Identification of Eupatilin from Artemisia argyi as a Selective PPARα Agonist Using Affinity Selection Ultrafiltration LC-MS

Peroxisome proliferator-activated receptors (PPARs) are key nuclear receptors and therapeutic targets for the treatment of metabolic diseases through the regulation of insulin resistance, diabetes, and dyslipidemia. Although a few drugs that target PPARs have been approved, more diverse and novel PPAR ligands are necessary to improve the safety and efficacy of available drugs. To expedite the search for new natural agonists of PPARs, we developed a screening assay based on ultrafiltration liquid chromatography-mass spectrometry (LC-MS) that is compatible with complex samples such as dietary foods or botanical extracts. The known PPARα and/or PPARγ ligands resveratrol and rosiglitazone were used as positive controls to validate the developed method. When applied to the screening of an Artemisia argyi extract, eupatilin was identified as a selective PPARα ligand. A PPAR competitive binding assay based on FRET detection also confirmed eupatilin as a selective PPARα agonist exhibiting a binding affinity of 1.18 μM (IC50). Furthermore, eupatilin activation of the transcriptional activity of PPARα was confirmed using a cell-based transactivation assay. Thus, ultrafiltration LC-MS is a suitable assay for the identification of PPAR ligands in complex matrixes such as extracts of dietary foods and botanicals

Impact of hospitalization duration before medical emergency team activation: A retrospective cohort study.

BackgroundThe rapid response system has been implemented in many hospitals worldwide and, reportedly, the timing of medical emergency team (MET) attendance in relation to the duration of hospitalization is associated with the mortality of MET patients. We evaluated the relationship between duration of hospitalization before MET activation and patient mortality. We compared cases of MET activation for early, intermediate, and late deterioration to patient characteristics, activation characteristics, and patient outcomes. We also aimed to determine the relationship, after adjusting for confounders, between the duration of hospitalization before MET activation and patient mortality.Materials and methodsWe retrospectively evaluated patients who triggered MET activation in general wards from March 2009 to February 2015 at the Asan Medical Center in Seoul. Patients were categorized as those with early deterioration (less than 2 days after admission), intermediate deterioration (2-7 days after admission), and late deterioration (more than 7 days after admission) and compared them to patient characteristics, activation characteristics, and patient outcomes.ResultsOverall, 7114 patients were included. Of these, 1793 (25.2%) showed early deterioration, 2113 (29.7%) showed intermediate deterioration, and 3208 (45.1%) showed late deterioration. Etiologies of MET activation were similar among these groups. The clinical outcomes significantly differed among the groups (intensive care unit transfer: 34.1%, 35.6%, and 40.4%; p ConclusionsNearly 50% of the acute clinically-deteriorating patients who activated the MET had been hospitalized for more than 7 days. Furthermore, they presented with higher rates of mortality and ICU transfer than patients admitted for less than 7 days before MET activation and had mortality as an independent risk factor