A Novel Method of Magnetic Nanoparticles Functionalized with Anti-Folate Receptor Antibody and Methotrexate for Antibody Mediated Targeted Drug Delivery.

Therapeutic effects of anticancer medicines can be improved by targeting the specific receptors on cancer cells. Folate receptor (FR) targeting with antibody (Ab) is an effective tool to deliver anticancer drugs to the cancer cell. In this research project, a novel formulation of targeting drug delivery was designed, and its anticancer effects were analyzed. Folic acid-conjugated magnetic nanoparticles (MNPs) were used for the purification of folate receptors through a novel magnetic affinity purification method. Antibodies against the folate receptors and methotrexate (MTX) were developed and characterized with enzyme-linked immunosorbent assay and Western blot. Targeting nanomedicines (MNP-MTX-FR Ab) were synthesized by engineering the MNP with methotrexate and anti-folate receptor antibody (anti-FR Ab). The cytotoxicity of nanomedicines on HeLa cells was analyzed by calculating the % age cell viability. A fluorescent study was performed with HeLa cells and tumor tissue sections to analyze the binding efficacy and intracellular tracking of synthesized nanomedicines. MNP-MTX-FR Ab demonstrated good cytotoxicity along all the nanocomposites, which confirms that the antibody-coated medicine possesses the potential affinity to destroy cancer cells in the targeted drug delivery process. Immunohistochemical approaches and fluorescent study further confirmed their uptake by FRs on the tumor cells' surface in antibody-mediated endocytosis. The current approach is a useful addition to targeted drug delivery for better management of cancer therapy along with immunotherapy in the future.

Clinical Features and Treatment of Distal Intracranial Aneurysms.

To analyze the clinical characteristics, therapies, and outcomes of distal intracranial aneurysms, the authors retrospectively studied the clinical and imaging data of 18 patients with distal intracranial aneurysms. There were 10 males and 8 females, aged from 11 months to 59 years (mean, 40.4 ±â€Š11.4 years). All patients were diagnosed by digital subtract angiography. Aneurysm locations were as follows: distal anterior cerebral artery (n = 5), distal middle cerebral artery (n = 2), distal posterior cerebral artery (n = 6), distal posterior inferior cerebellar artery (n = 3), distal anterior inferior cerebellar artery (n = 1), and distal superior cerebellar artery (n = 1). Endovascular embolization was performed on 16 patients, including coil embolization on 10 patients and embolization using Glubran 2 surgical glue on 6 patients, and 7 of the 16 patients also underwent parent artery occlusion. Aneurysms were all completely embolized at the first phase for these 16 patients. The other 2 patients underwent craniotomy with hematoma evacuation and complete aneurysm clipping. Postoperatively, 14 patients showed a good recovery, 2 patients had neurological deficits, 1 patient had seizures and was managed with drugs, 1 patient developed hydrocephalus, and a ventriculo-peritoneal shunt was performed. Follow-up angiographies showed no aneurysm recurrence. Clinical manifestations of distal intracranial aneurysms are varied. Their treatment should follow the principle of individual choice. Endovascular embolization is an effective way to treat distal intracranial aneurysms; and for those with intracranial hematoma, craniotomy with hematoma evacuation and aneurysm clipping may be a feasible treatment.

Alzheimer's Disease; Mechanism, Mutations, and Applications of Nano-Medicine.

BACKGROUND: In the past 10 years, significant progress has been made in understanding the pathogenic chain of events that causes Alzheimer's disease (AD). According to the most widely accepted concept, the production and aggregation of ß-amyloid (Aß) peptides play a critical role in AD. As a result, therapeutic intervention with these processes is the focus of intense research. The Aß peptide is cleaved by the α-secretase, ß-secretase, and γ-secretase enzymes in a region near the pathogenic amyloid precursor protein (APP) and mutations occurring site. METHODS: In the current review, a complete picture of the risk factors behind AD has been investigated. Mutations involved in AD progression have also been screened in various studies. RESULTS: Most of the mutations in the amyloid precursor protein (APP) can lead to the accumulation of APP oligomers in the brain, leading to AD. Several point mutations in APP can cause familial AD (FAD), including the Swedish mutation (K>M670/671N>L) and the A673>V mutation. The pathogenic A673>V mutation and Swedish mutation (M670>K/N671>L) are present in the same region of amyloid precursor protein (APP). However, the A673>T mutation has been shown to confer protection against AD. CONCLUSION: More investigations are needed from geographically distinct regions on mutations associated with AD development and applications of nanomedicines for better management of the disease burden in the future. Nanotechnology-produced metal nanoparticles (NPs) have gotten much attention because of their wide range of uses in the medicinal and agricultural industries. Nanomedicine containing potential phytochemicals, including GX-50 and curcumin conjugated with NPs, maybe a potential candidate for treating AD.

