Project description:To determine whether NRF2-mediated anti-inflammatory differentiation and its downstream consequences on tumor immunology are intrinsic macrophage processes, we conducted a series of in vitro studies. First, we performed scRNA-seq studies of WT, Keap1 KO, and Nrf2 KO BMDMs after short-term culture with GM-CSF for 5 days to capture a broad spectrum of differentiation and polarization states across the macrophage lineage trajectory.
Project description:Although the anti-cancer properties of Oligomeric Proanthocyanidins (OPCs) from grape seeds has been well recognized, the molecular mechanisms by which they exert anti-cancer effects are poorly understood. In this study, through comprehensive RNA-sequencing based gene-expression profiling in multiple colorectal cancer cell lines, we for the first time illuminate the genome-wide effects of OPCs from grape seeds in colorectal cancer. Our data revealed that OPCs affects several key cancer-associated genes. In particular, genes involved in cell cycle and DNA replication were most significantly and consistently altered by OPCs across multiple cell lines. Intriguingly, our in vivo experiments showed that OPCs was significantly more potent at decreasing xenograft tumor growth compared to the unfractionated grape seed extract (GSE) that includes the larger polymers of proanthocyanidins. These findings were further confirmed in colorectal cancer patient-derived organoids, wherein OPCs more potently inhibited the formation of organoids compared to GSE. Further, we validated alteration of cell cycle and DNA replication associated genes in cancer cell lines, mice xenografts as well as patient-derived organoids. Overall, this study provides an unbiased and comprehensive look at the mechanisms by which OPCs exerts anti-cancer properties in colorectal cancer.
Project description:To investigate the key mechanisms regulated by digested red grape anthocyanins in colorectal cancer cells, we employed whole-genome microarray expression profiling as a discovery tool to identify the signaling networks affected by this treatment, in vitro. Treatment of DLD1 cells with the digested red grape anthocyanin extract at IC50 concentration, significantly altered the expression of 873 genes (p adj.<0.05), showing a fold regulation greater than |±1.5|. Treatment with the extract impacted key cancer-related functional signaling networks, including apoptosis and cellular movement.
Project description:Effect of GA on PAC and PAO1 treated Arabidopsis seeds. Seeds were treated during 20h with paclobutrazol (PAC) or with lyophilized extracts of Pseudomonas aeruginosa liquid culture medium (PAO1). Experiments were also performed with exogenous application of gibberellic acid.