Temozolomide and chloroquine co-loaded mesoporous silica nanoparticles are effective against glioma.

The past decades have witnessed great progress in nanoparticle-based cancer-targeting drug delivery systems, but their therapeutic potentials is yet to be fully exploited. In this research, temozolomide (TMZ) and chloroquine (CQ) were loaded into the mesoporous silica nanoparticles (MSNs), the surface was coated with polydopamine (PDA), and the complex was coupled with arginine-glycine-aspartic (RGD) to successfully prepare TMZ/CQ@MSN-RGD. RGD-MSNs accumulated more in the cell and tumor models than in unmodified MSNs in the in vitro and in vivo experiments and can directly induce apoptosis and autophagy in tumor cells. In addition, TMZ/CQ@MSN-RGD therapy enhanced the apoptosis effect of the RGD-MSNs in glioma. Therefore, the combination of autophagy inhibitor with chemotherapy drugs in nanocarriers may promote therapeutic efficacy in treating glioma.

Prehospital Ultra-Early Neurological Deterioration in Intracerebral Hemorrhage: Definition, Prevalence, and Association with Outcomes.

INTRODUCTION: The objective of this study was to define prehospital ultra-early neurological deterioration (UND) and to investigate the association with functional outcomes in patients with intracerebral hemorrhage (ICH). METHODS: We conducted a prospective cohort study of consecutive acute ICH patients. The stroke severity at onset and hospital admission was assessed using the Chongqing Stroke Scale (CQSS), and prehospital UND was defined as a CQSS increase of ≥2 points between symptoms onset and admission. Early neurological deterioration (END) was defined as the increase of ≥4 points in NIHSS score within the first 24 h after admission. Poor outcome was defined as a modified Rankin Scale (mRS) of 4-6 at 3 months. RESULTS: Prehospital UND occurred in 29 of 169 patients (17.2%). Patients with prehospital UND had a median admission NIHSS score of 17.0 as opposed to those without prehospital UND with a median NIHSS score of 8.5. There were three patterns of neurological deterioration: prehospital UND only in 21 of 169 patients (12.4%), END but without prehospital UND in 20 of 169 patients (11.8%), and continuous neurological deterioration in both phases in 8 patients (4.7%). Prehospital UND was associated with worse 3-month outcomes (median mRS score, 4.0 vs. 2.0, p = 0.002). After adjusting for age, time from onset to admission, END, and systolic blood pressure, prehospital UND was an independent predictor of poor outcome (odds ratio [OR] 3.27, 95% confidence interval [CI] 1.26-8.48, p = 0.015). CONCLUSION: Prehospital UND occurs in approximately 1 in 7 patients between symptom onset and admission and is associated with poor functional outcome in patients with ICH. Further research is needed to investigate the prehospital UND in the prehospital phase in the triage of patients with ICH.

DNA-Based Daisy Chain Rotaxane Nanocomposite Hydrogels as Dual-Programmable Dynamic Scaffolds for Stem Cell Adhesion.

Interlocked DNA nanostructures perform programmable movements in nanoscales such as sliding, contraction, and expansion. However, utilizing nanoscaled interlocked movements to regulate the functions of larger length scaled matrix and developing their applications has not yet been reported. Herein we describe the assembly of DNA-based daisy chain rotaxane nanostructure (DNA-DCR) composed of two hollow DNA nanostructures as macrocycles, two interlocked axles and two triangular prism-shaped DNA structures as stoppers, in which three mechanical states─fixed extended state (FES), sliding state (SS), and fixed contracted state (FCS)─are characterized by using toehold-mediated strand displacement reaction (SDR). The DNA-DCRs are further used as nanocomposites and introduced into hydrogel matrix to produce interlocked hydrogels, which shows modulable stiffness by elongating the interlocked axles to regulate the hydrogel swelling with hybridization chain reaction (HCR) treatment. Then the DCR-hydrogels are employed as dynamic biointerfaces for human mesenchymal stem cells (hMSCs) adhesion studies. First, hMSCs showed lower cell density on bare DCR-hydrogel treated with HCR-initiated swelling for stiffness decreasing. Second, the cell adhesion ligand (RGD) modified DNA-DCRs are constructed for hydrogel functionalization. DCR(RGD) hydrogel endows the mobility of RGDs by switching the mechanical states of DNA-DCR. HMSCs showed increased cell density on DCRSS(RGD) hydrogel than on DCRFCS(RGD) hydrogel. Therefore, our DNA-DCR nanocomposite hydrogel exhibit dual-programmable performances including swelling adjustment and offering sliding for incorporated ligands, which can be both utilized as dynamic scaffolds for regulating the stem cell adhesion. The dual-programmable cross-scale regulation from interlocked DNA nanostructures to hydrogel matrix was achieved, demonstrating a new pathway of DNA-based materials.

