Enzymatic oxidation of apocynin, which may mimic in vivo metabolism, affords a large number of oligomers (apocynin oxidation products, AOP) that inhibit vascular NADPH oxidase. In vitro studies of NADPH oxidase activity were performed to identify active inhibitors, resulting in a trimer hydroxylated quinone (IIIHyQ) that inhibited NADPH oxidase with an IC(50)=31nM. Apocynin itself possessed min...

The p47 GTPases are essential for interferon-gamma-induced cell-autonomous immunity against the protozoan parasite, Toxoplasma gondii, in mice, but the mechanism of resistance is poorly understood. We show that the p47 GTPases, including IIGP1, accumulate at vacuoles containing T. gondii. The accumulation is GTP-dependent and requires live parasites. Vacuolar IIGP1 accumulations undergo a matur...

Interferon-inducible p47 GTPases are critical mediators of cell-autonomous resistance against several intracellular pathogens. Here we present the first crystal structure of a member of this novel GTPase family, IIGP1, in its nucleotide-free, GDP-, and GppNHp-bound form. The structure shows a Ras-like G domain between an N-terminal three-helix bundle and a complex system of C-terminal helices a...

chia coli, non-typhoid Salmonella species, Klebsiella pneumoniae, Serratia marcescens, and Burkholderia cepacia, as well as the fungal genus Aspergillus. 3-6) Isolation of the causative pathogens is essential for appropriate antimicrobial therapy, but it is difficult to identify the causative pathogen in most clinical CGD cases. 6) NADPH oxidase is a multi-component complex composed of a plasma...

Because atherosclerosis is a disease of many risk factors, a complex pathology, and diverse clinical manifestations, the as yet unattained Holy Grail of atherosclerosis research is a unifying pathway to explain its many aspects and provide a single point at which to measure risk or intervene in its clinical course. If vascular biology possesses such a relic, it would have many of the characteri...

BACKGROUND Reactive oxygen species are involved in many of the angiotensin II signalling pathways. We have thus investigated whether the angiotensin II type 1 (AT1) receptor antagonist, telmisartan, can inhibit the accelerated renal fibrosis and excess oxidative stress, which occurs after unilateral ureteral obstruction (UUO) in acatalasemic mice. METHODS The effect of daily intraperitoneal i...

Abstract Extramammary Paget disease (EMPD) is a rare epithelial malignancy predominantly affecting the anogenital skin. Primary EMPD carries risk of invasion and metastasis, as well in contiguous organs. No UK guidelines for management exist, resulting lack consensus staging screening associated cancers. We collected consecutive cases histologically diagnosed at regional centre (2017–2022). The...