[Retracted] Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells.

[This retracts the article DOI: 10.3892/ol.2016.5474.].

TSPO exacerbates acute cerebral ischemia/reperfusion injury by inducing autophagy dysfunction.

Autophagy is considered a double-edged sword, with a role in the regulation of the pathophysiological processes of the central nervous system (CNS) after cerebral ischemia-reperfusion injury (CIRI). The 18-kDa translocator protein (TSPO) is a highly conserved protein, with its expression level in the nervous system closely associated with the regulation of pathophysiological processes. In addition, the ligand of TSPO reduces neuroinflammation in brain diseases, but the potential role of TSPO in CIRI is largely undiscovered. On this basis, we investigated whether TSPO regulates neuroinflammatory response by affecting autophagy in microglia. In our study, increased expression of TSPO was detected in rat brain tissues with transient middle cerebral artery occlusion (tMCAO) and in BV2 microglial cells exposed to oxygen-glucose deprivation or reoxygenation (OGD/R) treatment, respectively. In addition, we confirmed that autophagy was over-activated during CIRI by increased expression of autophagy activation related proteins with Beclin-1 and LC3B, while the expression of p62 was decreased. The degradation process of autophagy was inhibited, while the expression levels of LAMP-1 and Cathepsin-D were significantly reduced. Results of confocal laser microscopy and transmission electron microscopy (TEM) indicated that autophagy flux was disordered. In contrast, inhibition of TSPO prevented autophagy over-activation both in vivo and in vitro. Interestingly, suppression of TSPO alleviated nerve cell damage by reducing reactive oxygen species (ROS) and pro-inflammatory factors, including TNF-α and IL-6 in microglia cells. In summary, these results indicated that TSPO might affect CIRI by mediating autophagy dysfunction and thus might serve as a potential target for ischemic stroke treatment.

Contrast-Enhanced Ultrasound Combined With 2D Strain Imaging and Histopathological Multimodal Assessment of Carotid Plaque Vulnerability.

OBJECTIVE: The aim of this study was to explore the value of contrast-enhanced ultrasound (CEUS) combined with 2-D strain imaging in evaluating carotid plaque vulnerability and the correlations among CEUS perfusion parameters, strain parameters and histopathological findings in different plaque segments. METHODS: Patients with carotid artery stenosis who underwent carotid endarterectomy (CEA) at the First Affiliated Hospital of Xinjiang Medical University from September 2020 to June 2021 underwent preoperative carotid artery 2-D ultrasonography and CEUS. The plaques were divided into three segments: the proximal end of the shoulder, central cap and distal end of the shoulder. The peak intensity (PI) value and strain rate parameters of the regions of interest were analyzed. Plaques were divided into a stable group (8 cases) and an unstable group (19 cases). The microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression of each patch in the unstable group were analyzed. RESULTS: The peak strain during the systolic period in each plaque segment in both groups showed the following pattern: proximal end shoulder > distal end shoulder > top (p < 0.05). The PI value for CEUS is also represented. In the unstable group, the PI values of each segment of the plaque were positively correlated with the MVD, near-center PI value and VEGF average optical density value. The average optical density of each segment was positively correlated with the MVD (p < 0.05). There were positive correlations between the PI values of the proximal and distal shoulder and the strain values (p < 0.05), and the MVD value of each segment, VEGF value and strain value were positively correlated (p < 0.05). CONCLUSION: PI and the pathological tissue components represented by CEUS were positively correlated with the mechanical parameters of the plaque along the long axis. There may be overlap between the high shear stress area of the plaque and the neovascular aggregation area, and the combination of the two has certain significance for assessing the vulnerability of the plaque.

An immunogenic cell death-related regulators classification patterns and immune microenvironment infiltration characterization in intracranial aneurysm based on machine learning.

