Increased serum levels of high-mobility group box 1 protein and the location characteristics in the patients of intracranial aneurysms.

OBJECTIVE: Inflammation-related factors play a crucial role in intracranial aneurysms (IA) initiation, progression, and rupture. High mobility group box 1 (HMGB-1) serves as an alarm to drive the pathogenesis of the inflammatory disease. This study aimed to evaluate the role of HMGB-1 in IA and explore the correlation with other inflammatory-related factors. METHODS: A total of twenty-eight adult male Japanese white rabbits were included in with elastase-induced aneurysms, n = 18) and the control group (normal rabbits, n = 10). To assess the expression of HMGB-1, both reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) was performed on serum samples obtained from human subjects (10 patients with IA and 10 healthy donors) as well as from rabbits (aneurysm group and control group). Immunohistochemistry and immunofluorescence were employed to evaluate the expression levels of elastic fibers, HMGB-1, tumor necrosis factor-alpha (TNF-α), and triggering receptor expressed on myeloid cells-1 (TREM-1). RESULTS: The expression of HMGB-1 was found to be significantly higher in the IA group compared to the control group, both at the mRNA and protein levels (P < 0.0001). Similar findings were observed in the rabbit aneurysm model group compared to the control group (P < 0.0001). HMGB-1 expression was observed to be more abundant in the inner wall of the aneurysm compared to the external wall, whereas in the control group, it was rarely scattered. Additionally, the localization patterns of TNF-α and TREM-1 exhibited similar characteristics to HMGB-1. CONCLUSION: Our findings demonstrate that HMGB-1 is highly expressed in both IA patients and rabbit aneurysm models. Furthermore, the similar localization patterns of HMGB-1, TNF-α, and TREM-1 suggest their potential involvement in the inflammatory processes associated with IA. These results highlight the potential of HMGB-1 as a novel therapeutic target for IA.

Preoperative Fibrinogen Levels and Function as Predictive Factors for Acute Bleeding in the Hematoma Cavity After Burr Hole Drainage in Patients with CSDH.

OBJECTIVE: Burr hole drainage (BHD) is the primary surgical intervention for managing chronic subdural hematoma (CSDH). However, it can lead to postoperative complications such as acute bleeding within the hematoma cavity and hematoma recurrence. The objective of this study is to identify the risk factors for these complications and develop a predictive model for acute hematoma cavity bleeding after BHD in patients with CSDH. METHODS: This study presents a retrospective cohort investigation conducted at a single center. The clinical dataset of 308 CSDH patients who underwent BHD at a hospital from 2016 to 2022 was analyzed to develop and assess a prognostic model. RESULTS: The nonbleeding group exhibited a significant correlation between fibrinogen (FIB) and thrombin time (TT), whereas no correlation was observed in the bleeding group. Notably, both FIB and TT were identified as risk factors for postoperative acute bleeding within the hematoma cavity. We developed a prognostic model to predict the occurrence of postoperative acute bleeding within the hematoma cavity after BHD in patients with CSDH. The model incorporated FIB, TT, coronary artery disease, and Glasgow Coma Scale scores. The model exhibited good discrimination (area under the curve: 0.725) and calibration (Hosmer-Leeshawn goodness of fit test: P > 0.1). Furthermore, decision curve analysis demonstrated the potential clinical benefit of implementing this prediction model. CONCLUSIONS: The predictive model developed in this study can forecast the risk of postoperative acute bleeding within the hematoma cavity, thus aiding clinicians in selecting the optimal treatment approach for patients with CSDH.

Right-to-Left Displacement of an Airgun Lead Bullet after Transorbital Entry into the Skull Complicated by Posttraumatic Epilepsy : A Case Report.

