Protective role of activating transcription factor 3 against neuronal damage in rats with cerebral ischemia.

BACKGROUND: The participation of activating transcription factor 3 (ATF3) in transient middle cerebral artery occlusion and reperfusion injury has been reported. However, the precise mechanism of ATF3 in cerebral ischemia is little known so far. Thus, the study examines the mechanism of action underlying the protective role of ATF3 following middle cerebral artery occlusion (MCAO) in rats. METHODS AND RESULTS: The MCAO rats exhibited reduced body weight and motor ability, while increased neurological deficits and brain infarct volume. Gene ontology (GO) enrichment and KEGG pathway analyses revealed that differentially expressed genes were mainly enriched in the TLR4/NF-κB signaling. Moreover, ATF3 was the most differentially expressed gene in brain tissues of MCAO rats versus sham-operated rats, which could bind to CCL2. ATF3 was reduced in MCAO rats, and ATF3 inhibited CCL2 expression to mediate the TLR4/NF-κB signaling. Functionally, ATF3 inhibited neuronal apoptosis, microglia activation, and pro-inflammatory cytokine production to alleviate brain injury in rats. By contrast, CCL2 was overexpressed in neurons and microglia, and CCL2 mitigated the effects of ATF3 to exacerbate brain injury in rats. CONCLUSION: Our findings suggested that ATF3 repressed neuronal apoptosis and microglia activation caused by cerebral ischemia via targeting CCL2 and mediating the TLR4/NF-κB signaling.

Long Intergenic Non-Protein Coding RNA 1094 Promotes Initiation and Progression of Glioblastoma by Promoting microRNA-577-Regulated Stabilization of Brain-Derived Neurotrophic Factor.

PURPOSE: The long intergenic non-protein coding RNA 1094 (LINC01094) plays a vital role in the oncogenicity of clear cell renal cell carcinoma. However, its expression profile and detailed roles in glioblastoma (GBM) remain unknown. In this study, we mainly investigated the expression and roles of LINC01094 in GBM and focused on the mechanism by which LINC01094 regulates the malignant characteristics of GBM. PATIENTS AND METHODS: LINC01094 expression in GBM was determined with quantitative reverse transcription polymerase chain reaction. The proliferation, apoptosis, migration, invasion in vitro, and tumor growth in vivo of GBM cells were evaluated using Cell Counting Kit-8 assay, flow cytometry analysis, migration assay, invasion assay, and tumor xenograft models, respectively. RESULTS: LINC01094 was overexpressed in GBM tissues and cell lines. Moreover, increased LINC01094 expression was associated with adverse clinicopathological parameters in patients with GBM. Loss of LINC01094 inhibited GBM cell proliferation, migration, and invasion; promoted cell apoptosis; and suppressed tumor growth in vivo. Mechanically, LINC01094 functioned as a molecular sponge for microRNA-577 (miR-577) and consequently enhanced the expression of brain-derived neurotrophic factor (BDNF) in GBM cells. Both miR-577 inhibition and BDNF expression enhancement reversed LINC01094 deficiency-mediated inhibition of malignant processes in GBM cells. CONCLUSION: Our results verified the involvement of the LINC01094/miR-577/BDNF pathway in GBM cells and its enhancing effects on the aggressive behaviors of GBM cells in vitro and in vivo. This pathway may be a novel and promising focus for the future development of targeted therapies for GBM.

Identification of potential hub-lncRNAs in ischemic stroke based on Subpathway-LNCE method.

Ischemic stroke is a devastating condition with a high burden of neurological disability and death. The aim of this study was to explore the potential long noncoding RNA (lncRNA) biomarkers underlying the mechanism of stroke. The Subpathway-LNCE method, which was specifically designed to identify lncRNAs competitively regulated functions in diseases, was applied in ischemic stroke dataset to identify ischemic-stroke-associated dysfunctional subpathway that regulated by lncRNAs. At first, based on the shared microRNA (miRNA) between miRNA-messenger RNA (mRNA) and lncRNA-miRNA interactions, lncRNA-mRNA interactions were constructed. Then, the transcription profiling of 18 631 genes was downloaded from Array Express database and was preprocessed, including normalization and gene expression difference (DEG) analysis, to identify candidate differential pathways using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Next, the pathway-lncRNA-mRNA networks were constructed by linking lncRNAs to candidate differential pathways. At last, there were 11 lncRNAs were identified in the top three subpathways as hub-lncRNAs totally, including LINC00240, LINC00472, LINC00265, LINC00473, MIR497HG, NEXN-AS1, HCG17, MEG8, EPB41L4A-AS1, SNHG7, and BCYRN1, five of which were validated to be very effective stroke biomarker by RT-PCR. In conclusion, we applied Subpathway-LNCE method and experimental verification to identify five lncRNAs, including LINC00265, LINC00473, NEXN-AS1, HCG17, and MEG8, which were considered as important lncRNAs biomarkers in ischemic stroke.

[The biomechanical study of rotating-arm self-locking intramedullary nails in comminuted femoral shaft fractures].

This study was sought to compare and evaluate the biomechanical properities of rotating-arm self-locking intramedullary nails (RSIN) with domestic femoral intramedullary nail (DFIN) in communited femoral shaft fractures. A 2 cm midshaft defect was created on seven pairs of cadaver femur, and fixed with two kinds of intramedullary nails. Then the torsion, four-point bending and axial loading to failure were tested on these models. The load versus deformation curve was generated from the load recorded by the load cell and the deformation simultaneously recorded by the linear variable displacement transducer. The mean torsional stiffness of the femora fixed with RSIN was 0.98 Nm/degree, which was significantly less than that fixed with the similar nails reported in documents, and the mean value of bending stiffness of the femur fixed with DFIN was larger than that of the femur fixed with RBIN, but there was no significant statistic difference. For use in fracture models under compression load beyond 1200 N, the RBIN was more rigid than DFIN, which provided the biggest load. All the parameters of the test with nails were greater than that for femur fixed with nails. In conclusion, FBIN probably provides enough strength and rigidity for use in communited femoral shaft fractures.