Background: Immunogenic Cell Death (ICD) is a novel way to regulate cell death and can sufficiently activate adaptive immune responses. Its role in immunity is still emerging. However, the involvement of ICD in Intracranial Aneurysms (IA) remains unclear. This study aimed to identify biomarkers associated with ICDs and determine the relationship between them and the immune microenvironment during the onset and progression of IA. Methods: The IA gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in IA were identified and the effects of the ICD on immune microenvironment signatures were studied. Techniques like Lasso, Bayes, DT, FDA, GBM, NNET, RG, SVM, LR, and multivariate analysis were used to identify the ICD gene signatures in IA. A consensus clustering algorithm was used for conducting the unsupervised cluster analysis of the ICD patterns in IA. Furthermore, enrichment analysis was carried out for investigating the various immune responses and other functional pathways. Along with functional annotation, the weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network and module construction, identification of the hub gene, and co-expression analysis were also carried out. Results: The above techniques were used for establishing the ICD gene signatures of HMGB1, HMGN1, IL33, BCL2, HSPA4, PANX1, TLR9, CLEC7A, and NLRP3 that could easily distinguish IA from normal samples. The unsupervised cluster analysis helped in identifying three ICD gene patterns in different datasets. Gene enrichment analysis revealed that the IA samples showed many differences in pathways such as the cytokine-cytokine receptor interaction, regulation of actin cytoskeleton, chemokine signaling pathway, NOD-like receptor signaling pathway, viral protein interaction with the cytokines and cytokine receptors, and a few other signaling pathways compared to normal samples. In addition, the three ICD modification modes showed obvious differences in their immune microenvironment and the biological function pathways. Eight ICD-regulators were identified and showed meaningful associations with IA, suggesting they could severe as potential prognostic biomarkers. Conclusions: A new gene signature for IA based on ICD features was created. This signature shows that the ICD pattern and the immune microenvironment are closely related to IA and provide a basis for optimizing risk monitoring, clinical decision-making, and developing novel treatment strategies for patients with IA.

Effect of hemodynamic changes on the risk of intracranial aneurysm rupture: a systematic review and meta-analysis.

OBJECTIVE: In this study, the hemodynamic parameters of ruptured intracranial aneurysms (IAs) in various studies were summarized and analyzed to provide predictive parameters for IA rupture in clinical work. METHODS: We searched PubMed, Web of science, Embase, and Cochrane databases for articles published before December 2021 to collect data on hemodynamic parameters associated with IA rupture. Differences in wall shear stress (WSS), oscillatory shear index (OSI), and low wall shear stress area (LSA) between ruptured and unruptured IAs in the literature were summarized and analyzed, and the standardized mean difference (SMD) of 95% CI was calculated by Review Manager 5.3. RESULTS: By searching and screening the literature, this meta-analysis included 17 studies comprising 1,373 IA patients. In the ruptured aneurysm group, the level of WSS decreased significantly, while OSI and LSA increased obviously. CONCLUSION: Low WSS, high OSI, and high LSA are closely related to the rupture of IAs, indicating the role of WSS, OSI, and LSA as important hemodynamic parameters for predicting the rupture of IAs in clinical work.

m6A regulator-mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms.

