Surgical Treatment and Long-Term Outcome of Cerebral Cavernous Malformations-Related Epilepsy in Pediatric Patients.

Cerebral cavernous malformations (CMs) are vascular malformations affecting any part of the central nervous system. Clinical data and surgical outcomes for 27 pediatric patients with CM-related epilepsy were retrospectively reviewed. The mean age of onset was 12.71 ± 4.09 years, and the mean duration of epilepsy was 2.34 ± 1.95 years. All 27 patients were treated with microsurgery for resection of the CMs, and the hemosiderin rim, and the secondary epileptogenic zone if necessary. The mean follow-up period was 6.34 ± 3.35 years, and the overall postoperative outcomes were positive. Note that 77.8% of patients were seizure-free postoperatively. The other patients with residual epilepsy received incomplete resection of the hemosiderin rim or the secondary epileptogenic zone due to retention of vital neurological functions. Surgical treatment for pediatric patients with symptomatic supratentorial CMs is safe and effective. Early intervention is recommended to resect CMs, the hemosiderin rim, and the epileptogenic cortex, even in cases of multiple CMs.

Investigation of the mechanism of dural arteriovenous fistula formation induced by high intracranial venous pressure in a rabbit model.

BACKGROUND: The causes of dural arteriovenous fistula have not been clearly defined. The aim of this study was to investigate the mechanism of dural arteriovenous fistula formation induced by high intracranial venous pressure using a rabbit model. RESULTS: By using rabbit model, dural arteriovenous fistula formation induced by high intracranial venous pressure could be produced by end-to-end and end-to-side anastomosis of the right side common carotid artery with the posterior facial vein plus ligation of the contralateral external jugular vein. As compared the post arteriovenous fistula formation among 1 week, 2 weeks, 3 weeks, and 90 days, the expression level of vascular endothelial growth factor in the 1- and 2-weeks groups was significantly higher compared with the control group, 3 weeks and 90 days groups (p ≤ 0.002). There was significantly higher hypoxia inducible factor-1α expression in the one week group compared with the control, 2 weeks, 3 weeks, and 90 days groups (p ≤ 0.002). The results of Western blotting showed that vascular endothelial growth factor expression level was highest in the 1 week group. The expression level of vascular endothelial growth factor was significantly different between all groups. CONCLUSIONS: The results of the experiments in our rabbit model indicate that high intracranial venous pressure is a key for dural arteriovenous fistula formation. Cerebral ischemia caused by lack of cerebral perfusion pressure plays a key role in the process that leads from high intracranial venous pressure to increased hypoxia inducible factor-1α expression and then increased vascular endothelial growth factor expression.

Clinical application of anatomy landmarks for microscopic endonasal transsphenoidal surgery for pituitary adenomas.

It is important to identify relevant anatomical landmarks on the route of endonasal transsphenoidal surgery (TSS) for pituitary adenomas to improve the gross total resection and the remission of disease. We therefore retrospectively studied the clinical outcomes of 148 patients who underwent single nostril endonasal TSS for pituitary adenomas. The anatomic basis of these procedures was evaluated. The important landmarks included the mucosal sphenoid ostia, the sphenoid keel, the osseous ostia and the nutrient arteries nearby, the sellar bulge, and the carotid protuberance, which outlined a clear route to the sella turcica with the best view and less tissue damage. Based on these landmarks, 148 cases of endonasal TSS were successfully performed to achieve 70.3% of gross total resection and remission, respectively. The complications were controlled to the least. Therefore, the application of these landmarks will help to prevent complications and improve the long-term outcomes.

Stereoscopic virtual reality models for planning tumor resection in the sellar region.

BACKGROUND: It is difficult for neurosurgeons to perceive the complex three-dimensional anatomical relationships in the sellar region. METHODS: To investigate the value of using a virtual reality system for planning resection of sellar region tumors. The study included 60 patients with sellar tumors. All patients underwent computed tomography angiography, MRI-T1W1, and contrast enhanced MRI-T1W1 image sequence scanning. The CT and MRI scanning data were collected and then imported into a Dextroscope imaging workstation, a virtual reality system that allows structures to be viewed stereoscopically. During preoperative assessment, typical images for each patient were chosen and printed out for use by the surgeons as references during surgery. RESULTS: All sellar tumor models clearly displayed bone, the internal carotid artery, circle of Willis and its branches, the optic nerve and chiasm, ventricular system, tumor, brain, soft tissue and adjacent structures. Depending on the location of the tumors, we simulated the transmononasal sphenoid sinus approach, transpterional approach, and other approaches. Eleven surgeons who used virtual reality models completed a survey questionnaire. Nine of the participants said that the virtual reality images were superior to other images but that other images needed to be used in combination with the virtual reality images. CONCLUSIONS: The three-dimensional virtual reality models were helpful for individualized planning of surgery in the sellar region. Virtual reality appears to be promising as a valuable tool for sellar region surgery in the future.

