MTHFD2 suppresses glioblastoma progression via the inhibition of ERK1/2 phosphorylation.

Glioblastoma (GBM) is a WHO grade 4 tumor and is the most malignant form of glioma. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme involved in folate metabolism, has been reported to be highly expressed in several human tumors. However, little is known about the role of MTHFD2 in GBM. In this study, we aimed to explore the biological functions of MTHFD2 in GBM and identify the associated mechanisms. We performed experiments such as immunohistochemistry, Western blot, and transwell assays and found that MTHFD2 expression was lower in high-grade glioma than in low-grade glioma. Furthermore, a high expression of MTHFD2 was associated with a favorable prognosis, and MTHFD2 levels showed good prognostic accuracy for glioma patients. The overexpression of MTHFD2 could inhibit the migration, invasion, and proliferation of GBM cells, whereas its knockdown induced the opposite effect. Mechanistically, our findings revealed that MTHFD2 suppressed GBM progression independent of its enzymatic activity, likely by inducing cytoskeletal remodeling through the regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, thereby influencing GBM malignance. Collectively, these findings uncover a potential tumor-suppressor role of MTHFD2 in GBM cells. MTHFD2 may act as a promising diagnostic and therapeutic target for GBM treatment.

Ferroptosis in Low-Grade Glioma: A New Marker for Diagnosis and Prognosis.

BACKGROUND The extent of glioma resection influences the overall survival (OS) and progression-free survival (PFS). Ferroptosis is a newly recognized type of cell death, which may be associated with low-grade glioma border detection and OS. This study is assessed an optimized ferroptosis gene panel for glioma treatment. MATERIAL AND METHODS We obtained 45 reports on ferroptosis-related proteins in PubMed and conducted a statistical test of the patients' overall survival (OS) in the TCGA GBMLGG and CGGA databases. The statistically significant genes were screened for an optimal panel, followed by GO and KEGG analysis and evaluated its correlation with known prognostic factors of glioma, including IDH1 mutation, methylated MGMT, tumor purity, 1p/19q LOH, and methionine cycle. RESULTS Eight genes panel (ALOX5, CISD1, FTL, CD44, FANCD2, NFE2L2, SLC1A5, and GOT1) were highly related to OS (P<0.001) and PFS (P<0.001) of low-grade glioma (LGG) patients, out of which 6 genes (ALOX5, CISD1, CD44, FTL, FANCD2, and SLC1A5) were correlated with IDH1_p.R132H (P<0.001) and 5 genes (ALOX5, CD44, FTL, NFE2L2, SLC1A5) showed a correlation with tumor purity (P<0.001). Five genes (ALOX5, CD44, CISD1, FTL, and SLC1A5) were associated with methylated MGMT (P<0.001), out of which 6 genes (ALOX5, CD44, FANCD2, NFE2L2, SLC1A5, and GOT1) had significantly different expression in healthy brain tissue vs. glioma (P<0.001). CONCLUSIONS Our panel of 8 ferroptosis genes showed a significant correlation with the diagnostic and prognostic factors of low-grade glioma and can be applied in neuroradiology and surgery.

Recurrent solitary fibrous tumor of the spinal cord: A case report and literature review.

Solitary fibrous tumor (SFT) is a benign mesenchymal neoplasm occurring anywhere in the body, such as the visceral pleura, while it is extremely rare in the central nervous system, especially within the spinal cord. Here, we present a case of recurrent spinal SFT in a 44-year-old woman who had the tumor resected 5 years before. This time, her magnetic resonance imaging revealed an intradural tumor at the level of C6-7. A secondary resection was performed completely, and the patient's neurological conditions recovered fully after resection. Histological and immunohistochemical findings revealed an SFT. Although rare, the preferred treatment for recurrent tumor in SFT is surgery, and postoperative follow-up is necessary for early detection of tumor progression.

Risk factors for decompressive craniectomy after endovascular treatment in acute ischemic stroke.