Background: The role of epigenetic modulation in immunity is receiving increased recognition-particularly in the context of RNA N6-methyladenosine (m6A) modifications. Nevertheless, it is still uncertain whether m6A methylation plays a role in the onset and progression of intracranial aneurysms (IAs). This study aimed to establish the function of m6A RNA methylation in IA, as well as its correlation with the immunological microenvironment. Methods: Our study included a total of 97 samples (64 IA, 33 normal) in the training set and 60 samples (44 IA, 16 normal) in the validation set to systematically assess the pattern of RNA modifications mediated by 22 m6A regulators. The effects of m6A modifications on immune microenvironment features, i.e., immune response gene sets, human leukocyte antigen (HLA) genes, and infiltrating immune cells were explored. We employed Lasso, machine learning, and logistic regression for the purpose of identifying an m6A regulator gene signature of IA with external data validation. For the unsupervised clustering analysis of m6A modification patterns in IA, consensus clustering methods were employed. Enrichment analysis was used to assess immune response activity along with other functional pathways. The identification of m6A methylation markers was identified based on a protein-protein interaction network and weighted gene co-expression network analysis. Results: We identified an m6A regulator signature of IGFBP2, IGFBP1, IGF2BP2, YTHDF3, ALKBH5, RBM15B, LRPPRC, and ELAVL1, which could easily distinguish individuals with IA from healthy individuals. Unsupervised clustering revealed three m6A modification patterns. Gene enrichment analysis illustrated that the tight junction, p53 pathway, and NOTCH signaling pathway varied significantly in m6A modifier patterns. In addition, the three m6A modification patterns showed significant differences in m6A regulator expression, immune microenvironment, and bio-functional pathways. Furthermore, macrophages, activated T cells, and other immune cells were strongly correlated with m6A regulators. Eight m6A indicators were discovered-each with a statistically significant correlation with IA-suggesting their potential as prognostic biological markers. Conclusion: Our study demonstrates that m6A RNA methylation and the immunological microenvironment are both intricately correlated with the onset and progression of IA. The novel insight into patterns of m6A modification offers a foundation for the development of innovative treatment approaches for IA.

Translocator Protein Regulate Polarization Phenotype Transformation of Microglia after Cerebral Ischemia-reperfusion Injury.

Microglia cells are activated after cerebral ischemia-reperfusion injury (CIRI), playing a dual role in aggravating the injury or promoting tissue repair by polarization. Translocator protein (TSPO) is a biomarker of neuroinflammation or microglia activation. Its expression is significantly increased while brain injury and neuroinflammation occur. However, the relationship between TSPO and microglia polarization in CIRI is still not clear. In the present study, the middle cerebral artery occlusion (MCAO) methods in rats were used to simulate CIRI. We found that the expressions of M1 markers (CD86, IL-1ß, and TNF-α) and M2 markers (CD206, IL-10, and TGF-ß) were significantly increased. Moreover, the injection of TSPO ligand, PK11195, inhibited the increase of M1 polarization markers but promoted the expressions of M2 polarization markers, which significantly ameliorated the neurological damage after MCAO in rats. In vitro studies showed that shRNA-mediated TSPO knock-down promoted M1 polarization but inhibited M2 polarization, accompanied by a significant decrease in cell viability. On the contrary, overexpression of TSPO inhibited M1 polarization, promoted M2 polarization, and significantly improved cell viability. In summary, TSPO plays a neuroprotective role in CIRI by inhibiting M1 polarization and promoting M2 polarization, which suggests that TSPO may have the potential to serve as a therapeutic target for stroke.

Current Status of Endovascular Treatment for Acute Large Vessel Occlusion in China: A Real-World Nationwide Registry.

