Enrichment of milk antioxidant activity by dietary supplementation of red clover isoflavone in cows and its improvement on mice intestinal health.

Red clover (Trifolium pratense) isoflavone was supplemented to dairy cows, and antioxidant capacity of milk was assessed. Treated cows increased the activities of antioxidant enzymes, reduced production of oxidation products, and enhanced the concentrations of vitamin E and vitamin C. Moreover, milk fatty acid profile was positive influenced by 8 g/kg red clover isoflavone, with changes in the lower saturated and higher unsaturated fatty acids. We further demonstrated the efficacy of antioxidant capacity of milk in mice, found that milk from cows feeding red clover isoflavone increased the expressions of antioxidant enzymes, and alleviated lipopolysaccharide (LPS)-stimulated tissue damage of duodenum and jejunum, which was related to upregulated metabolism pathways of carbohydrate, lipid, and amino acid, as well as downregulated inflammatory related pathways. Together, dietary supplementation of red clover isoflavone is an effective way to improve milk antioxidant capacity, providing a natural strategy for developing functional foods.

A Novel Urease Inhibitor of Ruminal Microbiota Screened through Molecular Docking.

Inhibition of the urease activity of ruminal microbiota is not only beneficial for increasing dietary and endogenic urea-N utilization efficiency in ruminants but also might be applicable for the preservation of nitrogen fertilizer in soil and treatment of gastrointestinal and urinary tract infections caused by ureolytic bacteria. To discover urease inhibitors to efficiently target ruminal microbiota, the identified ruminal microbial metagenomic urease gene was used to construct a homology model to virtually screen urease inhibitors from the ChemDiv database by molecular docking. The GMQE and QMEAN values of the homology model were 0.85 and -0.37, respectively, indicating a good model quality. The inhibition effect of the screened urease inhibitor for ruminal urea degradation was assessed by ruminal microbial fermentation in vitro. The toxic effect of the candidate inhibitor was performed using gut Caco-2 cells in vitro. The results showed that compound 3-[1-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-1H-pyrrol-2-yl] propanoic acid (ChemDiv_ID: 6238-0047, IC50 = 65.86 µM) was found to be the most effective urease inhibitor among the candidate compounds. Compound 6238-0047 significantly lowered the amount of urea degradation and ammonia production in ruminal microbial fermentation. The 24 h degradation rate of compound 6238-0047 in ruminal microbial fermentation was 3.32%-16.00%. In addition, compound 6238-0047 (10-100 µM) had no significant adverse effect on the cell viability of Caco-2 cells. Molecular docking showed that compound 6238-0047 could interact with Asp359 in the active site and Cys318 in the flap region by the hydrogen bond and Pi-Alkyl interaction, respectively. Compound 6238-0047 could be used as a novel inhibitor for decreasing the urease activity of ruminal microbiota.

Rescue fecal microbiota transplantation for antibiotic-associated diarrhea in critically ill patients.

BACKGROUND: Antibiotic-associated diarrhea (AAD) is a risk factor for exacerbating the outcome of critically ill patients. Dysbiosis induced by the exposure to antibiotics reveals the potential therapeutic role of fecal microbiota transplantation (FMT) in these patients. Herein, we aimed to evaluate the safety and potential benefit of rescue FMT for AAD in critically ill patients. METHODS: A series of critically ill patients with AAD received rescue FMT from Chinese fmtBank, from September 2015 to February 2019. Adverse events (AEs) and rescue FMT success which focused on the improvement of abdominal symptoms and post-ICU survival rate during a minimum of 12 weeks follow-up were assessed. RESULTS: Twenty critically ill patients with AAD underwent rescue FMT, and 18 of them were included for analysis. The mean of Acute Physiology and Chronic Health Evaluation (APACHE) II scores at intensive care unit (ICU) admission was 21.7 ± 8.3 (range 11-37). Thirteen patients received FMT through nasojejunal tube, four through gastroscopy, and one through enema. Patients were treated with four (4.2 ± 2.1, range 2-9) types of antibiotics before and during the onset of AAD. 38.9% (7/18) of patients had FMT-related AEs during follow-up, including increased diarrhea frequency, abdominal pain, increased serum amylase, and fever. Eight deaths unrelated to FMT occurred during follow-up. One hundred percent (2/2) of abdominal pain, 86.7% (13/15) of diarrhea, 69.2% (9/13) of abdominal distention, and 50% (1/2) of hematochezia were improved after FMT. 44.4% (8/18) of patients recovered from abdominal symptoms without recurrence and survived for a minimum of 12 weeks after being discharged from ICU. CONCLUSION: In this case series studying the use of FMT in critically ill patients with AAD, good clinical outcomes without infectious complications were observed. These findings could potentially encourage researchers to set up new clinical trials that will provide more insight into the potential benefit and safety of the procedure in the ICU. TRIAL REGISTRATION: ClinicalTrials.gov, Number NCT03895593 . Registered 29 March 2019 (retrospectively registered).

Comparison of Endoscopic and Open Resection for Small Gastric Gastrointestinal Stromal Tumor.

The National Comprehensive Cancer Network recommends conservative follow-up for gastric gastrointestinal stromal tumors (GISTs) less than 2 cm. We have previously reported that the mitotic index of 22.22% of small gastric GISTs exceeded 5 per 50 high-power fields and recommended that all small gastric GISTs should be resected once diagnosed. The aim of the present study is to compare the safety and outcomes of endoscopic and open resection of small gastric GISTs. From May 2010 to March 2014, a total of 90 small gastric GIST patients were enrolled in the present study, including 40 patients who underwent surgical resection and 50 patients who underwent endoscopic resection. The clinicopathological characteristics, resection-related factors, and clinical outcomes were recorded and analyzed. The clinicopathological characteristics were comparable between the two groups except for tumor location and DOG-1 expression. Compared with the surgical resection group, the operation time was shorter (P = .000), blood loss was less (P = .000), pain intensity was lower (P < .05), duration of first flatus and defecation was shorter (P < .05), and medical cost of hospitalization was lower (P = .027) in the endoscopic resection group. The complications and postoperative hospital stay were comparable between the two groups. No in situ recurrence or liver metastasis was observed during follow-up. Endoscopic resection of small gastric GISTs is safe and feasible compared with surgical resection, although perforation could not be totally avoided during and after resection. The clinical outcome of endoscopic resection is also favorable.