Dietary polysaccharides provide various beneficial effects for our health. We investigated the protective effects of wild jujube (Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou) sarcocarp polysaccharides (WJPs) against experimental inflammatory bowel disease (IBD) by enabling enhanced intestinal barrier function. Colitis was induced in rats by the intrarectal administration of TNBS. We found that WJPs markedly ameliorated the colitis severity, including less weight loss, decreased disease activity index scores, and improved mucosal damage in colitis rats. Moreover, WJPs suppressed the inflammatory response via attenuation of TNF-α, IL-1β, IL-6 and MPO activity in colitis rats. And then, to determine the effect of WJPs on the intestinal barrier, we measured the effect of WJPs on the transepithelial electrical resistance (TER) and FITC-conjugated dextran permeability in Caco-2 cell stimulation with TNF-α. We further demonstrated that the alleviation of WJPs to colon injury was associated with barrier function by assembly of tight junction proteins. Moreover, the effect of WJPs on TER was eliminated by the specific inhibitor of AMPK. AMPK activity was also up-regulated by WJPs in Caco-2 cell stimulation with TNF-α and in colitis rats. This study demonstrates that WJPs protect against IBD by enabling enhanced intestinal barrier function involving the activation of AMPK.

•MWNTs-ZnO/chitosan composites were first produced to modify the screen-printed electrode.•The modified electrode was employed to simultaneously detect norepinephrine and serotonin with low detection limits.•The lever of norepinephrine and serotonin in rat cerebrospinal fluid with the modified electrode was first examined.A new electrochemical sensor for simultaneous determination of norepinephrine (NE) and serotonin (5-HT) was fabricated. The electrochemical behavior of NE and 5-HT were investigated using CV and SWV at the MWNTs-ZnO/chitosan composites modified screen-printed electrode (MWNTs-ZnO/chitosan SPE). The results showed that the current responses of NE and 5-HT greatly enhanced due to the high catalytic activity of composites. The peak potentials of NE and 5-HT were separated at about 90 mV and 280 mV, respectively. The peak currents of NE and 5-HT were linearly dependent on their concentrations in the range of 0.5–30 μM and 0.05–1 μM, with the limit of detection of 0.2 μM and 0.01 μM, respectively. The modified electrode can be stored stably for at least 3 month at 4 °C in a refrigerator. Furthermore, the modified electrode was successfully applied to detect the level of NE and 5-HT in rat cerebrospinal fluid (CSF) with excellent selectivity and sensitivity.

•This is the first method for large-scale testing of mycotoxins in various matrices.•High-throughput was achieved by using PLE pre-treatment.•The limits of detection defined as CCα varied from 0.01 μg/kg to 0.69 μg/kg.•It can be used for seeking a link between mycotoxin exposure and diseases.•It could be a useful tool in toxicokinetic and toxicological studies.A high-throughput method for the determination of 28 mycotoxins involving pressurised liquid extraction (PLE) coupled with liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) has been optimised and validated for determination in various biological fluids and tissues of human and laboratory animals. High-throughput analysis was achieved using PLE pre-treatment and without the need for any cleanup. The extraction solvent was acetonitrile/water/acetic acid (80/19/1, v/v/v). The static extraction time was 5 min. The extraction pressure and temperature were 1500 psi and 140 °C, respectively. The flush volume was 60%. The limits of detection, which were defined as CCα, varied from 0.01 μg/kg (μg/L) to 0.69 μg/kg (μg/L). The recoveries of spiked samples from 0.20 μg/kg (μg/L) to 2 μg/kg (μg/L) ranged from 71% to 100.5% with relative standard deviations of less than 17.5%, except FB1 and FB2 recoveries, which were lower than 60%. The method was successfully applied in real samples, and the data indicate that this technique is a useful analytical method for the determination of mycotoxins from humans and animals. To the best of our knowledge, this method is the first for the large-scale testing of multi-class mycotoxins in all types of biological fluids and tissues that uses PLE and HPLC–MS/MS.