BACKGROUND AND PURPOSE: The benefit of endovascular treatment (EVT) for large vessel occlusion in clinical practice in developing countries like China needs to be confirmed. The aim of the study was to determine whether the benefit of EVT for acute ischemic stroke in randomized trials could be generalized to clinical practice in Chinese population. METHODS: We conducted a prospective registry of EVT at 111 centers in China. Patients with acute ischemic stroke caused by imaging-confirmed intracranial large vessel occlusion and receiving EVT were included. The primary outcome was functional independence at 90 days defined as a modified Rankin Scale score of 0 to 2. Outcomes of specific subgroups in the anterior circulation were reported and logistic regression was performed to predict the primary outcome. RESULTS: Among the 1793 enrolled patients, 1396 (77.9%) had anterior circulation large vessel occlusion (median age, 66 [56-73] years) and 397 (22.1%) had posterior circulation large vessel occlusion (median age, 64 [55-72] years). Functional independence at 90 days was reached in 45% and 44% in anterior and posterior circulation groups, respectively. For anterior circulation population, underlying intracranial atherosclerotic disease was identified in 29% of patients, with higher functional independence at 90 days (52% versus 44%; P=0.0122) than patients without intracranial atherosclerotic disease. In the anterior circulation population, after adjusting for baseline characteristics, procedure details, and early outcomes, the independent predictors for functional independence at 90 days were age <66 years (odds ratio [OR], 1.733 [95% CI, 1.213-2.476]), time from onset to puncture >6 hours (OR, 1.536 [95% CI, 1.065-2.216]), local anesthesia (OR, 2.194 [95% CI, 1.325-3.633]), final modified Thrombolysis in Cerebral Infarction 2b/3 (OR, 2.052 [95% CI, 1.085-3.878]), puncture-to-reperfusion time ≤1.5 hours (OR, 1.628 [95% CI, 1.098-2.413]), and National Institutes of Health Stroke Scale score 24 hours after the procedure <11 (OR, 9.126 [95% CI, 6.222-13.385]). CONCLUSIONS: Despite distinct characteristics in the Chinese population, favorable outcome of EVT can be achieved in clinical practice in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939.

Effect of endovascular treatment on high-risk patients with chronic carotid artery occlusion.

OBJECTIVE: This study aims to discuss the safety and short-term efficacy of endovascular treatment on high-risk patients with chronic carotid artery occlusion. METHODS: A retrospective analysis was performed on the clinical data of 16 high-risk patients with chronic carotid artery occlusion who received endovascular treatment at the Department of Neurosurgery of the First Affiliated Hospital of Xinjiang Medical University from November 2013 to July 2016. The incidence of adverse events at 1 week, 30 days and six months post-operation were observed, and NIHSS was adopted to assess the neurological function of patients six months before and after the operation. Follow-up time was 6-26 months, with an average of 18.4 months. RESULTS: The degree of carotid artery stenosis of these 16 patients was 100%. The degree of which after the operation was 24.9 ± 17.0%; and the difference was statistically significant (P<0.05). Iatrogenic carotid artery dissection occurred in one case, and persistent hypotension and sinus bradycardia occurred in one case. Furthermore, one case of endovascular treatment was not approved to be opened. Afterwards, temporal artery-STA-MCA bypass was performed; upon postoperative head CTA and DSA, the result showed that the perfusion was good. One case refused to undergo surgical treatment. The NHSS score of 14 cases of endovascular treatment that were successfully opened six months after the operation was 2.0 ± 1.36, which improved (P<0.05) compared with that of pre-operation. CONCLUSION: Endovascular treatment on high-risk patients with chronic carotid artery occlusion is safe and effective. And it has obvious curative effect in short mid-term. KEY WORDS: Arterial occlusive disease, Carotid artery, Endovascular treatment, Treatment outcome.

Short-term efficacy of pipeline embolization device for treating complex intracranial aneurysms.

OBJECTIVE: To observe the short-term efficacy of Pipeline embolization divice (PED) for the treatment of complex intracranial aneurysms. METHODS: The clinical data of 29 consecutive patients with 32 intracranial aneurysms treated with PED between April 2015 to September 2016 were analyzed retrospectively. There were 3 small aneurysm, 15 large aneurysms, 8 giant aneurysms, 5 fusiform ayneurysms and 1 recidivation. The vessels include 25 anterior circulation and 4 posterior circulation. RESULTS: We treated 31 aneurysms with 30 PEDs and all of the stents were implanted successfully. 1 case of single aneurysm was multiple divices implanted and 1 case of 3 aneurysms were treated by single PED. 12 of the 29 patients were implanted PED only, 17 were implanted PED with coils, 2 underwent balloon remodeling after the PED implanted. The ostia of 19 ophthalmic arteries, 10 posterior communicating arteries, 4 posterior inferior cerebellar arteries and 1 anterior cerebral artery were covered by PED during procedures; 1 ophthalmic arteries and 1 posterior communicating artery disappeared, no branch vessels occlusion and parent artery stenosis occurred.Hemorrhagic complacations occurred in 2 patients, 2 hours and 5 days after procedure respectively. Radiographic follow-up examnations were carried out in 24 patients and revealed complete occlusion in 21 patients, uncomplete occlusion in 3 patients. No neurological injure occurred in 27 patients who received a clinical follow-up. CONCLUSION: PED provide a safe and effective methord for the treatment of intracranial complex aneurysms like wide-neck aneurysms, fusiform aneurysms, giant aneurysms in low risk of procedural complications and high rates of aneurysm occlusion.

