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Neuroblastoma (NB) is one of the most commonly seen malignancies in childhood and infancy. Cantharidin is a highly potent natural toxin that possesses potent anti-tumor properties on various cancers including NB. However, exposure to cantharidin can cause severe chemical burns and application of cantharidin for cancer therapy is limited. Here we report a strategy of bundling cantharidin within a hybrid platinum (IV) prodrug conjugate. This hydrophobic drug conjugate, ie, CanPt can be further formulated into liposome for drug delivery to minimize the exposure of cantharidin to normal cells for efficient chemotherapeutic agent against NB. [ABSTRACT FROM AUTHOR]

Background: Ischemia stroke is a destructive cerebrovascular disease and a major cause of death and lifelong neurological disability. N-Acetyl-l-aspartyl-l-glutamate (NAAG) is a neurotransmitter in the mammalian brain and involves a variety of physiological and pathological functions including ischemia brain injury. Full understanding of the functions of NAAG peptidase (GCPII) in the pathogenesis of ischemia brain injury is extremely valuable for effective therapies to ischemia stroke.Methods: The expressions of GCPII and NAAG agonist metabotropic glutamate receptor (mGluR3) and TGFb1 were examined by real-time polymerase chain reaction and western blot. Moreover, GCPII knockdown cells were constructed using lentivirus-mediated transfection. Function and molecular mechanisms of GCPII knockdown on apoptosis induced from hypoxic-ischemic-induced injury in neuronal cells were analyzed.Results: In this study, we found that the expressions of GCPII and mGluR3 were upregulated in CoCl2-induced hypoxia environment in neuronal cells. Moreover, knockdown of GCPII in neuronal cells ameliorated apoptosis from hypoxic-ischemic-induced injury through suppressing expressions of caspase 3 and caspase 9.Conclusions: Our results highlighted the roles of GCPII in the ischemia brain injury, and might provide an important target in therapeutic implications. [ABSTRACT FROM AUTHOR]

Chronic subdural hematoma (CSDH) is still a mysterious disease. Though great success has been has achieved by neuro-surgery treatment, the origin and development of CSDH remains unknown. Tremendous clinical observations have found the correlation of subdural effusion (SDE) and CSDH. However, systematic elucidation of CSDH's origin and progression is lacking while almost all the current hypothesis only explained partial phenomenon. This hypothesis proposes Interleukin (IL)-8 inducing neutrophil respiratory burst is the crucial impact when SDE evolves into CSDH. IL-8 initially secreted by dural border layer cells, accumulates and the concentration of IL-8 rises in the SDE cavity. Accompanied by the formation of neo-membrane under the dura meninges, IL-8 firstly prompts to establish the neo-vasculature in it, and then attracts lymphocytes aggregation in the neo-membrane. Both the newly recruited lymphocytes and endothelial cells assist the further elevation of local IL-8 concentration. When the IL-8 concentration elevated to a particular level, it attracts neutrophils to the inner wall of neo-vessels and primes them to oxidative burst. Lysosomes and superoxide released by these neutrophils make the fragile neo-capillary became leaky, and subsequently the plasma and blood cells run into SDE. However, as long as the erythrocytes come into the cavity, they shall bind large quantity of IL-8 and decrease IL-8 concentration to a lower level relatively that reduce the neutrophils recruit. When this negative feedback is stagnancy, for example, the SDE space is so large in elder man who is experiencing brain atrophy, the neo-vessels have to release more erythrocytes to bind IL-8, the liquid cavity will expand and the high intracranial pressure symptoms appeared. Our hypothesis holds potential for the proper therapeutic intervention of CSDH. IL-8 antagonist and other anti-inflammation drugs like macrolides antibiotics, glucocorticoid and atorvastatin might be optional to resist the liquid cavity expanding as actually occurs obvious bleeding soon. [ABSTRACT FROM AUTHOR]

Abstract: We evaluated the effect of brain ischemic post-conditioning on cell apoptosis in the hippocampus following global brain ischemia in rats. Adult male Sprague-Dawley rats were randomly divided into three groups (n =15/group): sham operation, ischemia/reperfusion (I/R) and ischemic post-conditioning (I PostC). Global brain ischemia was induced by four-vessel occlusion. Ischemic post-conditioning consisted of six cycles of 10s/10s reperfusion/reocclusion at the onset of reperfusion. All rats were sacrificed 24hours or 72hours after reperfusion. The hippocampal CA1 regions were analysed using the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end-labelling (Tunel) staining technique for determining cell apoptosis. Levels of caspase-3 and Bcl-2 were measured by Western blotting. After 72hours, fewer Tunel-positive brain cells were observed in rats from the I PostC group than in rats from the I/R group (10.3±2.7% versus 40.8±6.2%, p <0.01). After reperfusion at 24hours and 72hours, expression of caspase-3 in the I PostC group was significantly decreased (p <0.01) and expression of Bcl-2 in the I PostC group was significantly increased (p <0.01) compared with the I/R group. We conclude that down-regulation of caspase-3 and up-regulation of Bcl-2 by ischemic post-conditioning may underlie the protective effects of post-conditioning. [Copyright &y& Elsevier]

