Neutralization of tumor necrosis factor alpha or Fas ligand had no effect on apoptosis. These results demonstrate that NS1 is sufficient to induce apoptosis in liver-derived cells and that it does so through the initiation of an intrinsic caspase pathway.

The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701).

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BackgroundAneurysmal subarachnoid hemorrhage (SAH) is a highly morbid and fatal condition with high rate of cognitive impairment and negative impact in quality of life among survivors. Delayed cerebral infarction (DCI) is one the major factors for these negative outcomes. In this study we compared the circulating microRNA profiles of SAH patients and healthy individuals, and the circulating microRNA profiles of SAH patients with and without DCI.MethodsPeripheral blood samples on Day 7 after the onset of SAH were subjected to microarray analysis with Affymetrix miRNA 3.0 array and quantitative PCR analysis. SAH patients with (N = 20) and without DCI (N = 20) and Healthy controls (N = 20) were included for analyses.ResultsWe demonstrated that 99 miRNAs were found to be dysregulated in the SAH patient group with DCI. 81 miRNAs were upregulated and 18 were downregulated. Findings from KEGG pathway analysis showed that miRNAs and target genes for axon guidance and TGF-beta signaling were involved, implying that the resulted differential miRNA expression pattern reflect the results of SAH instead of etiology of the disease. miR-132-3p and miR-324-3p showed distinctive upregulations in qPCR [miR-132: 9.5 fold (95%CI: 2.3 to 16.7) in DCI group and 3.4 fold (95%CI: 1.0 to 5.8) in Non-DCI group; miR-324: 4924 fold (95%CI: 2620 to 7228) in DCI group and 4545 fold (95%CI: 2408 to 6683) in non-DCI group]. However, there were no significant differences in fold changes between SAH patients with and without DCI [fold change ratios (mean+/-SD): 2.7+/-4.2 and 1.1+/-1.1 for miRNA-132 and miRNA-324].ConclusionOur study demonstrated that as compared to healthy control, miR-132 and miR-324 showed a upregulation in both SAH DCI and Non-DCI groups. However, the differences between the SAH DCI and non-DCI groups were not statistically significant.

AIM:To investigate the expression level and effects of leptin in human hepatocellular carcinoma cells in vitro and to explore the correlation between them. METHODS: Human hepatocellular carcinoma cell lineHepG2 was cultured in vitro , and (the expression level) mRNA of leptin and leptin receptors in HepG2 were assessed using reverse transcription polymerase chain reaction (RT-PCR). Effects of different concentrations of leptin (50 ng/mL, 100 ng/mL, 200 ng/mL) on HepG2 were detected with colorimetric assay by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) after incubation periods of 24 h, 48 h, and 72 h. Flow cytometry was performed to assess cell cycle progression of different concentrations of leptin as stated above after each 24 h incubation period.RESULTS: mRNA of leptin and leptin receptors (including short and long isoforms) were expressed in HepG2. The 72 h incubation of leptin at different concentrations ( 5 0 n g / m L , 1 0 0 n g / m L , 2 0 0 n g / m L ) p r o m o t e d proliferation of HepG2 in a concentration-and timedependent manner. The experimental group shows significant statistical differences when compared to the controlled group which contained 0 ng/mL of leptin. As the concentration of leptin increases, significant fewer cells were detected in G0-G1 phase and more cells in S and G2-M phases. C O N C L U S I O N :L e p t i n a n d l e p t i n r e c e p t o r a r e simultaneously expressed in human hepatocellular carcinoma cell line HepG2. Addition of leptin (0 ng/mL-200 ng/mL) in 72 h periods indicated there is a concentration-and time-dependent correlation in the stimulation of HepG2 cell proliferation. The effect of proliferation by leptin is due to promotion of DNA synthesis and enhancement of mitotic activity. The relationship between leptin and human hepatocellular carcinoma cells might indicate that adipokine could be associated with the progression of human hepatocellular carcinoma.

