New evidence has emerged in recent years to suggest a strong link between the human gut microbiota, its metabolites, and various physiological aspects of hosts along with important pathophysiological dimensions of diseases. The research indicates that the gut microbiota can facilitate metabolite production in two ways: first, the resident species of the gut microbiota use the amino acids produced from food or the host as elements for protein synthesis, and second, conversion or fermentation are used to drive nutrient metabolism. Additionally, the gut microbiota can synthesize several nutritionally essential amino acids de novo, which is a potential regulatory factor in amino acid homeostasis. The primary objective of this review is to summarize the current literature relating to the ways in which microbial amino acids contribute to host amino acid homeostasis.

A mononuclear iron-sulfur center, capable of reversible electron transfer, has been introduced into thioredoxin, a protein devoid of such sites, using an automated, structure-based design algorithm. One of the sites predicted by the Dezymer computer program to introduce a tetrahedral tetrathiolate iron center included the intrinsic Cys32-Cys35 disulfide of wild-type thioredoxin and two additional mutants, Trp28Cys and Ile75Cys, thereby converting a disulfide into a metal-based redox center. This designed protein forms a 1:1 monomeric complex with FeIII, whose electronic absorption and EPR spectra closely resemble those of the rubredoxins, as intended. CoII spectra provided further confirmation of tetrahedral tetrathiolate metal coordination. The designed protein is capable of undergoing successive cycles of oxidation and reduction. The computer-generated design only took into account the geometry of the primary coordination shell around the metal. We have therefore demonstrated that simple geometrical considerations can be sufficient to reproduce the dominant electronic structure and reactivity of a simple metal-based redox center.

BackgroundAccumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As >90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma.MethodsThe Apcmin/+ mice gavage with phosphate-buffered saline (PBS), feces from healthy controls or CRC patients after antibiotic cocktails. The intestinal tissues were isolated for histopathology, western blotting, and RNA-seq. The microbiota of feces and short-chain fatty acids (SCFAs) were analysed by 16S rDNA Amplicon Sequencing and gas chromatography.FindingsThe Apcmin/+mice gavaged by feces from CRC patients had more intestinal tumours compared with those fed with feces from healthy controls or PBS. Administration of feces from CRC patients increased tumour proliferation and decreased apoptosis in tumour cells, accompanied by impairment of gut barrier function and up-regulation the pro-inflammatory cytokines profile. The up-regulated the expression of β-catenin and cyclinD1 further indicating the activation of Wnt signalling pathway. The abundance of pathogenic bacteria was increased after FMT, while producing SCFAs bacteria and SCFAs production were decreased.InterpretationGut microbiota of CRC patients disrupted intestinal barrier, induced low-grade inflammation and dysbiosis. The altered gut microbiota enhanced the progression of intestinal adenomas in Apcmin/+mice, suggesting that a new strategy to target gut microbiota against CRC could be noted.FundThe study was supported by the , , and .

The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids–microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids–microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.

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Aim:To investigate whether the transfer of the IL-37b gene, a newly identified inhibitor of both innate and adaptive immunity, could improve the therapeutic efficacy of mesenchumal stromal cells (MSCs) in inflammatory bowel disease (IBD).Methods:The expression of IL-37 in biopsied specimens of the patients with active ulcerative colitis (UC) was detected using RT-PCR and immunohistochemistry. Mice were treated with 3% dextran sulfate sodium (DSS) for 8 days to induce colitis. Before DSS treatment, the mice were injected with MSCs, MSC-eGFP or MSC-IL37b. Their body weight was measured each day, and the colons and spleens were harvested on d 10 for pathological and biochemical analyses.Results:In biopsied specimens of the patients with active UC, the expression of IL-37 was dramatically elevated in inflamed mucosa, mainly in epithelial cells and infiltrating immune cells. Compared to MSC-eGFP or MSCs, MSC-IL37b administration significantly attenuated the body weight and colon length reduction, and decreased the histological score in DSS-induced colitis mice. Furthermore, MSC-IL37b administration increased the percentage of myeloid-derived suppressor cells (MDSCs) among total splenic mononuclear cells as well as the percentage of regulatory T cells (Tregs) among splenic CD4+ T cells in the mice. Moreover, MSC-IL37b administration increased the IL-2+ cells and decreased the IFN-γ+ cells among splenic CD4+ T cells.Conclusion:IL-37 is involved in the pathophysiology of UC. IL-37b gene transfer enhances the therapeutic efficacy of MSCs in DSS-induced colitis mice by inducing Tregs and MDSCs and regulating cytokine production.

ESD appears to be an effective, safe, and feasible treatment for large-size GISTs in the esophagus and stomach.

OBJECTIVE. Subepithelial tumors (SETs) in the stomach are usually considered benign. However, some do have potential for malignant transformation, especially when originating in the muscularis propria (MP). Our study aimed to evaluate the clinical efficacy and safety of endoscopic submucosal dissection (ESD) for gastric SETs originating in MP. MATERIAL AND METHODS. A total of 145 gastric MP SETs in 144 patients were treated by ESD between September 2008 and December 2012. Characteristics of patients and SETs, therapeutic outcomes, pathologic characteristics, complications and follow-up outcomes were evaluated. RESULTS. Among the 144 patients, 104 were female (72.22%) and 40 were male (27.78%), and the mean age was 55.75 ± 11.29 years (range 18-78 years). The mean size of the tumors determined by endoscopic ultrasound (EUS) was 15.14 ± 9.70 mm (range 3-50 mm). En bloc complete resection was achieved in 134 of 145 tumors, giving a complete resection rate of 92.41%. The final histopathologic diagnoses included 52 leiomyomas, 89 gastrointestinal stromal tumors, 3 neurogenic tumors and 1 lipoma. Perforations occurred in 21 patients (14.48%) and were endoscopically repaired with clips or nylon bands. Intraoperative bleeding occurred in seven patients (4.83%) and was corrected with argon plasma coagulation (APC) or hot biopsy forceps. No local recurrence or distant metastasis was detected during a mean follow-up of 19.14 ± 10.29 months (range 3-51 months). CONCLUSIONS. ESD appears to be an effective and safe treatment for gastric SETs originating in MP.