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Blocking VEGF by Bevacizumab Attenuates VEGF-Induced Vasospasm After Experimental Subarachnoid Hemorrhage in Rabbits
(Elsevier Science Inc, 2020) Akturk, Umut Dogu; Tuncer, Cengiz; Bozkurt, Huseyin; Sahin, Omer Selcuk; Bulut, Husamettin; Arikok, Ata; Turkoglu, Erhan
OBJECTIVE: Vasospasm after subarachnoid hemorrhage (SAH) plays a vital role in the development of delayed cerebral ischemia. Anti-vascular endothelial growth factor (VEGF) antibodies, like bevacizumab (BEV), may attenuate VEGF-stimulated angiogenesis, reduced vascular cell proliferation, and improve vasospasm after SAH. METHODS: Thirty-two adult male New Zealand white rabbits were randomly divided into 4 groups of 8 rabbits in each group: group 1 (control); group 2 (SAH); group 3 (SAH + vehicle); and group 4 (SAH + BEV). BEV (5 mg/kg, intraperitoneally) was administered 5 minutes after the intracisternal blood injection and continued for 72 hours once per day in the same dose for group 4. Animals were sacrificed 72 hours after SAH. Basilar artery cross-sectional areas, arterial wall thicknesses, and hippocampal degeneration scores were evaluated in all groups. RESULTS: VEGF is associated with the narrowing of the basilar artery. Treatment with BEV statistically significantly increased the cross-sectional area of the basilar artery when compared with the SAH and the vehicle groups. Basilar artery wall thicknesses in the BEV group was statistically significant smaller than in the SAH and vehicle groups. The hippocampal degeneration scores for the BEV and control groups were similar and significantly lower than those for the SAH and vehicle groups. CONCLUSIONS: Cellular proliferation and subsequent vessel wall thickening is a reason to delay cerebral ischemia and deterioration of the neurocognitive function. Intraperitoneal administration of BEV was found to attenuate cerebral vasospasm and prevent delayed cerebral ischemia and improve neurocognitive function after SAH in rabbits.
Borax induces ferroptosis of glioblastoma by targeting HSPA5/NRF2/GPx4/GSH pathways
(Wiley, 2024) Tuncer, Cengiz; Hacioglu, Ceyhan
Glioblastoma multiforme (GBM) is a highly aggressive and lethal form of primary brain tumour. Borax has been demonstrated to exhibit anti-cancer activity through cell death pathways. However, the specific impact of borax on ferroptosis in GBM is not well-established, and the underlying regulatory mechanisms remain unclear. Initially, the effective concentration of borax on cell viability and proliferation in U251 and A172 cells was determined. Subsequently, the effects of borax on the wound healing were analysed. Nuclear factor erythroid 2-related factor 2 (NRF2), glutathione peroxidase 4 (GPx4), glutathione (GSH), HSP70 protein 5 (HSPA5), malondialdehyde (MDA) levels and caspase-3/7 activity were determined in borax-treated and untreated cells. Finally, the protein expression levels of HSPA5, NRF2 and GPx4 were analysed. Borax suppressed cell viability and proliferation in U251 and A172 cells in a concentration- and time-dependent manner. In addition, borax treatment decreased GPx4, GSH, HSPA5 and NRF2 levels in U251 and A172 cells while increasing MDA levels and caspase-3/7 activity. Moreover, borax reduced mRNA and protein levels of HSPA5, NRF2 and GPx4 in U251 and A172 cells. Consequently, borax may induce ferroptosis in GBM cells and regulate the associated regulatory mechanisms targeting NRF2 and HSPA5 pathways. This knowledge may contribute to the development of novel therapeutic approaches targeting ferroptosis in GBM and potentially improve patient outcomes.
