Protective effects of human urinary kallidinogenase against corticospinal tract damage in acute ischemic stroke patients.

This study aimed to assess the effects of human urinary kallidinogenase (HUK) on motor function outcome and corticospinal tract recovery in patients with acute ischemic stroke (AIS). This study was a randomized, controlled, single-blinded trial. Eighty AIS patients were split into two groups: the HUK and control groups. The HUK group was administered HUK and standard treatment, while the control group received standard treatment only. At admission and discharge, the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and muscle strength were scored. The primary endpoint was the short-term outcomes of AIS patients under different treatments. The secondary endpoint was the degree of corticospinal tract fiber damage under different treatments. There was a significant improvement in the NIHSS Scale, BI and muscle strength scores in the HUK group compared with controls (Mann-Whitney U test; P  < 0.05). Diffusion tensor tractography classification and intracranial arterial stenosis were independent predictors of short-term recovery by linear regression analysis. The changes in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) decline rate were significantly smaller in the HUK group than in the control group ( P <  0.05). Vascular endothelial growth factor (VEGF) increased significantly after HUK treatment ( P  < 0.05), and the VEGF change was negatively correlated with changes in ADC. HUK is beneficial for the outcome in AIS patients especially in motor function recovery. It may have protective effects on the corticospinal tract which is reflected by the reduction in the FA and ADC decline rates and increased VEGF expression. The study was registered on ClinicalTrials.gov (unique identifier: NCT04102956).

Degradation of Mechanical Properties of Graphene Oxide Concrete under Sulfate Attack and Freeze-Thaw Cycle Environment.

In this paper, firstly, the effects of graphene oxide on the mechanical properties of concrete were investigated. Secondly, the degradation and mechanism of the mechanical properties of graphene oxide concrete (GOC) under sulfate attack and a freeze-thaw environment were investigated. In addition, the dynamic modulus of elasticity (MOEdy) and uniaxial compressive strength (UCS) of the GOC were measured under different environmental conditions. According to the test results, the incorporation of graphene oxide in appropriate admixtures could improve the mechanical properties of concrete in these two working environments. It is worth noting that this effect is most pronounced when 0.05 wt% graphene oxide is incorporated. In the sulfate attack environment, the MOEdy and UTS of the GOC0.05% specimen at 120 cycles decreased by 22.28% and 24.23%, respectively, compared with the normal concrete specimens. In the freeze-thaw environment, the MOEdy and UTS of the GOC0.05% specimen at 90 cycles decreased by 13.96% and 7.58%, respectively, compared with the normal concrete specimens. The scanning electron microscope (SEM) analysis showed that graphene oxide could adjust the aggregation state of cement hydration products and its own reaction with some cement hydration crystals to form strong covalent bonds, thereby improving and enhancing the microstructure density.

Enhancer-driven transcription of MCM8 by E2F4 promotes ATR pathway activation and glioma stem cell characteristics.

BACKGROUND: Glioma stem cells (GSCs) are responsible for glioma recurrence and drug resistance, yet the mechanisms underlying their maintenance remains unclear. This study aimed to identify enhancer-controlled genes involved in GSCs maintenance and elucidate the mechanisms underlying their regulation. METHODS: We analyzed RNA-seq data and H3K27ac ChIP-seq data from GSE119776 to identify differentially expressed genes and enhancers, respectively. Gene Ontology analysis was performed for functional enrichment. Transcription factors were predicted using the Toolkit for Cistrome Data Browser. Prognostic analysis and gene expression correlation was conducted using the Chinese Glioma Genome Atlas (CGGA) data. Two GSC cell lines, GSC-A172 and GSC-U138MG, were isolated from A172 and U138MG cell lines. qRT-PCR was used to detect gene transcription levels. ChIP-qPCR was used to detect H3K27ac of enhancers, and binding of E2F4 to target gene enhancers. Western blot was used to analyze protein levels of p-ATR and γH2AX. Sphere formation, limiting dilution and cell growth assays were used to analyze GSCs growth and self-renewal. RESULTS: We found that upregulated genes in GSCs were associated with ataxia-telangiectasia-mutated-and-Rad3-related kinase (ATR) pathway activation, and that seven enhancer-controlled genes related to ATR pathway activation (LIN9, MCM8, CEP72, POLA1, DBF4, NDE1, and CDKN2C) were identified. Expression of these genes corresponded to poor prognosis in glioma patients. E2F4 was identified as a transcription factor that regulates enhancer-controlled genes related to the ATR pathway activation, with MCM8 having the highest hazard ratio among genes positively correlated with E2F4 expression. E2F4 bound to MCM8 enhancers to promote its transcription. Overexpression of MCM8 partially restored the inhibition of GSCs self-renewal, cell growth, and the ATR pathway activation caused by E2F4 knockdown. CONCLUSION: Our study demonstrated that E2F4-mediated enhancer activation of MCM8 promotes the ATR pathway activation and GSCs characteristics. These findings offer promising targets for the development of new therapies for gliomas.