Endovascular treatment (EVT) is safe and effective for acute ischemic stroke (AIS) caused by large artery occlusion in the anterior circulation. However, some patients require decompressive craniectomy (DC), despite having undergone a timely EVT. This study aimed to evaluate the risk factors for subsequent DC after EVT. This retrospective cohort study comprised 138 patients who received EVT between April 2015 and June 2019 at our center. The need for subsequent DC was defined as cerebral edema or/and hemorrhagic transformation caused by large ischemic infarction, with a ≥ 5-mm midline shift and clinical deterioration after EVT. The relationship between risk factors and DC after EVT was assessed via univariate and multivariable logistic regression. Thirty (21.7%) patients required DC. These patients tended to have atrial fibrillation (P = 0.037), sedation (P = 0.049), mechanical ventilation (P = 0.008), poorer collateral circulation (P = 0.003), a higher baseline National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001), heavier thrombus burden (P < 0.001), a lower baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (P < 0.001), and unsuccessful recanalization (P < 0.001). In the multivariate analysis, higher baseline NIHSS score [odds ratio (OR), 1.17; 95% confidence interval (CI), 1.03-1.32], heavier thrombus burden [OR, 1.35; 95% CI, 1.02-1.79], baseline ASPECTS ≤ 8 [OR, 7.41; 95% CI, 2.43-22.66], and unsuccessful recanalization [OR, 7.49; 95% CI, 2.13-26.36] were independent risk factors for DC after EVT. DC remains an essential treatment for some AIS patients after EVT, especially those with higher baseline NIHSS scores, heavier thrombus burden, baseline ASPECTS ≤ 8, and unsuccessful recanalization.

Bone marrow stromal cells-derived exosomes reduce neurological damage in traumatic brain injury through the miR-124-3p/p38 MAPK/GLT-1 axis.

BACKGROUND: Mounting evidence indicates that stem cell-derived exosomal miRNAs have therapeutic effects on traumatic brain injury (TBI). This research is focused on exploring the molecular processes of miR-124-3p obtained from bone marrow stromal cells-derived exosomes (BMSCs-Exos) in attenuating posttraumatic glutamate-mediated excitotoxicity. METHODS: We created a TBI rat model and analyzed the expression profile of miRNA through miRNA microarray. The miR-124-3p and p38 MAPK levels were analyzed utilizing RT-qPCR and western blotting. Dual-luciferase reporter (DLR) assay showed the targeting relationship between miR-124-3p and p38 MAPK. We subsequently conducted a TUNEL assay and flow cytometry to evaluate the neuronal apoptotic rate in an in vitro glutamate-mediated excitotoxicity model treated with BMSCs-Exos enriched with miR-124-3p (BMSCs-ExosmiR-124-3p). Moreover, the levels of p38 MAPK and glutamate transporter-1 (GLT-1) were measured by western blotting. Furthermore, BMSCs-ExosmiR-124-3p were administered to the TBI rats, and their neuroprotective effects were observed using western blotting, immunohistochemistry, histological staining, magnetic resonance imaging (MRI), and Morris water maze (MWM). RESULTS: The results revealed that the brains of TBI rats exhibited lowered miR-124-3p and enhanced p38 MAPK levels. DLR assay demonstrated miR-124-3p's role in targeting p38 MAPK and negatively regulating its expression. In vitro and in vivo studies confirmed that BMSCs-ExosmiR-124-3p attenuated glutamate-mediated excitotoxicity by downregulating p38 MAPK and upregulating GLT-1 expressions via transferring exosomal miR-124-3p. Moreover, histopathological evaluation and MRI results showed that BMSCs-ExosmiR-124-3p remarkably alleviated neuronal cell death and minimized the lesion volumes post-TBI. MWM outcomes illustrated that BMSCs-ExosmiR-124-3p treatment could substantially improve neurological function post-TBI. Furthermore, the effects of treatment with p38 MAPK inhibitor SB203580 were similar to BMSCs-ExosmiR-124-3p. CONCLUSION: Overall, the outcomes of the current report highlighted that BMSCs-ExosmiR-124-3p can lead to the upregulation of GLT-1 in TBI rat models by inhibiting the p38 MAPK signaling pathway, hence alleviating glutamate-mediated excitotoxicity and attenuating neurological damage post-TBI.

GNA13 inhibits glioblastoma metastasis via the ERKs/FOXO3 signaling pathway.