Borax regulates iron chaperone- and autophagy-mediated ferroptosis pathway in glioblastoma cells
(Wiley, 2023) Hacioglu, Ceyhan; Kar, Fatih; Davran, Fatih; Tuncer, Cengiz
Glioblastoma (GBM) is classified as a stage-IV glioma. Unfortunately, there are currently no curative treatments for GBM. Poly(rC)-binding protein 1 (PCBP1) is a cytosolic iron chaperone with diverse functions. PCBP1 is also known to regulate autophagy, but the role of PCBP1 in ferroptosis, iron-dependent cell death pathway, remains unrevealed in GBM cells. Here, we investigated the effects of borax, a boron compound, on the ferroptosis signaling pathway mediated by PCBP1 and autophagy. The study analyzed cell viability, proliferation, and cell cycle on U87-MG and HMC3 cells to investigate the effects of borax. After determining the cytotoxic concentrations of borax, morphological analyzes and measurement of PCBP1, Beclin1, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPx4) and acyl-CoA synthetase long chain family member 4 (ACSL4) levels were performed. Finally, expression levels of PCBP1, Beclin1, GPx4 and ACSL4, and caspase-3/7 activity were determined. We found that borax reduced U87-MG cell viability in a concentration- and time-dependent manner. Additionally, borax altered cell proliferation and remarkably reduced S phase in the U87-MG cells and exhibited selectivity by having an opposite effect on normal cells (HMC3). According to DAPI staining, borax caused nuclear deficits in U87-MG cells. The result showed that borax in U87-MG cells induced reduction of the PCBP1, GSH, and GPx4 and enhancement of Beclin1, MDA, and ACSL4. Furthermore, borax triggered apoptosis by activating caspase 3/7 in U87-MG cells. Our study indicated that the borax has potential as an anticancer treatment for GBM via regulating PCBP1/Beclin1/GPx4/ACSL4 signaling pathways.
Boric acid Increases Susceptibility to Chemotherapy by Targeting the Ferritinophagy Signaling Pathway in TMZ Resistant Glioblastoma Cells
(Springernature, 2024) Hacioglu, Ceyhan; Tuncer, Cengiz
Glioblastoma (GBM) is a common and highly lethal form of brain cancer. Temozolomide (TMZ) is the primary chemotherapy used for GBM, but it has limited effectiveness, with about half of the patients developing resistance. Iron regulatory proteins (IRPs) modulate genes involved in iron metabolism, while the nuclear receptor coactivator 4 (NCOA4) controls iron metabolism through a process called ferritinophagy. In this study, we investigated whether boric acid increases chemosensitivity mediated by ferritinophagy via the NCOA4 and IRP2 signaling pathways in TMZ-resistant GBM cells. First, we generated TMZ-resistant GBM cells (A172-R and T98G-R cells). Next, we investigated the effects of boric acid on cell viability, proliferation, cell cycle, and cell morphology in these cells. Additionally, following boric acid treatment, we analyzed the expression and protein levels of various biochemical markers in these cells. Boric acid treatment in A172-R and T98G-R cells suppressed cell viability and proliferation, arrested these cells in the G1/G0 cell cycle, and induced morphological differences. Boric acid increased NCOA4, IRP2, iron, and malondialdehyde (MDA) levels in A172-R and T98G-R cells, while glutathione (GSH) and glutathione peroxidase 4 (GPx4) levels decreased. Moreover, boric acid treatment increased intracellular iron levels and lipid peroxidation by inducing NCOA4 and IRP2 expression levels in TMZ-resistant cells. According to our results, boric acid may regulate chemosensitivity in A172-R and T98G-R cells mediated by NCOA4 and IRP2. In conclusion, the manipulative effects of boric acid on the ferritinophagy pathway hold the potential to sensitize TMZ-resistant GBM cells to chemotherapy.
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, Adem
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, 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.
