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: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.
Project description:A screen of 5 anti-inflammatory compounds for their effects in explanted, cultured rat spinal cord slices. All injured (explanted) cords are cultured for 4 hrs.
Project description:Diet study comparing anti-inflammatory with western diet. Data was acquired on Orbitrap Exploris 240 with chromatographic separation on a Phenomenex polar C18 column (Kinetex 2.6 um, 100 x 2.1 mm). Reversed-phase, ESI positive.
Project description:Under conditions of erythrolytic stress, which accompanies many disease states, macrophages play key roles in phagocytosing damaged RBCs and preventing the toxic effects of cell-free hemoglobin and heme to maintain homeostasis. Using a genetic mouse model of spherocytosis and single-cell RNA sequencing, we show that erythrolytic stress promotes expansion of a specific macrophage population in the liver (which we named “erythrophagocytes”) expressing high levels of Marco and Hmox1 and low levels of MHC class II related genes with an anti-inflammatory gene expression signature. We confirmed the strong anti-inflammatory function of erythrophagocytes in two models of sterile inflammatory liver disease: anti-CD40 antibody-induced systemic inflammation syndrome with necrotizing hepatitis and diet-induced nonalcoholic fatty liver disease (NAFLD). The unique anti-inflammatory phenotype and function of erythrophagocytes was reproduced in vitro by heme-exposure of mouse macrophages, yielding a transcriptional profile that segregated heme-polarized from classical M1- and M2-polarized cells. The phenotype of anti-inflammatory erythrophagocytes coincided with NFE2L2/NRF2 driven gene expression and was abolished in Nfe2l2/Nrf2-deficient macrophages. Our findings point to a novel pathway that regulates macrophage functions to link RBC homeostasis and heme metabolism with innate immunity.