Interactions between the host and gut microbiota can affect gut metabolism. In this study, the individual performances of 252 hens were recorded to evaluate feed efficiency. Hens with contrasting feed efficiencies (14 birds per group) were selected to investigate their duodenal, cecal and fecal microbial composition by sequencing the 16S rRNA gene V4 region. The results showed that the microbial community in the cecum was quite different from those in the duodenum and feces. The highest biodiversity and all differentially abundant taxa between the different efficiency groups were observed in the cecal microbial community with false discovery rate (FDR) <0.05. Of these differentially abundant cecal microbes, Lactobacillus accounted for a greater proportion than the others. The abundances of Lactobacillus and Akkermansia were significantly higher while that of Faecalibacterium was lower (FDR < 0.05) in the better feed efficiency (BFE) group. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis revealed that the functions relating to glycometabolism and amino acid metabolism were enriched in the cecal microbiota of the BFE group. These results indicated the prominent role of cecal microbiota in the feed efficiency of chickens and suggested plausible uses of Lactobacillus to improve the feed efficiency of host.The gastrointestinal tract is the major site of food digestion and nutrient absorption. Cecum is the chief functional section in the distal intestine, and its importance in birds' metabolism has received increasing attention 1,2 . The cecum, which is full of microbial fermentations, plays important roles in preventing pathogen colonization, detoxifying harmful substances, recycling nitrogen and absorbing additional nutrients 3 . The digestibility and the ability to metabolize crude fiber or other nutrients are lower in birds with a cecectomy than in normal birds 4 . In addition, significant absorption of glucose was observed in the cecum 5 , and a higher ability to actively absorb sugars at low concentrations was found in the cecum compared with the jejunum 6 . Located at the beginning of the intestine, the duodenum is crucial for feed digestion and absorption; it has a lower pH than the hindgut and is the region that absorbs most glucose 7 and other nutrients within the small intestine 8,9 . Although the cecum and the duodenum themselves are important, interactions between the gut and commensal microbes may exert a significant influence on the function of the intestine. Previous studies showed that the digestion of uric acid, cellulose, starch and other resistant carbohydrates in the cecum was associated with the cecal microbial members 3,10,11 . In a recent study, numerous oligosaccharide-and polysaccharide-degrading enzyme-encoding genes and several pathways involved in the production of short-chain fatty acids (SCFAs) were observed in the cecal metagenome of the chicken 12 . The SCFAs were produced mainly by microbial fermentation in the hindgut and could be a...

Phytogenic compounds with anti-oxidant and anti-inflammatory properties, such as ginsenoside metabolite compound K (CK) or berberine (BBR), are currently discussed as promising complementary agents in the prevention and treatment of cancer and inflammation. The latest study showed that ginsenoside Rb1 and its metabolites could inhibit TNBS-induced colitis injury. However, the functional mechanisms of anti-inflammation effects of ginsenoside, particularly its metabolite CK are still not clear. Here, using dextran sulfate sodium (DSS)-induced colitis in mice, clinical parameters, intestinal integrity, pro-inflammatory cytokines production, and signaling pathways in colonic tissues were determined. In mild and sever colitis mice, CK and BBR (as a positive agent) alleviated colitis histopathology injury, ameliorated myeloperoxidase (MPO) activity, reduced pro-inflammatory cytokines production, such as, IL-6, IL-1β, TNF-α, and increased anti-inflammatory cytokine IL-10 production in both mice colon tissues and blood. Nevertheless, the results revealed that CK and BBR inhibited NF-κB p65 nuclear translocation, downregulated p-IκBα and upregulated IκBα, indicating that CK, as well as BBR, suppressed the activation of the NF-κB pathway in the progression of colitis with immunofluorescence, immunohistochemical and western blotting analysis. Furthermore, CK inhibited pro-inflammatory cytokines production in LPS-activated macrophages via down-regulation of NF-κB signaling pathway. Taken together, our results not only reveal that CK promotes the recovery of the progression of colitis and inhibits the inflammatory responses by suppressing NF-κB activation, but also suggest that CK downregulates intestinal inflammation through regulating the activation of macrophages and pro-inflammatory cytokines production.