Cerrahi Tedavi Uygulanan Kalça Kırığı olan Geriatrik Hastalardaki Erken Dönem Mortalite Oranları ve Cerrahi Tipleri
(2024) Özel, Zafer; Karaduman, Zekeriya Okan; Arıcan, Mehmet; Turhan, Yalçın; Tuncer, Cengiz; Uludağ, Veysel
Amaç: Bu çalışmanın amacı, basit düşme sonrası kalça kırığı gelişen ve cerrahi olarak tedavi edilen 65 yaş üstü hastalarda cerrahi sonrası 30 gün içinde mortalite ile kırık, implant tipi ve cerrahi zamanlaması arasındaki ilişkiyi araştırmaktır. Gereç ve Yöntemler: 01 Ocak 2010 - 31 Temmuz 2020 tarihleri Düzce Üniversitesi Tıp Fakültesi Ortopedi ve Travmatoloji Anabilim Dalına başvuran hastalar incelendi. Bu hastalar arasından belirtilen tarihler arasında izole kalça kırığı tanısı ile protez veya proksimal femoral çivi/plak vida ameliyatı yapılan 65 yaş üstü hastalarda cinsiyet, yaş, ameliyat zamanı, ameliyat tipi ve ameliyat sonrası mortalite oranları arasındaki ilişki retrospektif olarak değerlendirildi. Bu çalışmada, belirtilen zaman aralığında tedavi edilen 450 hasta değerlendirildi ve 308 hasta çalışmamızın kriterlerini karşıladı. Bulgular: Mortalite oranları ile cerrahi (implant) arasında istatistiksel olarak anlamlı bir fark vardı (p<0,05). Ayrıca Anestezi tipi ile mortalite oranları arasında istatistiksel olarak anlamlı bir fark vardı (p<0,001). Hastaneye yatış ile ameliyat arasında geçen süre (gün) ve ameliyat ile taburculuk arasında geçen süre (gün) ile mortalite oranları arasında istatistiksel olarak anlamlı bir fark yoktu (p=0,984). Ameliyat yaşı ile mortalite oranları arasındaki fark istatistiksel olarak anlamlıydı (p<0,001). Sonuç: Bu çalışmada ameliyat sonrası birinci ayda mortalite oranı %8,1 olarak bulundu ve mortaliteyi etkileyen en önemli faktörlerin ameliyat tipi ve anestezi tipi olduğu saptandı.
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, Adem
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-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.
Comparison of Range of Motion Outcomes in Patients Undergoing Open-Door Laminoplasty or Posterior Cervical Fusion Surgery for Cervical Spondylotic Myelopathy
(Duzce Univ, Fac Medicine, 2025) Ozdemir, Burak; Tuncer, Cengiz; Aydin, Levent; Altas, Kadir; Basaran, Recep; Musluman, Ahmet Murat
Aim: This study aimed to compare neurological and functional outcomes, including cervical range of motion (ROM), inApatients with cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL) who underwent either open-door laminoplasty (LP) or posterior cervical fusion (PCF) surgery. Material and Methods: This retrospective, single-center study included 38 patients, 11 female and 27 male, diagnosed with CSM and OPLL who underwent LP (n=20) or PCF (n=18) between 2014 and 2016. AClinical outcomes were assessed using the Japanese Orthopedic Association (JOA), visual analog scale (VAS), and Nurick scores. Cervical ROM values, including flexion, Aextension, lateral flexion, and rotation, were measured preoperatively and six months postoperatively in collaboration with physical therapy specialists. Results: Both LP and PCF groups showed significant postoperative improvement in JOA, VAS, and Nurick scores (all p<0.001), Awith no significant differences between groups (p=0.405, p=0.708, and p=0.963, respectively). Cervical ROM values significantly decreased in all directions postoperatively in both groups. Flexion (p<0.001), Aleft lateral flexion (p=0.007), and left rotation (p=0.003) Adeclined more severely in the PCF group, whereas the difference between groups did not reach statistical significance level in extension (p=0.105), right lateral flexion (p=0.065), and right rotation (p=0.067). Conclusion: LP and PCF offer similar neurological recovery inApatients with CSM. However, LP better preserves postoperative cervical ROM. Despite the observed ROM reduction, daily functional activities remained largely unaffected. Long-term, larger studies are recommended for further validate these findings.
CORRELATION BETWEEN SPINOPELVIC PARAMETERS AND THE DEVELOPMENT OF LUMBAR DISC HERNIATION
(2019) Tuncer, Cengiz; Polat, Ömer; Er, Uygur
Objective: The present study aimed to identify the correlation between spinopelvic parameters and the development of lumbar disc herniation,which is a condition usually surgically treated.Materials and Methods: A total of 147 consecutive patients with low back pain were divided into two groups according to treatment withmicrodiscectomy or treatment with some medications. In all patients, pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), and pelvic tilt(PT) angles were measured on standing profile roentgenograms of the lumbar spine and pelvis. Statistical differences were investigated betweenthe two groups.Results: The PI, LL, and SS values were significantly different between the two groups. However, the difference in terms of PT was not significant.Conclusion: Some spinopelvic parameters, such as PI, LL, SS, and PT, may be considered as predictive factors in the development of degenerativespinal diseases, and the restoration of sagittal balance may provide better results when these factors are considered.