The role of PI3K/AKT-related proteins in di(2-ethyl)hexylphthalate-induced BG-1 and MCF-7 cell proliferation, and inhibition by metformin.

OBJECTIVE: To investigate the molecular mechanism of the proliferation and migration of BG-1 and MCF-7cells induced by DEHP, and the antagonistic effect of metformin. METHODS: The proliferation, cell cycle progression, migration, and invasion abilities of BG-1 and MCF-7 cancer cells were examined via Cell Counting Kit-8, flow cytometry, Transwell, and scratch assays. E2F1, SKP2, cyclin D1, vimentin, E-cadherin, and GSK-3ß, all of which play key roles in cancer development via the PI3K/AKT signaling pathway, were examined by immunofluorescence and immunocytochemistry. RESULTS: Cell proliferation was significantly increased, and the wound closure and number of trans-membrane migrating cells were significantly increased, by DHEP treatment. The numbers of BG-1 and MCF-7 cells in the G0/G1 phase were significantly decreased, while those in the S phase were significantly increased. Increased E2F1, SKP2, cyclin D1, and vimentin levels and decreased E-cadherin and GSK-3ß levels were detected in BG-1 and MCF-7 cells treated with DEHP compared to that in control cells. Furthermore, DEHP-induced effects were markedly inhibited by LY294002 (a PI3K/AKT inhibitor) or metformin. CONCLUSION: We demonstrated that DEHP-induced cell proliferation and migration involves the PI3K/AKT signaling pathway and that metformin can be used to inhibit this proliferation and migration.

Assessment of reporting quality in randomized controlled trials of acupuncture for labor pain.

Objective: To evaluate the reporting quality of randomized controlled trials (RCTs) of acupuncture for labor pain, and to explore relevant factors for facilitating reporting transparency and integrity for future RCTs. Method: Eight Chinese and English databases were systematically searched from their inception until August 31, 2021. General characteristics and methodological quality of the included reports were evaluated based on the CONSORT statement and the STRICTA guidelines. Descriptive statistical analysis was performed. Cohen's κ-statistics were calculated to assess the agreement of all items between two reviewers. Results: A total of 84 RCTs were included. Based on the CONSORT statement, a positive reporting rate (greater than 80%) was evident for the items "trial design" "participants" "intervention" "outcomes" "numbers analyzed" and "generalizability". The quality of reporting for the items "randomized in the title or abstract" "sample size" "allocation concealment" "implementation" "blinding" "recruitment" "ancillary analyses" "harms" "interpretation" "registration" and "protocol" was poor with positive rates less than 10%. Based on the STRICTA guidelines, the items "extent to which treatment varied" "number of needle insertions per subject per session" and "control or comparator interventions" had poor reporting quality with positive rates of less than 10%. Substantial agreement was observed for most items and excellent agreement for some items. Conclusion: The reporting quality of RCTs of acupuncture for labor pain is suboptimal generally. Rigorous adherence to the CONSORT statement and the STRICTA guidelines should be emphasized in future studies to improve the quality of acupuncture RCT reports.

The effect of acupuncture on oxidative stress: A systematic review and meta-analysis of animal models.