Honokiol exerts protective effects on neural myelin sheaths after compressed spinal cord injury by inhibiting oligodendrocyte apoptosis through regulation of ER-mitochondrial interactions.

OBJECTIVE: To investigate the effect of honokiol on demyelination after compressed spinal cord injury (CSCI) and it's possible mechanism. DESIGN: Animal experiment study. SETTING: Institute of Neuroscience of Chongqing Medical University. INTERVENTIONS: Total of 69 Sprague-Dawley (SD) rats were randomly divided into 3 groups: sham group (n=15), honokiol group (n=27) and vehicle group (n=27). After established CSCI model by a custom-made compressor successfully, the rats of sham group were subjected to the limited laminectomy without compression; the rats of honokiol group were subjected to CSCI surgery and intraperitoneal injection of 20 mg/kg honokiol; the rats of vehicle group were subjected to CSCI surgery and intraperitoneal injection of an equivalent volume of saline.Outcome measures: The locomotor function of each group was assessed using the Basso, Beattie and Bresnahan (BBB) rating scale. The pathological changes of myelinated nerve fibers of spinal cord in 3 groups were detected by osmic acid staining and transmission electron microcopy (TME). Immunofluorescence and Western blot were used to research the experessions of active caspase-3, caspase-12, cytochrome C and myelin basic protein (MBP) respectively. RESULTS: In the vehicle group, the rats became paralyzed and spastic after injury, and the myelin sheath became swollen and broken down along with decreased number of myelinated nerve fibers. Western blot analysis manifested that active caspase-3, caspase-12 and cytochrome C began to increase 1 d after injury while the expression of MBP decreased gradually. After intervened with honokiol for 6 days, compared with the vehicle group, the locomotor function and the pathomorphological changes of myelin sheath of the CSCD rats were improved with obviously decreased expression of active caspase-3, caspase-12 and cytochrome C. CONCLUSIONS: Honokiol may improve locomotor function and protect neural myelin sheat from demyelination via prevention oligodendrocytes (OLs) apoptosis through mediate endoplasmic reticulum (ER)-mitochondria pathway after CSCI.

Adenosine A2A Receptor in Bone Marrow-Derived Cells Mediated Macrophages M2 Polarization via PPARγ-P65 Pathway in Chronic Hypoperfusion Situation.

Background: The role of adenosine A2A receptor (A2AR) in the ischemic white matter damage induced by chronic cerebral hypoperfusion remains obscure. Here we investigated the role of A2AR in the process of macrophage polarizations in the white matter damage induced by chronic cerebral hypoperfusion and explored the involved signaling pathways. Methods: We combined mouse model and macrophage cell line for our study. White matter lesions were induced in A2AR knockout mice, wild-type mice, and chimeric mice generated by bone marrow cells transplantation through bilateral common carotid artery stenosis. Microglial/macrophage polarization in the corpus callosum was detected by immunofluorescence. For the cell line experiments, RAW264.7 macrophages were treated with the A2AR agonist CHS21680 or A2AR antagonist SCH58261 for 30 min and cultured under low-glucose and hypoxic conditions. Macrophage polarization was examined by immunofluorescence. The expression of peroxisome proliferator activated receptor gamma (PPARγ) and transcription factor P65 was examined by western blotting and real-time polymerase chain reaction (RT-PCR). Inflammatory cytokine factors were assessed by enzyme-linked immunosorbent assay (ELISA) and RT-PCR. Results: Both global A2AR knockout and inactivation of A2AR in bone marrow-derived cells enhanced M1 marker expression in chronic ischemic white matter lesions. Under low-glucose and hypoxic conditions, CGS21680 treatment promoted macrophage M2 polarization, increased the expression of PPARγ, P65, and interleukin-10 (IL-10) and suppressed the expression of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). The CGS21680-induced upregulation of P65 and IL-10 was abolished in macrophages upon PPARγ knockdown. The downregulation of TNF-α and IL-1ß by CGS21680 was less affected by PPARγ knockdown. Conclusions: In the cerebral hypoperfusion induced white matter damage, A2AR signaling in bone marrow-derived cells induces macrophage M2 polarization and increases the expression of the anti-inflammatory factor IL-10 via the PPARγ-P65 pathway, both of which might explain its neuroprotective effect.

