Effect and Blood Flow Parameters of Biomaterials-Based Endovascular Interventional Embolization and Craniotomy Clipping in the Treatment of Cerebral Aneurysms.

Objective: The effects of interventional embolization and craniotomy clipping on the treatment of intracranial aneurysms were investigated in this study, as well as their influence on the hemodynamics of postoperative patients. Methods: 102 patients with intracranial aneurysms were selected as the research objects, and they were rolled into an experimental (group A) and a control group (group B) according to the random number table method, with 51 cases in each group. The group A was treated with intravascular interventional embolization, and the group B received craniotomy clipping. Besides, a biodegradable magnesium titanium alloy biological stent was independently developed in this study, which was applied to endovascular interventional embolization in the group A. The hemodynamic model was established by using three-dimensional (3D) computer hemodynamic numerical simulation technology. Besides, the effects of all the patients before and after treatment were evaluated, in terms of blood pressure (BP), average wall shear stress (WSS) (AWSS), AWSS gradient (AWSSG), oscillatory shear index (OSI), aneurysm formation index (AFI), gradient oscillation number (GON), and intraoperative complication rate. Results: After 3 days of treatment, the BP, AWSS, and AWSSG of patients from the two groups were higher than those before treatment. The index values of the group A were greater markedly than the values of the group B (P < 0.05); the BP of the group A and the group B at the 0th day, 1st day, 3rd day, 5th day, and 7th day after treatment was 21±5.1 Versus 20.1±4.7, 22±4.8 Versus 21.1± 5.17, 26±6.2 Versus 22.31±5.21, 27±5.77 Versus 24.02±5.11, and 30±6.09 Versus 24.99±5.03, respectively; AWSSG values were 120±10.11 Versus 120.1±10.98, 130.1±10.36 Versus 123.3±11.06, 162.5±9.92 Versus 131.31±10.97, 171±8.13 Versus 155.02±8.36, and 200.1±7.22 Versus 180.01±8.98 in turn. GON and OSI were both decreased, and the values of various indexes in the group A were sharply lower than those of the group B (P < 0.05); the values of GON at the 0th day, 1st day, 3rd day, 5th day, and 7th day after treatment in the group A and the group B were 0.077±0.01 Versus 0.08±0.011, 0.07±0.012 Versus 0.073 ± 0.01, 0.051 ± 0.02 Versus 0.071 ± 0.011, 0.045 ± 0.01 Versus 0.069 ± 0.011, and 0.042 ± 0.012 Versus 0.063±0.013, respectively; OSI values were 4.8±0.51 Versus 4.9±0.52, 3.6±0.52 Versus 3.62±0.51, 2.82±0.51 Versus 3.1 ± 0.57, 1.9 ± 0.512 Versus 2.91 ± 0.51, and 0.5 ± 0.51 Versus 1.8 ± 0.501 in turn. By comparing the intraoperative complications and postoperative mortality risk score (MRS) of patients in the two groups, it was found that the incidence of intraoperative complications and postoperative MRS scores in the group A were lower steeply than those of the group B, suggesting that endovascular interventional embolization had a better effect on the treatment of intracranial aneurysms. Conclusion: Endovascular interventional embolization based on biodegradable magnesium alloy coated scaffold could better improve the distribution of shear stress on the vascular wall, stabilize vascular blood flow, and achieve better therapeutic effect for patients.

BMAL1 may be involved in angiogenesis and peritumoral cerebral edema of human glioma by regulating VEGF and ANG2.

The rhythm gene BMAL1 (Brain and Muscle ARNT-Like 1) may play an important role in glioma tolerance for anti-angiogenesis therapy. In humans with glioma of different pathological grades, BMAL1 expression was significantly different, and the expression of ANG2 (Angiopoietin 2) and VEGF (Vascular endothelial growth factor) was positively correlated with the expression of BMAL1. Additionally, BMAL1 expression is positively correlated with the microvascular density and peritumoral edema of glioma. According to in vitro experiments, silencing the expression of BMAL1 in primary glioma cells results in a decrease in the expression of VEGF. In contrast, overexpression of BMAL1 promotes the expression of ANG2 and VEGF via HIF-1a pathway. Therefore, BMAL1 likely participates in the angiogenesis of glioma by modulating ANG2 and VEGF expression, alters the therapeutic effect of anti-angiogenic treatments, and promotes peritumoral brain edema of glioma.