Coexistence of ectopic pituitary adenoma and empty sella in a patient with acromegaly : a case report and review of literature.

Ectopic pituitary adenoma with an empty sella is extremely rare. We report an unusual patient with an ectopic growth hormone-secreting pituitary adenoma in the sphenoid sinus with an empty sella. The association is related to a development disorder of the anterior pituitary tissues. Tumor in the sphenoid sinus was completely removed by endoscopic endonasal transsphenoidal approach. During the follow-up, the patient met the criteria for endocrinological cure.

Microsurgical anatomy of Liliequist's membrane demonstrating three-dimensional configuration.

OBJECT: Liliequist's membrane (LM) is an important arachnoid structure in the basal cisterns. The relevant anatomic descriptions of this membrane and how many leaves it has are still controversial. The existing anatomical theories do not satisfy the needs of minimally invasive neurosurgery. We aimed to establish the three-dimensional configuration of LM. METHODS: Fifteen adult formalin-fixed cadaver heads were dissected under a surgical microscope to carefully observe the arachnoid mater in the suprasellar and post-sellar areas and to investigate the arachnoid structure and its surrounding attachments. RESULTS: It was found that the LM actually consists of three types of membranes. The diencephalic membrane (DM) was usually attached by the mesencephalic membrane (MM) from underneath, and above DM it was usually a pair of hypothalamic membranes (HMs) extending superomedially. The pair of HMs was stretched between the DM (or MM) and the hypothalamus and were seldom attached to the carotid-chiasmatic walls between the carotid cistern and the chiasmatic cistern. These three types of membranes (DM, MM, and HM) comprised the main arachnoid structure in the anterior incisural space and often presented as four connected leaves. However, only two thirds of the specimens had all three types of membranes, and there was considerable variation in the characteristics and shapes of the membranes among the specimens. CONCLUSION: All three types of membranes comprising LM serve as important anatomical landmarks and interfaces for surgical procedures in this area.

Analysis of changes in the volume of edema around brain contusions and the influencing factors: A single-center, retrospective, observational study.

ABSTRACT: Traumatic brain injury (TBI), a common neurosurgical condition, has well-known treatment guidelines. However, the mechanisms underlying the varying severity of brain edema secondary to TBI are largely unknown, leading to controversial treatments.This study seeks to measure edema volumes around brain contusions in different regions, analyze factors related to differences in edema volume and provide a theoretical basis for brain edema treatment.Data from 113 brain contusion patients treated at the Department of Neurosurgery of Fuzhou General Hospital from January 2017 to November 2019 were analyzed retrospectively. Based on computed tomography (CT) data, the patients were divided into the venous group (brain contusion in regions with large cortical veins, n = 47) and the nonvenous group (brain contusions in other regions, n = 66). Here, 3D Slicer software was used to calculate the brain contusion volume on the first CT obtained after injury and the brain contusion volume and its surrounding edema on the 5th day after injury. The brain contusion volume to surrounding edema volume ratio was calculated, and the number of patients who showed brain contusion progression requiring surgery was determined. Hematocrit (Hct), fibrinogen (Fg), and d-dimer levels within 6 hours and on the 5th day after admission were also compared.Patients in the venous group had a significantly increased percentage of area with edema around the brain contusion compared with patients in the nonvenous group (P < .05), and the 2 groups showed no significant difference in the number of patients with brain contusion progression or surgical treatment (P > .05) or Hct, Fg, or d-dimer (D-D) levels. For all patients, Hct, Fg, and D-D levels within 6 hours after admission were significantly different from those on the 5th day (P < .05 for all).Cortical venous obstruction may be the most important factor influencing edema around brain contusions. The Fg level decreased slightly, and the D-D level increased to its peak rapidly after mild-moderate TBI. This change was followed by a gradual increase in the former and a gradual decrease in the latter.