Emerging mutations in envelope protein of SARS-CoV-2 and their effect on thermodynamic properties.

Structural proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are potential drug targets due to their role in the virus life cycle. The envelope (E) protein is one of the structural proteins; plays a critical role in virulency. However, the emergence of mutations oftenly leads to drug resistance and may also play a vital role in virus stabilization and evolution. In this study, we aimed to identify mutations in E proteins that affect the protein stability. About 0.3 million complete whole genome sequences were analyzed to screen mutations in E protein. All these mutations were subjected to stability prediction using the DynaMut server. The most common mutations that were detected at the C-terminal domain, Ser68Phe, Pro71Ser, and Leu73Phe, were examined through molecular dynamics (MD) simulations for a 100ns period. The sequence analysis shows the existence of 259 mutations in E protein. Interestingly, 16 of them were detected in the DFLV amino acid (aa) motif (aa72-aa75) that binds the host PALS1 protein. The results of root mean square deviation, fluctuations, radius of gyration, and free energy landscape show that Ser68Phe, Pro71Ser, and Leu73Phe are exhibiting a more stabilizing effect. However, a more comprehensive experimental study may be required to see the effect on virus pathogenicity. Potential antiviral drugs, and vaccines may be developed used after screening the genomic variations for better management of SARS-CoV-2 infections.

Emerging Mutations in Nsp1 of SARS-CoV-2 and Their Effect on the Structural Stability.

The genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes 16 non-structural (Nsp) and 4 structural proteins. Among the Nsps, Nsp1 inhibits host gene expression and also evades the immune system. This protein has been proposed as a target for vaccine development and also for drug design. Owing to its important role, the current study aimed to identify mutations in Nsp1 and their effect on protein stability and flexibility. This is the first comprehensive study in which 295,000 complete genomes have been screened for mutations after alignment with the Wuhan-Hu-1 reference genome (Accession NC_045512), using the CoVsurver app. The sequences harbored 933 mutations in the entire coding region of Nsp1. The most frequently occurring mutation in the 180-amino-acid Nsp1 protein was R24C (n = 1122), followed by D75E (n = 890), D48G (n = 881), H110Y (n = 860), and D144A (n = 648). Among the 933 non-synonymous mutations, 529 exhibited a destabilizing effect. Similarly, a gain in flexibility was observed in 542 mutations. The majority of the most frequent mutations were detected in the loop regions. These findings imply that Nsp1 mutations might be useful to exploit SARS-CoV-2's pathogenicity. Genomic sequencing of SARS-CoV-2 on a regular basis will further assist in analyzing variations among the drug targets and to test the diagnostic accuracy. This wide range of mutations and their effect on Nsp1's stability may have some consequences for the host's innate immune response to SARS-CoV-2 infection and also for the vaccines' efficacy. Based on this mutational information, geographically strain-specific drugs, vaccines, and antibody combinations could be a useful strategy against SARS-CoV-2 infection.

AQP-4 in peritumoral edematous tissue is correlated with the degree of glioma and with expression of VEGF and HIF-alpha.

It is recognized that expression of AQP4 protein is much greater in gliomas than in normal tissue. The relationship between AQP4 and glioma-associated brain edema is affected by osmotic pressure and hypoxia. In this study, we detected changes of AQP4 expression in tumor and peritumoral edematous tissues to analyze the relationship between AQP4 protein and the edema index (EI). We also detected expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) to investigate their relationship with AQP4 protein, and thus to uncover the molecular biological mechanisms of AQP4 expression in glioma-associated brain edema. Sixty-five patients with brain glioma were divided into tumor and peritumor groups. Fresh tumor specimens, including six cases of grade I glioma, 18 of grade II, 11 of grade III and 30 of grade IV, and peritumoral edematous tissue specimens (1 cm distant from the tumor) were resected from these patients, and AQP4 protein expression levels were detected by western blot. Different AQP4 expression in the tumor and peritumor groups were compared. The relationship between AQP4 expression levels and the degree of peritumoral edema, and expression differences in different grades, were analyzed. Immunofluorescence cytochemistry was used to detect positive expression of AQP4 protein, VEGF protein, and HIF-1α protein in tumor tissue, and differences between expression were analyzed. Western blot showed that AQP4 expression in the peritumor (0.7697 ± 0.0941) and tumor (0.6934 ± 0.0625) groups was higher than in the control group (0.6215 ± 0.0884), and was highest in the peritumor group (both P < 0.01). AQP4 expression level in the peritumor group was positively correlated with EI (r = 0.677, P < 0.001) whereas AQP4 expression level in the tumor group was not correlated with EI (r = 0.096, P > 0.05). AQP4 expression increased with higher tumor grades in the peritumor group, but differences were not significant in the tumor group. Immunofluorescence cytochemical staining revealed that AQP4 protein in normal brain tissue was mainly expressed in the cell membrane surface, and that cytoplasm and nuclear staining was shallow. In glioma cells, AQP4 was widely distributed in the cytoplasm, particularly in the edematous area around the tumor. AQP4 protein expression in the tumor was significantly positively correlated with both VEGF protein (r = 0.877, P < 0.001) and HIF-1α protein (r = 0.876, P < 0.001). AQP4 expression was higher in brain tumor, especially peritumor. The degree of peritumoral edema correlates with AQP4 protein expression only in peritumor, whereas AQP4 expression is in accordance with expression of VEGF and HIF-1α. In glioma-associated brain edema, AQP4 is coregulated by osmotic pressure and hypoxia, with predominance of osmotic regulation, and is redistributed in glioma cells, mainly in the cytoplasm, and its expression level increased with higher glioma grades.

