Effect of Notch1 gene on remyelination in multiple sclerosis in mouse models of acute demyelination.

This study aims to explore the effects of Notch1 gene on remyelination in multiple sclerosis (MS). A mouse model of acute demyelination was successfully established and the model mice were grouped as cuprizone (CPZ) group, CPZ + small interfering RNA (siRNA)-Notch1 (siNotch1) group, and CPZ + siRNA negative control (NC) group. Meanwhile, another 3 groups (control, control + siNotch1, and control + siRNA NC) were established in normal mice. The changes of weight and maintenance time in rotating drum of mice were observed. Western blot analysis for the protein expressions related to Notch signaling pathway and oligodendrocyte (OL) differentiation in the corpus callosum of the mice. After model establishment, the weight of CPZ-induced demyelinated mice was decreased. During the repair period, the balance ability and movement of the mice was recovered, especially for those injected with siNotch1 plasmid. After model establishment, the number of myelinated axons was decreased. In comparison with the CPZ and CPZ siRNA NC groups, the CPZ + siNotch1 group had a decrease in the number of premature OLs, but increase in mature OLs, and a decrease in oligodendrocyte precursor cells and astrocytes. The expressions of proteins related to Notch signaling pathway, such as HES, Jagged-1 were decreased in the CPZ + siNotch1 group in contrast to the CPZ and CPZ + siRNA groups, but the OL-related transcription factor Sox10 was increased in the CPZ + siNotch1 group than in the CPZ + siRNA NC and CPZ groups, and Id2 was decreased. Our study provided evidence that the inhibition of Notch1 gene could accelerate remyelination in MS.

Sinomenine Protects PC12 Neuronal Cells against H2O2-induced Cytotoxicity and Oxidative Stress via a ROS-dependent Up-regulation of Endogenous Antioxidant System.

Sinomenine (SN), a purified alkaloid from Chinese herb Sinomenium acutum that was used preferentially in the treatment of rheumatoid diseases, has exerted neuroprotective effects and anti-inflammatory properties in many previous studies. Some studies have revealed that the antioxidant property of SN, acting mainly through inhibiting NADPH oxidase activation, was involved in the beneficial effects of SN. However, SN belongs to the family of dextrorotatory morphinan analogues, which may initiate elevation of reactive oxygen species (ROS) levels. Thus in the present report, we conducted studies to examine its impact and mechanism on the resistance of PC12 neuronal cells to oxidative stress. Precondition with SN (0.1-5 µM) for 12 h significantly decreased H2O2-induced cytotoxicity and remarkably alleviated oxidative injury. However, SN exhibited little direct free radical scavenging property in vitro and induced "appropriate" production of ROS in PC12 cell. Interestingly, the SN-triggering ROS production served as a signal to activate the Nrf2 antioxidant system including Nrf2, HO-1, and NQO-1, which was inhibited by the antioxidant trolox. Furthermore, Nrf2 knockdown largely attenuated the beneficial effects of SN precondition on oxidative stress. In conclusion, our findings suggested that SN increased the resistance to oxidative stress in neuronal cells via a ROS-dependent up-regulation of endogenous antioxidant system, and this mechanism may be involved in the neuroprotection of SN.

miR-146a negatively regulates the induction of proinflammatory cytokines in response to Japanese encephalitis virus infection in microglial cells.

Increasing evidence confirms the involvement of virus infection and miRNA, such as miR-146a, in neuroinflammation-associated epilepsy. In the present study, we investigated the upregulation of miR-146a with RT-qPCR and in situ hybridization methods in a mice infection model of Japanese encephalitis virus (JEV) and in vitro. Subsequently we investigated the involvement of miR-146a in modulating JEV-induced neuroinflammation. It was demonstrated that JEV infection promoted miR-146a production in BALB/c mice brain and in cultured mouse microglial C8-B4 cells, along with pro-inflammatory cytokines, such as IL-1ß, IL-6, TNF-α, IFN-ß and IFN-α. We also found that miR-146a exerted negative regulatory effects upon IL-1ß, IL-6, TNF-α, IFN-ß and IFN-α in C8-B4 cells. Accordingly, miR-146a downregulation with a miR-146a inhibitor promoted the upregulation of IL-1ß, IL-6, TNF-α, IFN-ß and IFN-α, whereas miR-146a upregulation with miR-146a mimics reduced the upregulation of these cytokines. Moreover, miR-146a exerted no regulation upon JEV growth in C8-B4 cells. In conclusion, JEV infection upregulated miR-146a and pro-inflammatory cytokine production, in mice brain and in cultured C8-B4 cells. Furthermore, miR-146a negatively regulated the production of JEV-induced pro-inflammatory cytokines, in virus growth independent fashion, identifying miR-146a as a negative feedback regulator in JEV-induced neuroinflammation, and possibly in epilepsy.

[A qualitative research on the psychological experience of hospitalized patients with acute myocardial infarction].

OBJECTIVE: To observe the psychological experience of patients with acute myocardial infarction (AMI) during hospitalization. METHODS: From November 2012 to February 2013, semi-structured interviews were conducted in 10 patients with AMI in the Cardiovascular Department of First Affiliated Hospital of Henan University of Science and Technology. Grounded theory approach was performed to analyze the collected data. RESULTS: The 6 themes and 3 secondary themes during their hospitalization were: helplessness and dependence when AMI was diagnosed fear of immediate death induced by AMI, confusion on various problems such as operation time, excretory after PCI and limited knowledge details, the feel of safety after PCI, the fear of AMI, and the worry about overtreatment. CONCLUSIONS: Hospitalized AMI patients have complicated psychological responses. Medical staff should provide targeted strategies and timely communication with AMI patients to reduce their psychological burden.

Furosemide with saline hydration for prevention of contrast-induced nephropathy in patients undergoing coronary angiography: a meta-analysis of randomized controlled trials.

BACKGROUND: The clinical efficacy of furosemide administration in preventing contrast-induced nephropathy (CIN) remains uncertain. This meta-analysis was designed to update data on the incidence of CIN with additional furosemide treatment beyond saline hydration in comparison with hydration alone in patients undergoing percutaneous coronary intervention (PCI). MATERIAL/METHODS: A computerized literature search of MEDLINE, EMBASE, and Cochrane databases was performed. Trials were eligible if they enrolled patients undergoing coronary angiography and randomly allocated participants to receive furosemide administration in addition to saline hydration or saline hydration alone. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for combinations of studies. RESULTS: Five trials involving 1294 patients (640 for additional furosemide treatment and 654 for hydration alone) were included in the meta-analysis. In the synthesis of data, additional furosemide administration had little impact on the incidence of CIN post-PCI compared with peri-procedural saline hydration alone (OR=0.96; 95% CI 0.33-2.84, p=0.95). Moreover, as for the subsequent need for dialysis, there was no statistical significant difference between the 2 groups (OR=1.01; 95% CI 0.38-2.67, p=0.99). Sensitivity analyses did not show any relevant influence on the overall results. There was no publication bias in the meta-analysis. CONCLUSIONS: Furosemide administration did not achieve additional benefit beyond saline hydration in reducing the incidence of CIN in patients undergoing PCI.