Abstract: Malignant gliomas are highly invasive tumours associated with high levels of mortality, and the treatment of gliomas remains a major neurosurgical challenge. Stat3, a member of the signal transducer and activator of transcription family, has a critical role in a variety of cancer cells. We have previously shown that downregulation of Stat3 decreases invasiveness and induces apoptosis in U251 human glioma cells in vitro, but to date it has been unclear whether this treatment would be beneficial in vivo. In the present study, we found that downregulation of Stat3 via RNAi suppressed tumour growth in a xenograft mouse model by inducing apoptosis of U251 tumour cells and inhibiting tumour neo-angiogenesis. We also found that Stat3 RNAi suppresses the expression of Bcl-2 in vivo to induce apoptosis. These results indicate that Stat3 is a critical factor in the survival of patients with glioma, and that targeting Stat3 may offer a potential therapeutic approach. [Copyright &y& Elsevier]

Abstract: Brain ischemic postconditioning is the induction of brief periods of ischemia–reperfusion during the early stages following ischemia, and it has been shown to produce neuroprotective effects. The mechanisms underlying these neuroprotective effects are poorly understood. Glutamate excitotoxicity is one cause of postischemic neuronal death. Glutamine synthetase (GS) is an enzyme that is expressed in glial cells and may affect glutamate excitotoxicity. We induced global ischemia in rats and performed postconditioning with 6 cycles of 10seconds reperfusion and 10seconds reocclusion before final reperfusion. Hematoxylin and eosin staining revealed extensive neuronal loss (44.0±2.8% cell survival) in the hippocampal CA1 region. Ischemic postconditioning decreased neuronal death (82.0±5.6% cell survival; p <0.05). Western blotting revealed significantly increased GS expression in the hippocampus for the ischemia–reperfusion group over time compared with the sham group (p <0.05). Ischemic postconditioning resulted in significantly increased (p <0.05) GS expression compared with both the sham and ischemia–reperfusion groups, suggesting that upregulation of GS expression after ischemia constitutes a neuroprotective mechanism. [Copyright &y& Elsevier]

Abstract: The objective of this study was to examine the prognostic significance of health-related quality of life (HQOL) parameters combined with baseline clinical factors in patients undergoing neurosurgery for treatment of meningioma. A total of 147 patients (61 male, 86 female; mean age 43years, range 5–77years) who underwent resection of a meningioma between January 2002 and December 2004 were studied. HQOL was evaluated using a modified questionnaire based on the World Health Organization Quality of Life-100 Scale and the Karnofsky Performance Scale. The relationships between HQOL and clinical history, radiological findings, extent of resection, histological grade and recurrence were investigated using multivariate analysis. The mean HQOL score was 73.94±1.79 for preoperative patients with meningioma, 84.88±2.14 for postoperative patients, and 91.13±1.61 for healthy controls. HQOL for patients with meningioma was significantly lower than that for normal controls (P <0.001), and postoperative patients had a more satisfactory HQOL than preoperative (P <0.05). Cox proportional hazards analysis showed that significant predictors of health-related quality of life were tumor size, extent of surgical excision, and histologic grade. Multivariate backward logistic regression yielded the regression equation HQOL=119.1097 – 1.5002X 3 – 8.6650X 6 – 10.4210X 7 (R=0.7466; where X 3 is tumor size, X 6 is extent of surgical excision, and X 7 is the histologic grade of the tumor). This equation can be used preoperatively to predict the HQOL of meningioma patients after neurosurgery. A specialized HQOL questionnaire for patients with meningioma provides useful information when planning the operative procedure, and may make it more likely that patients have a satisfactory HQOL after surgery. [Copyright &y& Elsevier]

An intracranial aneurysm in a pituitary adenoma (PA) is not uncommon; however, preoperative angiography is not clinically used as a routine screening test for PA patients. Therefore an intracranial aneurysm is often missed while diagnosing PA patients. When an aneurysm is missed in patients with pituitary tumors, the supporting power by the tumor to the blood vessels or aneurysm will disappear when the tumor is removed and patients may suffer intraoperative or postoperative aneurysm rupture, which may lead to fatal, catastrophic hemorrhage. Herein, we report a case of a PA patient with the signal shadow of vessel flow void, observed vaguely in the right internal carotid artery cavernous segment on magnetic resonance imaging, and a small aneurysm was found via digital subtraction angiography. In order to ensure the safety of surgery, we first performed embolization of the aneurysm and then resected the tumor. [ABSTRACT FROM AUTHOR]