Glioblastoma is a common malignant brain tumor and it is refractory to therapy because it usually contains a mixture of cell types. The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has been shown to induce apoptosis in a range of tumor cell types. Previously, we found that two human glioblastoma cell lines are resistant to TRAIL, while lovastatin sensitizes these glioblastoma cells to TRAIL-induced cell death. In this study, we investigated the mechanisms underlying the TRAIL-induced apoptosis in human glioblastoma cell lines by lovastatin. Furthermore, we have confirmed the anti-tumor effect of combination therapy with lovastatin and TRAIL in the subcutaneous brain tumor model. We showed that lovastatin significantly up-regulated the expression of death receptor 5 (DR5) in glioblastoma cell lines as well as in tumor-bearing mice with peri-tumoral administration of lovastatin. Further study in glioblastoma cell lines suggested that lovastatin treatment could inhibit NF-κB and Erk/MAPK pathways but activates JNK pathway. These results suggest that lovastatin sensitizes TRAIL-induced apoptosis by up-regulation of DR5 level via NF-κB inactivation, but also directly induces apoptosis by dysregulation of MAPK pathway. Our in vivo study showed that local peri-tumoral co-injection of lovastatin and TRAIL substantially reduced tumor growth compared with single injection of lovastatin or TRAIL in subcutaneous nude mice model. This study suggests that combined treatment of lovastatin and TRAIL is a promising therapeutic strategy to TRAIL-resistant glioblastoma.

Memory representations can be stored in a passive state in a visual working memory (VWM) task. However, it remains unclear whether the representations stored in the passive state are prone to interference and decay. To explore this issue, we asked participants to successively remember two sets of memory items (M1 and M2) in three test manners: a combined test (both M1 and M2 are probed simultaneously), a backward test (probe M2 first and M1 second), or a forward test (probe M1 first and M2 second). We found that the contralateral delay activity (CDA) amplitude after the onset of M2 only tracked M2 independently of M1 in the two separate tests (Experiments 1-3), and the accuracy of M1 was well above chance. These results implied that the M1 representations had been transferred from the online state into the passive state after the onset of M2. Furthermore, the accuracy of M1 (two representations were transferred from the online state into the passive state and retrieved later) in the backward test was worse than M2 (2 representations in the online state throughout) in the backward test (Experiments 1-2), but was comparable to M1 (two representations were transferred from the online state into the passive state and retrieved first) in the forward test (Experiment 2). These results demonstrated that the memory representations were impaired during state switching. Importantly, once the representations had been stored in the passive state, they were robust with little memory loss during latent retention.

BackgroundDelayed cerebral infarction (DCI) is a major cause of morbidities after aneurysmal subarachnoid hemorrhage (SAH) and typically starts at day 4 to 7 after initial hemorrhage. MicroRNAs (miRNAs) play an important role in posttranscriptional gene expression control, and distinctive patterns of circulating miRNA changes have been identified for some diseases. We aimed to investigate miRNAs that characterize SAH patients with DCI compared with those without DCI.Methods and ResultsCirculating miRNAs were collected on day 7 after SAH in healthy, SAH‐free controls (n=20), SAH patients with DCI (n=20), and SAH patients without DCI (n=20). We used the LASSO (least absolute shrinkage and selection operator) method of regression analysis to characterize miRNAs associated with SAH patients with DCI compared with those without DCI. In the 28 dysregulated miRNAs associated with DCI and SAH, we found that a combination of 4 miRNAs (miR‐4532, miR‐4463, miR‐1290, and miR‐4793) could differentiate SAH patients with DCI from those without DCI with an area under the curve of 100% (95% CI 1.000–1.000, P<0.001). This 4‐miRNA combination could also distinguish SAH patients with or without DCI from healthy controls with areas under the curve of 99.3% (95% CI 0.977–1.000, P<0.001) and 82.0% (95% CI 0.685–0.955, P<0.001), respectively.ConclusionsWe found a 4‐miRNA combination that characterized SAH patients with DCI. The findings could guide future mechanistic study to develop therapeutic targets.