Effect of fluoxetine on the depression-like behavior and mitogen-activated protein kinase-p38 signaling pathway in depression rats / 新乡医学院学报

Objective To investigate the effect of fluoxetine on the depression-like behavior and the expression of mitogen-activated protein kinase phosphatase-1 (MKP-1),phosphorylated p38 and p38 in hippocampus of rats with depression,in order to provide clues for the molecular pathological mechanism of depression.Methods Forty Sprague Dawley rats were randomly divided into normal group,depression group,normal saline group and fluoxetine group,with ten rats in each group.The rats in the depression group,normal saline group and fluoxetine group were treated with chronic unpredictable mild stress (CUMS) for eight weeks to prepare the depression models.The rats in the normal saline group and fluoxetine group were treated with normal saline and fluoxetine by intragastric administration respectively from the fifth to eighth week,but the rats in the normal group did not give CUMS and any intervention.The behavior changes of rats in the four groups were evaluated at the time points of before modeling,after modeling and postintervention.The hippocampal tissues of rats were taken after the last the last behavioral evaluations.The expression of MKP-1,p-p38 and p38 protein in hippocampus was detected by Western blot;and the ratio of the expression of p-p38 to p38 protein (p-p38/p38) was calculated.Results There was no significant difference in the behavioral indexes of rats among the four groups (P ＞ 0.05).Compared with pre-modeling,the sucrose preference index decreased,the horizontal movement distance and vertical frequency decreased in the open field test,and the inactivity time of rats in forced swimming test increased in the depression group,normal saline group and fluoxetine group,the differences were statistically significant (P ＜ 0.05).There was no significant difference in the behavioral indexes of rats among the depression group,normal saline group and fluoxetine group (P ＞ 0.05).Compared with the normal group,the sucrose preference index decreased,the horizontal movement distance and vertical frequency of rats in open field test decreased,and the inactivity time of rats in forced swimming test increased in the depression group,normal saline group and fluoxetine group after modeling,the differences were statistically significant(P ＜0.05).Compared with the depression group and normal saline group,the sucrose preference index of rats increased,the horizontal movement distance and vertical frequency of rats in open field test increased,and the inactivity time of rats in forced swimming test shortened in fluoxetine group,the differences were statistically significant (P ＜ 0.05).The expression of MKP-1 in the hippocampus of rats in the depression group and the normal saline group was significantly higher than that in the normal group (P ＜ 0.05).The expression of MKP-1 in the hippocampus of rats in the fluoxetine group was significantly lower than that in the depression group and normal saline group (P ＜ 0.05).There was no significant difference in the expression of MKP-1 in the hippocampus of rats between the depression group and the normal saline group (P ＞ 0.05).There was no significant difference in the expression of MKP-1 in the hippocampus of rats between the fluoxetine group and normal group(P ＞ 0.05).There was no significant difference in the expression of p-p38 and p38 protein and p-p38/p38 in the hippocampus of rats among the four groups (P ＞ 0.05).Conclusions MKP-1 may be associated with the pathogenesis of depression,and p38 may not be the signaling pathway for MKP-1 to take part in the pathogenesis of depression.Fluoxetine may play a role in the treatment of depression by down-regulating MKP-1 expression.MKP-1 may play a key role in the pathogenesis of depression.Fluoxetine may play a role in the treatment of depression by down-regulating.

Troubleshooting Arterial-Phase MR Images of Gadoxetate Disodium-Enhanced Liver

Gadoxetate disodium is a widely used magnetic resonance (MR) contrast agent for liver MR imaging, and it provides both dynamic and hepatobiliary phase images. However, acquiring optimal arterial phase images at liver MR using gadoxetate disodium is more challenging than using conventional extracellular MR contrast agent because of the small volume administered, the gadolinium content of the agent, and the common occurrence of transient severe motion. In this article, we identify the challenges in obtaining high-quality arterial-phase images of gadoxetate disodium-enhanced liver MR imaging and present strategies for optimizing arterial-phase imaging based on the thorough review of recent research in this field.

Prevalence and distribution of metabolic syndrome in a southern Chinese population Relation to exercise, smoking, and educational level

To investigate the prevalence and distribution of metabolic syndrome [MetS] and the impact of exercise, smoking, and educational level on the risk of MetS in a southern Chinese population. A cross-sectional study was conducted in Zhuhai City, China from June to August 2012. Data on exercise, smoking, and educational level, anthropometric parameters, blood pressure, lipid, and glucose levels were collected. The prevalence of MetS [as defined by the International Diabetes Federation] was determined. Data necessary to evaluate MetS, the socio-economic characteristics, and lifestyle were obtained for 4645 subjects aged 18-75 years old. A total of 19.8% of the participants had MetS. The adjusted odds of having MetS were lower among males [adjusted odds: 0.75; 95% confidence interval [CI]: 0.57-1.01] compared with females. Those participants who currently smoked had a higher risk of developing MetS compared with non-smokers [adjusted odds: 1.61; 95% CI: 1.13-2.50]. Those who had no physical exercise had a higher risk of developing MetS compared with those who physically exercised more than 60 minutes/day [adjusted odds: 1.51; 95% CI: 1.12-2.23;]. Compared with those with no education, every category of attained educational level had a lower risk of developing MetS [P<0.001]. The findings in this study revealed that current smokers had a greater risk of developing MetS compared with non-smokers. Increased physical activity and higher levels of education attained served as protective factors for the population

Candesartan inhibits LPS-induced expression increase of toll-like receptor 4 and downstream inflammatory factors likely via angiotensin II type 1 receptor independent pathway in human renal tubular epithelial cells / 生理学报

The present study was to determine whether candesartan, an angiotensin II type 1 receptor blocker (ARB), exerts anti-inflammatory effects through inhibiting the toll-like receptor 4 (TLR4) pathway in human renal tubular epithelial cells (HKCs). The experiments were carried on cultured HKCs. By means of flow cytometry, Western blot, RT-PCR and ELISA techniques, the TLR4 protein, angiotensin II type 1 receptor (AT1R) and phosphorylated nuclear factor-kappa B (NF-κB) p65 protein level, mRNA levels of macrophage chemoattractant protein-1 (MCP-1) and regulated upon expression normal T cell expressed and secreted (RANTES), as well as MCP-1 and RANTES protein concentrations in conditioned media were measured. The results showed that lipopolysaccharide (LPS) upregulated the TLR4 protein level in cultured HKCs. Application of LPS increased NF-κB activation and induced release of its downstream inflammatory factors including MCP-1 and RANTES. Candesartan reversed LPS-induced upregulation of TLR4 expression, inhibited NF-κB activation, and reduced MCP-1 and RANTES release. However, knockdown on AT1R by siRNA did not change those previous effects of candesartan. These results suggest that candesartan-induced anti-inflammatory effect may be through a novel pathway, independent of AT1R.