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Irritable bowel syndrome (IBS) is at high risk of co-morbid depression and anxiety, which reduces patients’ quality of life and increases the burden of health care costs. However, the pathophysiological mechanisms responsible for IBS still remain unknown. This study investigated the effects of resveratrol on stress-related depression, anxiety, intestinal and visceral dysfunction in rat model of IBS. Rats received chronic acute combining stress (CACS) for 22 days exhibited depression/anxiety-like behavior, visceral hypersensitivity and altered intestinal motility, as measured by the forced swimming, marble bury, abdominal withdrawal reflex (AWR) and intestinal tract motility (ITM) tests. These abnormalities were accompanied by reduced 5-hydroxytryptamine (5-HT) level in the hippocampus and increased 5-HT expression in the gut (ileum and colon) after CACS. Chronic treatment of IBS rats with resveratrol dose-dependently normalized CACS-induced both central nervous and peripheral dysfunction, which were consistent with its differentially regulating 5-HT contents in the brain and intestine. Pretreatment with the 5-HT1A receptor antagonist NAN-190 hydrobromide (NAN-190) prevented such effects. While sub-threshold of 5-HT1A receptor agonist 8-OH-DPAT potentiated the effects of low dose of resveratrol (10 mg/kg) on CACS-related behavioral abnormalities. Furthermore, resveratrol markedly increased PKA, p-cAMP-response element binding protein (p-CREB) and brain derived neurotrophic factor (BDNF) expression in the hippocampus of IBS rats, while decreased PKA, pCREB and BDNF levels were found in the ileum and colon. These effects were prevented by NAN-190, which were consistent with the behavioral changes. The present results suggested that resveratrol improved anti-IBS-like effects on depression, anxiety, visceral hypersensitivity and intestinal motility abnormality through regulating 5-HT1A-dependent PKA-CREB-BDNF signaling in the brain-gut axis.

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BackgroundDyslipidemia is an extremely prevalent but preventable risk factor for cardiovascular disease. However, many dyslipidemia patients remain undetected in resource limited settings. The study was performed to develop and evaluate a simple and effective prediction approach without biochemical parameters to identify those at high risk of dyslipidemia in rural adult population.MethodsDemographic, dietary and lifestyle, and anthropometric data were collected by a cross-sectional survey from 8,914 participants living in rural areas aged 35–78 years. There were 6,686 participants randomly selected into a training group for constructing the artificial neural network (ANN) and logistic regression (LR) prediction models. The remaining 2,228 participants were assigned to a validation group for performance comparisons of ANN and LR models. The predictors of dyslipidemia risk were identified from the training group using multivariate logistic regression analysis. Predictive performance was evaluated by receiver operating characteristic (ROC) curve.ResultsSome risk factors were significantly associated with dyslipidemia, including age, gender, educational level, smoking, high-fat diet, vegetable and fruit intake, family history, physical activity, and central obesity. For the ANN model, the sensitivity, specificity, positive and negative likelihood ratio, positive and negative predictive values were 90.41%, 76.66%, 3.87, 0.13, 76.33%, and 90.58%, respectively, while LR model were only 57.37%, 70.91%, 1.97, 0.60, 62.09%, and 66.73%, respectively. The area under the ROC cure (AUC) value of the ANN model was 0.86±0.01, showing more accurate overall performance than traditional LR model (AUC = 0.68±0.01, P<0.001).ConclusionThe ANN model is a simple and effective prediction approach to identify those at high risk of dyslipidemia, and it can be used to screen undiagnosed dyslipidemia patients in rural adult population. Further work is planned to confirm these results by incorporating multi-center and longer follow-up data.

In this study, molecular dynamic simulations are employed to investigate the nucleation of NaCl crystal in solutions. According to the simulations, the dissolved behaviors of NaCl in water are dependent on ion concentrations. With increasing NaCl concentrations, the dissolved Na + and Clions tend to be aggregated in solutions. In combination with our recent studies, the aggregate of dissolved solutes is mainly ascribed to the hydrophobic interactions. Thermodynamically, no barrier is needed to overcome in the formation of the solute aggregate. This is different from the two-step nucleation mechanism. In comparison with the classical nucleation theory (CNT), due to the aggregate of dissolved solutes, this lowers the barrier height of nucleation, and affects the nucleation mechanism of NaCl crystal in water.