[Retracted] Anticancer activity of taraxerol acetate in human glioblastoma cells and a mouse xenograft model via induction of autophagy and apoptotic cell death, cell cycle arrest and inhibition of cell migration.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that several figures (Figs. 3, 4, 7 and 10) contained apparent anomalies, including repeated patternings of data within the same figure panels. Furthermore, Fig. 3 contained data that bore striking similarities to data published in Fig. 6 in another paper published in Molecular Medicine Reports, which has now been retracted [Zhu Y­Y, Huang H­Y and Wu Y­L: Anticancer and apoptotic activities of oleanolic acid are mediated through cell cycle arrest and disruption of mitochondrial membrane potential in HepG2 human hepatocellular carcinoma cells. Mol Med Rep 12: 5012­5018, 2015]. After having conducted an independent investigation in the Editorial Office, the Editor of Molecular Medicine Reports has determined that the above paper should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published in Molecular Medicine Reports 13: 4541­4548, 2016; DOI: 10.3892/mmr.2016.5105].

Effect of HMGB1 and RAGE on brain injury and the protective mechanism of glycyrrhizin in intracranial­sinus occlusion followed by mechanical thrombectomy recanalization.

The key to successful treatment of cerebral venous­sinus occlusion (CVO) is the rapid recanalization of the sinus following venous­sinus occlusion; however, rapid recanalization of the sinus may also cause secondary cerebral injury. The present study examined mechanical thrombectomy­related brain injury and the possible molecular mechanisms following CVO recanalization, and investigated the protective effect of glycyrrhizin (GL) in CVO recanalization. The cerebral venous sinus thrombosis (CVST) model was induced in rats using 40% FeCl3. Mechanical thrombectomy was performed at 6 h post­thrombosis. GL was administered to rats following thromboembolism. Neurological function and brain water content were measured prior to sacrifice of the rats. Serum malondialdehyde, superoxide dismutase and nitric­oxide synthase concentrations were measured. The expression levels of high­mobility group box 1 (HMGB1) and receptor of advanced glycation end products (RAGE) and its downstream inflammatory mediators were measured in serum and brain tissues. Rapid CVO recanalization caused brain injury, and the brain parenchymal damage and neurological deficits caused by CVO were not completely restored following recanalization. Similarly, following rapid recanalization in the venous sinus, the expression levels of HMGB1 and RAGE were lower than those in the CVST group, but remained significantly higher than those of the sham group. The combination of mechanical thrombectomy and GL improved cerebral infarction and cerebral edema in rats, and inhibited the extracellular transport of HMGB1, and the expression of downstream inflammatory factors and oxidative­stress products. The administration of exogenous recombinant HMGB1 reversed the neural protective effects of GL. In conclusion, mechanical thrombectomy subsequent to CVO in rats can cause brain injury following recanalization. HMGB1 and RAGE promote inflammation in the process of brain injury following recanalization. GL has a relatively reliable neuroprotective effect on brain injury by inhibiting HMGB1 and its downstream inflammatory factors, and decreasing oxidative stress.

Neuronavigation-assisted surgical treatments for medically refractory epilepsy: Single-hospital experience with 4 surgical approaches.

OBJECTIVE: Surgical treatment should be considered for patients with medically refractory epilepsy, and neuronavigation may benefit and reduce the technical difficulties during surgery. In this study, we aimed to report our single-hospital experience of incorporating neuronavigation for treating patients with medically refractory epilepsy using 4 types of surgery. PATIENTS AND METHODS: Patients who were diagnosed as medically refractory epilepsy and received neuronavigation-assisted surgery were included in this retrospective analysis. The type of surgery was decided by the surgery committee after careful evaluation and discussion, including temporo-parietal-occipital (TPO) disconnection, anterior subtotal callosal section, functional hemispherectomy and resection of the epileptogenic zone(s). Postoperative seizure outcome at the last visit was evaluated using Engel classification. RESULTS: A total of 173 patients with medically refractory epilepsy who were treated surgically under the assistance of neuronavigation were included. The majority type of surgery was resection of epileptic zone, n = 104 (60.12%). An excellent seizure outcome, Engel Class I was found in 50.86% of the patients, followed by 23.12% patients with a good outcome of Engel Class II. CONCLUSION: Overall more than half of the patients could have excellent seizure outcome of Engel Class I, the postoperative complications were manageable. These results indicated that the applicability of neuronavigation, and the use of neuronavigation provides good efficacy and safety for all kinds of surgical procedures for patients with medically refractory epilepsy.

