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Gliomas are the most common primary intracranial tumor, accounting for more than 70% of brain malignancies. Studies indicate that highly upregulated in liver cancer (HULC), a long noncoding RNA (lncRNA), functions as an oncogene in gliomas. However, the underlying mechanism of HULC in gliomas remains under-studied and was subsequently investigated in the current study. Brain tissues were clinically collected from 50 patients with glioblastoma (GBM) and 35 patients with acute craniocerebral injury, followed by immunohistochemical detection of the expression patterns of Forkhead box M1 (FOXM1), anterior gradient 2 (AGR2), and hypoxia-inducible factor-1α (HIF-1α). After flow cytometry-based sorting of the CD133

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and has the highest mortality rate among cancers and high resistance to radiation and cytotoxic chemotherapy. Although some targeted therapies can partially inhibit oncogenic mutation-driven proliferation of GBM cells, therapies harnessing synthetic lethality are ‘coincidental’ treatments with high effectiveness in cancers with gene mutations, such as GBM, which frequently exhibits DNA-PKcs mutation. By implementing a highly efficient high-throughput screening (HTS) platform using an in-house-constructed genome-wide human microRNA inhibitor library, we demonstrated that miR-1193 inhibition sensitized GBM tumor cells with DNA-PKcs deficiency. Furthermore, we found that miR-1193 directly targets YY1AP1, leading to subsequent inhibition of FEN1, an important factor in DNA damage repair. Inhibition of miR-1193 resulted in accumulation of DNA double-strand breaks and thus increased genomic instability. RPA-coated ssDNA structures enhanced ATR checkpoint kinase activity, subsequently activating the CHK1/p53/apoptosis axis. These data provide a preclinical theory for the application of miR-1193 inhibition as a potential synthetic lethal approach targeting GBM cancer cells with DNA-PKcs deficiency.

Angiogenesis is a major pathologic characteristic of glioblastoma, which is one aggressive primary brain tumor. MicroRNA-221/222 (miR-221/222) cluster has been previously reported to function importantly in malignant glioma biological process. The current study aims at evaluating the effects of miR-221/222 cluster on angiogenesis of glioblastoma cells. Microarray data were analyzed to select glioblastoma-associated differentially expressed genes, and dual-luciferase reporter assay was performed to assess targeting correlation between miR-221/222 cluster and suppressor of cytokine signaling-3 (SOCS3). Subsequently, the expression patterns of miR-221 and miR-222 in glioblastoma cells were identified. miR-221 and miR-222 were overexpressed or silenced in glioblastoma cells to identify the effect of miR-221/222 cluster in cell invasion, migration, proliferation, and angiogenesis. To define downstream pathway of miR-221/222 cluster or SOCS3 in glioblastoma, levels of Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway-related proteins were assessed. Additionally, the functions of miR-221/222 on glioblastoma cell angiogenesis were measured in vivo with microvessel density assayed. miR-221 and miR-222 were expressed at a high level and SOCS3 was at a low level in glioblastoma. Downregulation of the miR-221/222 cluster diminished the invasion, migration, proliferation, and angiogenesis with reduced protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9, and vascular endothelial growth factor in glioblastoma cells. Also, silencing miR-221/222 cluster reduced p-JAK2/JAK2 and p-STAT3/STAT3. Consistently, the inhibitory role of silencing miR-221/222 cluster on tumorigenesis of glioblastoma cells was confirmed in vivo. Collectively, the inhibition of miR-221/222 cluster could attenuate the glioblastoma angiogenesis through inactivation of the JAK/STAT pathway by upregulating SOCS3.