Relationship of uric acid, C-reactive protein, and N-terminal pro-B-type natriuretic peptide with acute cerebral infarction.

OBJECTIVE: The objective was to study the relationship of serum uric acid, C-reactive protein, and N-terminal pro-B-type natriuretic peptide levels with acute cerebral infarction. METHODS: A total of 96 acute cerebral infarction patients were divided into small, middle, and large infarct size groups based on the size of infarct focus and mild, moderate, and severe infarction groups based on the evaluation criteria of nerve defect degree. In addition, 75 healthy people were selected as the control group. The serum uric acid, C-reactive protein, and N-terminal pro-B-type natriuretic peptide levels of all subjects were detected. RESULTS: The serum uric acid, C-reactive protein, and N-terminal pro-B-type natriuretic peptide levels in the acute cerebral infarction group were significantly higher than the control group (p<0.05). Compared with the small infarct size group, each index in middle and large infarct size groups was significantly increased (p<0.05). Compared with the middle infarct size group, each index in the large infarct size group was significantly increased (p<0.05). The serum uric acid, C-reactive protein, and N-terminal pro-B-type natriuretic peptide levels in moderate and severe infarction groups were significantly higher than the mild infarction group (p<0.05). Compared with the moderate infarction group, each index in the severe infarction group was significantly increased (p<0.05). The serum uric acid, C-reactive protein, and N-terminal pro-B-type natriuretic peptide levels were positively correlated with the infarct size and nerve defect degree (p<0.05). CONCLUSIONS: The serum uric acid, C-reactive protein, and N-terminal pro-B-type natriuretic peptide levels are closely correlated with the occurrence and development of acute cerebral infarction. The detection of these indexes has significance for understanding the severity of acute cerebral infarction, guiding the individual treatment scheme, and evaluating the prognosis.

miR-34c inhibits proliferation of glioma by targeting PTP1B.

Glioma is one of the most pervasive and invasive primary malignancies in the central nervous system. Due to its abnormal proliferation, glioma remains hard to cure at present. Protein tyrosine phosphatase 1B (PTP1B) has been proved to be involved in the process of proliferation in many malignancies. However, whether PTP1B is involved in the proliferation of glioma and how it acts are still unclear. In this study, the PTP1B expressions in glioma tissues and cells were determined by quantitative real-time PCR and western blot analysis. The effects of PTP1B on the proliferation characteristics of glioma were explored using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation assay, and tumor xenografts in mice. We found that the protein and mRNA levels of PTP1B in glioma tissues were significantly higher than those in paired nontumor tissues. MTT and clone formation assays showed that PTP1B is closely related to human glioma cell proliferation. In addition, TargetScan revealed that miR-34c regulates PTP1B. Mechanistically, we proved that miR-34c negatively regulates PTP1B and then participates in the regulation of glioma cell proliferation in vivo. Collectively, these results suggested that miR-34c inhibits the proliferation of human glioma cells by targeting PTP1B, which will provide a potential target for the treatment of glioma.

Knocking down of Polo-like kinase 2 inhibits cell proliferation and induced cell apoptosis in human glioma cells.