Penetrating head injury is a serious open cranial injury. In civilians, it is often caused by non-missile, low velocity flying objects that penetrate the skull through a weak cranial structure, forming intracranial foreign bodies. The intracranial foreign body can be displaced due to its special quality, shape, and location. In this paper, we report a rare case of right-to-left displacement of an airgun lead bullet after transorbital entry into the skull complicated by posttraumatic epilepsy, as a reminder to colleagues that intracranial metal foreign bodies maybe displaced intraoperatively. In addition, we have found that the presence of intracranial metallic foreign bodies may be a factor for the posttraumatic epilepsy, and their timely removal appears to be beneficial for epilepsy control.

FOXN3 inhibits cell proliferation and invasion via modulating the AKT/MDM2/p53 axis in human glioma.

This study aimed to evaluate the biological role of forkhead box N3 (FOXN3) in human glioma and clarify the possible molecular mechanisms. FOXN3 expression patterns in clinical tissue specimens were characterized via qPCR and Western blotting. Kaplan-Meier survival curve was applied to assess the correlation between FOXN3 expression and overall survival. Effects of FOXN3 over-expression and depletion on glioma cell proliferation, apoptosis, migration and invasion were assessed by CCK8, colony formation assay, flow cytometry, scratch wound healing assay and Transwell invasion assay, respectively. Moreover, the involvement of AKT/murine double minute 2 (MDM2)/p53 pathway was evaluated. Additionally, tumor transplantation model assay was performed to determine the effects of FOXN3 over-expression on glioma cell growth in vivo. Results showed that FOXN3 was significantly down-regulated in glioma tissues compared with normal tissues. Patients with lower FOXN3 expression exhibited a shorter overall survival time. Gain- and loss-of-function analyses demonstrated that FOXN3 over-expression significantly suppressed proliferation, survival and motility of glioma cells, whereas FOXN3 knockdown remarkably promoted glioma cell proliferation, survival and motility. Furthermore, FOXN3 over-expression inhibited the activation of AKT/MDM2/p53 signaling pathway in glioma cells, while FOXN3 depletion facilitated its activation. Additionally, tumor xenograft assays revealed that FOXN3 over-expression retarded glioma cell growth in vivo. Collectively, these findings indicate that FOXN3 inhibits cell growth and invasion through inactivating the AKT/MDM2/p53 signaling pathway and that FOXN3-AKT/MDM2/p53 axis may represent a novel therapeutic target for glioma patients.

An Effective and Simple Way to Establish Elastase-Induced Middle Carotid Artery Fusiform Aneurysms in Rabbits.

OBJECTIVE: Elastase-induced aneurysms in rabbits have been proposed as a preclinical tool for device development, but there is still much deficiency in those aneurismal models. So we need to explore the efficient and convenient animal models for the investigation of intracranial aneurysms. Then, we compared and analyzed three methods of elastase-induced carotid artery aneurysms in rabbits and aimed to find a simple, effective, and reproducible method for creating elastase-induced aneurysms. METHODS: 42 standard feeding male adult Japanese white rabbits (3.05 ± 0.65 kg) were randomly divided into 3 groups and treated with elastase ablation to create common carotid artery (RCCA) aneurysm models: Group A (root-RCCA medication group, n = 12), Group B (mid-RCCA medication group, n = 18), and Group C (ligated RCCA+medication group, n = 12). For Group A, the origin of the RCCA was blocked by two temporary aneurysm clips, and the resulting 2 cm cavity was infused with elastase for 20 min, then the clip was removed and the RCCA was not ligated. For Group B, the middle part of RCCA was treated the same way as Group A and the RCCA was not ligated. For Group C, the middle part of RCCA was treated as Group B, but the distal RCCA was ligated. After the aneurysm models were created for 3 weeks, prior to sacrificing the animals, color Doppler ultrasound and angiography were performed for blood flow measurements inside the aneurysms. Histological analysis (such as SMA-α, CD31, CD34, CD68, collagen IV, and Ki67) and the other relevant indexes were compared between the ideal model's aneurysmal tissues and the human intracranial aneurysm's tissues to confirm whether we have successfully established elastase-induced aneurysm models. RESULTS: Compared with human intracranial aneurysm specimens by the color Doppler ultrasound, angiography, and changes in the inner diameter of arteries, all three methods have successfully established the elastase-induced aneurysm models. Histology showed that biological responses were similar to both human cerebral aneurysms and previously published elastase-induced rabbit aneurysm models. Group A and Group B had the same morphology, but Group A had a higher mortality rate than Group B. Group B and Group C had different morphology. The aneurysm of Group C was more similar to human cerebral aneurysms but had a higher mortality rate than Group B. Group B was confirmed not only as an alternative method but also as a more safe and effective method for creating elastase-induced aneurysm models. CONCLUSION: Through analysis and comparison, the Group B is proven to be the simplest, reproducible, and most effective modeling method. The aneurysm model established by Group B can be used for basic research related to aneurysm mechanism. We have provided a new and effective method for basic research on aneurysm.

