Cell division cycle 42 (CDC42), which is a member of the Rho GTPase family, has been reported to regulate the metastasis of various human cancer cells; however, the role of CDC42 in gastric cancer (GC) remains unclear. The present study aimed to investigate the effects of CDC42 on the proliferation, migration and invasion of GC. Furthermore, the molecular mechanisms underlying the effects of CDC42 on GC were explored. The expression levels of CDC42 in the AGS and SGC7901 human GC cell lines were reduced by RNA interference. Knockdown of CDC42 significantly inhibited the proliferation of AGS and SGC7901 cells, and it was suggested that this inhibitory process may be due to cell cycle arrest at G1/S phase and downregulation of cyclin A, cyclin D1, cyclin E and proliferating cell nuclear antigen. Furthermore, knockdown of CDC42 markedly inhibited the migration and invasion of GC cells, and suppressed the expression of matrix metalloproteinase 9. These results indicated that CDC42 is a key regulator involved in regulating the proliferation, migration and invasion of GC, and it may be considered a potential therapeutic target in GC.

No abstract

HIGHLIGHTS The aim of the research was to determine the functional effects and molecular mechanisms of GABAB receptor on ischemia reperfusion-induced gastric injury in rats.The lateral hypothalamus area GABAB receptor attenuated the ischemia reperfusion-induced gastric injury by up-regulating the production of GABA, GABABR, and down-regulating P-GABABR in the brain.This work would provide a new therapeutic strategy for acute gastric injury.Gastric ischemia-reperfusion (GI-R) injury progression is largely associated with excessive activation of the greater splanchnic nerve (GSN). This study aims to investigate the protective effects of GABAB receptor (GABABR) in the lateral hypothalamic area (LHA) on GI-R injury. A model of GI-R injury was established by clamping the celiac artery for 30 min and then reperfusion for 1 h. The coordinate of FN and LHA was identified in Stereotaxic Coordinates and then the L-Glu was microinjected into FN, GABAB receptor agonist baclofen, or GABAB receptor antagonist CGP35348 was microinjected into the LHA, finally the GI-R model was prepared. The expression of GABABR, P-GABABR, NOX2, NOX4, and SOD in the LHA was detected by western blot, PCR, and RT-PCR. The expression of IL-1β, NOX2, and NXO4 in gastric mucosa was detected by western blot. We found that microinjection of L-Glu into the FN or GABAB receptor agonist (baclofen) into the LHA attenuated GI-R injury. Pretreatment with GABAB receptor antagonist CGP35348 reversed the protective effects of FN stimulation or baclofen into the LHA. Microinjection of baclofen into the LHA obviously reduced the expression of inflammatory factor IL-1β, NOX2, and NOX4 in the gastric mucosa.Conclusion: The protective effects of microinjection of GABABR agonist into LHA on GI-R injury in rats could be mediated by up-regulating the production of GABA, GABABR, and down-regulating P-GABABR in the LHA.

These results indicate that the protective effects of the FN stimulation against GI-R injury may be mediated by attenuation of the excessive GSN activation, gastric mucosal cell apoptosis, and Bax expression in GI-R rats.

Oxidative/nitrosative stress, neuroinflammation and their intimate interactions mediate sympathetic overactivation in hypertension. An immoderate inflammatory response is characterized not only by elevated proinflammatory cytokines (PICs) but by increases in mitochondrial dysfunction, reactive oxygen species (ROS), and nitric oxide (NO). Recent data pinpoint that both the phospholipid and lipid droplets (LDs) are potent modulators of microglia physiology. Methods: Stress rats underwent compound stressors for 15 days with PLIN2-siRNA or scrambled-siRNA (SC-siRNA) administrated into the rostral ventrolateral medulla (RVLM). Lipids were analyzed by mass spectroscopy-based quantitative lipidomics. The phenotypes and proliferation of microglia, LDs, in the RVLM of rats were detected; blood pressure (BP) and myocardial injury in rats were evaluated. The anti-oxidative/nitrosative stress effect of phosphatidylethanolamine (PE) was explored in cultured primary microglia. Results: Lipidomics analysis showed that 75 individual lipids in RVLM were significantly dysregulated by stress [PE was the most one], demonstrating that lipid composition changed with stress. In vitro, prorenin stress induced the accumulation of LDs, increased PICs, which could be blocked by siRNA-PLIN2 in microglia. PLIN2 knockdown upregulated the PE synthesis in microglia. Anti-oxidative/nitrosative stress effect of PE delivery was confirmed by the decrease of ROS and decrease in 3-NT and MDA in prorenin-treated microglia. PLIN2 knockdown in the RVLM blocked the number of iNOS + and PCNA + microglia, decreased BP, alleviated cardiac fibrosis and hypertrophy in stressed rats. Conclusion: PLIN2 mediates microglial polarization/proliferation via downregulating PE in the RVLM of stressed rats. Delivery of PE is a promising strategy for combating neuroinflammation and oxidative/nitrosative stress in stress-induced hypertension.