The effect of etanercept on Spinal epidural Fibrosis in a Postlaminectomy Rat Model
(2014) Türkoğlu, Erhan; Tuncer, Cengiz; Dinç, Cem; Serbes, Gökhan; Oktay, Murat; Şekerci, Zeki
AMAÇ: Posterior spinal cerrahi sonrası duramatere yapışık epidural fibrozis formasyonu vücudun cerrahiye karşı vermiş olduğu normal bir reaksiyondur. Aşırı epidural fibrozis postlaminektomi sendromuna yol açan önemli nedenlerden biridir. Etanersept tümör nekrozis faktör alfayı inhibe ederek fibroblast migrasyonunu engeller ve sonuç olarak fibrozis gelişmesini önler. Bu çalışmanın amacı; topikal uygulanan etanerseptin rat laminektomi modelinde gelişen epidural fibrozis üzerine etkisini araştırmaktır. YÖNTEM ve GEREÇLER: 24 Wistar rat rastgele ve eşit olarak üç gruba (Kontrol, spongostan ve etanersept) ayrıldı. Bütün ratlara L3-L5 laminektomi yapıldı. Spongostana emdirilmiş salin (0.1mg/kg) ve etanersept (300 µg/kg) direkt duramatere uygulandı ve duramater üzerinde bırakıldı. 4 hafta sonra ratların T10-L5 arası omurgaları enblok olarak çıkartılarak, epidural fibrozis ve araknoidal tutulum histopatolojik olarak incelendi ve derecelendirildi. BULGULAR: Kontrol grubu ile karşılaştırıldığında topikal uygulanan etanersept grubunda epidural fibrozisin istatistiksel olarak anlamlı derecede azaldığı görüldü (p0.05). SONUÇ: Çalışmamız; topikal uygulanan etanerseptin laminektomi yapılmış ratlarda gelişen epidural fibrozisin azaltılmasında etkili olduğunu göstermiştir.
The Effect of Etanercept on Spinal Epidural Fibrosis in a Postlaminectomy Rat Model
(Turkish Neurosurgical Soc, 2014) Türkoğlu, Erhan; Tuncer, Cengiz; Dinç, Cem; Serbes, Gökhan; Oktay, Murat; Şekerci, Zeki
AIM: The formation of epidural fibrosis adjacent to the dura mater after posterior spinal surgery is a normal reaction of the body to surgery. Extensive epidural fibrosis is one of the important causes of postlaminectomy syndrome. Etanercept inhibits tumor necrosis factor-alpha and decreases fibroblast migration. Thus, etanercept prevents the formation of fibrosis. The aim of this study was to investigate the effects of topical application of etanercept on epidural fibrosis after laminectomy in a rat model. MATERIAL and METHODS:Twenty-four Wistar rats were equally and randomly divided into three groups (control, spongostan and etanercept). Laminectomy was performed between L3 and L5 in all the rats. Spongostan soaked with saline (0.1 mg/kg) and etanercept (300 mu g/kg) was directly exposed to and left on the dura mater. Four weeks later, the vertebral columns of the rats were removed en bloc between T10 and L5, and epidural fibrosis and arachnoidal involvement were evaluated and graded histopathologically. RESULTS: Our data revealed that epidural fibrosis was reduced significantly in the rats treated with etanercept, compared to the control groups (p<0.05). CONCLUSION: Our study demonstrated that topical application of etanercept can be effective in reducing epidural fibrosis in rats after laminectomy.
