ADT-OH improves intestinal barrier function and remodels the gut microbiota in DSS-induced colitis / 医学前沿

Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H2S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H2S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H2S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.

Extracellular signal regulated kinase 5 promotes cell migration, invasion and lung metastasis in a FAK-dependent manner

This study was designed to evaluate ERK5 expression in lung cancer and malignant melanoma progression and to ascertain the involvement of ERK5 signaling in lung cancer and melanoma. We show that ERK5 expression is abundant in human lung cancer samples, and elevated ERK5 expression in lung cancer was linked to the acquisition of increased metastatic and invasive potential. Importantly, we observed a significant correlation between ERK5 activity and FAK expression and its phosphorylation at the Ser

Relationship between intestinal permeability and expression of intestinal trefoil factor mRNA in mice after total body irradiation / 中华放射医学与防护杂志

Objective To investigate the change of the intestinal permeability,the expression level of intestinal trefoil factor (ITF) mRNA and the relationship between them after total body irradiation (TBI),and explore the effect of TBI on the development of intestinal permeability and the expression level of ITF mRNA.Methods Twenty two BALB/c mice were randomly divided into 4 equal groups: 3 groups at 4,8 and 12 d after TBI with the total dose of 8.0 Gy and the dose rate of 1.0 Gy/min respectively,and a control group.Lactulose (L) and mannitol (M) were perfused into the esophagus before the experiment and urine samples were collected.Liquid chromatography was used to measure the L/M excretion ratio in the urine samples collected 4,8,and 12 days after the TBI.And then the mice were killed with their intestine were taken out.The expression of ITF mRNA in the jejunum tissue was detected by real-time fluorescence quantitative PCR.Results The urine L/M ratio levels of the groups 4,8 and 12 days after TBI were (0.5092 ± 0.0352),(0.7174 ± 0.0116),and (0.7295 ± 0.0533) respectively,all significantly higher than that of the control group [(0.2908 ± 0.0533),F = 321.47,P ＜ 0.05].The ITF mRNA expression levels of groups 4,8 and 12 days after TBI were (0.78612 ±0.1428),(0.2521 ±0.1223),and (0.2306 + 0.0221 ) respectively,all significantly lower than that of the control group [( 1.3498 + 0.0476),F = 235.71 ,P ＜ 0.05].The urine L/M ratio was significantly negatively correlated with the expression of ITF mRNA in all TBI groups (r = - 0.985,P ＜ 0.01 ).Conclusions The intestinal permeability increases and the expression level of ITF mRNA decreases after TBI.The urine L/M ratio is negatively correlated with the expression level of ITF mRNA after TBI.ITF is involved in protection against intestinal permeability induced by TBI.

Effect of macrophage on IL-2 production / 中国免疫学杂志

The effect of macrophage on IL-2 production by tonsillar T cells was investigated. The human tonsillar mononuclear cells were purified by a two-step procedure including depletion of plastic-adherent cel1s and rosetting with SRBC. The purity of Enriched T cel1s (ETC) was 98%. It was found that IL-2 production was greatly decreased in ETC by removing adherent cells and could be completely restored by replacing the adherent cells. The IL-2 production in the same extent was induced in ETC when TPA was substituted for adherent cells and the synergistic effect of TPA and macrophages greatly augmented the IL-2 secretion by ETC. Incubation of ETC with high concentration of PHA or ConA alone resultes in efficient IL-2 production. These results indicated that IL-2 production was macrophage dependent.