AIMS: Polo-like kinase 2 (PLK2) belongs to a family of serine/threonine kinases, and it is involved in tumorigenesis. The present study aimed to explore the potential clinical significance of PLK2 in the development of gliomas. MAIN METHODS: Immunohistochemistry (IHC) was performed to detect the expression of PLK2 in glioma tissues. Cell proliferation and apoptosis were determined by Cell Counting Kit 8 (CCK8) and flow cytometry analysis, respectively. KEY FINDINGS: PLK2 expression gradually increased with the degree of glioma malignancy. High PLK2 expression was associated with a poor prognosis in glioma. Short hairpin RNAs targeting PLK2 (shPLK2) inhibited the viability and induced apoptosis of glioma cells, both in vitro and in vivo. Ring finger protein 180 (RNF180), an E3 ubiquitin ligase, interacted with PLK2 and induced the ubiquitination of PLK2. Overexpression of PLK2 in glioma cells significantly inhibited RNF180 upregulation-induced cell apoptosis. The expression level of RNF180 gradually decreased with the degree of glioma malignancy. SIGNIFICANCE: Knocking down of PLK2 may suppress the glioma development through cancer cell proliferation inhibition and cell apoptosis promotion. Furthermore, RNF180 may mediate the ubiquitination of PLK2. The present findings may help improve the clinical management of glioma in the future.

Interaction network of immune-associated genes affecting the prognosis of patients with glioblastoma.

Glioblastoma multiforme (GBM) is a common malignant tumor type of the nervous system. The purpose of the present study was to establish a regulatory network of immune-associated genes affecting the prognosis of patients with GBM. The GSE4290, GSE50161 and GSE2223 datasets from the Gene Expression Omnibus database were screened to identify common differentially expressed genes (co-DEGs). A functional enrichment analysis indicated that the co-DEGs were mainly enriched in cell communication, regulation of enzyme activity, immune response, nervous system, cytokine signaling in immune system and the AKT signaling pathway. The co-DEGs accumulated in immune response were then further investigated. For this, the intersection of those co-DEGs and currently known immune-regulatory genes was obtained and a differential expression analysis of these overlapping immune-associated genes was performed. A risk model was established using immune-regulatory genes that affect the prognosis of patients with GBM. The risk score was significantly associated with the prognosis of patients with GBM and had a significant independent predictive value. The risk model had high accuracy in predicting the prognosis of patients with GBM [area under the receiver operating characteristic curve (AUC)=0.764], which was higher than that of a previously reported model of prognosis-associated biomarkers (AUC=0.667). Furthermore, an interaction network was constructed by using immune-regulatory genes and transcription factors affecting the prognosis of patients with GBM and the University of California Santa Cruz database was used to perform a preliminary analysis of the transcription factors and immune genes of interest. The interaction network of immune-regulatory genes constructed in the present study enhances the current understanding of mechanisms associated with poor prognosis of patients with GBM. The risk score model established in the present study may be used to evaluate the prognosis of patients with GBM.

Corrigendum: Immune and Clinical Features of CD96 Expression in Glioma by in silico Analysis.

[This corrects the article DOI: 10.3389/fbioe.2020.00592.].

Low Expression of APOB mRNA or Its Hypermethylation Predicts Favorable Overall Survival in Patients with Low-Grade Glioma.

BACKGROUND: This study was performed to explore the clinical and prognostic significance of APOB mRNA expression, DNA methylation and APOB mutation in patients with low-grade glioma (LGG). METHODS: Bioinformatic analysis was conducted using genomic, clinical and survival data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Serum APOB protein levels were measured via immunoturbidimetry in 150 patients with LGG and 100 healthy controls from Hubei General Hospital. RESULTS: There was a negative association between the levels of APOB mRNA and DNA methylation (r=-0.355, P<0.0001) in patients with LGG from the TCGA database. Additionally, LGG patients with low levels of APOB mRNA exhibited better overall survival (OS) than those with high levels of APOB mRNA (HR=0.637, P=0.0085). The survival time of LGG patients with APOB hypermethylation was markedly longer than that of patients with APOB hypomethylation (HR=0.423, P=0.0185). The prognostic significance of APOB mRNA and DNA methylation was also validated with the CGGA cohort, and a similar conclusion was reached. APOB gene mutations were observed in 3% of patients with LGG from the TCGA database, and no association was detected between APOB mutations and OS (P=0.164). Furthermore, the levels of APOB protein were much lower in patients with LGG than in normal individuals (P=0.0022), and the expression of APOB protein was markedly different among groups when stratified by histological type (P<0.0001) and histological-molecular classification (P<0.0001). CONCLUSION: APOB mRNA expression is negatively regulated by DNA methylation in patients with LGG. Low expression or hypermethylation of APOB might predict relatively favorable survival in patients with LGG.

