GEREDB: Gene expression regulation database curated by mining abstracts from literature.

Understanding how genes are expressed and regulated in different biological processes are fundamental and challenging issues. Considerable progress has been made in studying the relationship between the expression and regulation of human genes. However, it is difficult to use these resources productively to analyze gene expression data. GEREDB (www.thua45.cn/geredb) has been developed to facilitate analyses that will provide insights into the regulation of genes that govern specific biological responses. GEREDB is a publicly available, manually curated biological database that stores the data regarding relationships between expression and regulation of human genes. To date, more than 39,000 Links have been contextually annotated by reviewing more than 53,000 abstracts. GEREDB can be searched using the official NCBI gene symbol as a query, and it can be downloaded along with the GEREA software package. GEREDB has the ability to analyze user-supplied gene expression data in a causal analysis oriented manner using the GEREA bioinformatics tool.

MicroRNA responses associated with Salmonella enterica serovar typhimurium challenge in peripheral blood: effects of miR-146a and IFN-γ in regulation of fecal bacteria shedding counts in pig.

BACKGROUND: MicroRNAs are involved in a broad range of biological processes and are known to be differentially expressed in response to bacterial pathogens. RESULTS: The present study identified microRNA responses in porcine peripheral blood after inoculation with the human foodborne pathogen Salmonella enterica serovar Typhimurium strain LT2. We compared the microRNA transcriptomes of the whole blood of pigs (Duroc × Landrace × Yorkshire) at 2-days post inoculation and before Salmonella infection. The analysis identified a total of 29 differentially expressed microRNAs, most of which are implicated in Salmonella infection and immunology signaling pathways. Joint analysis of the microRNA and mRNA transcriptomes identified 24 microRNAs with binding sites that were significantly enriched in 3' UTR of differentially expressed mRNAs. Of these microRNAs, three were differentially expressed after Salmonella challenge in peripheral blood (ssc-miR-146a-5p, ssc-miR-125a, and ssc-miR-129a-5p). Expression of 23 targets of top-ranked microRNA, ssc-miR-146a-5p, was validated by real-time PCR. The effects of miR-146a, IFN-γ, and IL-6 on the regulation of fecal bacteria shedding counts in pigs were investigated by in vivo study with a Salmonella challenge model. CONCLUSIONS: The results indicated that induction of miR-146a in peripheral blood could significantly increase the fecal bacterial load, whereas IFN-γ had the reverse effect. These microRNAs can be used to identify targets for controlling porcine salmonellosis.

Regulators of Salmonella-host interaction identified by peripheral blood transcriptome profiling: roles of TGFB1 and TRP53 in intracellular Salmonella replication in pigs.

Peripheral blood transcriptome is an important intermediate data source for investigating the mechanism of Salmonella invasion, proliferation, and transmission. We challenged 4-week old piglets with Salmonella enterica serovar Typhimurium LT2 and investigated the peripheral blood gene expression profile before treatment (d0) and at 2 and 7 days post-inoculation (dpi) using deep sequencing. Regulator pathways were first predicted in silico and validated by wet-lab experiments. In total, 1255, 765, and 853 genes were differentially expressed between 2 dpi/d0, 7 dpi/d0, and 7 dpi/2 dpi, respectively. Additionally, 1333 genes showed a time effect during the investigated Salmonella infection period. Clustering analysis showed that the differentially expressed genes fell into six distinct expression clusters. Pathway annotation of these gene clusters showed that the innate immune system was first significantly upregulated at 2 dpi and then attenuated at 7 dpi. Toll-like receptor cascades, MyD88 cascade, phagosome pathway, cytokine signaling pathway, and lysosome pathway showed a similar expression pattern. Interestingly, we found that the ribosome pathway was significantly inhibited at 2 and 7 dpi. Gene expression regulation network enrichment analysis identified several candidate factors controlling the expression clusters. Further in vitro study showed that TGFB1 can inhibit Salmonella replication whereas TRP53 can promote Salmonella replication in porcine peripheral blood mononuclear cells and murine macrophages. These results provide new insights into the molecular mechanism of Salmonella-host interactions and clues for the genetic improvement of Salmonella infection resistance in pigs.