Long Noncoding RNA SNHG1 Promotes Lipopolysaccharide-Induced Activation and Inflammation in Microglia via Targeting miR-181b.

INTRODUCTION: Long noncoding RNA small nuclear host gene 1 (SNHG1) was involved in neuroinflammation in microglial BV-2 cells; however, its interaction with microRNA (miR)-181b in lipopolysaccharide (LPS)-induced BV-2 cells remained poor. METHODS: BV-2 cells were treated with LPS and then were subjected to observation on morphology and immunofluorescence staining. After transfection, levels of inflammatory cytokines interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) were determined with enzyme-linked immunosorbent assay (ELISA). The potential binding sites between SNHG1 and miR-181b were confirmed using dual-luciferase reporter assay. Quantitative real-time polymerase chain reaction and Western blot were applied for detecting the mRNA and protein expressions of proinflammatory cytokines, ionized calcium-binding adapter molecule 1 (Iba1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). RESULTS: LPS led to the morphological changes and activation of BV-2 cells. The transfection of SNHG1 overexpression vector further promoted LPS-induced SNHG1 upregulation, inflammatory cytokines (IL-1ß, IL-6, and TNF-α) generation and Iba-1, COX-2, and iNOS expressions, whereas silencing SNHG1 did the opposite. miR-181b functions as a downstream miRNA of SNHG1. In LPS-treated cells, the inhibition of miR-181b induced by SNHG1 promoted inflammation response and the expressions of Iba-1, COX-2, and iNOS. CONCLUSION: SNHG1 was involved in LPS-induced microglial activation and inflammation response via targeting miR-181b, providing another evidence of the roles of SNHG1 implicated in neuroinflammation of microglia.

Silencing lncRNA LINC01410 suppresses cell viability yet promotes apoptosis and sensitivity to temozolomide in glioblastoma cells by inactivating PTEN/AKT pathway via targeting miR-370-3p.

BACKGROUND: Long non-coding RNAs (LncRNAs) are involved in glioblastoma (GBM), but the role of long intergenic non-protein coding RNA 01410 (lncRNA LINC01410) is poorly understood. METHODS: The expression of LINC01410 in GBM tissues and cells was analyzed. After transfection or temozolomide (TMZ) treatment, the cell viability and apoptosis were detected using cell counting kit-8 assay and flow cytometry. The targeting relationship between LINC01410 and microRNA (miR)-370-3p was confirmed by dual-luciferase reporter assay. Expressions of LINC01410, miR-370-3p and drug resistance- and Phosphatase and Tensin Homolog (PTEN)/AKT pathway-related factors were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: LINC01410 expression was upregulated in GBM, and silencing of LINC01410 decreased cell viability. A slowed decreased trend in cell viability yet an increased half maximal inhibitory concentration (IC50 for TMZ) value and increased expressions of drug resistance-related factors as well as LINC01410 were found in TMZ-resistant GBM cells. Silencing of LINC01410 also decreased the IC50 value yet promoted the sensitivity and apoptosis in TMZ-resistant cells, while upregulating the expression of PTEN and downregulating the phosphorylation of AKT. MiR-370-3p could competitively bind to LINC01410 and its expression was decreased in both parental and TMZ-resistant GBM cells. Downregulation of miR-370-3p reversed the effects of LINC01410 silencing on cell viability, apoptosis and the expressions of miR-370-3p and PTEN/AKT pathway-related factors. CONCLUSION: Silencing of LINC01410 inhibits cell viability yet enhances apoptosis and sensitivity to TMZ in GBM cells by inactivating PTEN/AKT pathway via targeting miR-370-3p.

Development of transferrin-modified poly(lactic-co-glycolic acid) nanoparticles for glioma therapy.

Glioma is a primary intracranial malignant tumor with poor prognosis. In this study, we aimed to develop transferrin (Tf)-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles to deliver temozolomide (TMZ) to glioma and evaluate their efficacy to kill glioma. TMZ-loaded nanoparticles were prepared by nanoprecipitation technique and targeted by Tf. Tf-PLGA-TMZ and PLGA-TMZ were characterized for average particle sizes and zeta potentials, cellular uptake and cytotoxicity as well as in-vitro drug release of these nanoparticles were evaluated in human glioma U87MG cells. In-vivo antiglioma efficacy of Tf-PLGA-TMZ was evaluated in nude mice. Polydispersity ratio increased from 0.132 to 0.150, while encapsulation efficiency decreased from 69.4 to 55.8% after Tf modification of PLGA-TMZ. High performance liquid chromatography test showed that Tf-targeted nanoparticles were better internalized into U87MG cells than nontargeted nanoparticles. Moreover, Tf-PLGA-TMZ significantly decreased the viability of U87MG cells compared with nontargeted nanoparticles (P<0.05). In addition, Tf-PLGA-TMZ significantly decreased tumor volume and improved the survival of nude mice injected with U87MG cells. Tf-modified PLGA nanoparticles could be used for effective delivery of TMZ and have promise for the treatment of glioma.

