Ferroptosis, 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, Fe ²⁺ , 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 μM 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, Fe ²⁺ , 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.

Background: The integration of AI in healthcare, particularly in clinical decision-making, has shown promising results. This study focuses on evaluating the performance of GPT-4 and GPT-3.5, two advanced AI models, in the context of spinal neurosurgery and physiotherapy, areas that require precise and dynamic decision-making. Methods: We conducted a prospective, observational study with 64 participants, including neurosurgeons and physiotherapists, who evaluated AI-generated responses for 10 detailed clinical scenarios. The assessment criteria included diagnostic accuracy, treatment suitability, surgical technique detail, and rehabilitation planning. Each scenario was meticulously crafted to reflect common yet complex clinical situations. Results: The study revealed that the GPT-4 consistently outperformed the GPT-3.5 across all the evaluated criteria, with the most significant differences observed in treatment suitability and rehabilitation planning. Statistical analyses, including paired t tests and ANOVA, confirmed the superiority of the GPT-4, highlighting its advanced language processing capabilities and broader medical knowledge base. Reliability analyses further supported these findings. Cronbach’s alpha values indicated moderate internal consistency for GPT-4 (α = 0.344) and lower consistency for GPT-3.5 (α = 0.133). Additionally, Cohen’s Kappa values demonstrated moderate agreement for GPT-4 (κ = 0.65) and fair agreement for GPT-3.5 (κ = 0.48), further validating the reliability of the participants’ evaluations. Conclusions: While the GPT-4 has significant potential as a clinical decision support tool, especially in complex and multidisciplinary fields such as spinal neurosurgery and physiotherapy, its recommendations should be carefully integrated with clinical expertise. Further research is essential to enhance its application and ensure that AI can effectively support dynamic medical environments.

Background: 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-α), 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-α, 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-α, 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.

Objective: 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-α, CRP), and histopathological evaluations were conducted to assess vasospasm and apoptosis. Results: SAH significantly increased pro-inflammatory cytokines (IL-1, IL-6, TNF-α, 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.

Microglial activation is a central mediator of neuroinflammatory and neurodegenerative processes. Growing evidence indicates that dysregulated lipid metabolism and ferroptosis drive microglial dysfunction, yet pharmacological interventions targeting these interconnected pathways remain scarce. Fenofibrate is well-documented for its anti-inflammatory and antioxidant effects; nevertheless, its influence on microglial lipid metabolism and ferroptotic signaling remains unexplored. The present study was designed to examine the effects of fenofibrate on lipid remodeling, oxidative stress, and ferroptosis in human HMC3 microglia activated with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). HMC3 cells were pre-treated with fenofibrate followed by inflammatory activation. Cell viability, cytokine secretion, oxidative stress, lipid droplet (LD) accumulation, and ferroptosis-associated markers were analyzed by ELISA, fluorescence imaging, qRT-PCR, and Western blotting. Fenofibrate decreased the production of TNF-α, IL-1β, and IL-6, restored mitochondrial membrane potential, and suppressed ROS and malondialdehyde (MDA) generation while increasing intracellular glutathione (GSH). The treatment markedly decreased LD accumulation by downregulating the lipid metabolism–related enzymes PLIN2, DGAT1, and GPAT4. Functional assays demonstrated enhanced fatty acid oxidation and restored lipolysis, directly confirming reprogrammed lipid catabolism. Moreover, fenofibrate attenuated ferroptotic stress, evidenced by reduced intracellular Fe²⁺ levels, decreased ACSL4 expression, and significant increase of the ferroptosis-protective enzyme GPX4. These molecular changes were accompanied by improved cell survival and decreased oxidative damage, suggesting that fenofibrate may partially modulate metabolic and and redox balance in activated microglia under in vitro conditions. In conclusion, these findings suggest that fenofibrate may exert protective effects by modulating lipid metabolism and suppressing ferroptosis-related pathways in activated microglia.

Objective: 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. Cite this article as: Kılıç G, Polat Ö, Şensoy D, Soylu H. Effects of isotretinoin and acitretin on neuroregeneration in experimental spinal cord injury. Acta Orthop Traumatol Turc., 2023;57(4):127-133.