Glioblastoma (GBM) is a malignant tumor characterized by poor prognosis and low overall survival (OS) rate. Identification of novel biological markers for the diagnosis and treatment of GBM is crucial to developing interventions to improve patient survival. GNA13, a member of the G12 family, has been reported to play important roles in a variety of biological processes involved in tumorigenesis and development. However, its role in GBM is currently unknown. Here, we explored the expression patterns and functions of GNA13 in GBM, as wells its impact on metastasis process. Results showed that GNA13 was downregulated in GBM tissues and correlated with poor prognosis of GBM. Downregulation of GNA13 promoted the migration, invasion and proliferation of GBM cells; whereas its overexpression abolished these effects. Western blots revealed that GNA13 knockdown and overexpression upregulated and inhibited the phosphorylation of ERKs, respectively. Moreover, GNA13 was the upstream of ERKs signaling to regulating ERKs phosphorylation level. Furthermore, U0126 alleviated the metastasis effect induced by GNA13 knockdown. Bioinformatics analyses and qRT-PCR experiments demonstrated that GNA13 could regulate FOXO3, a downstream signaling molecule of ERKs pathway. Overall, our results demonstrate that GNA13 expression is negatively correlated with GBM and can suppress tumor metastasis by inhibiting the ERKs signaling pathway and upregulating FOXO3 expression.

Triglyceride-glucose index and the incidence of stroke: A meta-analysis of cohort studies.

Background: Insulin resistance (IR) is involved in the pathogenesis of atherosclerosis. As a new indicator, the triglyceride-glucose (TyG) index has greater operability for the evaluation of insulin resistance. Previous studies have shown inconsistent results in evaluating the association between the TyG index and stroke incidence in people without stroke at baseline. Therefore, this study aimed to systematically assess this association through a meta-analysis. Methods: Cohort studies with the multivariate-adjusted hazard ratio (HR) association between the TyG index and stroke were obtained by searching the PubMed, Cochrane Library, and EMBASE databases before 16 December 2021. We pooled the adjusted HR along with 95% CI using a random-effects model. The primary outcome was stroke including ischemic and hemorrhagic stroke. We conducted subgroup analyses stratified by study design, ethnicity, characteristics of participants, weight of studies, and length of follow-up duration. Review Manager 5.3 and Stata 17 were used to perform the meta-analysis. Results: Eight cohort studies with 5,804,215 participants were included. The results showed that participants with the highest TyG index category at baseline compared to those with the lowest TyG index category were independently associated with a higher risk of stroke (HR: 1.26, 95% CI: 1.24-1.29, I2 = 0%, P < 0.001). This finding was consistent with the results of the meta-analysis with the TyG index analyzed as a continuous variable (HR per each-unit increment of the TyG index: 1.13, 95% CI 1.09-1.18, I2 = 0%, P < 0.001). Subgroup analysis had no significant effects (for subgroup analysis, all P > 0.05). No significant heterogeneity was observed among the included cohort studies. Conclusion: A higher TyG index may be independently associated with a higher risk of stroke in individuals without stroke at baseline. The aforementioned findings need to be verified by a large-scale prospective cohort study to further clarify the underlying pathophysiological mechanism between the TyG index and stroke.

Exosomes derived from bone marrow mesenchymal stem cells attenuate neurological damage in traumatic brain injury by alleviating glutamate-mediated excitotoxicity.