THE EFFECT OF PREOPERATIVE CERVICAL SAGITTAL ALIGNMENT ON POSTOPERATIVE SURGICAL RESULTS IN PATIENTS TREATED BY ANTERIOR CERVICAL DISCECTOMY AND FUSION
(2019) Subaşı, Canan; Tuncer, Cengiz; Er, Uygur
Objective: Cervical degenerative disc diseases arise in some degenerative settings. These degenerative cervical changes may be a consequenceof cervical sagittal malalignment. The aim of this study is to assess preoperative profile and postoperative changes in cervical sagittal profiles;and correlation between these changes and surgical outcomes in patients undergoing anterior cervical discectomy and fusion.Materials and Methods: Eighty consecutive men and women who underwent anterior cervical discectomy and fusion (ACDF) were enrolled inthe study. Cervical alignment was classified into 4 types-lordotic, flat, sigmoid, and kyphotic. Lordosis angle was measured by the Cobb method.Segmental angle at the level of discectomy was measured. Preoperative, early postoperative, and the 1st and 3rd month visual analog scale resultswere recorded. Improvement of cervical sagittal alignment and visual analogue scale (VAS) changes were compared statistically.Results: The median preoperative VAS score was 7. This score decreased to 1 as a median immediately after operation. This change was statisticallysignificant. Sagittal alignment changes in early postoperative period were not statistically significant despite the observation of improvement insome patients. However, after 1st and 3rd months, results showed significant improvements.Conclusion: ACDF is an effective treatment of cervical degenerative disc diseases (CDDD). Decompression is still the main issue of the degenerativecervical diseases. Sagittal alignment may be restored by using lordotic cages. Patients with F sagittal shape may tend to develop CDDD more thanN sagittal profile. There is a correlation between clinical improvement and radiologic improvement.
Effect of topical rifamycin application on epidural fibrosis in rats
(Baycinar Medical Publ-Baycinar Tibbi Yayincilik, 2019) Dinç, Cem; Tuncer, Cengiz; Türkoğlu, Mehmet Erhan; Tokmak, Mehmet; Ocak, Pınar; Er, Uygur
Objectives: This study aims to investigate the effects of topical rifamycin SV application on epidural fibrosis formation in a rat model. Materials and methods: Between March 2015 and April 2015, a total of 20 Wistar rats were equally and randomly divided into laminectomy only group (control group) and laminectomy and rifamycin SV group (treatment group). Laminectomy was performed between L3-L5 in all rats. Surgical field was irrigated with 1 mL rifamycin SV (1 mL). After four weeks, vertebral columns of the rats were removed en bloc between the L1 and L5 levels, and epidural fibrosis and arachnoid involvement were histopathologically evaluated and graded. Results: Grade 3 epidural fibrosis formation ratio was lower in the treatment group (40%) compared to the control group (80%). However, there was no statistically significant difference between the treatment and control groups in terms of epidural fibrosis (p=0.164) and arachnoid involvement (p=0.303). Conclusion: Intraoperative rifamycin irrigation tends to reduce epidural fibrosis formation risk, although not statistically significant.
Emergency Department Neurosurgical Consultations in a Tertiary Care Hospital
(Duzce Univ, Fac Medicine, 2023) Senguldur, Erdinc; Selki, Kudret; Tuncer, Cengiz; Demir, Mehmet Cihat
Objective: To reveal the characteristics of patients in need of neurosurgery by examining neurosurgery consultations within the emergency department (ED) admissions of a tertiary academic hospital.Methods: This is a retrospective, single-centre observational study. Patients admitted to the ED between 01.01.2022 -31.12.2022 and consulted to the neurosurgery department were identified through the hospital computer system and included in the study. The demographic information of the patients, mode of admission to the ED, the reasons for admission, the time of admission, the number of brain computed tomography (CT) scans, whether they underwent surgery or not, and the mortality results were recorded.Results: A total of 441 neurosurgery consultations were examined. Fall 35.6% (n=157) and traffic accident 16.6% (n=73) were the most common reasons for consultation. It was observed that 92.5% (n=408) of the patients had a brain CT scan, and 19.5% (n=86) had two or more brain CTs. It was determined that 12.7% (n=56) of the patients consulted to neurosurgery were operated on, and 4.1% (n=18) of the patients' hospital admissions resulted in death. Only 53.7% (n=237) of the patients who underwent neurosurgery consultation were discharged from the ED. It was determined that significantly more Neurosurgery consultations were requested during working hours (p = 0.013).Conclusions: Most consultation calls from the ED to neurosurgery are for trauma patients. Brain CT examination is frequently used in neurosurgical patient evaluation. As a result of the consultations, almost half of the patients are hospitalized. Emergency physicians can select patients who need neurosurgery well.
Fenofibrate mitigates microglial activation by reprogramming lipid metabolism and inhibiting ferroptosis
(Springer, 2026) Taskesen, Ahmet; Hacioglu, Ceyhan; Tuncer, Sibel; Kilic, Guven; Tuncer, Cengiz
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-gamma (IFN-gamma). 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-alpha, IL-1 beta, 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 Fe & sup2;(+) 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.