Emerging evidence suggests that USP39 plays an important role in the development of hepatocellular carcinoma (HCC). However, the molecular mechanism by which USP39 promotes HCC progression has not been well defined, especially regarding its putative ubiquitination function. Zinc-finger E-box-binding homeobox 1 (ZEB1) is a crucial inducer of epithelial-to-mesenchymal transition (EMT) to promote tumor proliferation and metastasis, but the regulatory mechanism of ZEB1 stability in HCC remains enigmatic. Here, we reveal that USP39 is highly expressed in human HCC tissues and correlated with poor prognosis. Moreover, USP39 depletion inhibits HCC cell proliferation and metastasis by promoting ZEB1 degradation. Intriguingly, deubiquitinase USP39 has a direct interaction with the E3 ligase TRIM26 identified by co-immunoprecipitation assays and immunofluorescence staining assays. We further demonstrate that TRIM26 is lowly expressed in human HCC tissues and inhibits HCC cell proliferation and migration. TRIM26 promotes the degradation of ZEB1 protein by ubiquitination in HCC. Deubiquitinase USP39 and E3 ligase TRIM26 function in an antagonistic pattern, but not a competitive pattern, and play key roles in controlling ZEB1 stability to determine the HCC progression. In summary, our data reveal a previously unknown mechanism that USP39 and TRIM26 balance the level of ZEB1 ubiquitination and thereby determine HCC cell proliferation and migration. This novel mechanism may provide new approaches to target treatment for inhibiting HCC development by restoring TRIM26 or suppressing USP39 expression in HCC cases with high ZEB1 protein levels.

Mesenchymal stem cells (MSCs) are multi-potent progenitor cells with ability to differentiate into multiple lineages, including bone, cartilage, fat, and muscles. Recent research indicates that MSCs can be efficiently recruited to tumor sites, modulating tumor growth and metastasis. However, the underlying molecular mechanisms are not fully understood. Here, we first demonstrated that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), when mixed with human cholangiocarcinoma cell lines QBC939 in a xenograft tumor model, significantly increased the cancer cells proliferation and metastatic potency. MSCs and their conditioned media (MSC-CM) could improve the drug resistance of tumor when the compound K (CK) as an anti-cancer drug, a major intestinal bacterial metabolite of panaxoside, was administered to xenograft tumor mice. Furthermore, MSCs greatly increased the colony formation and invasion of cholangiocarcinoma cells QBC939 and Mz-ChA-1. Immunochemistry studies of cholangiocarcinoma tissue chips and transplantation tumor from nude mice showed that the expression of β-catenin was important for cholangiocarcinoma development. We further demonstrated that MSCs and MSCs-CM could promote proliferation and migration of cholangiocarcinoma cells through targeting the Wnt/β-catenin signaling pathway. hUC-MSCs or MSCs-CM stimulated Wnt activity by promoting the nuclear translocation of β-catenin, and up-regulated Wnt target genes MMPs family, cyclin D1 and c-Myc. Together, our studies highlight a critical role for MSCs on cancer metastasis and indicate MSCs promote metastatic growth and chemoresistance of cholangiocarcinoma cells via activation of Wnt/β-catenin signaling.

BackgroundFeed contributes to over 60 % of the total production costs in the poultry industry. Increasing feed costs prompt geneticists to include feed intake and efficiency as selection goals in breeding programs. In the present study, we used an F2 chicken population in a genome-wide association study (GWAS) to detect potential genetic variants and candidate genes associated with daily feed intake (FI) and feed efficiency, including residual feed intake (RFI) and feed conversion ratio (FCR).MethodsA total of 1534 F2 hens from a White Leghorn and Dongxiang reciprocal cross were phenotyped for feed intake and efficiency between 37 and 40 weeks (FI1, RFI1, and FCR1) and between 57 and 60 weeks (FI2, RFI2, and FCR2), and genotyped using the chicken 600 K single nucleotide polymorphism (SNP) genotyping array. Univariate, bivariate, and conditional genome-wide association studies (GWAS) were performed with GEMMA, a genome-wide efficient mixed model association algorithm. The statistical significance threshold for association was inferred by the simpleM method.ResultsWe identified eight genomic regions that each contained at least one genetic variant that showed a significant association with FI. Genomic regions on Gallus gallus (GGA) chromosome 4 coincided with known quantitative trait loci (QTL) that affect feed intake of layers. Of particular interest, eight SNPs on GGA1 in the region between 169.23 and 171.55 Mb were consistently associated with FI in both univariate and bivariate GWAS, which explained 3.72 and 2.57 % of the phenotypic variance of FI1 and FI2, respectively. The CAB39L gene can be considered as a promising candidate for FI1. For RFI, a haplotype block on GGA27 harbored a significant SNP associated with RFI2. The major allele of rs315135692 was favorable for a lower RFI, with a phenotypic difference of 3.35 g/day between opposite homozygous genotypes. Strong signals on GGA1 were detected in the bivariate GWAS for FCR.ConclusionsThe results demonstrated the polygenic nature of feed intake. GWAS identified novel variants and confirmed a QTL that was previously reported for feed intake in chickens. Genetic variants associated with feed efficiency may be used in genomic breeding programs to select more efficient layers.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-015-0161-1) contains supplementary material, which is available to authorized users.