Wheat bran-derived polysaccharides have attracted particular attention due to their immunomodulatory effects. However, the molecular mechanisms underlying their functions are poorly understood. The current study was designed to examine the effect of wheat bran polysaccharide (WBP) on RAW 264.7 cells and the underlying signaling pathways, which have not been explored. In addition, we also investigated the immuno-enhancement effects of WBP on cyclophosphamide (CTX)-induced immunosuppression in mice. WBP significantly increased the concentrations of intracellular nitric oxide (NO) and cytokines such as prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α) in RAW 264.7 cells. The result of RT-PCR analysis indicated that WBP also enhanced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α expression. Further analyses demonstrated that WBP rapidly activated phosphorylated p38 mitogen-activated protein kinase (MAPK) and the transcriptional activities of activator protein-1 (AP-1) and nuclear factor (NF)-κB via toll-like receptor 4 (TLR4). Furthermore, in vivo experiments revealed that WBP increased the spleen and thymus indices significantly, and markedly promoted the production of the serum cytokines IL-2 and IFN-γ in CTX-induced immunosuppressed mice. Taken together, these results suggest that WBP can improve immunity by enhancing immune function, and could be explored as a potential immunomodulatory agent in functional food.

Tumor necrosis factor-alpha (TNF-α)-induced protein 8 (TNFAIP8/TIPE) family, including TNFAIP8 (TIPE), TNFAIP8 like-protein 1 (TNFAIP8L1/TIPE1), TNFAIP8 like-protein 2 (TNFAIP8L2/TIPE2), and TNFAIP8 like-protein 3 (TNFAIP8L3/TIPE3), plays a vital role in regulating inflammatory responses, immune homeostasis, and cancer development. Over the last decade, studies have shown that TIPE2 protein is differentially expressed in diverse cells and tissues. The dysregulation of TIPE2 protein can lead to dysregulation of inflammatory responses and immune homeostasis, and change the basic characteristics of cancers. In consideration of the immeasurable values of TIPE2 in diagnosis, treatment, and prognosis of various human diseases, this review will focus on the expression pattern, structure, and regulatory roles of TIPE2 in inflammation, immunity, and cancers.

Background: Prognostic prediction models have been developed to detect new biomarkers of gastric cancer (GC). The identification of new biomarkers could provide theoretical foundations for the application of molecular targeted therapy in advanced GC. The aim of this study was to construct a prognostic prediction model for stomach adenocarcinoma (STAD) based on The Cancer Genome Atlas (TCGA) database. Methods: First, we used the "limma" package to screen differentially expressed genes (DEGs) based on TCGA database. Gene ontology (GO) analysis was performed using the "ClusterProfiler" package. The interactions between proteins and the relationships between differentially expressed genes and clinical features were analyzed by protein-protein interaction (PPI) network analysis and weighted gene coexpression network analysis (WGCNA), respectively. Then, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to identify differentially enriched pathways. The GenVisR package and CIBERSORT were used to identify mutations and assess immune infiltration. Finally, the expression of COL3A1 in STAD tissues was verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting.Results: Six differentially expressed genes were screened out, namely, COL3A1, ADAMTS12, BGN, FNDC1, AEBP1 and HTRA3. The enrichment results showed that differentially expressed genes were involved in multiple pathways in STAD, such as those related to the extracellular matrix, extracellular structure organization, and extracellular matrix organization. The differentially expressed genes were related to immune infiltration via the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways. The western blotting and RT-qPCR results suggested that COL3A1 was overexpressed in STAD tissues compared with normal tissues.Conclusion: COL3A1, ADAMTS12, BGN, FNDC1, AEBP1 and HTRA3 could play important roles in the tumorigenesis and progression of STAD via various pathways, including those involving the extracellular matrix, extracellular structure organization, and extracellular matrix organization. COL3A1, ADAMTS12, BGN, FNDC1, AEBP1, and HTRA3 act as oncogenes in most cancers and may be biomarkers. Additionally, the identification of COL3A1 as a candidate biomarker provides a direction for further research on the role of tumor immunity in gastric cancer.