Discovering new mode-of-action pesticide leads inhibiting protein-protein interactions: example targeting plant O-acetylserine sulfhydrylase.

Background: The widespread evolution of pesticide resistance poses a significant challenge to current agriculture, necessitating the discovery of molecules with new modes of action. Despite extensive efforts, no major molecules with new modes of action have been commercialized for decades. Most pesticides function by binding to specific pockets on target enzymes, enabling a single target site mutation to confer resistance.

Paraoxonase 1 in endothelial cells impairs vasodilation induced by arachidonic acid lactone metabolite.

Introduction: Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated lactonase, which is known for its antiatherogenic properties. Previous studies in PON1 knockout (PON1KO) mice revealed that PON1KO mice have low blood pressure, which is inversely correlated with the renal levels of the cytochrome P450 -derived arachidonic acid metabolite 5,6-epoxyeicosatrienoic acid (5,6-EET). Our previous studies revealed that 5,6-EET is unstable, transforming to the δ-lactone isomer 5,6-δ-DHTL, an endothelium-derived hyperpolarizing factor (EDHF) that mediates vasodilation, and it is a potential substrate for PON1.

5,6-δ-DHTL, a stable metabolite of arachidonic acid, is a potential EDHF that mediates microvascular dilation.

Objective: Prominent among the endothelium-derived hyperpolarizing factors (EDHFs) are the Cytochrome P450 (CYP) epoxygenase-derived arachidonic acid metabolites-the epoxyeicosatrienoic acids (EETs), that are known as vasodilators in the microcirculation. Among the EET isomers, 5,6-EET undergoes rapid lactonization in aqueous solution to the more stable 5,6-δ DHTL (5,6-dihydroxytrienoic lactone) isomer. It is unclear whether this metabolic transformation maintains its vasodilator potential and what is the mechanism of action.

A decrease in VEGF and inflammatory markers is associated with diabetic proliferative retinopathy.

Diabetic retinopathy is the most severe ocular complication of diabetes mellitus (DM), is associated with micro-vascular damage. The more advanced stage, proliferative diabetic retinopathy, has been linked to an increased risk of cardiovascular morbidity and mortality. Our hypothesis was that inflammatory and angiogenic markers will detect the different stages of type 2 diabetes, and may predict development of micro-vascular damage.

Gender effect on vascular inflammation following bariatric surgery.

Studies have shown that mortality was reduced by 31.6% in patients that underwent bariatric surgery compared with the non-operative control group. However, in most surgical series the majority of patients were women, and men had higher post-operative mortality rates and a higher postoperative morbidity, regardless of weight.

Endothelial dysfunction is reversible in Helicobacter pylori-positive subjects.

Background: Studies have shown an association between Helicobacter pylori (HP) infection and atherosclerosis. Although epidemiological studies have suggested an association between HP infection and atherosclerosis, the issue is still controversial. It is not clear whether HP eradication will reverse endothelial damage and prevent cardiovascular events.