Octreotide ameliorates hypoxia/reoxygenation-induced cerebral infarction by inhibiting oxidative stress, inflammation and apoptosis, and via inhibition of TLR4/MyD88/NF-κB signaling pathway

Purpose: To explore the effects of octreotide (OCT) on oxidative stress, inflammation and apoptosis in hypoxia/reoxygenation (H/R)-induced cerebral infarction.Methods: The in vitro model of cerebral infarction was established by treating N2A cells with hypoxia for 4 h and reoxygenation for 24 h. The viability of N2A cells was determined by CCK-8 assay. The cells were divided into 3 groups: control group, H/R group, and H/R+OCT group. The cells in H/R+OCT group were pretreated with OCT (60 ng/mL) before H/R treatment. The oxidative stress of N2A cells were assessed by determining the levels of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT), reactive oxygen species (ROS) and malondialdehyde (MDA). Inflammation of N2A cells was evaluated by evaluating the levels of TNF-α, IL-1β, IL-6, and IL-8, while the apoptosis of N2A cells was assessed by flow cytometry. Western blot analysis was used to determine the expression of Bcl-2, Bax, TLR4, MyD88, and NF-κB.Results: Octreotide treatment significantly reduced the level of oxidative stress. The inflammation of N2A cells caused by hypoxia/reoxygenation was inhibited by treatment with octreotide. Apoptosis of N2A cells was also inhibited by octreotide treatment. Hypoxia/reoxygenation activated TLR4/MyD88/NF-κB signaling pathway, while octreotide inhibits the activation of this pathway.Conclusion: The results reveal that octreotide inhibits hypoxia/reoxygenation-induced oxidative stress,as well as the inflammation, and apoptosis of N2A cells by inhibiting TLR4/MyD88/NF-κB signaling pathway. Thus, these findings may provide new insights into the treatment of cerebral infarction

Venlafaxine inhibits neuronal apoptosis in a depression rat model via ERK1/ERK2 pathway

Purpose: To investigate the effects and mechanism of action of venlafaxine on neuronal apoptosis of depressed rats. Methods: Rats were randomly divided into normal control (NC) group, depressed rats (depression) group or venlafaxine-treatment group. Changes in body weight and sucrose preference ratio were recorded and behaviors in open field test (OFT) were observed in each group. Pathological changes in and the apoptosis rate of the cerebral neurons, and the activity of extracellular signal-regulated kinase 1 (ERK1)/ERK2 pathway were observed under a microscope. Results: At weeks 2 and 4, the body weight and water consumption of rats in depression group dropped below those of rats in NC group. On the other hand, at week 2, the body weight and water consumption of rats in venlafaxine-treatment group were significantly higher than those of rats in depression group (p < 0.05). Besides, depression group had randomly arranged neuron cells and a thinner cell layer, while venlafaxine-treatment group had a relatively regular hippocampal neural cell arrangement and a thicker cell layer. Moreover, cell apoptosis rate was higher in depression group than in that NC group, and lower in venlafaxine-treatment group than that in depression group (p < 0.05). Finally, the protein expressions of phosphorylated (p)-ERK1 and p-ERK2 were significantly higher in depression group than those in NC group (p<0.05), and distinctly lower in venlafaxine-treatment group than those in depression group (p <0.05). Conclusion: By suppressing the activity of ERK1/ERK2 pathway, venlafaxine relieves the symptoms of depression and repairs neuronal injuries in rats, thereby suppressing neuronal apoptosis. Thus, these findings provide a novel approach for the development of new antidepressants

The NTSR1 gene modulates the association between hippocampal structure and working memory performance

The genetic and neural basis of working memory (WM) has been extensively studied. Many dopamine (DA) related genes, including the NTSR1 gene (a DA modulator gene), have been reported to be associated with WM performance. The NTSR1 protein is predominantly expressed in the cerebral cortex and the hippocampus, the latter of which is closely involved in WM processing based on both lesion and fMRI studies. Thus far, however, no study has examined the joint effects of NTSR1 gene polymorphism and hippocampal morphology on WM performance. Participants of the current study were 330 healthy Chinese college students. WM performance was measured with a 2-back WM paradigm. Structural MRI data were acquired and then analyzed using an automated procedure with atlas-based FreeSurfer segmentation software (v 4.5.0) package. Linear regression analyses were conducted with a NTSR1 C/T polymorphism which was previously reported to be associated with WM (rs4334545), hippocampal volume, and their interaction as predictors of WM performance, with gender and intracranial volume (ICV) as covariates. Results showed a significant interaction between NTSR1 genotype and hippocampal volume (p<.05 for both the left and right hippocampi). Further analysis showed that the correlation between hippocampal volume and WM scores was significant for carriers of the NTSR1 T-allele (p<.05 for both hippocampi), but not for CC homozygotes. These results indicate that the association between hippocampal structure and WM performance was modulated by variation in the NTSR1 gene, and suggest that further studies of brain-behavior associations should take genetic background information into account

Influence of Yb:YAG laser beam parameters on Haynes 188 weld fusion zone microstructure and mechanical properties

The weldability of 1.2 mm thick Haynes 188 alloy sheets by a disk Yb:YAG laser welding was examined. Butt joints were made, and the influence of parameters such as power, size, and shape of the spot, welding speed, and gas flow has been investigated. Based on an iconographic correlation approach, optimum process parameters were determined. Depending on the distribution of the power density (circular or annular), acceptable welds were obtained. Powers greater than 1700 W, welding speeds higher than 3.8 m mm1, and spot sizes between 160 and 320 lm were needed in the circular (small fiber) configuration. By comparison, the annular (large fiber) configuration required a power as high as 2500 W, and a welding speed less than 3.8 m min�1. The mechanical properties of the welds depended on their shape and microstructure, which in turn depended on the welding conditions. The content of carbides, the proportion of areas consisting of cellular and dendritic substructures, and the size of these substructures were used to explain the welded joint mechanical properties