Mean Platelet Volume/Platelet Count Ratio is Associated with Poor Clinical Outcome After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is both a hypercoagulable and inflammation state in which many biomarkers have been studied. Activated platelets have been identified to be of clinical importance in thrombosis and neuroinflammation after aSAH. The aim of this study was to investigate the relationship between mean platelet volume (MPV) to platelet count (PC) ratio, a surrogate parameter for activated platelets, and the functional outcome in aSAH patients. METHODS: A retrospective analysis was performed of patients with aSAH admitted to the stroke center of our institution between November 2018 and November 2019. The mean MPV/PC ratio during the first three days after aSAH onset was calculated. Poor outcome was defined as a modified Rankin Scale (mRS) score of 3-6 at 3 months. Receive operating characteristic (ROC) curve analysis was performed to determine the optimal value of MPV/PC ratio for the prediction of poor outcome in patients with aSAH. RESULTS: A total of 100 patients were included, 13 (13.0%) died and 35 (35.0%) had a poor outcome. Mean MPV/PC ratio (P < 0.001) when measured over the study period, was significantly higher among patients with poor outcome. In multivariable analysis, increased mean MPV/PC ratio was associated with poor functional outcome at 3 months (odds ratio (OR) = 1.94; 95% confidence interval (CI): 1.19-3.17; P = 0.008). The optimal cutoff of MPV/PC ratio for predicting poor outcome at 3 months was 6.77 (sensitivity 74.3%, specificity 61.5%). CONCLUSION: An increased MPV/PC ratio is associated with poor functional outcome in aSAH patients. MPV/PC ratio may be a useful predictor of outcome after aSAH.

Safety of neural stem cell transplantation in patients with severe traumatic brain injury.

Neural stem cell (NSC) therapy is a promising treatment for traumatic brain injury (TBI). In addition, mesenchymal stem cells (MSCs) have been investigated for the treatment of TBI due to their functions in neural regeneration and their neurotrophic effect. In the present study, the safety, feasibility and biological effects of autologous MSC-derived NSC-like cell transplantation were investigated in 10 patients with severe TBI. All patients received intravenous or intrathecal injections of human NSC-like cells and were evaluated with physical and neurological examinations, routine laboratory tests and neuroradiological findings. The results indicated that the majority of patients experienced improved neurological function in different degrees during the follow-up period. No mortality or serious adverse events were observed in any patient subsequent to transplantation. Higher serum levels of nerve growth factor and brain-derived neurotrophic factor were detected following the transplantation, as compared with the levels prior to treatment. Overall, the present results suggest that transplantation of autologous NSC-like cells is feasible and appears to be safe for the treatment of non-acute severe TBI.

The Circadian Gene Clock Plays an Important Role in Cell Apoptosis and the DNA Damage Response In Vitro.

The Clock gene, an indispensable component of the circadian clock, not only modulates circadian oscillations but also regulates organismal function. We examined whether silencing the expression of the human Clock gene in glioma cells influences cell growth and induces apoptosis after irradiation. Silencing the expression of Clock in a human glioma cell line (U87MG), but not in a control glioma cell line, resulted in increased apoptosis and cell cycle arrest. Moreover, silencing Clock expression altered the expression of apoptosis-related genes. The protein levels of c-Myc and Cyclin B1 were downregulated, but those of p53 were upregulated, in human Clock-silenced U87MG cells compared with control cells. Our results suggest that the circadian gene human Clock may play an important role in carcinogenesis by inhibiting apoptotic cell death via attenuating proapoptotic signaling.

The analysis of deregulated expression and methylation of the PER2 genes in gliomas.