Abstract. Excessive activation of the greater splanchnic nerve (GSN) has previously been determined to contribute to the progression of gastric ischemia-reperfusion (GI-R) injury. The present study was designed to estimate the protective effects of GABA A receptor (GABA A R) overexpression in the lateral hypothalamic area (LHA) against GI-R injury. The GI-R injury model was induced in rats by clamping the celiac artery for 30 min and then reperfusing for 1 h. Microinjection of recombinant adenoviral vectors overexpressing GABA A R (Ad-GABA A R) or control adenoviral vectors (Ad-Con) into the LHA was conducted in GI-R and normal control rats. Significant protective effects were observed on day 2 after Ad-GABA A R treatment in the GI-R injury rats. Ad-GABA A R treatment reduced plasma norepinephrine levels, plasma angiotensin II levels and peripheral GSN activity, but increased the gastric mucosal blood flow, as compared with Ad-Con treatment. These results indicate that adenoviral vector-induced GABA A R overexpression in the LHA blunts GSN activity and subsequently alleviates the effects of gastric injury in GI-R rats. IntroductionMajor surgery-evoked ischemia has been demonstrated to induce gastric mucosal injury and gastrointestinal dysmotility (1,2). Previous studies (3-5) have shown that the hypothalamic paraventricular nucleus and the lateral hypothalamic area (LHA) are two specific hypothalamic nuclei that modulate gastric activity and gastric mucosal injury. The microinjection of GABAA receptor blocker in the LHA enhances GI-R injury. However, little is known regarding GABAA receptor expression and the protective effects of GABA A R overexpression in the LHA against gastric ischemia-reperfusion (GI-R) injury in rats. As determined by a previous study (6), cerebellar-hypothalamic circuits regulate the gastric mucosal injury induced by ischemia-reperfusion. However, the detailed GABA A receptor (GABA A R)-mediated regulative mechanism in the LHA upon GI-R injury is not clear. In the present study, the effects of GABA A R overexpression induced by recombinant adenovirus vectors in the LHA following GI-R injury in rats were investigated. The aim of this study was to investigate the potential mechanisms of the GABA A receptor in GI-R injury. Materials and methods Animals

Misgurnus anguillicaudatus is a highly valued, aquaculture-relevant food fish in East Asian countries. Because of overfishing and environmental pollution, the number of wild Nansi loach has been sharply decreased in these years. In this study, the complete mitochondrial genome of Nansi loach was obtained by PCR. The genome is 16,646 bp in length, including 2 ribosomal RNA genes. 13 proteins-coding genes, 22 transfer RNA genes, and a non-coding control region, the gene composition and order of which was similar to most reported from other vertebrates. Sequence analysis showed that the overall base composition is 29.8% for A, 28.2% for T, 25.6% for C, and 16.4% for G. The phylogenetic tree showed that Misgurnus family got together for one branch, which includes Nansi M. anguillicaudatus, and the other loaches had their own branches. Also, the mitochondrial genome sequence of M. anguillicaudatus was aligned by BLAST, compared with Cobitinae the sequence similarity could reach >95%, and the similarity to Misgurnus was >99%.

Alzheimer's disease (AD) accounts for almost three quarters of dementia patients and interferes people's normal life. Great progress has been made recently in the study of Acetylcholinesterase (AChE), known as one of AD's biomarkers. In this study, acetylcholinesterase inhibitors (AChEI) were collected to build a two-dimensional structure-activity relationship (2D-SAR) model and three-dimensional quantitative structure-activity relationship (3D-QSAR) model based on feature selection method combined with random forest. After calculation, the prediction accuracy of the 2D-SAR model was 89.63% by using the tenfold cross-validation test and 87.27% for the independent test set. Three cutting ways were employed to build 3D-QSAR models. A model with the highest [Formula: see text] (cross-validated correlation coefficient) and [Formula: see text](non-cross-validated correlation coefficient) was obtained to predict AChEI activity. The mean absolute error (MAE) of the training set and the test set was 0.0689 and 0.5273, respectively. In addition, molecular docking was also employed to reveal that the ionization state of the compounds had an impact upon their interaction with AChE. Molecular docking results indicate that Ser124 might be one of the active site residues.