INTRODUCTION: Oxidative stress is involved in the occurrence and development of multiple diseases. Acupuncture shows an excellent clinical efficacy in practical application but its mechanism remains unclear. This systematic review and meta-analysis was aimed at assessing the effect of acupuncture on oxidative stress in animal models. METHODS: PubMed, Embase, and Web of Science database were retrieved for randomized controlled trials about acupuncture on oxidative stress in animal models from inception to August 2021. Two reviewers independently screened and extracted articles according to inclusion and exclusion criteria. We used the mean difference (MD)/standardized mean difference (SMD) to perform an effect size analysis and selected fixed-effect or random-effect models to pool the data, depending on a 95% confidence interval (CI). RESULTS: A total of 12 studies comprising 125 samples were included in the quantitative meta-analysis. Compared with sham acupuncture, acupuncture (manual acupuncture, electropuncture, and laser acupuncture) reduced the level of malondialdehyde (SMD, -3.03; CI, -4.40, -1.65; p < 0.00001) and increased the levels of superoxide dismutase (SMD, 3.39; CI, 1.99, 4.79; p < 0.00001), glutathione peroxidase (SMD, 2.21; CI, 1.10, 3.32; p < 0.00001), and catalase (SMD, 2.80; CI, 0.57, 5.03; p = 0.01). CONCLUSION: This meta-analysis indicated that acupuncture can regulate oxidative stress by lowering the lipid peroxidation and activating the antioxidant enzyme system. In consideration of heterogeneity between studies, future studies should be performed by complying with strict standards and increasing sample size in animal experiments to reduce bias.

Knockdown of PHLDA2 promotes apoptosis and autophagy of glioma cells through the AKT/mTOR pathway.

Pleckstrin homology like domain family A member 2 (PHLDA2) is an imprinted gene expressed in placenta and has been shown to be associated with tumor progression. However, the effect of PHLDA2 on glioma cell growth has not been reported yet. Data based on TCGA database showed that PHLDA2 was up-regulated in glioma tissues. Moreover, PHLDA2 was also elevated in glioma cells. Functional assays showed that siRNA-mediated knockdown of PHLDA2 reduced cell viability of glioma cells and suppressed the cell proliferation. Cell apoptosis of glioma cells was promoted by silencing of PHLDA2 with increased Bax and decreased Bcl-2. Silencing of PHLDA2 reduced protein expression of p62, enhanced LC3 and Beclin1 to promote autophagy. Phosphorylated AKT and mTOR were down-regulated in glioma cells by interference of PHLDA2. In conclusion, downregulation of PHLDA2 inhibited glioma cell proliferation, and promoted cell apoptosis and autophagy through inactivation of AKT/mTOR signaling.

Multi-End Physics-Informed Deep Learning for Seismic Response Estimation.

As a structural health monitoring (SHM) system can hardly measure all the needed responses, estimating the target response from the measured responses has become an important task. Deep neural networks (NNs) have a strong nonlinear mapping ability, and they are widely used in response reconstruction works. The mapping relation among different responses is learned by a NN given a large training set. In some cases, however, especially for rare events such as earthquakes, it is difficult to obtain a large training dataset. This paper used a convolution NN to reconstruct structure response under rare events with small datasets, and the main innovations include two aspects. Firstly, we proposed a multi-end autoencoder architecture with skip connections, which compresses the parameter space, to estimate the unmeasured responses. It extracts the shared patterns in the encoder and reconstructs different types of target responses in varied branches of the decoder. Secondly, the physics-based loss function, derived from the dynamic equilibrium equation, was adopted to guide the training direction and suppress the overfitting effect. The proposed NN takes the acceleration at limited positions as input. The output is the displacement, velocity, and acceleration responses at all positions. Two numerical studies validated that the proposed framework applies to both linear and nonlinear systems. The physics-informed NN had a higher performance than the ordinary NN with small datasets, especially when the training data contained noise.

m6A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability.