The role of high mobility group box 1 protein in acute cerebrovascular diseases.

The occurrence and development of acute cerebrovascular diseases involves an inflammatory response, and high mobility group box protein 1 (HMGB1) is a pro-inflammatory factor that is expressed not only in the early-injury stage of disease, but also during the post-repair process. In the initial stage of disease, HMGB1 is released into the outside of the cell to participate in the cascade amplification reaction of inflammation, causing vasospasm, destruction of the blood-brain barrier and apoptosis of nerve cells. In the recovery stage of disease, HMGB1 can promote tissue repair and remodeling, which can aid in nerve function recovery. This review summarizes the biological characteristics of HMGB1, and the role of HMGB1 in ischemic and hemorrhagic cerebrovascular disease, and cerebral venous thrombosis.

Microsurgical and Endovascular Treatments for Ruptured Paraclinoid Aneurysms.

BACKGROUND: The treatment of paraclinoid aneurysms can be challenging due to their relationship to the cavernous sinus, carotid siphon, and optic nerve. The goal of this retrospective analysis is to compare the efficacy and safety of microsurgical versus endovascular treatments for ruptured paraclinoid aneurysms. METHODS: Medical records were reviewed to collect information about patient demographics, risk factors, diagnosis (the position and size of aneurysms), Hunt and Hess grade, and surgical method and outcomes, including modified Rankin Scale (mRS) at the time of discharge and 6 months later, complications, and death. RESULTS: In total, 15 and 6 patients were recruited into the microsurgery and endovascular groups, respectively. No difference was detected regarding age, sex, risk factors, and Hunt and Hess grade. Most patients had ophthalmic segment aneurysms (87% versus 83%; p = 1.000) and small aneurysms (< 10 mm, 67% versus 100%; p = 0.102). In the microsurgical group, five patients (33%) had large aneurysms (10-25 mm); three patients (20%) had multiple aneurysms (all p > 0.05 compared with the endovascular group). The occlusion rate at 6 months was 93% in the microsurgical group and 100% in the endovascular group (p > 0.05). No difference was found regarding mRS or the complication and mortality rates between the two groups (all p > 0.05). The occurrence of complications was not related to the location and size of aneurysms (all p > 0.05). CONCLUSIONS: Our retrospective analysis indicates that good clinical outcomes can be achieved with both microsurgical and endovascular approaches. But further prospective randomized multicenter studies are needed to provide more evidence for clinical practice.

Suppression of microRNA-130b inhibits glioma cell proliferation and invasion, and induces apoptosis by PTEN/AKT signaling.

Glioblastoma is the most common malignant brain tumor in adults and is characterized by extensive proliferation and the diffused invasion of tumor cells. Due to the intricate signaling pathways involved in glioma progression, more effective targeted therapies and prognostic biomarkers in clinical practice are required. The suppression of proto-oncogene function or recovery of tumor suppressor gene function remains one of the primary approaches in gene therapy. The close association between the abnormal expression or mutation of microRNA (miRNA) and the tumorigenesis, progression and staging in glioma have been demonstrated previously. However, the expression pattern and specific role of microRNA­130b (miR­130b) in the tumor occurrence and progression of glioma are unclear. In the present study, quantitative polymerase chain reaction was performed to determine the expression level of miR-130b in 30 brain glioma patients and 3 glioma cell lines. An miR­130b inhibitor was transfected into U87 cells to downregulate the expression of miR-130b, and assessments of cell proliferation, cell cycle, apoptosis, cell invasion and migration in vitro and nude mouse tumorigenicity in vivo were conducted. Western blotting and luciferase reporter gene technology were used to verify the downstream target gene of miR-130b, namely phosphatase and tensin homolog (PTEN). The results demonstrated that miR-130b expression was increased in glioma tissues and cell lines in comparison with non-glioma tissues or cells. The downregulated expression of miR-130b inhibited the proliferation and invasion of glioma cells, induced apoptosis of the cells in vitro and inhibited their tumorigenicity in vivo. Western blotting and luciferase reporter assays demonstrated that the PTEN gene is a direct target of miR­130b. Western blotting revealed that the miR-130b inhibitor upregulated the expression of PTEN, inhibited AKT pathway activation, upregulated the tumor suppressor gene p27, and suppressed cyclin D1, matrix metalloproteinase 2 and 9 expression. These results suggest that the miR-130b inhibitor suppressed glioma cell proliferation and invasion via the PTEN/AKT pathway. Therefore, miR­130b is suggested to be an effective therapeutic target for glioma.

