Background: Stomach adenocarcinoma (STAD) is the most common histological type of stomach cancer, which causes a considerable number of deaths worldwide. This study aimed to identify its potential biomarkers with the notion of revealing the underlying molecular mechanisms.Methods: Gene expression profile microarray data were downloaded from the Gene Expression Omnibus (GEO) database. The “limma” R package was used to screen the differentially expressed genes (DEGs) between STAD and matched normal tissues. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for function enrichment analyses of DEGs. The STAD dataset from The Cancer Genome Atlas (TCGA) database was used to identify a prognostic gene signature, which was verified in another STAD dataset from the GEO database. CIBERSORT algorithm was used to characterize the 22 human immune cell compositions. The expression of LRFN4 and CTHRC1 in tissues was determined by quantitative real-time PCR from the patients recruited to the present study.Results: Three public datasets including 90 STAD patients and 43 healthy controls were analyzed, from which 44 genes were differentially expressed in all three datasets. These genes were implicated in biological processes including cell adhesion, wound healing, and extracellular matrix organization. Five out of 44 genes showed significant survival differences. Among them, CTHRC1 and LRFN4 were selected for construction of prognostic signature by univariate Cox regression and stepwise multivariate Cox regression in the TCGA-STAD dataset. The fidelity of the signature was evaluated in another independent dataset and showed a good classification effect. The infiltration levels of multiple immune cells between high-risk and low-risk groups had significant differences, as well as two immune checkpoints. TIM-3 and PD-L2 were highly correlated with the risk score. Multiple signaling pathways differed between the two groups of patients. At the same time, the expression level of LRFN4 and CTHRC1 in tissues analyzed by quantitative real-time PCR were consistent with the in silico findings.Conclusion: The present study constructed the prognostic signature by expression of CTHRC1 and LRFN4 for the first time via comprehensive bioinformatics analysis, which provided the potential therapeutic targets of STAD for clinical treatment.

Cucurbitacin B (CuB) is a triterpenoid compound derived from various medicinal plants, demonstrating potential anti-inflammatory, antioxidant, and neuroprotective properties, as well as significant anti-tumor effects. However, its efficacy in treating ulcerative colitis (UC) remains unclear. To investigate the therapeutic potential of CuB, a dextran sulfate sodium (DSS)-induced UC model in mice was employed, along with gut microbiota analysis. The results revealed that CuB significantly alleviated clinical symptoms, improved colonic tissue damage, and suppressed pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in colon tissues. Additionally, CuB was associated with changes in specific microbial populations, including the upregulation of Muribaculaceae, Rikenellaceae_RC9_gut_group, Muribaculum, and Bifidobacterium, and the downregulation of Desulfovibrionaceae, Helicobacter, Escherichia-Shigella, Streptococcus, Candidatus_Saccharimonas, and Clostridium, which may contribute to the recovery of colon injury. This study provides preliminary evidence supporting CuB's therapeutic potential in DSS-induced colitis by enhancing gut microbiota diversity. CuB shows promise as potential treatment for UC and other conditions related to disruptions in intestinal flora homeostasis.