Allograft inflammatory factor 1 is a potential diagnostic, immunological, and prognostic biomarker in pan-cancer.

BACKGROUND: Allograft Inflammatory Factor 1 (AIF-1) is a member of the allograft inflammatory factor gene family and plays an essential role in the occurrence and development of malignant tumors. However, little is known about the expression pattern, predictive value, and biological function of AIF-1 across cancers. MATERIALS AND METHODS: We first analyzed AIF-1 expression across cancers based on data from public databases. Univariate Cox regression and Kaplan-Meier analyses were used to explore the predictive value of AIF-1 expression in various cancers. Moreover, gene set enrichment analysis (GSEA) was applied to determine the cancer hallmarks associated with AIF-1 expression. Spearman correlation analysis was performed to investigate the association between AIF-1 expression and tumor microenvironment scores, immune cell infiltration, immune-related genes, TMB, MSI, and DNA methyltransferases. RESULTS: AIF-1 expression was upregulated in most cancer types and exhibited prognosis-predictive ability. AIF-1 expression was positively correlated with immune infiltrating cells and immune checkpoint-related genes in most cancers. Additionally, the promoter methylation level of AIF-1 was different in distinct tumors. High methylation levels of AIF-1 were associated with a worse prognosis in UCEC and melanoma, whereas they were associated with a better prognosis in GBM, KIRC, OV, and UVM. Finally, we found that AIF-1 was significantly highly expressed in KIRC tissues. Functionally, silencing AIF-1 dramatically decreased proliferation, migration, and invasion abilities. CONCLUSION: Our results reveal that AIF-1 acts as a robust tumor biomarker and is closely correlated with tumor immune infiltration. Furthermore, AIF-1 may function as an oncogene and promote tumor progression in KIRC.

A novel, highly-water-soluble apigenin derivative provides neuroprotection following ischemia in male rats by regulating the ERK/Nrf2/HO-1 pathway.

6"-O-succinylapigenin [apigenin-7-O-(6'-O-succinyl)-glucoside], a novel compound, is identified in chamomile. Although it is highly produced by Bacillus amyloliquefaciens FJ18, its bioactivity remains unknown. The neuroprotective effects and antioxidative mechanism of 6''-O-succcinylapigenin in the middle cerebral artery occlusion model in male rats was investigated in this study. The structure of this compound was determined by spectroscopic data analysis. After 2 h of occlusion and 24 h of reperfusion, magnetic resonance imaging and assessed neurological scores following middle cerebral artery occlusion (MCAO) in male rats to determine the infarction size and neurological deficits, respectively. In addition, we tested protein levels of the nuclear factor E2-related factor 2 (Nrf2), Kelch-like ECH-associated protein1 (Keap1), heme oxygenase-1 (HO-1), and extracellular-signal-regulated kinase (ERK), to investigate the mechanism of antioxidative action of 6''-O-succcinylapigenin. Finally, we employed immunofluorescence to determine the location of Nrf2 and Keap1 in HT22 cells cultured in vitro. Our results revealed that administration of 6''-O-succcinylapigenin induced a decrease in both infarct volume and neurological scores following MCAO, and significantly increased the activity of HO-1 and nuclear Nrf2 in vivo. Similarly, immunofluorescence assays indicated that Nrf2 is highly expressed in the nucleus following treatment with 6''-O-succcinylapigenin in vitro. Our study suggests that 6''-O-succcinylapigenin exerts an anti-ischemic effect by activating the ERK/Nrf2/HO-1 pathway.