Integrative transcriptome analysis identified a BMP signaling pathway-regulated lncRNA AC068643.1 in IDH mutant and wild-type glioblastomas.

Glioblastomas (GBMs) are classified into isocitrate dehydrogenase (IDH) mutant (IDH MT) and wild-type (IDH WT) subtypes, and each is associated with distinct tumor behavior and prognosis. The present study aimed to investigate differentially expressed long non-coding (lnc)RNAs and mRNAs between IDH MT and IDH WT GBMs, as well as to explore the interaction and potential functions of these RNAs. A total of 132 GBM samples with RNA profiling data (10 IDH MT and 122 IDH WT cases) were obtained from The Cancer Genome Atlas, and 62/78 and 142/219 up/downregulated lncRNAs and mRNAs between IDH MT and IDH WT GBMs were identified, respectively. Multivariate Cox analysis of the dysregulated lncRNAs/mRNAs identified three-lncRNA and fifteen-mRNA signatures with independent prognostic value, indicating that these RNAs may serve roles in determining distinct tumor behaviors and prognosis of patients with IDH MT/WT GBMs. Functional analysis of the three lncRNAs revealed that they were primarily associated with cell stemness or differentiation. Pearson's correlation analysis revealed that the protective lncRNA AC068643.1 was significantly positively correlated with two key bone morphogenetic protein (BMP) signaling-associated mRNAs, Bone morphogenetic protein 2 (BMP2) and Myostatin (MSTN), from the 15 mRNAs. Further in vitro studies demonstrated that BMP2 and MSTN directly stimulated AC068643.1 expression. In conclusion, the present study identified a BMP signaling pathway-regulated lncRNA AC068643.1, which may contribute to the different tumor behaviors observed between IDH MT and IDH WT GBMs.

[AQP4 expression in the brains of patients with glioblastoma and its association with brain edema].

OBJECTIVE: To investigate the expression of aquaporin-4 (AQP4) in the brains of patients with glioblastoma and its association with brain edema. METHODS: Immunofluorescence cytochemistry and western blot tests were performed to detect the expression of AQP4 in the brain tumors and the adjacent tissues in 30 patients with glioblastoma. The association between AQP4 and the extent of brain edema was analysed. RESULTS: The AQP4 immunoreactive cells were mainly astrocytes in the brains, which were extensively distributed in the intracytoplasm. Higher expressions of AQP4 were found in the brain tumors and adjacent tissues in the patients with glioblastoma than in the normal controls (P<0.05). More AQP4 were distributed in the tumor adjacent tissues than in the tumors (P<0.05). The AQP4 was positively correlated with the extent of brain edema. CONCLUSION: AQP4 overexpress in the brain tumors and adjacent tissues, which is associated with the extent of brain edema. Cytotoxic and vasogenic edemas may coexist in the cerebral edema induced by glioblastoma.

Stoichioproteomics reveal oxygen usage bias, key proteins and pathways in glioma.

