Inactivation of Group 1B Phospholipase A Enhances Disease Recovery and Reduces Experimental Colitis in Mice.

Phospholipase A (PLA) enzymes influence inflammatory bowel disease in both positive and negative manners depending on the type of PLA that is expressed. This study explored the influence of the abundantly expressed Group 1B PLA (PLA2G1B) on ulcerative colitis. Wild-type C57BL/6J mice and mice were treated with dextran sulfate sodium (DSS) for 5 days to induce epithelial injury, followed by another 5 days without DSS for recovery.

Different sensitivity to diet-induced hyperinsulinemia and hyperglycemia between mice with global or bone marrow-specific apoE receptor-2 deficiency.

This study explored the role of apoE receptor-2 (apoER2), a unique member of the LDL receptor family proteins with a restricted tissue expression profile, in modulating diet-induced obesity and diabetes. Unlike wild-type mice and humans in which chronic feeding of a high-fat Western-type diet leads to obesity and the prediabetic state of hyperinsulinemia before hyperglycemia onset, the mice with global apoER2 deficiency displayed lower body weight and adiposity, slower development of hyperinsulinemia, but the accelerated onset of hyperglycemia. Despite their lower adiposity, adipose tissues in Western diet-fed mice were more inflamed compared with wild-type mice.

Distinct pro-inflammatory properties of myeloid cell-derived apolipoprotein E2 and E4 in atherosclerosis promotion.

Polymorphisms in the apolipoprotein E (apoE) gene are risk factors for chronic inflammatory diseases including atherosclerosis. The gene product apoE is synthesized in many cell types and has both lipid transport-dependent and lipid transport-independent functions. Previous studies have shown that apoE expression in myeloid cells protects against atherogenesis in hypercholesterolemic ApoE mice.

Base-modified thymidines capable of terminating DNA synthesis are novel bioactive compounds with activity in cancer cells.

Current FDA-approved chemotherapeutic antimetabolites elicit severe side effects that warrant their improvement; therefore, we designed compounds with mechanisms of action focusing on inhibiting DNA replication rather than targeting multiple pathways. We previously discovered that 5-(α-substituted-2-nitrobenzyloxy)methyluridine-5'-triphosphates were exquisite DNA synthesis terminators; therefore, we synthesized a library of 35 thymidine analogs and evaluated their activity using an MTT cell viability assay of MCF7 breast cancer cells chosen for their vulnerability to these nucleoside derivatives. Compound 3a, having an α-tert-butyl-2-nitro-4-(phenyl)alkynylbenzyloxy group, showed an IC50 of 9±1μM.