Operative managements of extracranial carotid artery aneurysms: a report of three cases and literature review.

BACKGROUND: The purpose of this study is to report the treatment approaches and postoperative outcomes of extracranial carotid artery aneurysms (ECAAs) and discuss the symptoms, related risk factors, etiology, diagnostic methods, treatments, and follow-up period complications. CASE PRESENTATION: We describe three patients with symptomatic extracranial carotid artery aneurysms; one of them was treated with end-to-end anastomosis of the extracranial internal carotid artery (EICA) after the resection of the aneurysm, while the other two patients were deployed with Willis covered stents in the extracranial internal carotid artery. All of the patients were in good condition when discharged home. After a mean follow-up period of 8 months, all the patients were alive and only one of them had the neurologic deficit. Additionally, we reviewed the relative literatures. CONCLUSION: Both of the surgical and endovascular treatments have relatively satisfactory outcomes in ECAA patients. However, it is necessary to provide individualized treatments to different patients according to the characteristics of the aneurysms.

Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells.

The aim of the current study was to investigate the anticancer potential of arctigenin, a natural lignan compound, in malignant gliomas. The U87MG and T98G human glioma cell lines were treated with various concentrations of arctigenin for 48 h and the effects of arctigenin on the aggressive phenotypes of glioma cells were assessed. The results demonstrated that arctigenin dose-dependently inhibited the growth of U87MG and T98G cells, as determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine incorporation assays. Arctigenin exposure also induced a 60-75% reduction in colony formation compared with vehicle-treated control cells. However, arctigenin was not observed to affect the invasiveness of glioma cells. Arctigenin significantly increased the proportion of cells in the G0/G1 phase and reduced the number of cells in the S phase, as compared with the control group (P<0.05). Western blot analysis demonstrated that arctigenin increased the expression levels of p21, retinoblastoma and p53 proteins, and significantly decreased the expression levels of cyclin D1 and cyclin-dependent kinase 4 proteins. Additionally, arctigenin was able to induce apoptosis in glioma cells, coupled with increased expression levels of cleaved caspase-3 and the pro-apoptotic BCL2-associated X protein. Furthermore, arctigenin-induced apoptosis was significantly suppressed by the pretreatment of cells with Z-DEVD-FMK, a caspase-3 inhibitor. In conclusion, the results suggest that arctigenin is able to inhibit cell proliferation and may induce apoptosis and cell cycle arrest at the G0/G1 phase in glioma cells. These results warrant further investigation of the anticancer effects of arctigenin in animal models of gliomas.

Microsurgery with or without Neuroendoscopy in Petroclival Meningiomas.

AIM: This study aimed to investigate the operative procedure for neuroendoscope-assisted microscopic resection of petroclival meningioma to improve prognosis. MATERIAL AND METHODS: Twelve patients with petroclival meningioma who had undergone neuroendoscope-assisted microscopic resection at the Department of Neurosurgery, First Affiliated Hospital of Xinjiang Medical University were selected. In addition, 12 patients with petroclival meningioma who had undergone microscopic surgery were used as control. Clinical data from the 24 cases of petroclival meningioma were analyzed. RESULTS: For the neuroendoscope-assisted group, six, five, and one cases were respectively subjected to total resection, subtotal resection, and most resection. For the microscopic surgery group, two, three, and seven cases were respectively subjected to total resection, subtotal resection, and most resection. Both the total and subtotal resection rates of petroclival meningioma in the neuroendoscope-assisted group were significantly higher than those in the microscopic surgery group (p < 0.05). No difference was observed for short-term and long-term complications (p > 0.05) between the two groups. CONCLUSION: Neuroendoscope-assisted microscopic resection for petroclival meningioma can improve the total and subtotal resection rates of the tumor. Moreover, this method does not increase postoperative short-term and long-term complications.