BACKGROUND: The five-year survival rate and therapeutic effect of malignant glioma is low. Identification of key/associated proteins and pathways in glioma is necessary for developing effective diagnosis and targeted therapy of glioma. In addition, Glioma involves hypoxia-specific microenvironment, whether hypoxia restriction influences the stoichioproteomic characteristics of expressed proteins is unknown. METHODS: In this study, we analyzed the most comprehensive immunohistochemical data from 12 human glioma samples and 4 normal cell types of cerebral cortex, identified differentially expressed proteins (DEPs), and researched the oxygen contents of DEPs, highly and lowly expressed proteins. Further we located key genes on human genome to determine their locations and enriched them for key functional pathways. RESULTS: Our results showed that although no difference was detected on whole proteome, the average oxygen content of highly expressed proteins is 6.65% higher than that of lowly expressed proteins in glioma. A total of 1480 differentially expressed proteins were identified in glioma, including 226 up regulated proteins and 1254 down regulated proteins. The average oxygen content of up regulated proteins is 2.56% higher than that of down regulated proteins in glioma. The localization of differentially expressed genes on human genome showed that most genes were on chromosome 1 and least on Y. The up regulated proteins were significantly enriched in pathways including cell cycle, pathways in cancer, oocyte meiosis, DNA replication etc. Functional dissection of the up regulated proteins with high oxygen contents showed that 51.28% of the proteins were involved in cell cycle and cyclins. CONCLUSIONS: Element signature of oxygen limitation could not be detected in glioma, just as what happened in plants and microbes. Unsaved use of oxygen by the highly expressed proteins and DEPs were adapted to the fast division of glioma cells. This study can help to reveal the molecular mechanism of glioma, and provide a new approach for studies of cancer-related biomacromolecules. In addition, this study lays a foundation for application of stoichioproteomics in precision medicine.

MiR-206 is down-regulated and suppresses cell proliferation by targeting FOXP1 in brain gliomas.

Aberrant expression of miR-206 has been repeatedly found and demonstrated to play crucial roles in cancers. However, the role of miR-206 in brain glioma remains unclear. To address this issue, we detected miR-206 expression of 60 gliomas and 18 normal peritumor tissues, and found that miR-206 is significantly down-regulated in gliomas. Further in silico analysis of 198 glioma samples from the Chinese Glioma Genome Atlas (CGGA) indicated that miR-206 is significantly down-regulated in high grade gliomas and that miR-206 predicts favorable patients' prognosis. Notably, we found that miR-206 expression is negatively correlated with Ki-67 staining, indicating a proliferative inhibition of miR-206 in gliomas. To explore the crucial role of miR-206 in gliomas, we constructed miR-206 stably overexpressed LN229 glioma cell lines and found that the proliferation is significantly inhibited. Through flow cytometry (FCM) analyses, we found that the apoptotic rate is increased and the cell cycle is arrested in LN229 cells after overexpression of miR-206. Bioinformatic analysis, qPCR, western blot and luciferase assay indicated that the Forkhead Box Protein 1 (FOXP1) is a direct target of miR-206 in gliomas. Overexpression of FOXP1 could partially rescue the proliferative inhibition in the miR-206 stably overexpressed LN229 cells. In summary, our results suggest that miR-206 might function as a tumor suppressor of gliomas by inhibition of proliferation and could serve as a promising candidate for therapeutic applications in glioma by targeting FOXP1.

p53-Mediated oligodendrocyte apoptosis initiates demyelination after compressed spinal cord injury by enhancing ER-mitochondria interaction and E2F1 expression.

Oligodendrocyte apoptosis mediated demyelination is a pathological change characteristic of compressed spinal cord injury (CSCI). However, the mechanism of demyelination due to oligodendrocyte apoptosis is not known. In this study, after successfully establishing a rat CSCI model using a custom-made compressor, we investigated the pathological changes, MBP expression, as well as apoptosis-related protein (p53, active caspase-3) expression to determine whether or not apoptosis and demyelination occurred after injury. To understand the possible mechanism of oligodendrocyte apoptosis, caspase-12 and cytochrome C were analyzed to explore the relationship between oligodendrocyte apoptosis and endoplasmic reticulum(ER)-mitochondria interaction. The transcription factor, E2F1, was also detected by immunofluorescence and Western blot assays. The results showed that CSCI increased the expression levels of p53, E2F1 and active caspase-3 followed by the swelling and breakdown of myelin sheaths. The number of myelinated nerve fibers also decreased with down-regulated expression of MBP. Expression levels of caspase-12 and cytochrome C were enhanced along with a reduction in the number of oligodendrocytes. After treatment of CSCI in rats with Pifithrin-µ(PFT-µ), a specific inhibitor of p53, pathomorphological changes of myelin sheath improved significantly. Expression levels of E2F1, active caspase-3, caspase-12 and cytochrome C were down-regulated, consistent with reduced the number of apoptotic oligodendrocytes. These results demonstrated that over-expression of p53 could mediate oligodendrocyte apoptosis thus resulting in demyelination in two ways; by enhancing ER-mitochondria interaction and by triggering the E2F1 mediated apoptosis pathway.