CONTEXT: Growing evidence shows that disruption of circadian rhythm may be a risk factor in the development of glioma. However, the molecular mechanisms of genes controlling circadian rhythm in glioma cells have not been explored and differential expression of the circadian clock genes in glioma and non-tumor cells may provide a molecular basis for manifesting this mechanism. AIMS: The aim of the following study is to analyze the PER2 expression involved in the pathogenesis of glioma. MATERIALS AND METHODS: Using immunohistochemical staining, methylation specific polymerase chain reaction techniques, we examined the expression of the most important clock genes, PER2, in 92 gliomas. STATISTICAL ANALYSIS USED: The association between tumor grade (high-grade/low-grade gliomas) and expression of the investigated proteins (negative/positive) was assessed using the Spearman, Chi-square test and two-sample t-test, included in the Statistical Package for the Social Science, version 13.0. Using Spearman Correlation to analyse correlation between the expression of PER 2 and PER2 promoter methylation. RESULTS: Our results reveal disturbances in the expression of the period 2 (PER2) genes in most (52.17%) of the glimoa cells in comparison with the nearby non-cancerous cells and the PER2 gene deregulation is most probably by methylation of the PER2 promoter. CONCLUSIONS: Since, the circadian clock controls expression of cell-cycle related genes, we suggest that disturbances in PER2 gene expression may result in disruption of the control of the normal circadian clock, thus benefiting the survival of cancer cells and promoting carcinogenesis. Differential expression of circadian genes in non-cancerous and cancerous cells may provide a molecular basis for chronotherapy of glioma.

Correlation between deregulated expression of PER2 gene and degree of glioma malignancy.

AIMS AND BACKGROUND: Growing evidence indicates that disruption of circadian rhythms may be a risk factor for the development of glioma. However, the molecular mechanisms underlying the genetic regulation of circadian rhythms in glioma cells have yet to be explored. METHODS AND STUDY DESIGN: Using immunohistochemical staining and methylation-specific PCR techniques, we examined the expression of the period 2 (PER2) gene, one of the most important clock genes, epidermal growth factor receptor (EGFR), and proliferating cell nuclear antigen (PCNA) in 92 gliomas. RESULTS: Our results revealed disturbances in the expression of PER2 in most (52.17%) glioma cells compared with the expression in nearby noncancerous cells, and indicated that PER2 gene deregulation most likely occurs via methylation of PER2 promoters. The protein expression of PCNA and EGFR was significantly higher in high-grade than low-grade gliomas (P < 0.05). Furthermore, a negative correlation was detected between the protein expression of PER2 and PCNA and EGFR in glioma. CONCLUSIONS: Because the circadian clock regulates the expression of cell cycle-related genes, we suggest that disturbances in PER2 gene expression may disrupt the regulation of the circadian clock, thus enhancing the survival of cancer cells and promoting carcinogenesis.

Deregulated expression of cry1 and cry2 in human gliomas.

Growing evidence shows that deregulation of the circadian clock plays an important role in the development of malignant tumors, including gliomas. However, the molecular mechanisms of gene chnages controlling circadian rhythm in glioma cells have not been explored. Using real time polymerase chain reaction and immunohistochemistry techniques, we examined the expression of two important clock genes, cry1 and cry2, in 69 gliomas. In this study, out of 69 gliomas, 38 were cry1-positive, and 51 were cry2-positive. The expression levels of cry1 and cry2 in glioma cells were significantly different from the surrounding non-glioma cells (P<0.01). The difference in the expression rate of cry1 and cry 2 in high-grade (grade III and IV) and low-grade (grade 1 and II) gliomas was non-significant (P>0.05) but there was a difference in the intensity of immunoactivity for cry 2 between high-grade gliomas and low-grade gliomas (r=-0.384, P=0.021). In this study, we found that the expression of cry1 and cry2 in glioma cells was much lower than in the surrounding non-glioma cells. Therefore, we suggest that disturbances in cry1 and cry2 expression may result in the disruption of the control of normal circadian rhythm, thus benefiting the survival of glioma cells. Differential expression of circadian clock genes in glioma and non-glioma cells may provide a molecular basis for the chemotherapy of gliomas.