Endovascular embolization of large and giant intracranial aneurysms of long-term angiographic fol-low-up / 中国神经精神疾病杂志

Objective To investigate the outcome of endovascular treatment of large or giant intracranial aneu?rysm by long-term angiographic follow-up. Methods Clinical data of 72 patients with large or giant intracranial aneu?rysms receiving endovascular treatment were analyzed retrospectively. Thirty aneurysms were treated with coil emboliza?tion alone, 14 with stent-assisted coiling, 15 with covered stent-deployment and 13 with parent artery occlusion. Results complete occlusion was achieved in 10 cases of pure coil embolization, 7 cases of stent assisted coil embolization,11 cas?es of completely covered stent-deployment and,13 cases of parent artery occlusion. The postoperative immediate com?plete embolism rate was 56.9%. Nearly completely occlusion was achieved in 17 cases of pure coil embolization, in 6 cas?es of stent auxiliary coil embolization, 4 cases of covered stent-deloyment and zero case of parent artery occlusion. The total postoperative immediate nearly completely embolism rate was 37.5%. Incomplete occlusion was achieved in 3 cases of pure coil thrombosis, 1 case of stent assisted coil, zero case of ,covered stent-deloyment and zero case of parent artery occlusion. The total immediate postoperative incomplete embolization rate was 5.6%. Patients were followed up for 6 to 72 months, with an average follow-up of 24.2 months . All patients had no bleeding. The total periprocedural complica?tion rate was 9.7%and there were no death cases. The recurrence of aneurysm in pure spring coil embolization treatment was higher compared with other treatments. The overall recurrence rate was 23.6%. The recurrent 14 aneurysms were suc?cessfully treated endovascularly. Conclusions Endovascular embolization treatment of intracranial large or giant aneu?rysm is safe and effective but its long-term recurrence rate is high. Thus a close follow-up is needed. Endovascular inter?ventional therapy based on the location of aneurysm and shape characteristics can improve treatment effectiveness and re?duce recurrence rate.

Pituitary hormone level changes and hypxonatremia in aneurysmal subarachnoid hemorrhage.

The aim of this study was to investigate the changes in serum pituitary hormone levels and the mechanism of hyponatremia in aneurysmal subarachnoid hemorrhage (SAH). Nuclear medical tests and serum electrolyte monitoring were performed in 49 aneurysmal SAH cases and 10 healthy volunteers. The levels of serum pituitary hormones were significantly higher in the SAH patients compared with the control group on days 1-3 and 7-9 after SAH onset (P<0.05). The peak value occurred on days 7-9. The rate of hyponatremia was 49.0% in the 49 SAH patients. The incidence of severe hyponatremia was significantly higher in Fisher grades III-IV and Hunt-Hess grades III-IV compared with Fisher grades I-II and Hunt-Hess grades I-II, respectively (P<0.05). There was no correlation between the site of aneurysm and the rate of hyponatremia. The incidence of symptomatic cerebral vasospasm was significantly higher in the hyponatremia group and Fisher grades III-IV compared with the normal serum sodium group and Fisher grades I-II, respectively. Serum pituitary hormone levels were positively correlated with blood loss and disease severity in patients with aneurysmal SAH. Hyponatremia may be considered an important indicator of SAH. SAH patients are likely to benefit from intense monitoring and regulation of serum sodium.