Potential implications of hydrogen peroxide in the pathogenesis and therapeutic strategies of gliomas.

Glioma is the most common type of primary brain tumor, and it has a high mortality rate. Currently, there are only a few therapeutic approaches for gliomas, and their effects are unsatisfactory. Therefore, uncovering the pathogenesis and exploring more therapeutic strategies for the treatment of gliomas are urgently needed to overcome the ongoing challenges. Cellular redox imbalance has been shown to be associated with the initiation and progression of gliomas. Among reactive oxygen species (ROS), hydrogen peroxide (H2O2) is considered the most suitable for redox signaling and is a potential candidate as a key molecule that determines the fate of cancer cells. In this review, we discuss the potential cellular and molecular roles of H2O2 in gliomagenesis and explore the potential implications of H2O2 in radiotherapy and chemotherapy and in the ongoing challenges of current glioma treatment. Moreover, we evaluate H2O2 as a potential redox sensor and potential driver molecule of nanocatalytic therapeutic strategies for glioma treatment.

Decreased expression of miR-410-3p correlates with poor prognosis and tumorigenesis in human glioma.

BACKGROUND: Gliomas are the most common type of primary tumors in the central nervous system. This study aimed to investigate the biological role of miR-410-3p in glioma and elucidate the potential molecular mechanisms involved. METHODS: The expression levels of miR-410-3p in clinical tissue samples and glioma cell lines were determined using qRT-PCR analysis. The clinical significance of miR-410-3p in glioma was evaluated using Kaplan-Meier survival analysis and Fisher's exact test. The effects of miR-410-3p on glioma cell proliferation, apoptosis, migration and invasion were investigated using MTT assays, flow cytometry, transwell migration and invasion assays. Besides, corresponding mechanistic studies were carried out. RESULTS: miR-410-3p was significantly down-regulated in glioma tissues. Besides, Kaplan-Meier analysis demonstrated that patients with low miR-410-3p expression had a shorter overall survival. Decreased miR-410-3p expression was associated with larger tumor size, lower Karnofsky performance score (KPS), and higher World Health Organization (WHO) grade. Over-expression of miR-410-3p suppressed cell proliferation, migration, and invasion, and accelerated apoptosis; whereas depletion of miR-410-3p facilitated cell proliferation, migration, and invasion, and inhibited apoptosis. Mechanistic investigations demonstrated that Ras-related protein 1A (RAP1A) was a direct target of miR-410-3p, and that rescue of RAP1A expression reversed miR-410-3p over-expression-induced inhibitory effects on cell proliferation, migration, and invasion. Notably, miR-410-3p over-expression repressed tumor growth in mouse xenograft models. CONCLUSION: Our findings indicate that miR-410-3p functions as a tumor suppressor in glioma by directly targeting RAP1A. Thus, this study may provide some new insights into gliomagenesis and progression.

The active participation of p22phox-214T/C in the formation of intracranial aneurysm and the suppressive potential of edaravone.