N6-methyladenosine (m6A) has been identified to exert critical roles in human cancer; however, the regulation of m6A modification on glioblastoma multiforme (GBM) and long non-coding RNA (lncRNA) CASC9 (cancer susceptibility 9) is still unclear. Firstly, MeRIP-Seq revealed the m6A profile in the GBM. Moreover, the m6A-related lncRNA CASC9 expression was significantly elevated in the GBM tissue and its ectopic high expression was associated with poor survival, acting as an independent prognostic factor for GBM patients. Functionally, the aerobic glycolysis was promoted in the CASC9 overexpression transfection, which was inhibited in CASC9 knockdown in GBM cells. Mechanistically, m6A reader IGF2BP2 (insulin-like growth factor 2 mRNA binding protein 2) could recognize the m6A site of CASC9 and enhance its stability, then CASC9 cooperated with IGF2BP2, forming an IGF2BP2/CASC9 complex, to increase the HK2 (Hexokinase 2) mRNA stability. Our findings reveal that CASC9/IGF2BP2/HK2 axis promotes the aerobic glycolysis of GBM.

PINK1 antagonize intracerebral hemorrhage by promoting mitochondrial autophagy.

BACKGROUND: Intracerebral hemorrhage (ICH) causes neurotransmitter release, oligemia, membrane depolarization, mitochondrial dysfunction, and results in the high rate of mortality and functional disability. Here, we focus on PTEN-induced kinase 1 (PINK1), a mitochondrial-targeted protein kinase, and explore its role in ICH progression. METHODS: The qPCR and Western blot were performed to examine the expression of PINK1 in ICH patients and mouse model. PINK1 gain- and loss-of-function mice were used to evaluate their protective role on brain injury and behavioral disorders. Flow cytometry was carried out, mitochondrial membrane potential and reactive oxygen species production were detected to explore the distribution and neuroprotective function of PINK1. RESULTS: PINK1 mRNA was upregulated, however, its protein was downregulated in ICH patients. The reduction of PINK1 was mainly happened in microglial cells in ICH model. Overexpression of PINK1 is able to rescue ICH-induced behavioral disorders. PINK1 protects ICH-induced brain injury by promoting mitochondrial autophagy in microglia. CONCLUSION: PINK1 possesses a neuroprotective role and antagonizes ICH by promoting mitochondrial autophagy, which may be of value as a therapeutic target for ICH treatment.

Study on quantitative diagnosis model of TCM syndromes of post-stroke depression based on combination of disease and syndrome.

BACKGROUND: Post-stroke depression (PSD) is one of the most common stroke complications with high morbidity. Researchers have done much clinical research on Traditional Chinese Medicine (TCM) treatment, but very little research on diagnosis. Based on the thought of combination of disease and syndrome, this study will establish a unified and objective quantitative diagnosis model of TCM syndromes of PSD, so as to improve the clinical diagnosis and treatment of PSD. OBJECTIVE: First: To establish a unified and objective quantitative diagnosis model of TCM syndromes in PSD under different disease courses, and identify the corresponding main, secondary, and concurrent symptoms, which are based on the weighting factor of each TCM symptom. Second: To find out the relationship between different stages of PSD and TCM syndromes. Clarify the main syndrome types of PSD under different stages of disease. Reveal the evolution and progression mechanism of TCM syndromes of PSD. METHODS AND ANALYSIS: This is a retrospective study of PSD TCM diagnosis. Three hundred patients who were hospitalized in the First Teaching Hospital of Tianjin University of TCM with complete cases from January 2014 to January 2019 are planned to be recruited. The study will mainly collect the diagnostic information from the cases, find the related indicators of TCM and Western medicine in PSD, and clarify the relationship between different disease stages and TCM syndromes. Finally, the PSD TCM syndrome quantitative diagnosis model will be established based on the operation principle of Back Propagation (BP) artificial neural network. CONCLUSION: To collect sufficient medical records and establish models to speed up the process of TCM diagnosis.

The comparison of different acupuncture therapies for post stroke depression: A protocol for a Bayesian network meta-analysis.