Analysis of Factors Related to Hypopituitarism in Patients with Nonsellar Intracranial Tumor.

OBJECTIVE: Previous studies have suggested that postoperative hypopituitarism in patients with nonsellar intracranial tumors is caused by traumatic surgery. However, with development of minimally invasive and precise neurosurgical techniques, the degree of injury to brain tissue has been reduced significantly, especially for parenchymal tumors. Therefore, understanding preexisting hypopituitarism and related risk factors can improve perioperative management for patients with nonsellar intracranial tumors. METHODS: Chart data were collected retrospectively from 83 patients with nonsellar intracranial tumors admitted to our hospital from May 2014 to April 2015. Pituitary function of each subject was determined based on results of preoperative serum pituitary hormone analysis. Univariate and multivariate logistic regression methods were used to analyze relationships between preoperative hypopituitarism and factors including age, sex, history of hypertension and secondary epilepsy, course of disease, tumor mass effect, site of tumor, intracranial pressure (ICP), cerebrospinal fluid content, and pituitary morphology. RESULTS: A total of 30 patients (36.14%) presented with preoperative hypopituitarism in either 1 axis or multiple axes; 23 (27.71%) were affected in 1 axis, and 7 (8.43%) were affected in multiple axes. Univariate analysis showed that risk factors for preoperative hypopituitarism in patients with a nonsellar intracranial tumor include an acute or subacute course (≤3 months), intracranial hypertension (ICP >200 mm H2O), and mass effect (P < 0.05). Multivariate logistic regression analysis showed that mass effect is an independent risk factor for preoperative hypopituitarism in patients with nonsellar intracranial tumors (P < 0.05; odds ratio, 3.197). CONCLUSIONS: Prevalence of hypopituitarism is high in patients with nonsellar intracranial tumors. The occurrence of hypopituitarism is correlated with factors including an acute or subacute course (≤3 months), intracranial hypertension (ICP >200 mm H2O), and mass effect (P < 0.05). Mass effect is an independent risk factor for hypopituitarism.

Analysis of the diffusion tensor imaging parameters of a normal cervical spinal cord in a healthy population.

BACKGROUND: Diffusion tensor imaging (DTI) shows great advantage in the diagnosis of brain diseases, including cervical spinal cord (CSC) disease. This study aims to obtain the normal values of the DTI parameters for a healthy population and to establish a baseline for CSC disease diagnosis using DTI. METHODS: A total of 36 healthy adults were subjected to magnetic resonance imaging (MRI) for the entire CSC using the Siemens 3.0 T MR System. Sagittal DTI acquisition was carried out with a single-shot spin-echo echo-planar imaging (EPI) sequence along 12 non-collinear directions. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were determined at different cervical levels using a region of interest (ROI) method, following which they were correlated with parameters, like age and sex. Further, diffusion tensor tracking (DTT) was carried out to reconstruct the white matter fiber bundles of the CSC. RESULTS: The full and complete fiber bundle structure of a normal CSC was confirmed in both the T2-weighted and DTI images. The FA and ADC values were significantly negatively correlated with each other and showed strongly negative and positive correlations with age, respectively, but not with sex. Additionally, there was no significant difference between the FA and the ADC values at different cervical levels. CONCLUSION: The DTI technique can act as an important supplement to the conventional MRI technique for CSC observation. Moreover, the FA and ADC values can be used as sensitive parameters in the DTI study on the CSC by taking the effects of age into consideration.

Three-dimensional reconstruction and morphological characterization of pituitary macroadenomas.