Immune and Clinical Features of CD96 Expression in Glioma by in silico Analysis.

Background: Immune checkpoints target regulatory pathways in T cells that enhance antitumor immune responses and elicit durable clinical responses. As a novel immune checkpoint, CD96 is an attractive key target for cancer immunotherapy. However, there has been no integrative investigation of CD96 in glioma. Our study explored the relationship between CD96 expression and clinical prognosis in glioma. Methods: RNA and clinical data for a total of 1,001 samples were included in this study, including 325 samples from the Chinese Glioma Genome Atlas (CGGA) database and 676 samples from The Cancer Genome Atlas (TCGA) dataset. The R programming language was employed to perform statistical analysis and draw figures. Results: CD96 had a consistently positive relationship with glioblastoma and was highly enriched in IDH-wildtype and mesenchymal subtype glioma. Gene ontology enrichment and gene set variation analysis analyses suggested that CD96 was mostly involved in immune functions and was especially related to T cell-mediated immune response in glioma. Subsequent immune infiltration analysis showed that CD96 was positively correlated with infiltrating levels of CD4 + T and CD8 + T cells, macrophages, neutrophils, and DCs in glioblastoma multiforme and low-grade glioma. Additionally, CD96 was tightly associated with other immune checkpoints, including PD-1, CTLA-4, TIGIT, and TIM-3. Univariate and multivariate Cox analysis demonstrated that CD96 acts as an independent indicator of poor prognosis in glioma. Conclusion: CD96 expression was increased in malignant phenotype and negatively associated with overall survival in glioma. CD96 also showed a positive correlation with other immune checkpoints, immune response, and inflammatory activity. Our findings indicate that CD96 is a promising clinical target for further immunotherapeutic use in glioma patients.

Involvement of MEK5/ERK5 signaling pathway in manganese-induced cell injury in dopaminergic MN9D cells.

BACKGROUND: Over-exposure to manganese (Mn) causes irreversible movement disorders with signs and symptoms similar, but not identical, to idiopathic Parkinson's disease (IPD). Recent data suggest that Mn toxicity occurs in dopaminergic (DA) neurons, although the mechanism remains elusive. This study was designed to investigate whether Mn interfered the apoptotic signaling transduction cascade in DA neurons. METHODS: Mouse midbrain dopaminergic MN9D cells were exposed to Mn in a concentration range of 0, 400, 800, or 1200 µM as designated as control, low, medium, and high exposure groups, respectively. The flow cytometry with Annexin V/PI double staining and immunohistochemistry were used to assess the apoptosis. RESULTS: Data indicated that Mn exposure caused morphological alterations typical of apoptosis, increased apoptotic cells by 2-8 fold, and produced reactive oxidative species (ROS) by 1.5-2.2 fold as compared to controls (p < 0.05). Studies by qPCR and Western blot revealed that Mn exposure significantly increased the protein expression of extracellular signal-regulated kinase-5 (ERK5) and mitogen-activated ERK kinase-5 (MEK5) (p < 0.05). The presence of BIX02189, a specific inhibitor of MER/ERK, caused a much greater cytotoxicity, i.e., higher cell death, more ROS production, and worsened apoptosis, than did the treatment with Mn alone. Following Mn exposure, the expression of a downstream effector Bcl- 2 was reduced by 48 % while those of Bax and Caspase-3 were increased by 266.7 % and 90.1 %, respectively, as compared to controls (p < 0.05). CONCLUSION: Taken together, these data provide the initial evidence that the signaling transduction cascade mediated by MEK5/ERK5 is responsible to Mn-induced cytotoxicity; Mn exposure, by suppressing anti-apoptotic function while facilitating pro-apoptotic activities, alters neuronal cell's survival and functionally inhibits DA production by MN9D cells.

IL-4 Switches Microglia/macrophage M1/M2 Polarization and Alleviates Neurological Damage by Modulating the JAK1/STAT6 Pathway Following ICH.

