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Öğe Boric Acid Suppresses Glioblastoma Cellular Survival by Regulating Ferroptosis via SOX10/GPx4/ACSL4 Signalling and Iron Metabolism(Wiley, 2025) Kilic, Guven; Hacioglu, Ceyhan; Tuncer, Cengiz; Kar, Ezgi; Kar, Fatih; Taskesen, Ahmet; Kurtulus, AdemFerroptosis, a distinct form of regulated cell death, plays a role in glioma pathogenesis. SRY-box (SOX) transcription factors are key regulators of cancer progression. In this study, we investigated the role of SOX10 in ferroptosis induction in U87 cells following boric acid treatment. First, the cytotoxic effects of boric acid on HMC3 and U87 cells were assessed using CCK8 and BrdU incorporation assays. Subsequently, SOX10, GPX4, ACSL4, GSH, MDA, total ROS, Fe2+, and TFR levels were analysed using ELISA, Western blot, and RT-PCR techniques. Additionally, DAPI staining was performed to evaluate nuclear abnormalities. According to the CCK8 analysis, the IC50 value for boric acid was determined to be 3.12 mM for HMC3 cells and 532 mu M for U87 cells, a finding further supported by BrdU incorporation analysis, which indicated that U87 cells were more sensitive to boric acid. Western blot and RT-PCR analyses revealed that SOX10 expression was significantly higher in U87 cells compared to HMC3 cells. Boric acid treatment led to a reduction in GSH, GPX4, and SOX10 levels in U87 cells, while inducing an increase in MDA, total ROS, ACSL4, Fe2+, and TFR levels. Moreover, microscopic analysis demonstrated that boric acid treatment induced both morphological and nuclear abnormalities in U87 cells. In conclusion, our findings demonstrate that SOX10 is involved in the ferroptosis signalling pathway and that boric acid effectively suppresses U87 cell viability by targeting the SOX10/GPX4/ACSL4 axis.Öğe The Comparative Effects of Anakinra and Tocilizumab on Inflammation and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model(Mdpi, 2024) Kilic, Guven; Engin, Berk Enes; Halabi, Amir; Tuncer, Cengiz; Sungur, Mehmet Ali; Alpay, Merve; Kurtulus, AdemObjective: Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular condition that triggers a robust inflammatory response and cerebral vasospasm. This study aimed to evaluate the effects of anakinra, an interleukin-1 receptor antagonist, and tocilizumab, an interleukin-6 receptor antagonist, on inflammation and vasospasm in an experimental rat SAH model. Methods: Forty male Sprague Dawley rats (200-250 g) were randomly assigned to five groups: control, SAH, SAH + anakinra (ANA), SAH + tocilizumab (TCZ), and SAH + anakinra + tocilizumab (ANA+TCZ). SAH was induced by injecting non-heparinized arterial blood into the cisterna magna. Treatment groups received anakinra (50 mg/kg twice daily), tocilizumab (8 mg/kg once daily), or their combination for three days. Blood and cerebrospinal fluid (CSF) samples were analyzed for inflammatory markers (IL-1, IL-6, TNF-alpha, CRP), and histopathological evaluations were conducted to assess vasospasm and apoptosis. Results: SAH significantly increased pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha, CRP) and fibrinogen levels in serum and CSF while reducing the basilar artery lumen diameter (p < 0.001). Anakinra and tocilizumab treatments significantly reduced inflammatory markers and vasospasm severity compared to the SAH group (p < 0.05). Combination therapy was more effective in reducing inflammation and vasospasm than either treatment alone (p < 0.05). Anakinra showed a stronger effect on IL-1 reduction, while tocilizumab was more effective in lowering IL-6 levels. The ANA+TCZ group exhibited a significant decrease in caspase activity, indicating reduced apoptosis (p < 0.05). Conclusions: Anakinra and tocilizumab effectively mitigated inflammation and vasospasm in an experimental SAH model, with combination therapy showing superior efficacy. These findings suggest that targeting both IL-1 and IL-6 pathways may be a promising therapeutic strategy for managing SAH complications. Further studies are warranted to evaluate long-term outcomes and clinical implications.