Study of brain network alternations in non-lesional epilepsy patients by BOLD-fMRI

ObjectiveTo investigate the changes of brain network in epilepsy patients without intracranial lesions under resting conditions.MethodsTwenty-six non-lesional epileptic patients and 42 normal controls were enrolled for BOLD-fMRI examination. The differences in brain network topological characteristics and functional network connectivity between the epilepsy group and the healthy controls were compared using graph theory analysis and independent component analysis.ResultsThe area under the curve for local efficiency was significantly lower in the epilepsy patients compared with healthy controls, while there were no differences in global indicators. Patients with epilepsy had higher functional connectivity in 4 connected components than healthy controls (orbital superior frontal gyrus and medial superior frontal gyrus, medial superior frontal gyrus and angular gyrus, superior parietal gyrus and paracentral lobule, lingual gyrus, and thalamus). In addition, functional connectivity was enhanced in the default mode network, frontoparietal network, dorsal attention network, sensorimotor network, and auditory network in the epilepsy group.ConclusionThe topological characteristics and functional connectivity of brain networks are changed in in non-lesional epilepsy patients. Abnormal functional connectivity may suggest reduced brain efficiency in epilepsy patients and also may be a compensatory response to brain function early at earlier stages of the disease

MicroRNA-125a Regulates Cell Proliferation Via Directly Targeting E2F2 in Osteosarcoma

Background/Aims: Increasing evidence has shown that miR-125a plays important role in human cancer progression. However, little is known about the function of miR-125a in osteosarcoma. Methods: The expression of miR-125a in osteosarcoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-125a in osteosarcoma cell proliferation was examined in vitro. The targets of miR-125a were identified by a dual-luciferase reporter assay. Results: The results showed that the expression of miR-125a expression is significantly lower in osteosarcoma tissues and cell lines. Survival curves showed that the survival of patients in high miR-125a expression was significantly longer than that of patients with low miR-125a expression, and multivariate analysis suggested that miR-125a is an independent prognostic factor for osteosarcoma patients. In addition, it was found in this study that miR-125a can inhibit the growth of osteosarcoma cells. The dual-luciferase reporter assay demonstrated that E2F2 is a novel target gene for miR-125a. In addition, in a recovery experiment, it was shown that miR-125a inhibits the biological function of osteosarcoma cells by inhibiting the expression of E2F2. Conclusion: Our results suggest that miR-125a acts as a tumor suppressor via regulation of E2F2 expression in osteosarcoma progression, and miR-125a may represent a novel therapeutic target for the treatment of osteosarcoma

Anti-CTGF single-chain variable fragment dimers inhibit human airway smooth muscle (ASM) cell proliferation by down-regulating p-Akt and p-mTOR levels.

Connective tissue growth factor (CTGF) contributes to airway smooth muscle (ASM) cell hyperplasia in asthma. Humanized single-chain variable fragment antibody (scFv) was well characterized as a CTGF antagonist in the differentiation of fibroblast into myofibroblast and pulmonary fibrosis in our previous studies. To further improve the bioactivity of scFv, we constructed a plasmid to express scFv-linker-matrilin-6×His fusion proteins that could self-assemble into the scFv dimers by disulfide bonds in matrilin under non-reducing conditions. An immunoreactivity assay demonstrated that the scFv dimer could highly bind to CTGF in a concentration-dependent manner. The MTT and EdU assay results revealed that CTGF (≥10 ng/mL) promoted the proliferation of ASM cells, and this effect was inhibited when the cells were treated with anti-CTGF scFv dimer. The western blot analysis results showed that increased phosphorylation of Akt and mTOR induced by CTGF could be suppressed by this scFv dimer. Based on these findings, anti-CTGF scFv dimer may be a potential agent for the prevention of airway remodeling in asthma

EZH2 Mutations Are Related to Low Blast Percentage in Bone Marrow and -7/del(7q) in De Novo Acute Myeloid Leukemia

<div><p>The purpose of the present work was to determine the incidence and clinical implications of somatic EZH2 mutations in 714 patients with de novo acute myelogenous leukemia by sequencing the entire coding region. EZH2 mutations were identified in 13/714 (1.8%) of AML patients were found to be more common in males (<i>P</i> = 0.033). The presence of EZH2 mutations was significantly associated with lower blast percentage (21–30%) in bone marrow (<i>P</i><0.0001) and -7/del(7q) (<i>P</i> = 0.025). There were no differences in the incidence of mutation in 13 genes, ASXL1, CBL, c-KIT, DNMT3A, FLT3, IDH1, IDH2, MLL, NPM1, NRAS, RUNX1, TET2, and WT1, between patients with and without EZH2 mutations. No difference in complete remission, event-free survival, or overall survival was observed between patients with and without EZH2 mutation (<i>P</i>>0.05). Overall, these results showed EZH2 mutation in de novo acute myeloid leukemia as a recurrent genetic abnormality to be associated with lower blast percentage in BM and -7/del(7q).</p></div

Schematic representations of the expression vector pET28a-scFv-matrilin (A), the scFv-matrilin fusion protein sequence (B) and the scFv dimer structure (C) are shown.

<p>Schematic representations of the expression vector pET28a-scFv-matrilin (A), the scFv-matrilin fusion protein sequence (B) and the scFv dimer structure (C) are shown.</p

ScFv-matrilin analyzed using native-PAGE and Western blot.

<p>M marker, lanes 1, 2 show the fusion protein purified by nickel affinity chromatography, lanes 3, 4 show immunodotting bands with.anti-6xHis tag antibody.</p