•Anthocyanins (ACs) from red cabbage inhibited Irinotecan-induced mucositis in mice.•ACs protected the integrity of epithelial cells in vivo and in vitro.•ACs regulated autophagy through suppressing the mTOR pathway.Intestinal mucositis is a common side effect of Irinotecan (CPT-11). Anthocyanins (ACs) from red cabbage against CPT-11-induced mucositis were studied. Mice were given CPT-11 (75 mg/kg, i.p. for 4 days) and treated with ACs (50, 100 mg/kg, i.g. for 7 days). On day 8, diarrhea and leukocyte count in blood were assessed. Samples of intestine were obtained for morphometric analysis, myeloperoxidase (MPO), TBARS and GSH assay. The effects of ACs on cytoprotection and intestinal permeability were studied in Caco-2 cells. ACs effectively reversed the signs of intestinal injury, including MPO activity, length of ileum and colon, leukopenia, intestinal architecture, and quantity of ileum mucus. In vitro, pretreatment with ACs enhanced transepithelial electrical resistance (TER) and the expression of ZO-1. Furthermore, the protective effects of ACs were associated to modulate autophagy through mTOR pathway. In conclusion, ACs from red cabbage are candidate for supplementary therapy of CPT-11-induced mucositis.

•Tramiprosate dose-dependently provides neuroprotection against ischemic stroke.•The therapeutic time window of tramiprosate (50 mg/kg) is up to 6 h after MCAO.•Tramiprosate confers functional recovery of rats following ischemic stroke.•Tramiprosate treatment could disrupt the PSD95–nNOS interaction.•Tramiprosate inhibits the translocation of nNOS from cytosol to membrane.Tramiprosate, a small aminosulphonate compound, is present in various species of red marine algae. In this study, we examined whether tramiprosate protects neurons and improves functional recovery following ischemic stroke in rats subjected to the intraluminal filament model of MCAO and further explored the underlying mechanisms. Tramiprosate dose-dependently reduced the infarct volume after MCAO, and the therapeutic time window of tramiprosate (50 mg/kg) for cerebral ischemia was at least 6 h. Moreover, functional assays and histochemical staining were performed. Significant neurological functional recovery was found after tramiprosate (50 mg/kg) administration in all three functional assays performed (modified neurological severity score, foot-fault test and adhesive-removal somatosensory test). Tramiprosate significantly attenuated OGD- or NMDA-induced injury in NGF-differentiated PC12 cells and primary cortical neurons. Furthermore, the neuroprotective effect of tramiprosate was partially blunted by the NMDA receptor (NMDAR) antagonist MK801 both in vitro and in vivo, indicating that tramiprosate might confer neuroprotection against stroke via the NMDAR. Based on co-immunoprecipitation and western blotting, tramiprosate decreased the intensity of the association between nNOS and PSD95, and tramiprosate also inhibited the translocation of nNOS from the cytosol to the membrane without affecting the total nNOS expression level both in vitro and in vivo. In conclusion, tramiprosate dose-dependently provides neuroprotection in vitro and in vivo against ischemic stroke, and the neuroprotective effect of tramiprosate may be partially attributed to disruption of the interaction between PSD95 and nNOS and inhibition of nNOS translocation.

Alpha-subtype protein kinase C (PKCα) is closely related to cardiovascular disease. Ritonavir (RTV), which is a human immunodeficiency virus (HIV) protease inhibitor, can induce atherosclerosis in a PKC-dependent manner. However, it remains unclear how RTV acts on PKCα to induce pathological phenotypes. In this study, we obtained mouse peritoneal macrophages from adult female Kunmin mice. The results of Oil Red O staining and immunofluorescence using confocal laser scanning microscope demonstrated that RTV could induce foam cell formation and plasma membrane translocation of PKCα like phorbol-12-myristate-13-acetate (PMA, a PKC activator). Computational modeling also exhibited similar docking of RTV and PMA to PKCα and similar patterns of hydrophobic interaction and hydrogen bond formation. Further in vitro kinase activity studies revealed that RTV could elevate PKC activity. These data provided insight into the PKC-dependent induction of atherosclerosis and useful information for more in-depth toxicity research of HIV protease inhibitor (PI). In addition, western blot analysis proved RTV also up-regulate PKCα expression, which may be related to its influence on estrogen responsiveness in target cells and needs further prove.Highlights► We obtained mouse peritoneal macrophages and examined the effect of RTV on PKCα. ► RTV could induce foam cell formation and plasma membrane translocation of PKCα like PMA. ► RTV and PMA were similar docking to PKCα. ► RTV could activate PKC activity and up-regulate PKCα expression.