BACKGROUND: Traumatic brain injury (TBI) is one of the major contributors to disability and death worldwide. Glutamate-mediated excitotoxicity, one of the secondary injuries occurring after TBI, leads to extreme neuronal apoptosis, and can be a potential target for intervention. Bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exos) have demonstrated neuroprotective effects on TBI. However, their precise role and the underlying mechanism by which they regulate glutamate-mediated excitotoxicity have not yet been determined. Therefore, this study aimed to determine whether BMSCs-Exos alleviate glutamate excitotoxicity post-TBI and their associated mechanism. METHODS: BMSCs-Exos were extracted from the BMSCs incubation medium and identified by transmission electron microscopy, nanoparticle trafficking analysis, and western blotting. The neuroprotective effects of BMSCs-Exos on glutamate excitotoxicity were investigated in the glutamate-mediated excitotoxicity neuronal cell model and the TBI rat model (TBI induced by controlled cortical impact) using western blotting and TUNEL assay. Cortical lesion samples were collected post-TBI on day-1 and day-14 to study histology. In addition, cortical lesion volume on days 1, 3 and 7 following TBI was determined using T2-weighted magnetic resonance imaging (MRI), and cognitive function was assessed at 4 weeks following TBI using the Morris water maze (MWM) test. RESULTS: BMSCs-Exos were observed to be spherical with a mean diameter of 109.9 nm, and expressed exosomal markers CD9, CD81 and TSG101. BMSCs-Exos were efficiently endocytosed by astrocytes after co-incubation for 24 h. In vitro studies revealed that 125 µM of glutamate significantly induced neuronal apoptosis, which was attenuated by BMSCs-Exos in astrocyte-neuron co-cultures. This attenuation was mediated by the upregulation of glutamate transporter-1 (GLT-1) level and the downregulation of p-p38 MAPK level in astrocytes. Similar results were obtained in vivo, wherein we verified that PKH67-labeled BMSCs-Exos administered intravenously could reach the perilesional cortex crossing the blood-brain barrier and significantly reduce glutamate levels in the perilesional cortex of the TBI rat, accompanied by increased GLT-1 level and downregulation in p-p38 MAPK level. Additionally, western blotting and TUNEL staining also revealed that BMSCs-Exos significantly downregulated the expression of pro-apoptosis markers, including cleaved caspase-3 and cleaved caspase-9, and attenuated neuronal apoptosis following TBI. Immunohistochemical analysis and Nissl staining showed that BMSCs-Exos significantly increased GLT-1-positive cells, and the number of apoptotic neurons decreased in the perilesional cortex. Moreover, MRI and MWM results revealed that BMSCs-Exos significantly minimized cortical lesion volume and ameliorated cognitive function after TBI. The underlying neuroprotective mechanism of BMSCs-Exos may be due to an increase in GLT-1 level in astrocytes by blocking the p38 MAPK signaling pathway. CONCLUSION: Taken together, our findings demonstrate that the implementation of BMSCs-Exos may be an effective prospective therapy for attenuating post-TBI neurological damage.

NGAL and NGALR are frequently overexpressed in human gliomas and are associated with clinical prognosis.

Recently, neutrophil gelatinase-associated lipocalin (NGAL) and its cell surface receptor, NGALR, have been shown to have critical roles in the biology of various tumors. Therefore, we investigated the expression of NGAL and NGALR in tumor sections obtained from patients with gliomas, and compared these results with the clinical characteristics of the patients. Using immunohistochemical assays, the expression levels of NGAL and NGALR were found to be up-regulated in tumor tissues, and to be related to tumor grade (p < 0.001). A positive correlation between expression of the two markers was also observed in these assays (r = 0.849; p < 0.001). Overexpression of NGAL and NGALR in glioma tissues was also confirmed in western blot analysis and real-time quantitative RT-PCR assays. Furthermore, overexpression of NGAL and NGALR was found to be significantly associated with poor prognosis (p < 0.001 in each case). Multivariate analysis identified patient age, tumor grade, and expression levels of NGAL and NGALR to be independent prognostic factors. In particular, NGAL(2+)/NGALR(2+) tissues were associated with lower rates of survival (risk ratio, 1.378; 95% CI, 1.102-1.724; p = 0.005). These findings suggest that NGAL and NGALR expression are frequently up-regulated in gliomas, and are closely associated with poor clinical outcome.

Overexpressed GNA13 induces temozolomide sensitization via down-regulating MGMT and p-RELA in glioma.

Temozolomide (TMZ), one of the few effective drugs used during adjuvant therapy, could effectively prolong the overall survival (OS) of glioma patients. In our previous study, the mRNA level of G Protein Subunit Alpha 13 (GNA13) was found to be inversely correlated with OS and was therefore identified as a potential biomarker for the prognosis of glioma. Henceforth, this study aims to identify the molecular mechanism of GNA13 in enhancing TMZ sensitization through bioinformatic analyses of GSE80729 and GSE43452 and other experiments. In glioma, overexpression of GNA13 downregulated PRKACA, which is a subunit of PKA, hence reducing phosphorylated RELA and MGMT. Since p-RELA and MGMT were proven to be closely associated with TMZ resistance, we therefore investigated whether thetwo signaling pathways, "GNA13/PRKACA/p-RELA", and "GNA13/PRKACA/MGMT", were involved in the molecular mechanism of GNA13 in TMZ sensitization. Our conclusion was that, GNA13 overexpression in glioma cells were more sensitive in TMZ treatment.

TCF7L2 and EGR1 synergistic activation of transcription of LCN2 via an ERK1/2-dependent pathway in esophageal squamous cell carcinoma cells.