Inflammatory damage following ICH is often attributed to microglia/macrophage activation. In many diseases, IL-4 has been proven to switch microglia/macrophages from the pro-inflammatory to the anti-inflammatory subtype. However, the role and underlying mechanism of IL-4 in ICH, especially in neuroprotection, remain unknown. In our study, we constructed a microglia/macrophage polarization model in BV2 cells to verify that the M2 shift of microglia/macrophages was mediated by JAK1/STAT6 after IL-4 treatment and then revealed that in vitro administration of IL-4 decreased M1 markers, pro-inflammatory cytokines and neuroapoptosis markers but significantly increased M2 markers and anti-inflammatory cytokines. Using an ICH model in mice, we observed that IL-4 administration decreased neurological deficits, brain edema and infarct lesions induced by ICH. We verified that IL-4 mediates inflammation by regulating M1/M2 polarization in ICH and explored the underlying mechanism. Furthermore, we discovered that pathway components and apoptosis-related proteins showed consistent trends based on their respective roles, and inferred that the process that TNF-α activates caspase-3 may be the crosstalk that microglia phagocytosis developed into accelerate apoptosis of cells in ICH. In conclusion, our study demonstrates that IL-4 may promote M2 microglia/macrophage polarization partly through the JAK1/STAT6 pathway to alleviate neuroinflammation after ICH.

Assessment of the value of 3D-DSA combined with neurointerventional thrombolysis in the treatment of senile cerebrovascular occlusion.

Assessment of the value of three-dimensional digital subtraction angiography (3D-DSA) combined with neurointerventional thrombolysis in the treatment of senile cerebrovascular occlusion was investigated. A total of 129 patients with senile cerebrovascular occlusion admitted to the Affiliated Hospital of Zunyi Medical University from August 2015 to September 2017 were collected. Among them, 69 patients who underwent neurointerventional catheter thrombolysis under 3D-DSA were included in the study group, and 60 patients treated with neurointerventional thrombolysis were the control group. The levels of inflammatory cytokines IL-6, IL-1ß and IL-8 in the two groups were measured by enzyme linked immunosorbent assay (ELISA) before treatment (T0), 7 days (7d) after treatment (T1) and 14 days (14d) after treatment (T2). The score of the National Institute of Health Stroke Scale and the clinical efficacy of patients in the two groups were compared before and after treatment, and Barthel index (BI) was used for investigation before and after treatment. The recurrence rate of disease in the two groups within 1 year was recorded. At T1, IL-6, IL-1ß and IL-8 in the study group were significantly lower than those in the control group (P<0.05). The NIHSS score in the study group was lower than that in the control group after treatment (P<0.05). The BI score in the study group was significantly higher than that in the control group after treatment (P<0.05). After the prognostic follow-up, the disease recurrence rate of the study group was significantly lower than that of the control group (P<0.05). In conclusion, 3D-DSA combined with neurointerventional thrombolysis can significantly reduce the expression of inflammatory cytokines and improve the quality of life in patients with cerebrovascular occlusion, which has a high clinical value.

Integration of Transcriptome Resequencing and Quantitative Proteomics Analyses of Collagenase VII-Induced Intracerebral Hemorrhage in Mice.