Ferroptosis-inducing effects of cromolyn in microglia through NCOA4-mediated ferritinophagy
(Springer/Plenum Publishers, 2025) Kilic, Mustafa; Hacioglu, Ceyhan; Tuncer, Sibel; Taskesen, Ahmet; Tuncer, Cengiz
Cromolyn has anti-inflammatory and neuroprotective effects. However, its influence on microglial cell viability and death pathways remains largely unexplored. This study aimed to elucidate the cellular and molecular mechanisms underlying the effects of cromolyn exposure on microglial viability, with a particular focus on ferroptosis and ferritinophagy. HMC3 microglial cells were treated with cromolyn for 24, 48, and 72 h. Cell viability, nuclear morphology, cell cycle, MDA, GSH, and intracellular iron levels were assessed. Western blot analysis evaluated the expression of ferroptosis-related (GPX4, ACSL4, SLC7A11) and autophagy-associated (NCOA4, FTH1) proteins. Functional validation was performed using ferroptosis and autophagy inhibitors, and NCOA4-silencing. Cromolyn induced time- and dose-dependent cytotoxicity (IC50 at 48 h = 9.4 mu M), with prominent G0/G1 cell cycle arrest and nuclear abnormalities emerging at 48 h. At 72 h, excessive cell death limited mechanistic analyses. Cromolyn triggered ferroptosis via the GPX4-regulated pathway, evidenced by increased MDA, iron accumulation, and altered expression of GPX4, ACSL4, and SLC7A11. This ferroptotic response was mechanistically linked to NCOA4-mediated ferritinophagy, leading to GPX4 suppression and lipid peroxidation. NCOA4 knockdown rescued cell viability, restored FTH1 levels, and reduced lipid peroxidation. Our findings suggest, for the first time, that cromolyn may regulate microglial survival through an NCOA4-dependent ferritinophagy-ferroptosis axis. Given the dual roles of microglia in neuroinflammation and neurodegeneration, these data highlight both the therapeutic potential and risks of cromolyn in neurodegenerative disorders.
Investigation of Lateral Epicondylitis in Neurosurgeons
(2019) Polat, Ömer; Tuncer, Cengiz; Katı, Yusuf Alper; Uckun, Ozhan Merzuk; Er, Uyğur
AIM: To investigate the frequency of lateral epicondylitis (LE), depending on the tasks performed by neurosurgeons, and to determinewhether it can be accepted as an occupational disease depending on its frequency.MATERIAL and METHODS: All neurosurgery specialists enrolled in the Turkish Neurosurgical Society website were prospectively included. A questionnaire form was shared, and the subsequent responses were recorded. Those who provided incomplete responseswere excluded from the study. The respondents diagnosed with LE were recorded. Exclusion criteria were investigated on complaints ofpain. They were examined by an orthopedics and traumatology specialist with application of Thomsen test and necessary maneuvers.RESULTS: The study was conducted with 216 neurosurgeons. Those with more than 30 operations per month (p=0.002), those with aspecialization duration of 10–20 years and >20 years (p=0.001), and those who specialized in spinal surgery (p=0.014) had a significantlyhigher prevalence of epicondylitis. Considering the relationship between lumbar/thoracic pedicle screw insertion and epicondylitis, theepicondylitis diagnosis rate was significantly higher in physicians inserting 20–60 screws per month than those inserting <20 screws(p=0.009).CONCLUSION: LE frequently occurs in neurosurgeons who regularly perform spinal instrumentation and appears to be an occupationaldisease. However, data obtained during the current study should be combined with findings from case-control studies of neurosurgeons.
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, Veysel
Objective: 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.
Is IL-8 level an indicator of clinical and radiological status of traumatic brain injury?
