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The accumulation of lipid droplets in the cytoplasm of hepatocytes, known as hepatic steatosis, is a hallmark of non-alcoholic fatty liver disease (NAFLD). Inhibiting hepatic steatosis is suggested to be a therapeutic strategy for NAFLD. The present study investigated the actions of Neurotropin (NTP), a drug used for chronic pain in Japan and China, on lipid accumulation in hepatocytes as a possible treatment for NAFLD. NTP inhibited lipid accumulation induced by palmitate and linoleate, the two major hepatotoxic free fatty acids found in NAFLD livers. An RNA sequencing analysis revealed that NTP altered the expression of mitochondrial genes. NTP ameliorated palmitate-and linoleate-induced mitochondrial dysfunction by reversing mitochondrial membrane potential, respiration, and β-oxidation, suppressing mitochondrial oxidative stress, and enhancing mitochondrial turnover. Moreover, NTP increased the phosphorylation of AMPK, a critical factor in the regulation of mitochondrial function, and induced PGC-1β expression. Inhibition of AMPK activity and PGC-1β expression diminished the anti-steatotic effect of NTP in hepatocytes. JNK inhibition could also be associated with NTP-mediated inhibition of lipid accumulation, but we did not find the association between AMPK and JNK. These results suggest that NTP inhibits lipid accumulation by maintaining mitochondrial function in hepatocytes via AMPK activation, or by inhibiting JNK. [ABSTRACT FROM AUTHOR]

The Shiba shrimp Metapenaeus joyneri is a commercially important species in China, Korea, and Japan. Thus far, genetic information, which is essential for the sustainable management of the resource, is quite limited for this species. In this study, the complete mitochondrial genome of M. joyneri was originally determined. Its mitogenome is 16,008 bp in length and contains 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes, and one control region (CR). The overall base composition is 35.5, 32.7, 19.4, and 12.4% for A, T, C, and G, respectively. All PCGs are initiated by ATN codons. Four of the 13 PCGs harbor the incomplete termination codon T. Phylogenetic analysis among the available malacostracans species supports the current morphology-based hypothesis that M. joyneri grouped with Metapenaeus species. These data provide fundamental information for further conservation genetic and phylogenetic studies of M. joyneri. [ABSTRACT FROM AUTHOR]

Objectives It is known that the efficacy of azithromycin, in animal infection models, is best correlated with AUC/MIC. The pharmacokinetic–pharmacodynamic (PK–PD) relationship for azithromycin, however, has not been previously confirmed with clinical data. The objectives of this PK–PD analysis were to characterize exposure–response relationships for the efficacy and safety of azithromycin extended release (ER) in Japanese patients, and to evaluate the effects of potential covariates on the prediction of response. Methods Sparse serum azithromycin concentration, MIC, efficacy and safety data were collected from three Japanese Phase 3 studies of a 2 g single dose of azithromycin-ER for respiratory tract infections. These sparse concentration data were combined with data from eight Phase 1 PK studies in Japanese and Western populations, to develop a robust population PK model using a non-linear mixed effects approach. The exposure–response relationships for efficacy and safety were evaluated using logistic regression. Results A two-compartment model with first-order absorption and first-order elimination with a lag time adequately described the PK of azithromycin-ER, without any significant ethnic differences in AUC. The percentage of bacteriological and clinical success in patients with AUC/MIC > 5 (95.8% and 100%, respectively) was much higher than in those with AUC/MIC ≤ 5 (60.0% and 83.3%, respectively). Conclusions As expected, the probabilities of success in the clinical and bacteriological responses were positively associated with AUC/MIC, but not with AUC. For the exposure–safety relationship, the incidence of treatment-related diarrhoea was inversely associated with azithromycin exposure. [ABSTRACT FROM PUBLISHER]

Glycyrrhizic acid (GA) is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra). GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities. GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease. This review summarizes the current biological activities of GA and its medical applications in liver diseases. The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. This paper will be a useful reference for physicians and biologists researching GA and will open the door to novel agents in drug discovery and development from Chinese herbs. With additional research, GA may be more widely used in the treatment of liver diseases or other conditions.