Effects of compound-326, a selective delta-5 desaturase inhibitor, in ApoE knockout mice with two different protocols for atherosclerosis development.

Purpose: We previously confirmed its anti-atherosclerotic effects by pre-treatment with compound-326, a selective delta-5 desaturase (D5D) inhibitor, in Western diet-fed ApoE knockout mice. In the present study, we evaluated effects of compound-326 in ApoE knockout mice with two different protocols for atherosclerosis development.

Methods: In a post-treatment protocol, where the compound treatment started after 10 weeks pre-feeding of Western diet, compound-326 (1 and 3 mg/kg/day, p.

Metabolomic/lipidomic-based analysis of plasma to diagnose hepatocellular ballooning in patients with non-alcoholic fatty liver disease: A multicenter study.

Aim: Liver biopsy is still required for the diagnosis of hepatocellular ballooning and inflammation, which are important histological features of non-alcoholic steatohepatitis. We undertook this multicenter, cross-sectional study to identify novel blood markers for the diagnosis of hepatocellular ballooning.

Methods: We enrolled 176 patients, of whom 132 were proven by liver biopsy as having non-alcoholic fatty liver disease (NAFLD) and classified as non-ballooning (ballooning grade 0) (n = 83) or ballooning (ballooning grade 1 and 2) (n = 49) by a central pathology review.

Characterization of Postprandial Effects on CSF Metabolomics: A Pilot Study with Parallel Comparison to Plasma.

Cerebrospinal fluid (CSF) metabolites reflect biochemical diffusion/export from the brain and possibly serve as biomarkers related to brain disease severity, pathophysiology, and therapeutic efficacy/toxicity. Metabolomic studies using blood matrices have demonstrated interindividual and preanalytical variation of blood metabolites, whereas those of CSF metabolites remain unclear. In this study, we aimed to delineate the postprandial effects on CSF metabolites because fasting of patients with brain-related disorders is challenging.

Discovery of 1,8-naphthyridin-2-one derivative as a potent and selective sphingomyelin synthase 2 inhibitor.

Sphingomyelin synthase 2 (SMS2) has attracted attention as a drug target for the treatment of various cardiovascular and metabolic diseases. The modification of a high throughput screening hit, 2-quinolone 10, enhanced SMS2 inhibition at nanomolar concentrations with good selectivity against SMS1. To improve the pharmaceutical properties such as passive membrane permeability and aqueous solubility, adjustment of lipophilicity was attempted and 1,8-naphthyridin-2-one 37 was identified as a potent and selective SMS2 inhibitor.

Development of novel highly sensitive methods to detect endogenous cGAMP in cells and tissue.

Intracellular DNA triggers interferon release during the innate immune response. Cyclic GMP-AMP synthase (cGAS) senses intracellular double-stranded DNA not only in response to viral infection but also under autoimmune conditions. Measuring the levels of cyclic GMP-AMP (cGAMP) as a second messenger of cGAS activation is important to elucidate the physiological and pathological roles of cGAS.