High level expression of lipocalin 2 (LCN2) usually indicates poor prognosis in esophageal squamous cell carcinoma (ESCC) and many other cancers. Our previous study showed LCN2 promotes migration and invasion of ESCC cells through a novel positive feedback loop. However, the key transcription activation protein (KTAP) in the loop had not yet been identified. In this study, we first predicted the most probable KTAPs by bioinformatic analysis. We then assessed the transcription regulatory regions in the human LCN2 gene by fusing deletions of its 5'-flanking region to a dual-luciferase reporter. We found that the region -720/-200 containing transcription factor 7-like 2 (TCF7L2) (-273/-209) and early growth response 1 (EGR1) (-710/-616) binding sites is crucial for LCN2 promoter activity. Chromatin immunoprecipitation (ChIP) experiments demonstrated that TCF7L2 and EGR1 bound directly to their binding sites within the LCN2 promoter as KTAPs. Mechanistically, overexpression of TCF7L2 and EGR1 increased endogenous LCN2 expression via the ERK signaling pathway. Treatment with recombinant human LCN2 protein enhanced activation of the ERK pathway to facilitate endogenous LCN2 expression, as well as increase the expression level of TCF7L2 and EGR1. Treatment with the MEK inhibitor U0126 inhibited the activation by TCF7L2 or EGR1 overexpression. Moreover, overexpression of TCF7L2 or EGR1 accelerated the migration and invasion of ESCC cells. A synergistic effect was observed between TCF7L2 and EGR1 in amplifying the induction of LCN2 and enhancing migration and invasion. Taken together, our study indicates that TCF7L2 and EGR1 are the KTAPs of LCN2, within a positive "LCN2 → MEK/ERK → LCN2" path, to promote the migration and invasion of ESCC cells. Based on their clinicopathological significance, LCN2 and its two expression regulators TCF7L2 and ERG1 might be therapeutic targets for ESCC.

LCN2-interacting proteins and their expression patterns in brain tumors.

Lipocalin 2 (LCN2) is a member of the lipocalin family. Elevated expression of LCN2 has been observed in many human tumors, suggesting it might be a potential biomarker and/or therapeutic target in malignancies. In this study, we aimed to explore LCN2 interacting proteins through bioinformatics, as well as their biological functions. Protein-protein interaction networks (PPIN) were constructed using LCN2 and its interacting proteins as the core node. These PPINs were scale free biological networks in which LCN2 and its interacting proteins could connect or cross-talk with at least one partner protein. Both functional and KEGG pathway enrichment analyses identified the known and potential biological functions of the PPIN, such as cell migration and cancer-related pathways. Expression levels of the PPIN proteins, as well as their expression correlations, in five types of brain tumor, were analyzed and integrated into the PPIN to illustrate a dynamic change. A significant correlation was found between the survival time of glioblastoma patients and the expression level of 10 genes (LCN2, MMP9, MMP2, PDE4DIP, L2HGDH, HNRNPA1, DDX31, LOXL2, FAM60A and RNF25). Taken together, our results suggest that LCN2 and its interacting proteins are mostly differentially expressed and have a distinguishing co-expression pattern. They might promote proliferation and migration via cell migration signaling and cancer-related pathways. LCN2 and its interacting proteins might be potential biomarkers in glioblastoma.

The analyses of SRCR genes based on protein-protein interaction network in esophageal squamous cell carcinoma.

The scavenger receptor cysteine-rich (SRCR) proteins, with one to several SRCR domains, play important roles in human diseases. A full view of their functions in esophageal squamous cell carcinoma (ESCC) remain unclear. Sequence alignment and phylogenetic tree for all human SRCR domains were performed. Differentially-expressed SRCR genes were identified in ESCC, followed by protein-protein interaction (PPI) network construction, topological parameters, subcellular distribution, functional enrichment and survival analyses. The variation of conserved cysteines in each SRCR domain suggested a requirement for new classification of the SRCR family. Six genes (LGALS3BP, MSR1, CD163, LOXL2, LOXL3 and LOXL4) were upregulated, and four genes (DMBT1, PRSS12, TMPRSS2 and SCARA5) were downregulated in ESCC. These 10 SRCR genes form a unique biological network. Functional enrichment analyses provided important clues to investigate the biological functions for SRCR gene network in ESCC, such as extracellular structure organization and the PI3K-Akt signaling pathway. Kaplan-Meier curves confirmed that high expression of SCARA5, LOXL2, LOXL3, LOXL4 were related to poor survival, whereas high expression of DMBTI and PRSS12 showed the opposite result. SRCR genes promote the development of ESCC through its network and could serve as potential prognostic factors and therapy targets of ESCC.

