results. According to our results, oxidative stress decreased in the HC+B12 25 µg/ml group, and cell viability increased. Significant changes were also observed in Vasoactive Peptide (VIP) and Galanin (GAL) levels in correlation with other analyses obtained. Conclusion: This study is the first to report the potential of vitamin B12 combined with hydrocortisone to prevent oxidative stress and glutamate excitotoxicity in primary neurons. It provides a basis for further investigating its clinical application in neurodegenerative diseases.