OBJECTIVE: Intracerebral hemorrhage (ICH) is a subtype of stroke with high mortality and morbidity rates. Our aim was to comprehensively analyze transcriptome and proteome in an experimental ICH model. METHODS: All mice were divided into ICH model (n = 3) and sham groups (n = 3). ICH was induced by collagenase VII. The ipsilateral hemisphere was used for whole transcriptome and proteomics resequencing. After preprocessing, differentially expressed lncRNAs (DElncRNAs), mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and DEproteins between ICH and sham groups were identified. Functional enrichment analysis was performed using the clusterProfiler package, followed by protein-protein interaction (PPI) analysis. After that, the Pearson correlation coefficient between DEmRNAs and DElncRNAs or between DEmRNAs and DEproteins was calculated. DElncRNAs with similar functions were analyzed by the GOSemSim package. After prediction of DEmiRNA-DEmRNA and DElncRNA-DEmiRNA relationships, a competing endogenous RNA (ceRNA) network was constructed. Several DEmRNAs and DElncRNAs were validated in ipsilateral hemisphere tissues of the ICH model and control groups using RT-qPCR and western blot. RESULTS: Between the ICH and sham groups, 31 DElncRNAs, 367 DEmRNAs, 35 DEmiRNAs, and 96 DEproteins were identified. DEmRNAs were mainly enriched in inflammation, such as cytokine-cytokine receptor interaction, IL-17, and TNF signaling pathways. A PPI network of DEmRNAs was constructed and hub genes were identified, such as IL6 (degree = 59), TNF (degree = 44), and CXCR2 (degree = 39). 24 DElncRNAs with similar functions were identified, including 15 up- and 9 down-regulated lncRNAs. After integration of DEmiRNA-DEmRNA and DElncRNA-DEmiRNA relationships, we constructed a ceRNA network, composed of 71 DEmRNAs, 17 DEmiRNAs, and 12 DElncRNAs. RT-qPCR and western blot results confirmed that C3, Fga, and Slc4a1 proteins were more lowly expressed and Penk was more highly expressed in ICH than control groups, which could become potential markers for ICH. CONCLUSION: Our findings identified ICH-related DE-RNAs and proteins and potential molecular mechanisms of ICH by transcriptome resequencing and quantitative proteomic analyses.

Low expression or hypermethylation of PLK2 might predict favorable prognosis for patients with glioblastoma multiforme.

BACKGROUND: As the most aggressive brain tumor, patients with glioblastoma multiforme (GBM) have a poor prognosis. Our purpose was to explore prognostic value of Polo-like kinase 2 (PLK2) in GBM, a member of the PLKs family. METHODS: The expression profile of PLK2 in GBM was obtained from The Cancer Genome Atlas database. The PLK2 expression in GBM was tested. Kaplan-Meier curves were generated to assess the association between PLK2 expression and overall survival (OS) in patients with GBM. Furthermore, to assess its prognostic significance in patients with primary GBM, we constructed univariate and multivariate Cox regression models. The association between PLK2 expression and its methylation was then performed. Differentially expressed genes correlated with PLK2 were identified by Pearson test and functional enrichment analysis was performed. RESULTS: Overall survival results showed that low PLK2 expression had a favorable prognosis of patients with GBM (P-value = 0.0022). Furthermore, PLK2 (HR = 0.449, 95% CI [0.243-0.830], P-value = 0.011) was positively associated with OS by multivariate Cox regression analysis. In cluster 5, DNA methylated PLK2 had the lowest expression, which implied that PLK2 expression might be affected by its DNA methylation status in GBM. PLK2 in CpG island methylation phenotype (G-CIMP) had lower expression than non G-CIMP group (P = 0.0077). Regression analysis showed that PLK2 expression was negatively correlated with its DNA methylation (P = 0.0062, Pearson r = -0.3855). Among all differentially expressed genes of GBM, CYGB (r = 0.5551; P < 0.0001), ISLR2 (r = 0.5126; P < 0.0001), RPP25 (r = 0.5333; P < 0.0001) and SOX2 (r = -0.4838; P < 0.0001) were strongly correlated with PLK2. Functional enrichment analysis results showed that these genes were enriched several biological processes or pathways that were associated with GBM. CONCLUSION: Polo-like kinase 2 expression is regulated by DNA methylation in GBM, and its low expression or hypermethylation could be considered to predict a favorable prognosis for patients with GBM.

Tripartite motif containing protein 37 involves in thrombin stimulated BV-2 microglial cell apoptosis and interleukin 1ß release.

Intracerebral hemorrhage (ICH) is the most common of stroke with high mortality and severe morbidity. Peroxisome proliferator-activated receptor gamma (PPARγ) plays a neuronprotective role in ICH. In the current study, TRIM37 mRNA expression in peripheral blood mononuclear cells (PBMCs) was found to be increased in ICH patients compared to that in healthy controls (n = 15). TRIM37 bound to PPARγ and enhanced its ubiquitination in mouse microglial BV-2 cell line. According to previous studies, thrombin is produced in the brain instantaneously after ICH and triggers the activation of microglia. Here, thrombin induced TRIM37 expression, cell apoptosis and interleukin-1ß (IL-1ß) release in BV-2 cells, while TRIM37 knockdown partially reversed the effects of thrombin on BV-2 cells. TRIM37 overexpression showed similar effects as thrombin on BV-2 cells, and PPARγ agonist rosiglitazone abolished the effects of TRIM37. In summary, TRIM37 involved in apoptosis and IL-1ß release in BV-2 microglia by regulating PPARγ ubiquitination. The present data established a potential biological role of TRIM37 in ICH-induced brain damage and may provide insight into the development of therapy strategies for ICH.