BACKGROUND: Depression is a common disease which occurs after stroke, affecting approximately one third of stroke survivors at any 1 time after stroke (compared with 5%-13% of adults without stroke), with a cumulative incidence of 55%. Acupuncture, which has a long history in China, is the generic name of different kinds of acupuncture therapies, including manual acupuncture (MA), electroacupuncture (EA), fire needle (FN), dry needling (DN), and so on. Clinical studies have shown that acupuncture has a good therapeutic effect on post stroke depression (PSD), but the evidence-based medicine of it is insufficient. The purpose of this study is to systematically evaluate the efficacy of different kinds of acupuncture therapies in the treatment of PSD, and to provide evidence-based basis for the clinical application of acupuncture in the treatment of PSD. METHODS: A systematic search will be performed on English databases (PubMed, The Cochrane Library, Medline, Embase) and Chinese databases (China National Knowledge Infrastructure (CNKI), WanFang Data, VIP and Chinese biomedical databases). The retrieval time limit will be from the establishment of the database to August 2020. Two researchers will independently screen the literatures, extract data, and evaluate the quality of the included studies. Bayesian network analysis will be conducted by using STATA V.14.0 and ADDIS V.1.16.7. RESULTS: In this study, the efficacy of different kinds of acupuncture therapies in the treatment of PSD will be evaluated by the degree of reduction in depression, total numbers of adverse events, quality of life indices, improvement of social and life functions and the expression of nerve cell factors. CONCLUSIONS: This study will provide reliable evidence-based evidence for the clinical application of acupuncture in PSD.

Long noncoding RNA LINC00511 induced by SP1 accelerates the glioma progression through targeting miR-124-3p/CCND2 axis.

Mounting evidence suggests the vital roles of long noncoding RNA (lncRNAs) in the glioma. However, the role of LINC00511 in gliomagenesis is still uncovered. Here, in this study, we aim to investigate the effects of LINC00511 on the glioma cancer phenotype and its deepgoing mechanism. Results indicated that LINC00511 was up-regulated in glioma tissues and cell lines, moreover its overexpression positively correlated with the poor prognosis and advanced pathological stages. For the upstream regulation, LINC00511 was epigenetically up-regulated by transcription factor specificity protein 1 (SP1). Gain and loss of functional experiments demonstrated that LINC00511 promoted the proliferation and invasion of glioma cells in vitro. The knockdown of LINC00511 repressed the tumour growth in vivo. Mechanistically, LINC00511 positively regulated the CCND2 expression via competitively sponging with miR-124-3p. Overall, our finding illuminates that LINC00511 is induced by SP1 and accelerates the glioma progression through targeting miR-124-3p/CCND2 axis, constructing the SP1/LINC00511/miR-124-3p/CCND2 axis.

LATS2 inhibits cell proliferation and metastasis through the Hippo signaling pathway in glioma.

As a core kinase in the Hippo pathway, large tumor suppressor kinase 2 (LATS2) regulates cell proliferation, migration and invasion through numerous signaling pathways. However, its functions on cell proliferation, migration and invasion in glioma have yet to be elucidated. The present study revealed that LATS2 was downregulated in glioma tissues and cells, as determined by reverse transcription­quantitative polymerase chain reaction and immunohistochemistry. In addition, Cell Counting Kit­8, scratch wound healing and Transwell assays revealed that overexpression of LATS2 in U­372 MG cells inhibited cell proliferation, migration and invasion. Furthermore, western blot analysis indicated that the expression levels of phosphorylated (p)­yes­associated protein and p­tafazzin were increased in cells with LATS2 overexpression. These results indicated that LATS2 is a potential tumor suppressor, and downregulation of LATS2 in glioma may contribute to cancer progression.

Exosomal miR-214-5p Released from Glioblastoma Cells Modulates Inflammatory Response of Microglia after Lipopolysaccharide Stimulation through Targeting CXCR5.

BACKGROUND AND OBJECTIVE: Exosomes communicate inter-cellularly and miRNAs play critical roles in this scenario. MiR-214-5p was implicated in multiple tumors with diverse functions uncovered. However, whether miR-214-5p is mechanistically involved in glioblastoma, especially via exosomal pathway, is still elusive. Here we sought to comprehensively address the critical role of exosomal miR-214-5p in glioblastoma (GBM) microenvironment. METHODS: The relative expression of miR-214-5p was determined by real-time PCR. Cell viability and migration were measured by MTT and transwell chamber assays, respectively. The secretory cytokines were measured with ELISA kits. The regulatory effect of miR-214-5p on CXCR5 expression was interrogated by luciferase reporter assay. Protein level was analyzed by Western blot. RESULTS: We demonstrated that miR-214-5p was aberrantly overexpressed in GBM and associated with poorer clinical prognosis. High level of miR-214-5p significantly contributed to cell proliferation and migration. GBM-derived exosomal miR-214-5p promoted inflammatory response in primary microglia upon lipopolysaccharide challenge. We further identified CXCR5 as the direct target of miR-214- 5p in this setting. CONCLUSION: Overexpression of miR-214-5p in GBM modulated the inflammatory response in microglia via exosomal transfer.

