Design, purification and assessment of GRP78 binding peptide-linked Subunit A of Subtilase cytotoxic for targeting cancer cells

The sequence of primers for GBP-SubA and optimization of E. coli strain and vector of GBP-SubA expression. (DOC 710 kb

Ferulic Acid and P-Coumaric Acid Synergistically Attenuate Non-Alcoholic Fatty Liver Disease through HDAC1/PPARG-Mediated Free Fatty Acid Uptake

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and has become a growing public health concern worldwide. Polyphenols may improve high-fat diet (HFD)-related NAFLD. Our previous study found that ferulic acid (FA) and p-coumaric acid (p-CA) were the polyphenols with the highest content in foxtail millet. In this study, we investigated the mechanism underlying the impact of ferulic acid and p-coumaric acid (FA/p-CA) on non-alcoholic fatty liver (NAFLD). The association of FA and p-CA with fatty liver was first analyzed by network pharmacology. Synergistic ameliorating of NAFLD by FA and p-CA was verified in oleic acid (OA) and palmitic acid (PA) (FFA)-treated hepatocytes. Meanwhile, FA/p-CA suppressed final body weight and TG content and improved liver dysfunction in HFD-induced NAFLD mice. Mechanistically, our data indicated that FA and p-CA bind to histone deacetylase 1 (HDAC1) to inhibit its expression. The results showed that peroxisome proliferator activated receptor gamma (PPARG), which is positively related to HDAC1, was inhibited by FA/p-CA, and further suppressed fatty acid binding protein (FABP) and fatty acid translocase (CD36). It suggests that FA/p-CA ameliorate NAFLD by inhibiting free fatty acid uptake via the HDAC1/PPARG axis, which may provide potential dietary supplements and drugs for prevention of NAFLD

Proteomics of immune cells from liver tumors reveals immunotherapy targets.

Elucidating the mechanisms by which immune cells become dysfunctional in tumors is critical to developing next-generation immunotherapies. We profiled proteomes of cancer tissue as well as monocyte/macrophages, CD4+ and CD8+ T cells, and NK cells isolated from tumors, liver, and blood of 48 patients with hepatocellular carcinoma. We found that tumor macrophages induce the sphingosine-1-phospate-degrading enzyme SGPL1, which dampened their inflammatory phenotype and anti-tumor function in vivo. We further discovered that the signaling scaffold protein AFAP1L2, typically only found in activated NK cells, is also upregulated in chronically stimulated CD8+ T cells in tumors. Ablation of AFAP1L2 in CD8+ T cells increased their viability upon repeated stimulation and enhanced their anti-tumor activity synergistically with PD-L1 blockade in mouse models. Our data reveal new targets for immunotherapy and provide a resource on immune cell proteomes in liver cancer