Pyrrolidine dithiocarbamate sensitizes U251 brain glioma cells to temozolomide via downregulation of MGMT and BCL-XL.

The current study investigated the effect of pyrrolidine dithiocarbamate (PDTC) on the proliferation, apoptosis, cell cycle and sensitivity to temozolomide (TMZ) of the U251 glioma cell line. Proliferation, apoptosis and cell cycle analysis of U251 cells following treatment with PDTC and TMZ was determined by an MTT assay and flow cytometry, respectively. The mRNA and protein expression levels of O-6-methylguanine-DNA methyltransferase (MGMT), B-cell lymphoma extra-large (BCL-XL) and survivin were further determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting analysis. The results revealed that treatment with TMZ, PDTC and TMZ + PDTC significantly inhibited cell proliferation, induced apoptosis and contributed to cell cycle arrest in U251 cells. A combination of PDTC and TMZ induced the highest rates of proliferation inhibition and apoptosis. PDTC treatment markedly reduced the expression levels of MGMT, BCL-XL and survivin. The expression levels of MGMT and BCL-XL, were significantly upregulated by TMZ but not by combination treatment of TMZ and PDTC. The results of the present study suggest that treatment with PDTC inhibits cell proliferation, induces apoptosis and cell cycle arrest, and enhances sensitivity to TMZ in U251 cells, which is partly induced by downregulation of MGMT and BCL-XL.

Risk Factors for the Rupture of Middle Cerebral Artery Bifurcation Aneurysms Using CT Angiography.

BACKGROUND AND PURPOSE: To investigate the clinical and morphological characteristics associated with risk factors for the rupture of bifurcation-type middle cerebral artery aneurysms (MCAAs). METHODS: A total of 169 consecutive patients with 177 bifurcation-type MCAAs were reviewed from August 2011 to January 2016. Based on the clinical and morphologic characteristics findings, the risk factors of aneurysm rupture were assessed using statistical methods. RESULTS: Age, cerebral atherosclerosis, no hypertension, hypertension grade 2 and coronary artery disease (CAD) were negatively correlated with aneurysm rupture. The mean diameter (MD) of the parent and two daughter arteries was negatively correlated with rupture. Aneurysms with irregularity, depth, width, maximum size, aspect ratio, depth-to-width ratio, bottleneck factor, and size ratio were positively correlated with rupture. The multivariate logistic regression model revealed that irregular shape (odds ratio (OR) 2.697) and aspect ratio (OR 3.723) were significantly and positively correlated with rupture, while cerebral atherosclerosis (OR 0.033), CAD (OR 0.080), and MD (OR 0.201) were negatively correlated with rupture. Receiver operating characteristic analysis revealed that the threshold value of the aspect ratio and MD were 0.96 and 2.43 mm, respectively. CONCLUSIONS: Cerebral atherosclerosis and CAD are protective factors against rupture. Morphological characteristics such as an aneurysm with an irregular shape, a high aspect ratio (>0.96) and a small MD (<2.43 mm) are likely better predictors of rupture.

Microarray analysis of the aberrant microRNA expression pattern in gliomas of different grades.

Previous studies have focused on miRNA expression in brain gliomas. However, both the expression pattern of miRNAs in gliomas of different grades and various miRNAs involved in malignant progression of gliomas are poorly understood. In the present study, we used miRNA microarray-based screening to investigate the miRNA expression profile in gliomas, which was further verified by qRT-PCR in selected miRNAs. In total, we found 13 differentially expressed miRNAs between gliomas and their matched surrounding tissues. Among them, 12 miRNAs were upregulated and only one (miR-4489) was downregulated compared with the control. Furthermore, the lower expression level of miR-4489 was confirmed by qRT-PCR in 26 glioma samples. Our microarray result revealed 8, 9 and 15 aberrantly expressed miRNAs in gliomas of World Health Organization (WHO) grade II-IV, respectively. Gene Ontology (GO) and Pathway analysis indicated that target genes of the 13 miRNAs were significantly enriched in central nervous system- and tumor-related biological processes and signaling pathways. The dysregulated miRNAs identified in the present study contribute to the tumorigenesis and malignant progression of gliomas and may serve as useful markers for advanced glioma pathological grading and prognosis.