Responses of bacterial and three sub-microeukaryote communities in the water of white shrimp Penaeus vannamei aquaculture ponds in two polyculture models.

Polyculture operations in freshwater aquaculture ponds can disrupt microbial communities. High-throughput sequencing was used to assess the impact of polyculture operations on bacterial and three sub-microeukaryote communities (fungi, zooplankton, and eukaryotic phytoplankton) in Penaeus vannamei aquaculture ponds containing oriental river prawns and giant freshwater prawns, respectively. The results showed that the bacterial community was less sensitive than the microeukaryote communities to both the polyculture activity and environmental variations. The polyculture of giant freshwater prawns rather than oriental river prawns was the primary factor affecting the beta diversity of the three sub-microeukaryote communities. This may be due to the larger biomass of the polyculture varieties of giant freshwater prawns compared with oriental river prawns. The polyculture activity of giant freshwater prawns with a higher density and that of oriental river prawns with a lower density increased the stochasticity of the community assembly of the three sub-microeukaryote communities. It also affected the topological properties of the microbial communities, including greater correlations between ecosystem elements, and reducing the correlations among zooplanktons. The eukaryotic phytoplankton was the only microbial community that could also be explained by nutrient variation (mainly the total nitrogen). This highlights the potential role of the eukaryotic phytoplankton as a suitable indicator of the effects of nutrient input into ecosystems.

Madecassic acid alleviates colitis-associated colorectal cancer by blocking the recruitment of myeloid-derived suppressor cells via the inhibition of IL-17 expression in γδT17 cells.

INTRODUCTION: Madecassic acid (MA), a triterpene compound isolated from Centella Asiatica herbs, has previously been shown to attenuate colitis induced by DSS in mice. In the present study, we address whether and how MA ameliorates colitis-associated colorectal cancer (CAC), which accounts for a considerable proportion of colorectal cancer. METHODS: CAC was induced by AOM/DSS in mice, and MA was administered orally once a day. To identify the source cells of IL-17 and the target cells for MA reducing the expression of IL-17 in the colons of CAC mice, single-cell suspensions were prepared from the colons of CAC mice and analyzed by flow cytometry. An adoptive transfer experiment was performed to verify the importance of the decreasing γδT17 cell population in the anti-CAC effect of MA. RESULTS: Oral administration of MA reduced the burden and incidence of tumors in the CAC mice. MA decreased the number of MDSCs in the colon tissues of CAC mice and ameliorated anti-tumor immune responses. MA could prevent the migration of MDSCs by inhibiting the activation of γδT17 cells and the expression of chemokines. The population of activated-γδT17 cells in the tumor microenvironment of CAC mice positively correlated with the number of MDSCs and tumors as well as tumor load. Moreover, the anti-CAC effect of MA was significantly counteracted by the adoptive transfer of γδT17 cells. CONCLUSIONS: MA alleviates CAC by blocking the recruitment of MDSCs to increase the population of anti-tumor immune cells in tumor microenvironment via inhibition of the activation of γδT17 cells.

Tetrandrine attenuates intestinal epithelial barrier defects caused by colitis through promoting the expression of Occludin via the AhR-miR-429 pathway.

The elevated intestinal permeability due to mucosal barrier defects is not only secondary to inflammatory bowel disease but also precedes enteritis. Tetrandrine, a bisbenzyl isoquinoline alkaloid isolated from the dried roots of Stephamis tetlandra S. Moor, was previously demonstrated to ameliorate colitis induced by dextran sulfate sodium (DSS) in mice. Here, we investigate whether and how tetrandrine protects against the disruption of the intestinal epithelial barrier under colitis condition. The data show that oral administration of tetrandrine significantly counteracted the increase of intestinal permeability in DSS-treated mice, enhanced the mRNA and protein expression of Occludin and Claudin1 in the colon, but hardly affected the expression of ZO-1 and Mucin2. In vitro, tetrandrine treatment rescued the decrease of monolayer transmembrane resistance and the increase of epithelial cell permeability induced by TNF-α, upregulated the expression of Occludin, and downregulated the expression of Claudin1 but did not affect the expression of ZO-1. The siRNA of Occludin largely weakened the protective effect of tetrandrine on the epithelial barrier function in Caco-2 cells. MiR-429 mimic obviously counteracted the upregulation of tetrandrine on the expression of Occludin and the amelioration on epithelial barrier defects, in contrast, miR-429 inhibitor showed the opposite effects. The antagonist (CH223191) and siAhR of aryl hydrocarbon receptor (AhR) nearly completely diminished the effects of tetrandrine, including inhibition of the miR429 expression, the upregulation of Occludin expression, and amelioration of intestinal epithelial barrier defects in Caco-2 cells. In colitis mice, CH223191 significantly weakened the protective effect of tetrandrine on colitis and intestinal mucosal barrier and diminished the downregulation on miR-429 expression and the promotion on Occludin expression in the colon. In summary, tetrandrine can attenuate the intestinal epithelial barrier defects in colitis through promoting Occludin expression via the AhR/miR-429 pathway, and it might be used to treat colitis as a barrier protector.

Synthesis of norisoboldine derivatives and bioactivity assay for inducing the generation of regulatory T cells.

In this study, we used chemical modification to improve the pharmacological activity of norisoboldine (NOR). A new NOR-benzoic acid derivative, named DC-01, showed more potent induction of Treg cell differentiation than NOR. The in vitro effective concentration of DC-01 (1 µM) is about an order of magnitude lower than that of NOR (10 µM). DC-01 (28, 56 mg/kg) showed better amelioration of dextran sodium sulfate-induced colitis in mice than NOR (20, 40 mg/kg), and DC-01 (28 mg/kg) increased the number of Treg cells slightly better than NOR (20 mg/kg). In summary, DC-01 exerts more potent induction of Treg cell generation, which might be a candidate drug for the treatment of inflammation- and immune-related diseases.