(2019) Polat, Ömer; Uckun, Ozhan Merzuk; Tuncer, Cengiz; Belen, Ahmet Deniz
BACKGROUND: Since understanding the fact that traumatic brain injury includes an inflammatory process, the number of studiesof cytokines has increased. The objective of this study was to analyze and discuss the association of interleukin (IL)-8 level with theclinical and radiological status of patients with head trauma.METHODS: Patients who were admitted to our hospital due to head trauma were included in the study. Findings of clinical and laboratory examinations were analyzed. Data regarding patient age, gender, available clinical findings, Glasgow Coma Scale (GCS) score,trauma cause, brain tomography findings, and biochemical laboratory test results were recorded. The patients were divided into 3groups according to their GCS score: Group I: GCS ?13, Group II: GCS = 9–12, and Group III: GCS = 3–8.RESULTS: A total of 23 (76.7%) patients were male and 7 (23.3%) were female. Overall, 17 (56.7%) patients were admitted due to afall, 8 (26.7%) due to a traffic accident, and 5 (16.7%) due to assault. Each group comprised 10 patients. As the GCS score increased,the IL-8 level decreased. The mean IL-8 level was 1.2 pg/mL in Group I, 6.6 pg/mL in Group II, and 4.7 pg/mL in Group III; however,there was no statistically significant difference between the groups (p=0.147). Moreover, the IL-8 level was significantly greater in patients who demonstrated an abnormal tomography finding (p=0.023).CONCLUSION: IL-8 may be a beneficial indicator for monitoring the clinical and radiological status of traumatic brain injury.Nonetheless, studies of larger cohorts in which IL-8 levels are measured at all stages of brain injury and follow-up of long-term prognosis are warranted.
Kronik Bel Ağrısı Olan Hastalarda Ağrı Fonksiyonel Kısıtlılık ve Uyku Kalitesinin Değerlendirilmesi
(2025) Tuncer, Cengiz; Kılıç, Rabia Tuğba; Uludağ, Veysel; Kurtuluş, Adem; Kılıç, Güven; Taşkesen, Ahmet; Sungur, Mehmet Ali
AMAÇ: Bu çalışma, kronik bel ağrısı olan hastalarda ağrıya bağlı yetersizlik, uyku kalitesi ve çeşitli demografik ve klinik özellikler arasındaki ilişkiyi değerlendirmeyi amaçlamaktadır. Çalışmanın bilime katkısı, kronik bel ağrısı olan hastaların yönetiminde biopsikososyal modelin önemine dikkat çekmektir. GEREÇ ve YÖNTEMLER: Çalışmaya, en az 6 haftadır geçmeyen bel ağrısı şikayetiyle Düzce Üniversitesi Beyin Cerrahisi polikliniğine başvuran 151 hasta dahil edilmiştir. Ağrı, görsel analog skalar kullanılarak istirahat, uyku ve yürüme ağrıları şeklinde değerlendirilmiştir. Fonksiyonel kısıtlılık, geçerliliği ve güvenilirliği sağlanmış bir ağrı fonksiyonel kısıtlılık anketi ile, uyku kalitesi ise Pittsburg Uyku Kalitesi İndeksi ile değerlendirilmiştir. BULGULAR: Çalışmaya katılan hastaların yaş ortalaması 46.68 yıl olup, %55’i kadın ve %45’i erkektir. Erkekler, kadınlara kıyasla istatistiksel olarak anlamlı düzeyde daha yüksek istirahat ağrısı (p=0.044), mesleki fonksiyon kaybı (p=0.002) ve daha kötü uyku kalitesi (p=0.041) bildirmiştir. Kronik hastalığı olan hastalar, kronik hastalığı olmayanlara kıyasla daha yüksek istirahat ağrısı (p=0.027) ve daha kötü uyku kalitesi (p=0.002) bildirmiştir. İlaç kullanan bireyler, kronik hastalıklara bağlı ilaç (örneğin, hipertansiyon, diyabet) veya düzenli ağrı kesici ilaç kullanan hastalardır. İlaç kullanan bireyler, kullanmayanlara göre daha yüksek istirahat ağrısı (p=0.001) ve daha kötü uyku kalitesi (p<0.001) bildirmiştir. Sigara içenler, içmeyenlere göre daha yüksek istirahat ağrısı (p=0.042) ve daha kötü uyku kalitesi (p=0.029) bildirmiştir. Ağrı ve ağrıya bağlı yetersizlik arasında pozitif ve anlamlı korelasyonlar bulunmuştur. SONUÇ: Bu çalışma, kronik bel ağrısı olan hastalarda ağrı, uyku kalitesi ve çeşitli demografik ve klinik faktörler arasındaki karmaşık etkileşimi vurgulamaktadır. Bu bulgular, kronik bel ağrısının yönetiminde biopsikososyal yaklaşımların önemini ve bireyselleştirilmiş tedavi stratejilerinin gerekliliğini göstermektedir.

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