INTRODUCTION: The aim was to investigate the relationship between the tumor (clinicopathologic and radiological) characteristics and the morphological parameters of pituitary macroadenoma or giant adenoma patients using a three-dimensional (3D) reconstructed model. MATERIAL AND METHODS: Magnetic resoanance imaging (MRI) was performed preoperatively; tumor grade was determined by the Knosp-Steiner classification and tumor morphology by the SIPAP classification. Pituitary adenomas and adjacent structures were reconstructed three-dimensionally by volume rendering. RESULTS: Fifty-two and 6 patients underwent surgery via the transnasal transsphenoidal or pterional approach, respectively. Knosp-Steiner grades I to IV adenomas were observed in 5.2%, 25.9%, 22.4% and 46.6% of the patients, respectively. The 3D model was reconstructed in all cases with superb delineation of tumor morphology and the spatial relationship between the tumor and adjacent tissues. Pituitary adenomas were categorized into intrasellar (13.8%), suprasellar (20.7%), infrasellar (17.2%), and lobulated adenomas (48.3%). Suprasellar adenomas had the smallest (2.27 ±3.22 cm(3)) and lobulated adenomas the largest volume (24.61 ±30.50 cm(3)). Intrasellar adenomas were all functioning, while 75%, 60% and 60.7%, respectively, of suprasellar, infrasellar and lobulated adenomas were nonfunctioning, with a significant association between tumor morphology and secretory function (p = 0.005). CONCLUSIONS: Three-dimensional reconstruction of pituitary macroadenomas offers a simplified morphological classification of pituitary adenomas and may be helpful for neurosurgeons to categorize and characterize pituitary adenomas.

MicroRNA-130b promotes cell proliferation and invasion by inhibiting peroxisome proliferator-activated receptor-γ in human glioma cells.

MicroRNA-130b (miR-130b) is a novel tumor-related miRNA that has been found to be involved in several biological processes. However, there is limited evidence regarding the role of miR-130b in the tumorigenesis of human gliomas. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays were used to quantify miR-130b expression levels in human glioma tissues and glioma cell lines (U251, U87, SNB19 and LN229). The expression level of miR-130b was found to be markedly higher in human glioma tissues than in non­neoplastic brain specimens. Specifically, higher expression levels of miR­130b were observed in the glioma cell lines, compared with those in normal human astrocytes (NHA). We also confirmed that miR­130b interacted with the 3'-untranslated region of peroxisome proliferator­activated receptor-γ (PPAR­Î³), which negatively affected the protein levels of E-cadherin. Furthermore, its effects on cell proliferation and invasion were examined using CCK8, colony formation, cell cycle and Transwell assays. We found that the upregulation of miR-130b induced cell proliferation, decreased the percentage of cells in the G0/G1 phase and enhanced the invasiveness of U251 glioma cells whereas the downregulation of miR-130b exerted opposing effects. Moreover, it was demonstrated that the downregulation of miR­130b in U251 glioma cells restored the expression of PPAR-γ and E-cadherin, and inhibited the expression of ß-catenin. Notably, PPAR-γ knockdown abolished the inhibitory effect of miR-130b inhibitor on the proliferation and invasivness of U251 cells. Taken together, these findings suggest that miR­130b promotes the proliferation and invasion of U251 glioma cells by inhibiting PPAR-γ.

TPX2 promotes glioma cell proliferation and invasion via activation of the AKT signaling pathway.

Glioblastoma multiforme (GBM) is the most common and most malignant type of primary adult brain cancer. The most common phenotype associated with GBM is cellular invasion; however, the molecular mechanisms governing this process are poorly understood. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a nuclear protein with roles in cellular proliferation and mitotic spindle assembly. TPX2 is overexpressed in various malignancies, including human malignant astrocytoma. Despite this finding, the exact role of TPX2 in human glioma is not well defined. The present study reports the elevated expression of TPX2 in a number of glioma cell lines. TPX2 overexpression promoted cellular proliferation, decreased the percentage of cells in G0/G1 phase, and increased invasion of both U251 and U87 cells. Overexpression of TPX2 also significantly enhanced the phosphorylation of AKT, decreased the expression of p21, and increased the expression of cyclin D1 and matrix metallopeptidase (MMP)-9. In both U251 and U87 cells, knockdown of TPX2 resulted in phenotypes that are in direct contrast to those observed following TPX2 overexpression. Specifically, TPX2 knockdown inhibited cell proliferation, increased the percentage of cells in G0/G1 phase, inhibited invasion, decreased AKT phosphorylation, decreased the expression of MMP-9 and cyclin D1, and increased p21 expression. The AKT inhibitor IV in large part phenocopied the effect of TPX2 knockdown. The present data suggest that TPX2 promotes glioma cell proliferation and invasion via AKT signaling.