Oxidative stress reactions play an important role in the pathogenesis of intracranial aneurysm (IA). p22phox is involved in the oxidative stress reaction, and it is a critical subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The present study investigated the association of genetic variants within the gene encoding p22phox­214T/C with IA. The p22phox­214T/C gene polymorphisms in 192 cases of IA and 112 controls were analyzed by polymerase chain reaction­restriction fragment length polymorphism (PCR­RFLP). The mRNA expression of NADPH oxidase was also analyzed by RT­PCR. The results of RT­PCR were validated by ELISA. In a rabbit model of elastase­induced aneurysm, we used edaravone for anti­oxidative stress treatment to observe the curative effects. In the clinical cases, a significant difference in p22phox­214T/C allele frequencies in the IA group was observed compared with the control group (P<0.001). The expression level of NADPH oxidase was differed significantly between the IA group and the control group. In the rabbit model of elastase­induced aneurysm, the success rate of the aneurysmal model in the edaravone group and the wound ulcer rate were lower than those in the control group. In addition, the diameter of the aneurysm was smaller than in the edaravone group than in the control group (3.26±0.13 mm vs. 3.85±0.07 mm), and the expression of matrix metalloproteinase­9 (MMP­9) was significantly lower than that in the control group (P<0.0001). Thus, these data suggest the active participation of p22phox­214T/C in the formation of IA and the suppressive potential of edaravone against IA formation.

Association of TNF-α-3959T/C Gene Polymorphisms in the Chinese Population with Intracranial Aneurysms.

Recent studies have demonstrated that cytokines play an important role in the pathogenesis of intracranial aneurysm (IA). Tumor necrosis factor-α (TNF-α) is an important proinflammatory cytokine, which was shown to influence the development of IA, but there is no research data from China. Hence, the purpose of this study was to explore the relationship between TNF-α polymorphisms and IA in China. The association of genetic variants of TNF-α gene expression was investigated in a Chinese population with IA. The TNF-α-3959T>C(rs1799964), 4127C>A(rs1800630), 4133C>T(rs1799724), 4184C>T(rs4248158), and 4752G>A(rs361525) gene polymorphisms in 192 IA cases and 112 controls were analyzed using polymerase chain reaction (PCR). Differences in genotype and allele frequencies between patients and controls were tested. There were no significant differences in 4127C>A (p = 0.072), 4133C>T (p = 0.373), 4184C>T (p = 0.749), and 4752G>A (p = 0.184) genotype frequencies between the IA group and the control group. But this case-control association study revealed that TNF-α-3959T>C (p < 0.001) was significantly associated with increased risk of IA. These results suggested that a novel TNF-α locus was found to be closely correlated with the occurrence of IA in Chinese.

MicroRNA-520c inhibits glioma cell migration and invasion by the suppression of transforming growth factor-ß receptor type 2.

Dysregulation of microRNAs (miRNAs) is actively involved in the development and progression of glioma. miR-520c was previously found to inhibit glioblastoma cell migration. However, the clinical significance of miR-520c and its biological function in glioma remain largely unknown. In the present study, we found that miR-520c expression in glioma tissues was significantly decreased compared to adjacent non­cancerous tissues. The low level of miR-520c was prominently correlated with advanced World Health Organization (WHO) grade and decreased overall survival of glioma patients. Overexpression of miR-520c in U251 cells significantly decreased the migration and invasion of the cancer cells, while miR-520c silencing promoted U87 cell migration and invasion in vitro. Mechanistically, miR-520c inversely regulated transforming growth factor-ß receptor type 2 (TGFBRII) abundance in the glioma cells. Herein, TGFBRII was found to be a downstream target of miR-520c in glioma. Furthermore, an inverse correlation between TGFBRII and miR-520c expression was observed in the glioma cases. In constrast, restoration of TGFBRII expression abrogated the effects of miR-520c overexpression in U251 cells with increased cell migration and invasion. In addition, miR-520c overexpression blocked TGF-ß1­induced cell migration and invasion in U251 cells. Collectively, miR-520c may serve as a prognostic predictor and a therapeutic target for glioma patients.