PubMed · 11511533
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R N Eisenman. 2001-08-15. Deconstructing myc.. https://doi.org/10.1101/gad928101
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To test our hypothesis that proatherogenic lysophosphatidylcholine (LPC) upregulates trained immunity pathways (TIPs) in human aortic endothelial cells (HAECs), we conducted an intensive analyses on our RNA-Seq data and histone 3 lysine 14 acetylation (H3K14ac)-CHIP-Seq data, both performed on HAEC treated with LPC. Our analysis revealed that: 1) LPC induces upregulation of three TIPs including glycolysis enzymes (GE), mevalonate enzymes (ME), and acetyl-CoA generating enzymes (ACE); 2) LPC induces upregulation of 29% of 31 histone acetyltransferases, three of which acetylate H3K14; 3) LPC induces H3K14 acetylation (H3K14ac) in the genomic DNA that encodes LPC-induced TIP genes (79%) in comparison to that of in LPC-induced effector genes (43%) including ICAM-1; 4) TIP pathways are significantly different from that of EC activation effectors including adhesion molecule ICAM-1; 5) reactive oxygen species generating enzyme NOX2 deficiency decreases, but antioxidant transcription factor Nrf2 deficiency increases, the expressions of a few TIP genes and EC activation effector genes; and 6) LPC induced TIP genes(81%) favor inter-chromosomal long-range interactions (CLRI, trans-chromatin interaction) while LPC induced effector genes (65%) favor intra-chromosomal CLRIs (cis-chromatin interaction). Our findings demonstrated that proatherogenic lipids upregulate TIPs in HAECs, which are a new category of qualification markers for chronic disease risk factors and conditional DAMPs and potential mechanisms for acute inflammation transition to chronic ones. These novel insights may lead to identifications of new cardiovascular risk factors in upregulating TIPs in cardiovascular cells and novel therapeutic targets for the treatment of metabolic cardiovascular diseases, inflammation, and cancers. (total words: 245).
A group of isomers possessing a 2-, 3-, or 4-acetoxy moiety on the 3-phenyl substituent of rofecoxib were synthesized that exhibit highly potent, and selective, COX-2 inhibitory activity that have the potential to acetylate the COX-2 isozyme.
Four new indoles, ancorinolates A-C and bis-ancorinolate B, which contain sulfamate and sulfate groups, were isolated from the aqueous extract of the sponge Ancorina sp. In addition, ancorinazole, an indolo[3,2-a]carbazole also possessing sulfamate and sulfate groups, was isolated from two separate New Zealand collections of Ancorina sp. Ancorinazole is the first indolo[3,2-a]carbazole described as a natural product. Ancorinolates A (1) and C (3) showed weak HIV-inhibitory activity in the XTT-based, anticytopathicity assay.