The Identification of Key Genes and Pathways in Glioma by Bioinformatics Analysis.

Glioma is the most common malignant tumor in the central nervous system. This study aims to explore the potential mechanism and identify gene signatures of glioma. The glioma gene expression profile GSE4290 was analyzed for differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied for the enriched pathways. A protein-protein interaction (PPI) network was constructed to find the hub genes. Survival analysis was conducted to screen and validate critical genes. In this study, 775 downregulated DEGs were identified. GO analysis demonstrated that the DEGs were enriched in cellular protein modification, regulation of cell communication, and regulation of signaling. KEGG analysis indicated that the DEGs were enriched in the MAPK signaling pathway, endocytosis, oxytocin signaling, and calcium signaling. PPI network and module analysis found 12 hub genes, which were enriched in synaptic vesicle cycling rheumatoid arthritis and collecting duct acid secretion. The four key genes CDK17, GNA13, PHF21A, and MTHFD2 were identified in both generation (GSE4412) and validation (GSE4271) dataset, respectively. Regression analysis showed that CDK13, PHF21A, and MTHFD2 were independent predictors. The results suggested that CDK17, GNA13, PHF21A, and MTHFD2 might play important roles and potentially be valuable in the prognosis and treatment of glioma.

Matrix Metalloproteinase-9/Neutrophil Gelatinase-Associated Lipocalin Complex Activity in Human Glioma Samples Predicts Tumor Presence and Clinical Prognosis.

Matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin (MMP-9/NGAL) complex activity is elevated in brain tumors and may serve as a molecular marker for brain tumors. However, the relationship between MMP-9/NGAL activity in brain tumors and patient prognosis and treatment response remains unclear. Here, we compared the clinical characteristics of glioma patients with the MMP-9/NGAL activity measured in their respective tumor and urine samples. Using gelatin zymography assays, we found that MMP-9/NGAL activity was significantly increased in tumor tissues (TT) and preoperative urine samples (Preop-1d urine). Activity was reduced by seven days after surgery (Postop-1w urine) and elevated again in cases of tumor recurrence. The MMP-9/NGAL status correlated well with MRI-based tumor assessments. These findings suggest that MMP-9/NGAL activity could be a novel marker to detect gliomas and predict the clinical outcome of patients.

Chitosan-capped gold nanoparticles for selective and colorimetric sensing of heparin.

In this contribution, novel chitosan-stabilized gold nanoparticles (AuNPs) were prepared by mixing chitosan with citrate-reductive AuNPs under appropriate conditions. The as-prepared chitosan-stabilized AuNPs were positively charged and highly stably dispersed in aqueous solution. They exhibited weak resonance light scattering (RLS) intensity and a wine red color. In addition, the chitosan-stabilized AuNPs were successfully utilized as novel sensitive probes for the detection of heparin for the first time. It was found that the addition of heparin induced a strong increase of RLS intensity for AuNPs and the color change from red to blue. The increase in RLS intensity and the color change of chitosan-stabilized AuNPs caused by heparin allowed the sensitive detection of heparin in the range of 0.2-60 µM (~6.7 U/mL). The detection limit for heparin is 0.8 µM at a signal-to-noise ratio of 3. The present sensor for heparin detection possessed a low detection limit and wide linear range. Additionally, the proposed method was also applied to the detection of heparin in biological media with satisfactory results.

Functionalized gold nanorods as an immunosensor probe for neuron specific enolase sensing via resonance light scattering.

A novel resonance light scattering assay for neuron specific enolase (NSE) with high selectivity and sensitivity has been developed by using functionalized gold nanorods as an immunosensor probe.

miR-24-3p and miR-27a-3p promote cell proliferation in glioma cells via cooperative regulation of MXI1.

