Wheat peptides inhibit the activation of MAPK and NF-κB inflammatory pathways and maintain epithelial barrier integrity in NSAID-induced intestinal epithelial injury.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) has negative effects on the gastrointestinal tract, but the proton pump inhibitors currently in use only protect against gastrointestinal disease and may even make NSAID-induced enteropathy worse. Therefore, new approaches to treating enteropathy are required. This study aimed to investigate the protective effect of wheat peptides (WPs) against NSAID-induced intestinal damage in mice and their mechanism. Here, an in vivo mouse model was built to investigate the protective and reparative effects of different concentrations of WPs on NSAID-induced intestinal injury. WPs ameliorated NSAID-induced weight loss and small intestinal tissue damage in mice. WP treatment inhibited NSAID-induced injury leading to increased levels of oxidative stress and expression levels of inflammatory factors. WPs protected and repaired the integrity and permeability injury of the intestinal tight junction induced by NSAIDs. An in vitro Caco-2 cell model was built with lipopolysaccharide (LPS). WP pretreatment inhibited LPS-induced changes in the Caco-2 cell permeability and elevated the levels of oxidative stress. WPs inhibited LPS-induced phosphorylation of NF-κB p65 and mitogen-activated protein kinase (MAPK) signaling pathways and reduced the expression of inflammatory factors. In addition, WPs increased tight junction protein expression, which contributed to improved intestinal epithelial dysfunction. Our results suggest that WPs can ameliorate NSAID-induced impairment of intestinal barrier functional integrity by improving intestinal oxidative stress levels and reducing inflammatory factor expression through inhibition of NF-κB p65 and MAPK signaling pathway activation. WPs can therefore be used as potential dietary supplements to reduce NSAID-induced injury of the intestine.

Coronary artery calcium and cystatin C for risk stratification of MACCEs and all-cause death in symptomatic patients.

OBJECTIVES: The aim of this study was to examine the independent and joint associations of baseline coronary artery calcium score (CACS) and cystatin C (Cys-C) with the risk of major adverse cardiac and cerebrovascular events (MACCEs) and all-cause death in symptomatic populations. METHODS: The study included 7140 patients with symptom of chest pain who underwent cardiac computerized tomography examinations to measure CACS. All of them had serum Cys-C results. Endpoints were set for MACCEs and all-cause death events. RESULTS: A total of 7140 participants were followed for a median of 1106 days. A total of 305 patients had experienced MACCEs and 191 patients had experienced all-cause death. CACS ≥ 100 and Cys-C ≥ 0.995 mg/L were independently associated with an increased risk of MACCEs (adjusted hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.15-1.85; p = .002 and adjusted HR: 1.57; 95% CI: 1.24-2.00; p < .001, respectively). Compared with CACS < 100 and Cys-C < 0.995 mg/L patients, CACS ≥ 100 and Cys-C ≥ 0.995 mg/L patients had the highest risk of MACCEs and all-cause death (adjusted HR: 2.33; 95% CI: 1.64-3.29; p < .001 and adjusted HR: 2.85; 95% CI: 1.79-4.55; p < .001, respectively). Even in patients with CACS < 100, Cys-C ≥ 0.995 mg/L was also associated with a higher risk of MACCEs and all-cause death than Cys-C < 0.995 mg/L (adjusted HR: 1.76; p = .003 and adjusted HR: 2.02; p = .007, respectively). CONCLUSIONS: The combined stratification of CACS and Cys-C showed an incremental risk of MACCEs and all-cause death, reflecting complementary prognostic value. Our results support the combination of the two indicators for risk stratification and event prediction.

[Chemoinformatics study on antibacterial activity of traditional Chinese medicine compounds].

OBJECTIVE: The structure-activity relationship between traditional Chinese medicine (TCM) compounds and antibacterial activity was studied by chemoinformatics approach. METHOD: Cytoscape and its plug-in ChemViz were applied to compute the 2D chemical structure similarity and topological parameter TPSA (topological molecular polar surface area), which measures cell permeability of chemicals, between TCM compounds and clinical antibacterials. The overall degree of structure similarity was then calculated and represented by E-value for the eight categories of TCM compounds and the known antibacterials. RESULT: Our results indicated that flavonoids showed good structural similarity with antibacterials and appropriate cell permeability, compared with those of the TCM compounds of the other categories. As flavonoids were featured by good drug safety, it suggested that they can be regarded as the preferred lead compounds skeleton structure source for further antibacterials synthesis. CONCLUSION: The application of chemoinformatics helps explore the structure-activity relationship between TCM compounds and the antibacterial activity and search for suitable antibacterial lead compounds skeleton structure source.