Endoscopic endonasal approach for craniopharyngioma (CP) resection provides a wide view and direct observation of hypothalamus and origin of tumor. Under endoscopy, 92 CPs were classified into 2 types: Peripheral and Central, according to its relation to pituitary stalk. Peripheral type was further divided into 3 subtypes: Hypothalamic stalk, Suprasellar stalk and Intrasellar stalk CP, according to the different origin site along hypothalamus-pituitary axis. Peripheral type arisen from the stalk but expanded and grown laterally in an exophytic pattern, accounting for 71.7% of all CPs, preservation rate of stalk was higher (76.0%). Central type grew within and along pituitary stalk and located strictly in the midline. The pituitary stalk was hardly preserved (only15.4%). Hypothalamic stalk CPs (n = 36, 54.6%) developed from the junction of hypothalamus and stalk, hypothalamus damage was found in all of this subtype after surgery. Suprasellar stalk CPs (n = 14, 21.2%) originated from the lower portion of stalk and displaced hypothalamus upward rather than infiltrated it. Intrasellar stalk CPs (n = 16, 24.2%) arose from the subdiaphragma portion of the stalk, with less hypothalamus damage. Recoginzing the origin of CP is helpful to understand its growth pattern and relation to hypothalamus, which is critical in planning the most appropriate surgical approach and degree of excision.

Background Delayed cerebral ischemia (DCI) is a late phase of consequences of subarachnoid hemorrhage (SAH) that causes poor outcome and has become the focus of current research. The aim of this study was to characterize an experimental SAH technique for studying DCI after SAH. New method A double injection SAH rat model with a tiny incision was introduced. At 7 days post-SAH induction, the diameter and luminal cross-sectional area (CSA) of the basilar artery (BA) were measured. In vivo fluorescence microscopy and magnetic resonance perfusion-weighted imaging (MRPWI) were used to evaluate the occurrence of DCI. Normal and sham-operated groups served as References Results Compared to the sham group, in SAH group, the diameter and CSA of the BA were decreased, and the CBF in the SAH group was also reduced to barely half of the level in the sham group. Moreover, both the proportion and severity of microarterial constrictions were increased significantly in the SAH group when compared to those in the sham group. Comparison with existing methods Complete exposure of the atlanto-occipital membrane is avoided, only a tiny region is exposed to identify the puncture spot. Lower mortality, reduced operative trauma and shorter procedure time are advantages to existing models. Multiple techniques for DCI assessment were used including in vivo microscopy and MRPWI. Conclusions The current study demonstrates that our SAH model was successfully established and may serve to help identify a novel target for the treatment of DCI after SAH.

The present study aimed to investigate the effect of dihydroartemisinin on the proliferation of chemotherapy‑resistant C6 rat glioma cells. The results revealed that incubation of C6 glioma cells with a range of dihydroartemisinin concentrations for 48 h led to a significant (P

Additional file 1: Fig. S1. Full length blots of Fig. 1A, which include western blotting analysis of Cx43 expression time-course change after OxyHb incubation in vivo. The numbers represent different treatment groups: 1: normal; 2: 24h; 3: 48h; 4: 72h; 5: 96h. Fig. S2. Full length blots of Fig. 1B: Western blotting analysis of the effect of PKC inhibitors on Cx43 protein expression at the time of 48h after OxyHb incubation. The numbers represent different treatment groups: 1: normal; 2: OxyHb-only; 3: OxyHb+CHE; 4: OxyHb+GF; 5: CHE-only; 6: GF-only. Fig. S3. Fluorescence images and corresponding brightfield images in each group. The injected cell is marked with a black arrow. Scale bar = 50 μm. Fig. S4. Blot images of Fig. 3B: Western blotting analysis of Cx43 in BAs derived from the sham and SAH groups. The numbers represent different treatment groups: 1: sham; 2: SAH. Fig. S5. Blot images of Fig. 4A: Western blotting analysis of Cx43 in BAs derived from the non-targeting siRNA (control) or Cx43-targeting siRNA groups after SAH. The numbers represent different treatment groups: 1: control siRNA; 2: Cx43 siRNA. Fig. S6. Blot images of Fig. 4B: Western blotting analysis of Cx43 in BAs derived from the 2 PKC inhibitors groups after SAH. The numbers represent different treatment groups: 1: sham; 2: SAH-only; 3: SAH+CHE; 4: SAH+GF. Fig. S7. Immunolocalization for DAPI and Cx43 in rat subjected to surgery. Tissues were taken 1,3,5 and 14 days after SAH in each group. Scale bar = 5 μm.