Öğe Effects of isotretinoin and acitretin on neuroregeneration in experimental spinal cord injury(Turkish Assoc Orthopaedics Traumatology, 2023) Kilic, Guven; Polat, Omer; Sensoy, Dogan; Soylu, HakanObjective: This study aimed to determine whether isotretinoin and acitretin have beneficial effects on neural tissue damage following acute spinal cord injury. Methods: Thirty-six rats were randomly divided into 6 groups: control, sham spinal cord injury, spinal cord injury with isotretinoin 15 mg/ kg for 14 days, spinal cord injury with isotretinoin 15 mg/kg for 28 days, spinal cord injury with acitretin 10 mg/kg for 14 days, and spinal cord injury with acitretin 10 mg/kg for 28 days. The damage to the spinal cord was formed by the clip compression technique. A neurological evaluation was conducted on days 1, 14, and 28. All rats were sacrificed following the treatment period, and samples of their spinal cords were collected for histopathological analysis. Results: The inclined plane angle was significantly increased on the 14th and 28th days in the isotretinoin 15 mg and acitretin 10 mg groups, compared to the spinal injury group (P=.049 and P=.009, respectively). The Drummond-Moore criterion was significantly higher in the acitretin 10 mg group than in the injury group (P=.026). Cleaved Caspase-3 expression was similar in the isotretinoin 15 mg day 28 group and the control group (P > .05), but significantly decreased in the acitretin 10 mg 14th-day and acitretin 10 mg 28th-day groups compared to spinal injury isotretinoin 15 mg 14th-day and isotretinoin 15 mg 28th-day groups (P < .05). Conclusion: This was the first study elaborating that isotretinoin and acitretin reduced neuronal apoptosis and improved functional recovery after spinal cord injury. These neuroprotective effects might open a window of opportunity for patients.Öğe Investigation of the Relationship Between Cervical Disc Herniations and Shoulder Complex Pathologies(Duzce Univ, Fac Medicine, 2024) Tuncer, Cengiz; Kilic, Rabia Tugba; Kilic, Guven; Karaduman, Zekeriya Okan; Arican, Mehmet; Akbari, Pouriya; Uludag, VeyselObjective: The aim of our study was to investigate whether there is a relationship between shoulder complex pathologies and cervical disc herniations. Materials and Methods: This study retrospectively included 524 patients with both dominant extremity shoulder and neck magnetic resonance examinations obtained from the information processing unit of Duzce University Faculty of Medicine between 01.08.2009-01.08.2023. The results were compared in Statistical Package for Social Sciences (SPSS). Results: A total of 524 patients, 153 (29.2%) males and 371 (70.8%) females, with a mean age of 51.17 +/- 13.70 (range, 13-93) years, were included in the study. According to the statistical analysis of our study, 410 of the participants had supraspinatus pathology, 234 had infraspinatus pathology, 243 had subscapularis pathology and 11 had teres minor pathology. In addition, a statistically significant relationship was found between other shoulder pathologies and herniations at the C4 -C5 and C5 -C6 disc level (p<0.05). Conclusions: In conclusion, even if there is a significant relationship between cervical disc herniations and shoulder pathologies, different methods should be developed for treatment algorithms and pain management. Evaluation of the cervical region should not be neglected in patient groups with shoulder pathologies.