Application of Micromirror in Microsurgical Clipping to the Intracranial Aneurysms.

OBJECTIVE: The aim of the study was to explore the values and disadvantages of micromirror in the intracranial aneurysm clipping surgery. METHODS: Micromirror was used to assist microsurgical clipping to 36 intracranial aneurysms in 31 patients, of which 3 were carotid-ophthalmic artery aneurysms, 3 were anterior choroidal artery aneurysms, 11 were posterior communicating artery aneurysms, 7 were middle cerebral artery aneurysms, 10 were anterior communicating artery or anterior cerebral artery aneurysms, and the rest were a posterior cerebral artery aneurysm and a posterior inferior cerebellar artery aneurysm. The micromirror was used before and after clipping to observe the anatomic features of necks hidden behind and medial to aneurysms, to visualize surrounding neurovascular structures, and to verify the optimal clipping position. Intraoperative indocyanine green fluorescein angiography, postoperative computerized tomography angiography, and digital subtraction angiography confirmed the success of sufficient clipping. RESULTS: Intraoperative indocyanine green angiography, postoperative computerized tomography angiography , or digital subtraction angiography were performed and showed no case of wrong or insufficient clipping of aneurysm. CONCLUSIONS: Micromirror-assisted microsurgical clipping to the intracranial aneurysm is safe, sufficient, convenient, and practical.

Neuronavigation-Assisted Aspiration and Electro-Acupuncture for Hypertensive Putaminal Hemorrhage: A Suitable Technique on Hemiplegia Rehabilitation.

AIM: To identify whether neuronavigation-assisted aspiration (NA) combined with electro-acupuncture (EA) provides better motor recovery in events of hypertensive putaminal hematoma (HPH) sized 30 to 50 ml. This study aims to examine whether neuronavigation-assisted aspiration and electro-acupuncture have additional value to cerebral hemorrhage motor rehabilitation. MATERIAL AND METHODS: 240 patients with HPH sized 30 to 50 ml and admitted within 6 to 10 hours after stroke ictus were included in this study. Group 1 contained 60 patients who underwent neuronavigation-assisted aspiration and electro-acupuncture (NAEA), group 2 contained 60 patients who underwent neuronavigation-assisted aspiration (NA), group 3 contained 60 patients who underwent electro-acupuncture (EA), and group 4 contained 60 patients who received conservative therapy consisting solely of medications. All the patients received the same therapeutic plan on admission and functional exercises three days after stroke onset. Electro-acupuncture was performed on the third day of admission; motor recovery was examined on weeks zero and eight by blinded assessors. Outcome measures included Fugl-Meyer assessment, modified Ashworth Scale and Functional Independence Measure. RESULTS: Group one showed significantly improved motor outcomes compared to group four (p < 0.01). Group one also showed significant motor improvement when pre-and post- therapy functioning was examined (p < 0.01). Cerebral edema and ischemia were significantly decreased in group one compared to group 3 and 4 (p < 0.05). While not as effective as group one treatment, group two and group three patients had significant motor recovery after intervention when compared to group four (p < 0.05). Muscular tension secondary to stroke was considerably improved between group one and group four, group two and group four, group three and group four respectively (p < 0.05). Activities of daily living (ADL) improved a lot with EA together with NA. CONCLUSION: Neuronavigation-assisted aspiration and electro-acupuncture of HPH at the early stage can provide improved motor recovery with fewer complications. Significant motor recovery can be achieved by neuronavigation-assisted aspiration with acupuncture. Based on our findings, we recommend early intervention with NA and EA in order to promote early rehabilitation of hemiplegia secondary to HPH.

[Regulatory mechanisms of interleukin-1ß on the cyclooxygenase-2 system expression of human neuroglioma cells].