microRNAs (miRNAs) have been found to affect various cancers, and expression of numerous miRNAs is revealed in glioma. However, the role of microRNA-30b-3p (miR-30b-3p) in glioma remains elusive. Therefore, the present study aims to explore the specific mechanism by which miR-30b-3p influence the development of glioma in relation to the AKT signaling pathway. First, glioma cell lines were collected with miR-30b-3p and reversion-inducing cysteine-rich protein with kazal motifs (RECK) expression measured. The functional role of miR-30b-3p and RECK in glioma was determined via gain- and loss-of-function approaches. Subsequently, the expression of invasion- and migration-related factors (MMP-2 and MMP-9) and the AKT signaling pathway-related factors (AKT, p-AKT and PI3K-p85) was detected. Moreover, in vivo experiments were also conducted to investigate how miR-30b-3p influences in vivo tumorigenesis. The results showed that miR-30b-3p was up-regulated and RECK was down-regulated in glioma. RECK was a target gene of miR-30b-3p. Decreased miR-30b-3p and overexpressed RECK led to decreased expression of MMP-2, MMP-9 and p-AKT. Overexpressed RECK and LY294002 could decrease p-AKT and PI3K-p85 expression accompanied with unchanged expression of total protein of AKT. Additionally, proliferation, migration and invasion of glioma cells and tumor formation in nude mice were repressed owing to reduced expression of miR-30b-3p or elevated expression of RECK. In summary, miR-30b-3p inhibition suppresses metastasis of glioma cells by inactivating the AKT signaling pathway via RECK up-regulation, providing a new target for glioma treatment.

In recent years, it has been widely identified that the stromal cell-derived factor 1 (SDF-1) and anterior gradient 2 (AGR2) were implicated in the development of epithelial-mesenchymal transition (EMT) in a variety of cancers. However, the involvement of SDF-1-AGR2 pathway in the EMT of glioblastoma has not been investigated. In the present study, the in vitro assays were used to investigate the role of AGR2 in cell cycle, migration, and invasion. We found that the expressions of AGR2 and chemokine (C-X-C motif) receptor 4 (CXCR4) were obviously upregulated in glioblastoma cells T98G, A172, U87, and U251 than those in normal human astrocytes (NHA) (all p 0.01), among which both U87 and U251 cells presented the highest expression (p 0.05). Western blot revealed that SDF-1 induced the expression of p-AKT, AGR2, and EMT markers (N-cadherin, matrix metalloproteinase-2 (MMP2), and Slug) in a dose-dependent manner in U87 and U251 cells. However, the depletion of AGR2 reversed SDF-1-induced upregulation of EMT markers rather than p-AKT. Furthermore, functional analysis identified that knockdown of AGR2 induced cell cycle arrest in G0/G1 phase and suppressed the migration and invasion of U87 and U251 cells. Taken together, SDF-1-CXCR4 pathway induced the expression of AGR2 to control the progression of EMT likely via AKT pathway in the development of glioblastoma. Our findings lay a promising foundation for the SDF-1-AGR2 axis-targeting therapy in patients with glioblastoma.

To analyze the clinical features, surgical strategy and management outcomes of petroclival meningioma invading into cavernous sinus.Fifteen cases with petroclival meningioma invading into cavernous sinus were retrospectively analyzed. The presigmoidal approach was selected to remove tumors. The surgical strategy for tumor in cavernous sinus was partial resection combined with radiosurgery. Postoperative cranial nerve function and patient survival status were analyzed.The main symptoms of subtype of petroclival meningiomas were headache, abducens nerve palsy and trigeminal neuropathy. Gross total tumor removal was achieved in 13 cases and more than 90% resection in 2 cases. There was no operative death. Nine cases suffered from new postoperative cranial nerve deficits. After a follow-up of 6 - 59 months, complete improvement was achieved in oculomotor nerve deficits, much improvement in VII nerve deficit, but V and VI nerve function deficits improved slightly. The tumor progression-free survival rate was 86.7%.Rational surgical strategy to petroclival meningiomas invading into cavernous sinus should be suggested to reduce the operative morbidity and improve the survival quality of these patients.