Silibinin-Albumin Nanoparticles: Characterization and Biological Evaluation Against Oxidative Stress-Stimulated Neurotoxicity Associated with Alzheimer's Disease.

Alzheimer's disease (AD) is strongly associated with oxidative stress which can damage neural cells. Silibinin has shown potential antioxidative effects. However, due to its low solubility in water, silibinin provides low biological activity and bioavailability. Therefore, to increase its pharmacological effects, silibilin was encapsulated into human serum albumin (HSA) nanoparticles and well-characterized by DLS and TEM techniques. The antioxidant activity of silibinin-HSA nanoparticles was evaluated on LPS-induced oxidative stress in neuron-like cells (SH-SY5Y) through MTT, antioxidant activity and apoptotic assay. It was shown that the mean diameter of HSA and silibinin-HSA nanoparticles were 88 and 105 nm, respectively with a drug loading of 24.08%, drug encapsulation rate of 94.72%, and the yield of silibinin-HSA nanoparticles of around 83.41% and the HSA nano-formulation released silibinin for 15 h. The results displayed that cell viability was reduced by LPS (10 µg/mL), who's also determined to stimulate oxidative stress and apoptosis. However, co-incubation of cells with silibinin (50 µg/mL) or silibinin-HSA nanoparticles led to the recovery of cell viability, activation of SOD and CAT, increase of GSH content, and reduction of ROS level, Caspase-3 activity and fragmentation of DNA. It was also indicated that the neuroprotective and antioxidant activities of silibinin-HAS nanoparticles was greater than free silibinin, indicating that using albumin can be a potential formulation approach for improving the antioxidant efficacy of silibinin.

TERT Mutation Is Accompanied by Neutrophil Infiltration and Contributes to Poor Survival in Isocitrate Dehydrogenase Wild-Type Glioma.

Mutation of the telomerase reverse transcriptase (TERT) promoter has been demonstrated as an unfavorable prognostic marker in patients with isocitrate dehydrogenase wild-type (IDHwt) glioma. This study aimed to investigate the immune role of TERT promoter mutation status which could improve prognostic prediction in IDHwt. TERT mutation status, IDH mutation, and 1p-19q codeletion status data were obtained from 614 glioma cases from the Cancer Genome Atlas, and 325 cases from the Chinese Glioma Genome Atlas. The same information was obtained from 49 clinical glioma tissues. TERT mutation is preferentially present in glioblastoma and IDH-wt gliomas and is associated with poor prognosis. Moreover, TERT mutation was associated with infiltration of neutrophils and expression of neutrophil chemokines. which might partially contribute to the poor outcome in IDH-wt glioma. Furthermore, patients with IDH-wt glioma did not harbor increased peripheral neutrophils, implying that the infiltrated neutrophil in the tumor environment might due to cytokine chemotaxis. In this study, we hereby propose that TERT mutation might be a molecular driver of the dysfunctional immune microenvironment in IDH-wt glioma. TERT mutation may be a potential immune therapeutic target for optimizing treatment combinations and patient selection for glioma immunotherapy.

Antioxidant activity of calycosin against α-synuclein amyloid fibrils-induced oxidative stress in neural-like cells as a model of preventive care studies in Parkinson's disease.

Protein misfolding and aggregation result in induction of a number of neurodegenerative diseases. In the present study, the anti-fibrillation activity of calycosin and its influence on the amyloid formation of α-synuclein (α-syn) and associated cytotoxicity on neuron-like cells (PC-12) as a model of Parkinson's disease were explored. Therefore, in combination with ThT and ANS fluorescence assay, CD, Congo red absorbance, TEM and cytotoxicity assays (MTT, ROS, SOD activity, CAT activity, GSH content, and caspase-3 activity assays), we showed that calycosin remarkably inhibits α-syn fibril formation through a concentration-dependent manner. The experimental analysis indicated that calycosin exert its antioxidant effects against α-syn amyloid-triggered neurotoxicity by modifying the aggregation pathway toward formation of nontoxic spices via recovering the activity of SOD/CAT and GSH content and reducing the ROS content and caspase-3 activity. This work may provide useful information about the mechanism of α-syn amyloid inhibition by calycosin and pave the way for developing some small molecules-based therapeutic platforms against Parkinson's disease.

Silencing of Long Non-Coding RNA (lncRNA) Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) Protects PC-12 Cells from LPS-Induced Injury via Targeting miR-29a.