Pseudogenes, which are long noncoding RNAs that originate from protein-coding genes, have been suggested to play important roles in disease. Although studies have revealed high expression of legumain (LGMN) in many types of tumors, the regulation of LGMN remains largely unknown. Here, we found that a novel LGMN pseudogene (LGMNP1) was upregulated in glioblastoma (GBM) tissues and high LGMNP1 expression in GBM cells enhanced proliferation and invasion. Biochemical analysis showed that cytoplasmic LGMNP1 functionally targeted miR-495-3p in a manner involving an RNA-induced silencing complex. Dual-luciferase reporter assays demonstrated that LGMN was a target of miR-495-3p, and LGMN was upregulated and positively correlated with LGMNP1 in GBM. Moreover, miR-495-3p was downregulated and negatively correlated with LGMNP1 in GBM tissues. Notably, the tumor-promoting effects of LGMNP1 upregulation could be alleviated by miR-495-3p mimics. Furthermore, GBM cells overexpressing LGMNP1 exhibited more aggressive tumor progression and elevated LGMN expression in vivo. Thus, our data illustrate that LGMNP1 exerts its oncogenic activity, at least in part, as a competitive endogenous RNA (ceRNA) that elevates LGMN expression by sponging miR-495-3p. CeRNA-mediated miRNA sequestration might be a novel therapeutic strategy in GBM. [ABSTRACT FROM AUTHOR]

This study aimed to perform a survival analysis of patients with multicentric low-grade gliomas (MLGGs) and to assess the influence of various prognostic factors on progression-free survival (PFS) and overall survival. A literature search on Web of Science and PubMed was performed for literature in English published from 1963 to September 2018. Detailed information including demographics, clinical characteristics, treatments, critical events, and time to events for survival analysis were extracted from the included articles. A total of 36 cases from published articles were selected for analysis. Univariate analysis showed that age (<31 years or ≥31 years), grade (pure low grade/low and high grade) and glioma type (astrocytoma/oligodendroglioma) had a significant relationship with PFS. Cox regression analysis showed that tumor grade was an independent prognostic factor for PFS. No factors correlated with overall survival. This integrative analysis of MLGGs patients revealed that age younger than 31 years, pure MLGG, and oligodendroglioma were significantly associated with improved PFS, and pure MLGGs was an independent prognostic factors for PFS. [ABSTRACT FROM AUTHOR]

Cerebral ischemic stroke has long been recognized as a prevalent and serious neurological disease that was associated with high mortality and morbidity. However, the current therapeutic protocols remain suboptimal with major mechanisms underlying stroke urgently warranted. Inhibitor of DNA binding/differentiation 2 (Id2) is found to be up-regulated in neuronal cells following hypoxia/ischemia (H/I). This study was aimed to investigate whether knockdown of Id2 in neuronal cells could protect them from hypoxic and ischemic injury both in vitro and in vivo . Flow cytometric analysis was employed to assess neuronal apoptosis in CoCl 2 -treated neuroblastoma B35 cells engineered to overexpress or knockdown Id2 expression. In vivo knockdown of Id2 was performed in Sprague-Dawley rats by a single intracerebroventricular injection of Cy3-labeled and cholesterol-modified Id2-siRNA. We found that knockdown of Id2 attenuated H/I-induced neuronal apoptosis in vitro while overexpression of Id2 produced an opposite effect. In a rat model of middle cerebral artery occlusion (MCAO), in vivo knockdown of Id2 significantly improved neurological deficits, reduced the volume of ischemic infarction and diminished the neuronal apoptosis in the penumbra area. Double immunofluorescence staining showed less co-localization of retinoblastoma tumor suppressor protein (Rb)-Id2 but greater co-localization of Rb-E2F1 in the penumbra area. Cell cycle assay further demonstrated that Id2 knockdown induced G0/G1 cell cycle arrest in CoCl 2 -treated B35 cells. The present data support the implication of Id2 in the modulation of H/I-induced neuronal apoptosis and may provide a potential therapeutic option to protect brain tissues from ischemic injury by inhibition of its expression. [ABSTRACT FROM AUTHOR]

A number of studies have been done to investigate the role of brain-derived neurotrophic factor (BDNF) in patients with post-traumatic stress disorder (PTSD). In this study we aimed to test the relationship between plasma BDNF levels and PTSD. We solicited 65 subjects having recently experienced road traffic accidents (RTA) conforming to screening criteria. They were given follow-up examinations after one month, three months, and six months. PTSD was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-R-TR, American Psychiatric Association, 2000) using the Mini International Neuropsychiatric Interview (MINI). All participants were divided into two groups: a group with PTSD and a group without PTSD. There were no significant differences in plasma BDNF levels between the two groups at either the 48 h or six-month examination. Within the PTSD group, no significant differences were found in plasma BDNF levels between the two examinations. BDNF levels in those without PTSD showed a higher trend over time after trauma. Higher BDNF levels may be an important protective factor for the prevention of traumatized subjects from developing PTSD. [ABSTRACT FROM AUTHOR]

Highlights: [•] Id2 mRNA and protein are up-regulated in neuronal cells in vivo and in vitro. [•] The increased expression of Id2 might be associated with neuronal apoptosis. [•] The up-regulation of Id2 is consistent with the enhanced expression of Bax. [•] Co-localization of Id2, TUNEL and NeuN was observed in ischemic neurons. [ABSTRACT FROM AUTHOR]