Öğe Long-term Outcomes of Children with Myelomeningocele and the Quality of Life in Survivors(Duzce Univ, Fac Medicine, 2024) Cakmak, Hatice Mine; Onbas, Omer; Tuncer, Cengiz; Kocabay, Kenan; Kilic, Guven; Zamur, Cagatay; Sav, Nadide MelikeObjective: Myelomeningocele, a condition that causes chronic health conditions and diminished quality of life, affects not just the children but also their families. Therefore, we comprehensively evaluated the data of 101 children with MMC (myelomeningocele) and aimed to compare the quality of life between children with MMC and their siblings. It is crucial to understand that children with MMS have a diminished quality of life with social and behavioral aspects and health issues, which can be emotionally challenging for them and their families. Methods: In this retrospective study, we collected data from electronic files, ensuring a comprehensive and accurate representation of the participants' medical history. To measure the quality of life, we used the KIDSCREEN 10 instrument, a widely recognized and validated tool in pediatric research. Results: Of the 101 children, 93 were survivors. Comparing the survivors (n=93) with their siblings, survivors had lower HRQoL (health-related quality of life) scores in subdimensions of physical well-being (p<0.001), relationships with family (p<0.001) Aand friends (p<0.001), Aschool performance and attention (p<0.001). On the other hand, the psychological wellness score was higher in survivors than in siblings (p<0.001). Most 44 (43.5%) had average mental capacity. The HRQoL score, a measure of the impact of health conditions on a person's overall well-being, was lower in the Chiari type 2 group than in the other survivors (p=0.035). Serum and folic acid levels did not correlate with HRQoL measures. Conclusions: This study illuminates the quality of life measures in MMC survivors and the Chiari type 2 group and utilizes new MRI findings, which provide groundbreaking insights into the health conditions and well-being of these populations. These findings are of utmost importance for medical professionals, researchers, and healthcare providers specializing in pediatric care and neurology, as they can significantly impact the treatment and care of these patients.Öğe Mitigating Post-Subarachnoid Hemorrhage Complications: Anti-Inflammatory and Anti-Apoptotic Effects of Anakinra in an Experimental Study(Mdpi, 2025) Kilic, Guven; Engin, Berk Enes; Halabi, Amir; Tuncer, Cengiz; Sungur, Mehmet Ali; Alpay, Merve; Kurtulus, AdemBackground: Subarachnoid hemorrhage (SAH) is a severe neurological condition with high mortality and morbidity rates, often exacerbated by secondary complications such as inflammation, cerebral vasospasm, and apoptosis. Proinflammatory cytokines, including interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), play critical roles in these pathological processes. Anakinra, an IL-1 receptor antagonist, has demonstrated significant anti-inflammatory effects in various disease models. This study aimed to evaluate the efficacy of anakinra in mitigating inflammation, vasospasm, and apoptosis in an experimental rat model of SAH. Methods: Thirty-two male Sprague Dawley rats were divided into four groups: Control (healthy), SAH (no treatment), Saline (0.2 mL saline subcutaneously), and Anakinra (50 mg/kg subcutaneously, twice daily). Proinflammatory markers (CRP, TNF-alpha, IL-1, IL-6, and fibrinogen) were measured in serum and cerebrospinal fluid (CSF) at 3, 7, and 10 days post-SAH. Basilar artery diameter was evaluated histopathologically, and Caspase-3 expression was assessed immunohistochemically to determine apoptotic activity. Results: SAH significantly increased levels of CRP, TNF-alpha, IL-1, IL-6, and fibrinogen in both serum and CSF, reduced basilar artery diameter, and elevated Caspase-3 expression compared to the Control group. Saline treatment provided limited improvements, with inflammatory markers and histopathological parameters remaining elevated. Anakinra treatment significantly reduced inflammatory markers, restored basilar artery diameter, and lowered Caspase-3 expression, highlighting its efficacy in mitigating inflammation, vasospasm, and apoptosis. Conclusions: Anakinra effectively suppresses inflammation, alleviates cerebral vasospasm, and inhibits apoptosis in an experimental model of SAH. These findings suggest its potential as a therapeutic agent for managing SAH and its complications. Further research is needed to explore its clinical applicability and long-term effects.