Programming Rotary Motions with a Hexagonal DNA Nanomachine.

Biological macromolecular machines perform impressive mechanical movements. F-adenosine triphosphate (ATP) synthase uses a proton gradient to generate ATP through mechanical rotations. Here, a programmed hexagonal DNA nanomachine, in which a three-armed DNA nanostructure (TAN) can perform stepwise rotations in the confined nanospace powered by DNA fuels, is demonstrated. The movement of TAN can precisely go through a 60° rotation, which is confirmed by atomic force microscopy, and each stepwise directional rotating is monitored by fluorescent measurements. Moreover, the rotary nanomachine is used to spatially organize cascade enzymes: glucose oxidase (GOx) and horseradish peroxidase (HRP) in four different arrangements. The multistep regulations of the biocatalytic activities are achieved by employing TAN rotations. This work presents a new prototype of rotary nanodevice with both angular and directional control, and provides a nanoscale mechanical engineering platform for the reactive molecular components, demonstrating that DNA-based framework may have significant roles in futuristic nanofactory construction.

Early or late cranioplasty following decompressive craniotomy for traumatic brain injury: A systematic review and meta-analysis.

Objective To evaluate the effectiveness of early (<3 months) cranioplasty (CP) and late CP (>3 months) on post-operative complications in patients receiving decompressive craniotomy (DC) for traumatic brain injury (TBI). Methods The Cochrane Library, PubMed and EMBASE databases were systematically searched for studies published prior to May 21, 2017. A meta-analysis examined post-operative overall complication rates, infection rates, subdural fluid collection and operating times according to early and late CP. Results Of the initial 1675 references, five studies, all cohort, involving a total of 413 patients, were selected for the review. There was no difference between early and late CP in post-operative overall complication rate (RR=0.68, 95%CI [0.36, 1.29]) and the post-operative infection rate (RR=0.50, 95%CI [0.20, 1.24]) in patients receiving DC for TBI. However, there was a significant difference in post-operative subdural effusion (RR=0.24, 95%CI [0.07, 0.78]) and mean operative time (mean difference = -33.02 min, 95%CI [-48.19, -17.84]) both in favour of early CP. Conclusions No differences were found between early and late CP in post-operative overall complications and procedural related infections in patients receiving DC for TBI, but early CP reduced the complication of subdural effusion and the mean operating time. These findings need to be confirmed by large, randomised controlled trials.

IL-6 increases SDCBP expression, cell proliferation, and cell invasion by activating JAK2/STAT3 in human glioma cells.

Syndecan-binding protein (SDCBP), which is induced by tumor necrosis factor-α and interferon-γ, controls the proliferation and invasion of several different types of cancer cells. Interleukin-6 (IL-6) is known to play an important role in the glioma cell growth and invasion. The present study aimed to investigate the relationship between IL-6 and SDCBP in glioma cells. SDCBP expression was knocked down in two glioma cell lines (T98G and U87) by small interfering RNA (siRNA) transfection. Cell proliferation and invasion were significantly repressed following SDCBP knockdown, and there was a positive correlation between SDCBP and IL-6 expression levels in glioma tissues. IL-6 stimulation dose- and time-dependently induced SDCBP expression at both mRNA and protein levels. Furthermore, pre-treatment with the Janus kinase 2 (JAK2) inhibitor AG490 abolished the IL-6-induced SDCBP expression, suggesting that the effect of IL-6 on SDCBP transcription is dependent on JAK2/signal transducer and activator of transcription 3 (STAT3) signaling. Finally, IL-6 did not stimulate glioma cell growth or invasion when SDCBP expression was suppressed. In summary, our results suggest that IL-6 promotes glioma cell proliferation and invasion by inducing SDCBP expression, which is mediated by JAK2/STAT3 signaling.