Auxiliary roles of nardilysin in the early diagnosis of acute coronary syndrome: a prospective cohort study, the Nardi-ACS study.

Acute coronary syndrome (ACS) includes myocardial infarction (MI) and unstable angina (UA). MI is defined by elevated necrosis markers, preferably high-sensitivity cardiac troponins (hs-cTn). However, it takes hours for cTn to become elevated after coronary occlusion; therefore, difficulties are associated with diagnosing early post-onset MI or UA. The aim of this prospective cohort study was to examine the diagnostic ability of serum nardilysin (NRDC) for the early detection of ACS. This study consisted of two sequential cohorts, the Phase I cohort, 435 patients presenting to the emergency room (ER) with chest pain, and the Phase II cohort, 486 patients with chest pain who underwent coronary angiography. The final diagnosis was ACS in 155 out of 435 patients (35.6%) in the phase I and 418 out of 486 (86.0%) in the phase II cohort. Among 680 patients who presented within 24 h of onset, 466 patients (68.5%) were diagnosed with ACS. Serum NRDC levels were significantly higher in patients with ACS than in those without ACS. The sensitivity of NRDC in patients who presented within 6 h after the onset was higher than that of hsTnI, and the AUC of NRDC within 1 h of the onset was higher than that of hsTnI (0.718 versus 0.633). Among hsTnI-negative patients (300 of 680 patients: 44.1%), 136 of whom (45.3%) were diagnosed with ACS, the sensitivity and the NPV of NRDC were 73.5 and 65.7%, respectively. When measured in combination with hsTnI, NRDC plays auxiliary roles in the early diagnosis of ACS.

Curcumin may induce lipolysis via proteo-stress in Huh7 human hepatoma cells.

Curcumin has been shown to have anti-obesity effects in animal studies. Although several molecular mechanisms of action have been reported, the initial or upstream molecular events remain to be revealed. In this study, we found that curcumin or heat shock treatment up-regulated the expression of adipose triglyceride lipase (ATGL) in Huh7 hepatoma cells, which resulted in acceleration of lipolysis. Interestingly, perturbation of protein homeostasis was seen in curcumin-treated cells, as detected by formation of numerous ubiquitinated proteins and conjugated proteins with p62 (SQSTM). Curcumin activated the protein expression of molecular chaperones, such as heat shock protein (HSP)40 and HSP70. Pre-treatment of the cells with 4-phenylbutyric acid, a chemical chaperone, suppressed proteo-stress induced by curcumin and reduced its lipolysis effect. Importantly, the cytotoxicity of curcumin was markedly alleviated when intracellular triglyceride was consumed by the polyphenol. Thus, energy supplementation from lipolysis may play substantial roles in adaptation and survival of curcumin-exposed cells. To support this notion, the cytotoxicity of curcumin was aggravated in ATGL-knockdown cells. Curcumin decreased intracellular ATP for activating AMP-activated protein kinase, which initiates catabolic pathways including ATGL-dependent lipolysis. Taken together, we propose a hypothesis that curcumin induces lipolysis to compensate for ATP reduction due to its proteo-stress effects.