Beta amyloid peptides (Aβ) are found to be associated with dysfunction of hypothalamic-pituitary-adrenal axis (HPA axis) that leads to memory and cognitive deficits in patients with Alzheimer's disease (AD). Phosphodiesterase 4 (PDE4) inhibitors increase the intracellular cAMP activities, which may ameliorate cognitive deficits associated with AD. However, it remains unclear whether PDE4-mediated reversal of cognitive impairment in mouse model of AD is related to HPA axis and downstream cAMP-dependent pathway. The present study investigated the effects of PDE4 inhibitor rolipram on Aβ1-42-induced cognitive dysfunction and its underlying mechanisms. The step-down passive avoidance (PA) and Morris water-maze (MWM) tests were conducted 1 week (1 W), 2 months (2 M), and 6 months (6 M) after intracerebroventricular microjection (i.c.v.) of Aβ1-42. The results suggested that memory impairment emerged as early as 1 W, peaked at 2 M, and lasted until 6 M after injection. Chronic treatment with rolipram (0.1, 0.5, 1.0 mg/kg/d, i.p.) for 2 weeks (i.e., treatment started at 1.5 months after Aβ1-42 microinjection) dose-dependently improved memory performance in both MWM and PA tests. Moreover, rolipram reversed the Aβ-induced increases in serum corticosterone (CORT), corticotropin-releasing factor, and glucocorticoid receptors (CRF-R and GR) levels, whereas it decreases in brain-derived neurotropic factor (BDNF) and the ratio of pCREB to CREB expression. These effects of rolipram were prevented by pre-treatment with PKA inhibitor H89. The findings indicated that the protective effects of rolipram against Aβ1-42-induced memory deficits might involve HPA axis and cAMP-CREB-BDNF signaling.

The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is found to have antidepressant-like effects through regulating serotonergic and noradrenergic function. The present study examined the synergistic effect of low doses of FA combined with subthreshold dose of piperine, a bioavailability enhancer, on depression-like behaviors in mice, and investigated the possible mechanism. The administration of FA, even in the highest dose tested, reduced immobility time by 60 % in the tail suspension and forced swimming tests (TST and FST) in mice when compared to control. The maximal antidepressant-like effect of FA was obtained with 200 mg/kg. In addition, piperine only produced a weak antidepressant-like effect in the TST and FST. However, the evidence from the interaction analysis suggested a synergistic effect when low doses of FA were combined with a subthreshold dose of piperine. Further neurochemical evidence such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and measurements of monoamine oxidase activity also supported a synergistic effect of FA and piperine in the enhancement of monoaminergic function. This finding supports the concept that the combination strategy might be an alternative therapy in the treatment of psychiatric disorders with high efficacy and low side effects.

The two multiple-antibiotic resistance (Mar) phenotypes (n = 8, respectively) and susceptible isolates (n = 4) of Shigella flexneri from China were characterized involving the efflux pump AcrAB-TolC. The accumulation of ciprofloxacin, acrAB-tolC PCR, and levels of mRNA with northern blots were performed in three groups. Sequencing of acrAB-tolC was performed in selected isolates. An efflux inhibition was performed with Phe-Arg-beta-naphthylamide. The accumulation of ciprofloxacin at steady state in susceptible isolates was significantly higher than that in the two Mar groups (p < 0.05). The level of accumulation in the Mar strains was increased upon the addition of the protonophore carbonyl cyanidem-chlorophenylhydrazone. The expression level of acrA mRNA in the Mar isolates was significantly higher than that in the susceptible isolates (p < 0.05). Mar strain H26 had a single-nucleotide substitution in locus 322(G-->T) of acrA, and Mar 0008 in locus 171(C-->A). The susceptible strain N15 had a base deletion in locus 36 (C) of tolC gene. The role of the inhibitors of efflux pumps was significant in some isolates with the high expression of Mar pump genes. In conclusion, overexpression of acrA gene leads to Mar in clinical isolates of S. flexneri, and ciprofloxacin acquired susceptible to S. flexneri with Phe-Arg-beta-naphthylamide.