Extracellular Vesicle lncRNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 Released From Glioma Stem Cells Modulates the Inflammatory Response of Microglia After Lipopolysaccharide Stimulation Through Regulating miR-129-5p/High Mobility Group Box-1 Protein Axis.

Glioma stem cell (GSC)-derived extracellular vesicles (EVs) can mediate the communication between GSCs and microglia. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in GSCs, EVs, and supernatant was detected by real-time PCR. The direct targeting between MALAT1 and miR-129-5p, miR-129-5p, and HMGB1 were tested with luciferase reporter analysis. The expression and secretion of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were determined in lipopolysaccharide-stimulated microglia or miR-129-5p inhibitor transferred to microglia exposed to GSC EVs or EVs derived from siMALAT1 pre-transferred GSCs. MALAT1 was enriched in GSC EVs compared with GSCs, and up-regulated MALAT1 was also observed in microglia upon GSC EVs incubation. The relative expression and secretion of IL-6, IL-8, and TNF-α in lipopolysaccharide-stimulated microglia were up-regulated in the GSC supernatant group, which could be reversed by dimethyl amiloride (DMA) (EV secretion inhibitor) co-administration or si-MALAT1 pre-transfection of GSCs. Luciferase reporter assay testified the direct binding of MALAT1 and miR-129-5p, miR-129-5p, and HMGB1, and si-MALAT1 could up-regulate miR-129-5p expression and down-regulate HMGB1 expression in microglia cells. The concentration of IL-6, IL-8, and TNF-α in lipopolysaccharide-stimulated microglia exposed to EVs from siMALAT1 transfected GSCs could be up-regulated by miR-129-5p inhibition. EVs lncRNA MALAT1 released from GSCs could modulate the inflammatory response of microglia after lipopolysaccharide stimulation through regulating the miR-129-5p/HMGB1 axis.

Long noncoding RNA CASC9/miR-519d/STAT3 positive feedback loop facilitate the glioma tumourigenesis.

Emerging evidence have illustrated the vital roles of long noncoding RNAs (lncRNAs) in glioma. Nevertheless, the majority of their roles and mechanisms in gliomagenesis are still largely unclear. In this study, we investigate the roles of lncRNA CASC9 on glioma tumourigenesis and authenticate its potential mechanisms. Results manifested that CASC9 was highly expressed in glioma specimens and cells, moreover, the ectopic overexpression was correlated with glioma patients' clinic. Functional studies found that siRNA-mediated CASC9 silencing inhibited the proliferative ability, invasion in vitro, and impaired the tumour growth in vivo. Mechanical studies revealed that miR-519d both targeted the 3'-UTR of CASC9 and STAT3 mRNA, which was identified by luciferase reporter assay and RNA immunoprecipitation (RIP). Moreover, chromatin immunoprecipitation (ChIP) and luciferase reporter assay revealed that STAT3, an oncogenic transcription factor, could bind with the promoter of CASC9 and activate its transcriptional level. In conclusion, our results concluded that CASC9 promotes STAT3 expression via sponging miR-519d, in return, STAT3 activate CASC9 transcription, forming a positive feedback loop of CASC9/miR-519d/STAT3. The novel finding provides a potential therapeutic target for glioma.

Long noncoding RNA SNHG12 facilitates the tumorigenesis of glioma through miR-101-3p/FOXP1 axis.

