Four-octyl itaconate (OI), the itaconate's cell-permeable derivative, can activate Nrf2 signaling via alkylation of Keap1 at its cysteine residues. The current study tested the potential neuroprotective function of OI in hydrogen peroxide (H2O2)-treated neuronal cells.SH-SY5Y neuronal cells and epigenetically de-repressed (by TSA treatment) primary murine neurons were treated with OI and/or H2O2. Nrf2 pathway genes were examined by Western blotting assay and real-time quantitative PCR analysis. Neuronal cell death was tested by the LDH and trypan blue staining assays. Apoptosis was tested by TUNEL and Annexin V assays.In SH-SY5Y neuronal cells and primary murine neurons, OI activated Nrf2 signaling, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization and nuclear translocation, as well as expression of Nrf2-regulated genes (HO1, NQO1 and GCLC) and ninjurin2 (Ninj2). Functional studies showed that OI attenuated H2O2-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage as well as neuronal cell death and apoptosis. shRNA-mediated knockdown, or CRISPR/Cas9-induced knockout of Nrf2 almost abolished OI-induced neuroprotection against H2O2. Keap1 is the primary target of OI. Keap1 knockout by CRISPR/Cas9 method mimicked and abolished OI-induced actions in SH-SY5Y cells. Introduction of a Cys151S mutant Keap1 in SH-SY5Y cells reversed OI-induced Nrf2 activation and anti-H2O2 neuroprotection.OI activates Keap1-Nrf2 signaling to protect SH-SY5Y cells and epigenetically de-repressed primary neurons from H2O2 in vitro.
Abstract Background: Angiosarcoma, also known as malignant hemangioendothelioma, is a rare vasogenic malignant tumor, commonly found on the skin of the head and neck, rarely occurring in the intracranial region.As for intracranial meningeal angiosarcoma, only 7 cases have been reported and there is no clinical study with large sample size. We report here a case of parasagittal meningeal angiosarcoma. Case Description: A 48-year-old Asian male patient was admitted to our hospital due to headache accompanied by bilateral lower limb weakness. On admission, CT showed a high-density mass on both sides of the sagittal sinus at the top of the frontal lobe. We performed exploratory surgical resection of the tumor. During the operation, it was found that the tumor originated from the dura mater and extensively invaded the surrounding brain tissue and skull, and the surrounding hemosiderin deposition was observed. Postoperative pathology suggested angiosarcoma. Conclusions: Intracranial meningeal angiosarcoma is difficult to accurately diagnose before surgery, so radiologists and neurosurgeons need to strengthen their understanding of this disease. The presence of extensive superficial hemosiderin deposition during operation may contribute to the diagnosis, and immunohistochemistry is very important for the diagnosis of intracranial angiosarcoma.
During retrosigmoid craniotomy, the mastoid emissary vein (MEV) can be a source of considerable bleeding during the operation, especially when the larger diameter MEV or sigmoid sinus is torn. In this study, we evaluated the relevant structure of the MEV for their anatomy and applied the data in surgery to summarize their clinical significance.The posterior craniocervical regions of 15 silicon-injected Chinese human cadaver specimens were dissected to expose the MEV and adjacent structures. Fifty-one patients who were scheduled to undergo retrosigmoid craniotomy were selected. All patients underwent preoperative routine CT of the head. The relevant data were collected on cadaveric anatomy and CT. Eventually, all patients underwent retrosigmoid craniotomy and the MEV was observed during the operation.In cadaver specimens, the prevalence of the MEV was 90.0%. It originated from the middle and lower parts of the posterior wall of the sigmoid sinus and extended in the posterior direction in the mastoid process, usually having 1-2 external openings (86.7%) and only 1 internal opening. The intraosseous courses of the MEV were classified as straight and curved. The straight type accounted for 57.9%, and the curved type for 42.1%. The mean diameter of the MEV was 1.84 ± 0.85 mm, and the straight length of the MEV inside the mastoid process was 11.93 ± 3.58 mm. In 16.7% and 6.7% of all cadaver specimens, the MEV diameter was greater than 2.5 and 4 mm, respectively. In 51 patients (bilateral), routine head CT scan showed the MEV in 49.0% of the patients, and the MEV diameter was greater than 2.5 and 4 mm, respectively, in 17.6% (18/102) and 3.9% (4/102) of the cases. During surgery (unilateral) in the 51 patients, 48 had the MEV and 3 had no MEV. None of the patients had sigmoid sinus tears or massive bleeding.In the process of retrosigmoid craniotomy, detailed anatomical knowledge of the MEV, well-planned CT scan, and meticulous microsurgical techniques are key for successful operation, which can reduce the occurrence of complications.