OBJECTIVE: To explore the molecular mechanisms by which interleukin-1ß (IL-1ß) regulates the expression of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2) in human neuroglioma cell. METHODS: H4 neuroglioma cells were treated with IL-1ß (2.5 µg/L) for different timepoints up to 72 h. For MAPK study, cells were incubated for 1 h with MAPK inhibitors, SB203580 and PD98059 and subsequently stimulated with IL-1ß (1 µg/L) for 24 h. Northern and Western blot were used to determine the protein expressions of cPLA2 and COX-2 respectively. And the content of PGE2 in supernatant was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: A dose of 2.5 µg/L IL-1ß induced the protein expressions of cPLA2 and COX-2 and a subsequent release of PGE2 in a time-dependent manner. And the expressions of cPLA2 and COX-2 peaked at 24 h after stimulation (P < 0.05). The expression of PGE2 increased 250 folds after a 72 h culture. Both SB203580 and PD98059 inhibitors reduced IL-1ß-induced PGE2 production while SB203580 alone reduced the expressions of both cPLA2 and COX-2. CONCLUSION: IL-1ß induces the expressions of cPLA2 and COX-2 and affects COX-2 at the post-translational level by modulating PGE2 production through the signal transduction pathways of p38 and p42/44 MAPKs.

How to identify pediatric cerebral and pulmonary arteriovenous malformation earlier: non-hereditary hemorrhagic telangiectasia case.

OBJECTIVE: Cerebral and pulmonary arteriovenous malformations (AVMs) are well known respectively by doctors. However, there are few cases that a single patient suffers both cerebral AVM and pulmonary AVM. Hereditary hemorrhagic telangiectasia (HHT) is universally accepted as an autosomal dominant inherited disease, which represents telangiectasia is frequently multiple AVMs in internal organs. Very few non-HHT cases were diagnosed as cerebral and pulmonary arteriovenous malformations. We report one case with cerebral and pulmonary AVMs diagnosed as non-HHT to share our experience. This report aims to find the way of identifying non-HHT case with cerebral and pulmonary AVMs in early periods. DESIGN: To our knowledge, the primary goals in the treatment are early identification and intervention to prevent bleeding secondary to child cerebral hematoma. For these cases, systemic examination is necessary. RESULTS: If one child suffered cerebral hematoma and also suffers polypnea cyanosis and respiratory distress simultaneously, which indicates signs of oxygen deprivation, a pulmonary CT and brain CT should be performed without delay except for all efforts to diagnose cerebral AVM. CONCLUSIONS: All cases in childhood suffered cerebral hematoma and other systemic disorder, more detailed examination was necessary. Most cases were diagnosed as multiple AVMs. A cerebral digital subtraction angiography (DSA) and bronchoscope are necessary to reveal AVMs in the brain and lung.

Effects of transsylvian-transinsular approach to hypertensive putaminal hematoma operation and electroacupuncture on motor recovery.

OBJECTIVE: In this study, a comparison of motor recovery on hypertensive putaminal hematoma (HPH) with 30 mL or more has been made between conventional treatment and decompressive craniectomy (DC) combined with electroacupuncture (EA). This study aims to examine whether transsylvian-transinsular approach (TTA) to HPH evacuation, DC, and EA have additional value to post-cerebral hemorrhage motor rehabilitation. METHODS: One hundred twenty patients with HPH of 30-mL volume or greater, who were admitted within 6 hours after ictus, were included in this study. Of the 120 patients, 80 were operated on for hematoma evacuation DC through TTA. The postoperative patients were divided into combined therapy group (CTG) and operation with exercises group (OEG). Combined therapy group (n = 40) was treated with EA, functional exercises from 1 to 3 days after hematoma evacuation DC through TTA, twice each day, and OEG (n = 40) accepted only the same operation and functional exercises. Another 40 patients were classified as functional exercises group to be treated conservatively and with functional exercises only after their relatives declined authorization for surgery and EA. The habilitation effects were assessed by blinded assessors at weeks 0 and 8. Outcome measures included Fugl-Meyer assessment, Barthel Index, and Functional Independence Measure. RESULTS: The statistical difference on the motor recovery was considerable (P < 0.05) between CTG and OEG. Significant differences were observed between CTG and physical therapy group (P < 0.01), and we also found statistical difference (P < 0.05) between OEG and functional exercises group. Surgically treated patients received significantly better motor recovery than did the conservatively treated patients. CONCLUSIONS: Microsurgical treatment via TTA of HPH and postoperative EA at an early stage result in improved outcome of motor recovery. Transsylvian-transinsular approach for HPH operation and postoperative EA at an early stage are advocated.