The increasing vital roles of long coding RNA (lncRNAs) in the glioma tumorigenesis have renewedly and roundly recognized. Nevertheless, the in-depth that lncRNAs modulate the gliomagenesis is still elusive. In this research, we focus on the functional study of lncRNA SNHG12 in the glioma pathogenesis. SNHG12 expression was enhanced and high-expressed in the glioma clinical tissue samples and cell lines, especially in the advanced clinical grade. In functional study, knockdown of SNHG12 impaired the proliferation, induced the apoptosis in vitro and, meanwhile, inhibited the tumor growth in vivo. In mechanistic study, it was found that SNHG12 harbored the complementary binding sites with miR-101-3p at 3'-UTR, acting as a miRNA 'sponge'. Furthermore, miR-101-3p also targeted the 3'-UTR of FOXP1 mRNA. The three elements construct the SNHG12/miR-101-3p/FOXP1 axis. Overall, we confirmed a functional regulatory pathway that SNHG12 and miR-101-3p regulated the expression of FOXP1 in glioma cells, forming the SNHG12/miR-101-3p/FOXP1 pathway. This finding might act as a valuable target for glioma.

Methylene Blue Exerts Anticonvulsant and Neuroprotective Effects on Self-Sustaining Status Epilepticus (SSSE) Induced by Prolonged Basolateral Amygdala Stimulation in Wistar Rats.

BACKGROUND This study was designed to investigate the potential anticonvulsant and neuroprotective effects of methylene blue (MB) on self-sustaining status epilepticus (SSSE) induced by prolonged basolateral amygdala stimulation (BLA) in Wistar rats. MATERIAL AND METHODS The rats were randomly divided into 4 groups: (1) the Control group (rats without any treatment); (2) the Sham group (rats received electrode implantation but without electrical stimulation); (3) the SSSE group (rats received electrode implantation and additional electrical stimulation); and (4) the SSSE+MB group (rats received 1 mg/kg MB intraperitoneal injection 5 min after SSSE). SSSE models were established by prolonged BLA stimulation. The severities of SSSE were assessed by the number of separate seizures and the accumulated time of seizures. The variations of malondialdehyde/glutathione (MDA/GSH) were assessed 24 h after the establishment of SSSE. Nissl staining was performed to detect the surviving neurons in hippocampal CA1 and CA3 regions, and Western blotting assays were used to detect Caspase-3 (CASP3), B cell lymphoma 2 (BCL2), and BCL2-associated X protein (BAX). RESULTS Compared with the SSSE group, treatment with MB (1) markedly reduced the number and accumulated time of seizure activities; (2) significantly attenuated the increase of MDA and the decrease of GSH hippocampal levels; (3) markedly improved the cell morphology and alleviated the neuronal loss in hippocampal CA1 and CA3 regions; (4) significantly attenuated the increase of CASP3 and BAX and the decrease of BCL2 hippocampal levels. CONCLUSIONS MB has a protective effect in the SSSE model and may be useful as an adjuvant for preventing or treating epilepsy in humans.

Downregulation of ZMYND11 induced by miR-196a-5p promotes the progression and growth of GBM.

ZMYND11 (zinc finger MYND-type containing 11) has been widely regarded to be involved in a variety of cancers as a potential suppressor. However, the biological role and mechanism of ZMYND11 in glioblastoma multiform (GBM) remain unknown. In this study, we found that ZMYND11 expression was remarkably decreased in GBM tissues from 20 cases and cell line (U87) compared to normal brain tissue from 10 cases (P < 0.001). Furthermore, we explored that ZMYND11 upregulation significantly suppressed U87 cells proliferation and invasion, induced cell cycle arrest and apoptosis in vitro. Subsequently, we identified increased ZMYND11 inhibited the tumor growth using tumor cells xenograft experiment on rude mice. Moreover, we explored that ZMYND11 was a new direct and functional target of miR-196a-5p in U87 via luciferase reporter assay. In addition, we confirmed the negative correlation between miR-196a-5p and ZMYND11 in GBM tissue and U87 cells by changing the expression level of miR-196a-5p with lentivirus and plasmid vector. Furthermore, we demonstrated that decreased ZMYND11 could reverse suppressive effect of downregulated miR-196a-5p on U87 by rescue experiment. Taken together, ZMYND11 was demonstrated to be a potential and extremely promising suppressor of GBM, while miRNA-196a-5p was quite an important target of treatment of GBM.