Abstract Objective Postoperative complications are common in patients who underwent decompressive craniectomy (DC) after traumatic brain injury (TBI). However, little is known about the degree of association between the postoperative complications and the long‐term outcome of adult TBI patients after DC. The aim of this study was to evaluate the risk of postoperative complications that influenced the long‐term outcome of DC in TBI patients. Method A total of 121 patients were studied up to 6 months after DC in TBI. The collected data included demographic, clinical and radiological information, postoperative complications, and Glasgow Outcome Scale‐Extended (GOSE) scores at follow‐up 6 months after DC. Based on their GOSE scores, they were divided into two functional groups: favorable (GOSE = 5–8) or unfavorable outcome (GOSE = 2–4) group. The characteristics of the two groups were compared using statistical analysis. Finally, a regression model was established and a receiver operating characteristic (ROC) curve was applied to analyze its performance power. Results Of 121 admitted patients, 31 (25.62%) sustained an unfavorable outcome. A logistic regression analysis showed that the presence of Glasgow Coma Scale (GCS) scores on admission (odds ratio [OR] 0.285, p = 0.001), posttraumatic hydrocephalus (PTH) (OR 8.688, p = 0.003), craniectomy site (OR 8.068, p = 0.033), and postoperative progressive hemorrhagic injury (PHI) (OR 6.196, p = 0.026) were independent risk factors that correlated with an unfavorable outcome. Analysis using ROC curves demonstrated that these factors had different accuracies in predicting an unfavorable outcome (AUC = 0.852 for GCS scores on admission; AUC = 0.826 for PTH, AUC = 0.617 for craniectomy site; AUC = 0.616 for postoperative PHI). The performance power of the GCS scores on admission and PTH influenced the patient's outcomes to a similar degree ( p = 0.623), and either predicted the outcome better than the craniectomy site or the postoperative PHI ( p < 0.05, respectively). Conclusion These findings suggest that the occurrence of PTH and postoperative PHI were independently associated with an unfavorable long‐term outcome after DC in patients with TBI. Early prevention and treatment of PTH and postoperative PHI may be beneficial to improve the long‐term outcome, especially in patients with lower admission GCS scores or bilateral DC.
Epilepsy is one of the most common glioma complications, and the two may be connected in more ways than we understand. We aimed to investigate the clinical features of glioma-associated epilepsy and explore the risk factors associated with it.We collected clinical information from 485 glioma patients in the Nanjing Brain Hospital and conducted 4 periodic follow-up visits. Based on the collected data, we analyzed the clinical characteristics of glioma patients with or without epilepsy and their relationship with survival.Among glioma patients, younger people were more likely to have epilepsy. However, epilepsy incidence was independent of gender. Patients with grade II gliomas were most likely to develop epilepsy, while those with grade IV gliomas were least likely. There was no difference in Karnofsky Performance Status scores between patients with glioma-associated epilepsy and those without epilepsy. Additionally, epilepsy was independently associated with longer survival in the World Health Organization grade IV glioma patients. For grades II, III, and IV tumors, the 1-year survival rate of the epilepsy group was higher than that of the non-epilepsy group.Epilepsy did not lead to worse admission performance and correlated with a better prognosis for patients with grade IV glioma.
Background: Gliomas are the most prevalent primary malignant tumors of the central nervous system.Our previous study showed that miR-204-5p is a tumor suppressor gene in glioma.Bioinformatic analyses suggest that long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) is a potential target gene of miR-204-5p.Methods: We analyzed the expression of XIST and miR-204-5p in glioma tissues and the correlation with glioma grade.A series of in vitro experiments were carried out to elucidate the role of XIST in glioma progression.A mouse xenograft model was established to detect whether knockdown of XIST can inhibit glioma growth.A luciferase assay was performed to determine whether XIST can bind to miR-204-5p and the binding specificity.Cells stably expressing shXIST or shNC were transfected with anti-miR-204-5p or anti-miR-204-5p-NC to evaluate whether XIST mediates the tumor-suppressive effects of miR-204-5p.Results: XIST was upregulated in glioma tissues compared with normal brain tissues (NBTs), while miR-204-5p expression was significantly decreased in glioma tissues compared with NBTs.Both XIST and miR-204-5p expression levels were clearly related to glioma grade, and the expression of XIST was obviously negatively correlated with miR-204-5p expression.Knockdown of XIST inhibited glioma cell proliferation, migration, and invasion, promoted apoptosis of glioma cells, inhibited tumor growth and increased the survival time in nude mice.miR-204-5p could directly bind to XIST and negatively regulate XIST expression.XIST mediated glioma progression by targeting miR-204-5p in glioma cells.XIST crosstalk with miR-204-5p regulated Bcl-2 expression to promote apoptosis.Conclusion: Our results provide evidence that XIST, miR-204-5p and Bcl-2 form a regulatory axis that controls glioma progression and can serve as a potential therapeutic target for glioma.
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