Recombinant human soluble thrombomodulin protects against brain injury in a CVST rat model, via downregulation of the HMGB1-RAGE axis.

Cerebral venous sinus thrombosis (CVST) is a distinct cerebrovascular disorder, and ~50% of CVST patients progress to cerebral venous infarction, resulting in elevation of cerebral venous pressure. Anticoagulation is the standard initial treatment and is associated with a reduced relative risk of mortality and dependency. Recombinant human soluble thrombomodulin (rhs­TM) is a promising therapeutic natural anticoagulant comparable to antithrombin, tissue factor pathway inhibitor, and activated protein C. The present study aimed to investigate the protective effects of rhs­TM in a CVST rat model, and identify any underlying mechanisms. Rats were treated with rhs­TM intravenously prior to CVST. Following neurological function evaluation, animals were sacrificed and brain water content and infarct volume were assessed. Brain tissue was collected from the infarcted segments and mRNA and protein expression levels of high mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE), tumor necrosis factor (TNF)­α, interleukin (IL)­1ß, IL­6, caspase­3, B­cell lymphoma­2 and Bcl­2 associated X were analyzed by reverse transcription-quantitative polymerase chain reaction and western blot analysis. rhs­TM significantly prevented neurological deficits in locomotor function and reduced infarct volume. The expression levels of HMGB1­RAGE were upregulated in the infarcted segments of rat brains following CVST. Pretreatment with rhs­TM inhibited the HMGB1­RAGE axis, alleviating the expression levels of the proinflammatory cytokines, TNF­α, IL­1ß and IL­6; however, expression levels of the apoptosis-associated genes and proteins remained unaffected. The results of the present study indicated that rhs­TM protects against CVST in the rat model via inhibition of the HMGB1­RAGE axis and inflammation, but not via apoptosis.

Anticancer activity of taraxerol acetate in human glioblastoma cells and a mouse xenograft model via induction of autophagy and apoptotic cell death, cell cycle arrest and inhibition of cell migration.

The aim of the present study was to investigate the in vitro and in vivo anticancer and apoptotic effects of taraxerol acetate in U87 human glioblastoma cells. The effects on cell cycle phase distribution, cell cycle-associated proteins, autophagy, DNA fragmentation and cell migration were assessed. Cell viability was determined using the MTT assay, and phase contrast and fluorescence microscopy was utilized to determine the viability and apoptotic morphological features of the U87 cells. Flow cytometry using propidium iodide and Annexin V-fluorescein isothiocyanate demonstrated the effect of taraxerol acetate on the cell cycle phase distribution and apoptosis induction. Western blot analysis was performed to investigate the effect of the taraxerol acetate on cell cycle­associated proteins and autophagy­linked LC3B­II proteins. The results demonstrated that taraxerol acetate induced dose­ and time­dependent cytotoxic effects in the U87 cells. Apoptotic induction following taraxerol acetate treatment was observed and the percentage of apoptotic cells increased from 7.3% in the control cells, to 16.1, 44.1 and 76.7% in the 10, 50 and 150 µM taraxerol acetate­treated cells, respectively. Furthermore, taraxerol acetate treatment led to sub­G1 cell cycle arrest with a corresponding decrease in the number of S­phase cells. DNA fragments were observed as a result of the gel electrophoresis experiment following taraxerol acetate treatment. To investigate the inhibitory effects of taraxerol acetate on the migration of U87 cell, a wound healing assay was conducted. The number of cells that migrated to the scratched area decreased significantly following treatment with taraxerol acetate. In addition, taraxerol acetate inhibited tumor growth in a mouse xenograft model. Administration of 0.25 and 0.75 µg/g taraxerol acetate reduced the tumor weight from 1.2 g in the phosphate­buffered saline (PBS)­treated group (control) to 0.81 and 0.42 g, respectively. Similarly, 0.25 and 0.75 µg/g taraxerol acetate injection reduced the tumor volume from 1.3 cm3 in the PBS-treated group (control) to 0.67 and 0.25 cm3, respectively.