Understanding the Genetic Basis of Immune Responses to Enterotoxigenic Bacteroides fragilis Infection

Bacteria have been proposed to contribute to the initiation and progression of tumorigenesis. The enterotoxigenic strain of a commensal bacterium in the human gut, enterotoxigenic Bacteroides fragilis (ETBF) induces distal colon adenomas in the ApcMin/+ mouse model by causing a tumorigenic inflammatory cascade and, thus, ETBF-colonized ApcMin/+mice serve as a model for colorectal cancer (CRC). Meanwhile, human CRC is a highly heterogeneous disease with subtypes defined by genetic, histologic, and immunologic features. It is not currently well understood if or how host genetic factors other than Apc mutations modify ETBF-driven tumorigenesis. We have previously shown that upon ETBF infection, mice carrying a common oncogenic mutation in the MAPK signaling component BRAF (BRAFV600E) display a striking accumulation of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. The addition of BRAFV600E, but not a closely related activating mutation in the MAPK pathway KrasG12D, to the ApcMin/+ model results in the formation of pathologically distinct colonic tumors in a new mid-proximal locus. Here we examine the immune responses against ETBF infection in mice carrying only KrasG12D or BRAFV600E. We show that genotypes have no effects on ETBF colonization. Our preliminary data reveal that BRAFV600E and KrasG12D mutations in colonic epithelium result in distinct phenotypes upon ETBF challenge. Specifically, BRAFV600E leads to more DNA damage despite less severe mucosal injury and inflammatory infiltrates compared with KrasG12D. Furthermore, differentially regulated gene expression in the distal colon is driven by genotype and KrasG12D, but not BRAFV600E, results in robust IL-22 expression in the immune microenvironment. Surprisingly, the recruitment of MDSCs does not differ between genotypes. Together, our results indicate that, by interacting with oncogenic mutations, commensal organisms play roles in defining the immune microenvironment and may contribute to the shaping of CRC subtypes

Effects of the Dietary Replacement of Soybean Oil with Rubber Seed Oil on the Growth Performance, Carcass Trait, and Status of Lipid Metabolism in Pekin Ducks

The objective of this study is to determine the effects of the dietary replacement of soybean oil (SO) with rubber seed oil (RSO) on the growth performance, carcass trait, and lipid metabolism in Pekin ducks. A total of 160 1-day-old Pekin ducks were randomly allocated to four experimental treatments and fed diets with different ratios of SO to RSO as follows: 3:0 (control), 2:1, 1:2, and 0:3. Dietary RSO supplementation had no effect on their growth performance; however, it significantly decreased the yield of abdominal fat (p p p p p FABP1, ME1, SREBP1c, FASN, DGAT2, and HMGCR (p ABCA1 gene (p < 0.05) in the liver of the ducks. In conclusion, dietary RSO supplementation reduced fat deposition and enhanced n-3 PUFA levels without affecting the growth performance of Pekin ducks

Secretome profiling identifies neuron-derived neurotrophic factor as a tumor-suppressive factor in lung cancer

© 2019, American Society for Clinical Investigation. Clinical and preclinical studies show tissue-specific differences in tumorigenesis. Tissue specificity is controlled by differential gene expression. We prioritized genes that encode secreted proteins according to their preferential expression in normal lungs to identify candidates associated with lung cancer. Indeed, most of the lung-enriched genes identified in our analysis have known or suspected roles in lung cancer. We focused on the gene encoding neuron-derived neurotrophic factor (NDNF), which had not yet been associated with lung cancer. We determined that NDNF was preferentially expressed in the normal adult lung and that its expression was decreased in human lung adenocarcinoma and a mouse model of this cancer. Higher expression of NDNF was associated with better clinical outcome of patients with lung adenocarcinoma. Purified NDNF inhibited proliferation of lung cancer cells, whereas silencing NDNF promoted tumor cell growth in culture and in xenograft models. We determined that NDNF is downregulated through DNA hypermethylation near CpG island shores in human lung adenocarcinoma. Furthermore, the lung cancer–related DNA hypermethylation sites corresponded to the methylation sites that occurred in tissues with low NDNF expression. Thus, by analyzing the tissue-specific secretome, we identified a tumor-suppressive factor, NDNF, which is associated with patient outcomes in lung adenocarcinoma