BACKGROUND Spinal cord injury (SCI) is a debilitating neuropathological condition that significantly affects the quality of life. The present study is basic research examining the underlying mechanisms of NEAT1 and miR-29a in regulating LPS-induced PC-12 cell injury. MATERIAL AND METHODS The model of cell injury was induced by the treatment of PC-12 cells with LPS. The expressions of NEAT1, miR-29a, and inflammatory cytokines were measured by real-time quantitative polymerase chain reactions (RT-qPCR). Cell proliferation and apoptosis were evaluated by CCK-8 and flow cytometry, respectively. Finally, the target between miR-29a and NEAT1 as well as miR-29a and BCL2L11 was investigated by luciferase and RNA pull-down assays. RESULTS Knockdown of NEAT1 can inhibit inflammatory cytokine expression and PC-12 cell apoptosis and promote PC-12 cell proliferation by targeting miR-29a. However, the variation caused by NEAT1 knockdown can be reversed by the silencing of miR-29a and the overexpression of BCL2L11, which is the direct target gene of miR-29a. CONCLUSIONS High NEAT1 levels can increase LPS-induced injury in PC-12 cells through the miR-29a/BCL2L11 pathway. lncRNA NEAT1 may, therefore, be a promising target for SCI treatment.

MicroRNA-1298-3p inhibits proliferation and invasion of glioma cells by downregulating Nidogen-1.

Glioma is the most prevalent tumor of the central nervous system. To identify differentially expressed miRNAs (DEMs) in gliomas of different grades, bioinformatics analysis was performed. The DEMs between low-grade gliomas (LGGs) and high-grade gliomas (HGGs) were identified by screening the Gene Expression Omnibus and The Cancer Genome Atlas databases using the LIMMA package. Six overlapping DEMs were identified by comparing LGGs and HGGs. Downregulation of miR-1298-3p correlated with poor overall survival rates in glioma patients. Overexpression of miR-1298-3p induced apoptosis of glioma cells and inhibited glioma cell proliferation, migration, and invasion. The basement membrane protein Nidogen-1 (NID1) was identified as a direct binding target of miR-1298-3p in glioma cells. MiR-1298-3p agonist downregulated the NID1 and vimentin levels, but upregulated the level of E-cadherin in glioma cells. Importantly, overexpression of miR-1298-3p induced apoptosis and reduced tumor growth in a mouse xenograft model of glioma. Our results show that miR-1298-3p functions as a tumor suppressor in glioma cells, and suggest that it might serve as a potential biomarker and therapeutic target in glioma patients.

Multiple secondary cauda equina non-Hodgkin's lymphoma: a case report and literature review.

BACKGROUND: Secondary central nervous system involvement of non-Hodgkin's lymphoma (NHL) is rare and with poor prognosis, the most common pathological type is diffuse large B cell lymphoma (DLBCL). Although it can occur in any part of central nervous system, it rarely directly infiltrates the spinal cord or cauda equina. CASE PRESENTATION: We present the case of 64-year-old immunocompetent man with a worsening pain of waist and left lower extremity, accompanied by numbness and paresis of bilateral lower extremity for 20 days. His previous medical history included a resection of painless mass in the left groin in another hospital 7 months ago, and the pathological diagnosis was non-Hodgkin small B cell lymphoma. Gd-enhanced MRI and F-18 FDG PET-CT scan demonstrated multiple infiltrations in the cauda equina. During the operation, we removed as many as 11 subdural-extramedullary bean-size lesions involving multiple nerve roots. The paralysis of his left leg recovered rapidly after the operation. During the follow-up period of more than one year, he underwent standard R-CHOP chemical therapy, no evidence of recurrence was noted until the 13th month, the patient died because of intracranial relapse. CONCLUSIONS: Imaging examination is important in the diagnosis of multiple secondary cauda equina non-Hodgkin's lymphoma, and we highlight the significance of gadolinium-enhanced MRI and F-18 FDG-PET/CT in preoperative diagnosis as well as the previous history.

Intraoperative assessment of anterior circulation aneurysms using the indocyanine green video angiography technique.

We performed a prospective study to evaluate the intraoperative value of indocyanine green (ICG) video angiography in anterior circulation aneurysms. From January 2007 to April 2008, 42 patients with anterior circulation aneurysms who were to undergo aneurysm clipping were enrolled in the study. Intraoperative ICG video angiography was performed using a fluorescence microscope. After the operation, three-dimensional CT angiography (CTA), digital substraction angiography (DSA) and magnetic resonance angiography (MRA) were used to evaluate the use of intraoperative ICG video angiography. Of the 42 patients, on ICG video angiography after initial clip placement, neck remnants of the aneurysm were found in two patients, inadvertent clipping of branching vessels in one patient, and inadvertent clipping of perforating vessels in two patients. ICG video angiography after adjustment of the clip position showed a perfect residual elimination with no abnormal findings. Post-operative DSA, CTA and MRA results corresponded to the intraoperative ICG video angiography findings. Therefore, ICG video angiography is an important tool to monitor residual aneurysm, parent artery stenosis or perforating artery occlusion during intracranial aneurysm clipping.