MicroRNAs (miRNAs) are small, non­coding RNAs which regulate gene expression at the post-transcriptional level. Abnormal expression of miRNAs occurs frequently in tumors. Although the two miRNAs miR­24­3p and miR­27a­3p come from two duplicated gene clusters of miR­23a~27a~24­2 and miR­23b~27b~24­1 which are found to be deregulated in a variety of cancers, the role of cooperation of the two clusters and the function of the two miRNAs in tumors have not been completely characterized. Here, we show that overexpression of miR­24­3p and miR­27a­3p could promote cell proliferation using the MTT assay. By integrated bioinformatic analysis and experimental confirmation, we identified MXI1, which has been found to act as a tumor suppressor gene by affecting c­Myc, as a direct target of miR­24­3p and miR­27a­3p. While targeting the MXI1 3' untranslated region by miR­24­3p or miR­27a­3p, luciferase activity was attenuated. The two miRNAs promote glioma cell proliferation via targeting MXI1 and the experiment was confirmed by the rescue experiments. Furthermore, our results show that two clusters of miR-23a~27a~24-2 and miR­23b~27b~24­1 regulate MXI1 synergistically. These findings reveal, for the first time, the novel functions of cooperation of miR­24­3p and miR­27a­3p from two clusters in promoting cell proliferation through MXI1. Additionally, we observed that miR­27a­3p is upregulated in glioma tissues.

MicroRNA-155 promotes glioma cell proliferation via the regulation of MXI1.

Gliomas are the most common and aggressive primary tumors in the central nervous system. Recently, Max interactor-1 (MXI1), an antagonist of c-Myc that is involved in brain tumor progression, has been reported to be deregulated in a variety of tumors including glioma. However, the mechanism of MXI1 deregulation in gliomas remains unclear. In this study, we show that the relative expression level of MXI1 is markedly down-regulated in glioma cell lines. Using integrated bioinformatic analysis and experimental confirmation, we identified several miRNAs by screening a panel of predicted miRNAs that may regulate the MXI1 3'UTR. The strongest inhibitory miRNA, miR-155, can attenuate the activity of a luciferase reporter gene that is fused with the MXI1 3'UTR and decrease the expression levels of MXI1 mRNA and protein in U87 glioma cells. The potential role of miR-155 in promoting glioma cell proliferation by targeting MXI1 was confirmed in various glioma cell lines by rescue experiments using MTT assays, EdU incorporation assay, and cell counting experiments. In addition, we determined that the level of MXI1 mRNA was inversely correlated with the expression of miR-155 in 18 sets of glioblastoma multiforme specimens. These findings reveal for the first time that the targeting of MXI1 by miR-155 may result in a reduction in MXI1 expression and promote glioma cell proliferation; this result suggests a novel function of miR-155 in targeting MXI1 in glioma-genesis.

Metallothionein 3 attenuated the apoptosis of neurons in the CA1 region of the hippocampus in the senescence-accelerated mouse/PRONE8 (SAMP8).

OBJECTIVE: Metallothionein 3 (MT-3) has been shown to protect against apoptotic neuronal death in the brains of patients with Alzheimer's disease. Zinc is a potent inhibitor of caspase-3 and its deficiency was found to promote apoptosis. Here, we measured the zinc and copper content in the brains of senescence-accelerated mouse/PRONE8 (SAMP8) and sought to investigate the effect of MT-3 on the apoptosis of neurons in the hippocampal CA1 region of these mice. METHOD: The zinc and copper content in the brain samples of SAMP8 and normal control SAMR1 mice were determined using an atomic absorption spectrophotometer. The mice were administered intraperitoneally for four weeks with MT-3 or MT1 and thereafter apoptosis was measured using the TUNEL method and the expression of anti-apoptotic protein Bcl-2 and proapoptotic protein Bax was examined by immunohistochemistry. RESULTS: Compared with that in SMAR1 mice, the content of zinc in the brains of SAMP8 mice was significantly reduced (P<0.05). Moreover, significant levels of apoptosis of neurons were observed in the hippocampus of SAMP8 mice, which, compared with those in SMAR1 mice, also showed significantly lower levels of Bcl-2 and higher levels of Bax (P<0.05). MT-3 increased zinc concentration in the hippocampus of SAMP8 mice and also significantly decreased apoptosis in these neurons dose-dependently and increased the levels of Bcl-2 and decreased the levels of Bax. CONCLUSION: MT-3 could attenuate apoptotic neuron death in the hippocampus of SAMP8, suggesting that the protein may lessen the development of neurodegeneration.