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Backgrounds: Drug-induced liver injury (DILI) is a major causal factor for failure in clinical trials and withdrawal of drugs from pharmaceutical markets. Therefore, a human cell-based in vitro system has been established to overcome the limitations of preclinical trials. However, previous studies focused on the drug metabolism in each cell line or described to be superior in one single cell line for assessing DILI. In this study, we used Huh7, HepaRG, and Hepatosight-S cells to evaluate the liver toxicity and dysfunction driven by DILI-inducing drugs. Methods: Cytotoxicity of 17 DILI-inducing drugs was assessed by LDH release assay and the drug-induced liver dysfunction was confirmed by albumin secretion. Furthermore, we analyzed the expression levels of phase I and phase II enzymes and nuclear receptors in each cell lines. Results: DILI-inducing drugs were differently detected in each cell line because each cell line differs on the expression of drug metabolic enzymes which associated with reactivity on DILI inducing drugs. Conclusion: To predict the responses of DILI-inducing drugs in human liver cells, using diverse cell lines having different drug metabolic capabilities is more suitable for predicting DILI.

Aims and objectives To identify whether meaning in life has moderating and mediating effects on the relationship between depression and quality of life in patients with dysphagia. Background Dysphagic patients typically have multidimensional problems, such as depression, which can negatively influence their quality of life. Meaning in life, therefore, can be used as a psychological resource that may enhance quality of life for these patients. Design A descriptive cross-sectional research design was used. Methods Ninety patients with dysphagia were recruited for a survey from eight general and rehabilitation hospitals in Korea. The questionnaires, which included the Korean version of the Swallowing Quality of Life scale developed by Cha, the Center for Epidemiological Studies-Depression Scale developed by Radloff, and the Purpose in Life test developed by Crumbaugh and Maholick, were used for data collection. Descriptive statistics, Hayes' PROCESS macro and Cronbach's alpha were used for data analyses. Results Meaning in life was found to mediate the relationship between depression and quality of life in patients with dysphagia. However, the index of moderation was not statistically significant, which mean that meaning in life did not moderate the relationship between the patients' depression and quality of life. Conclusions Meaning in life had a mediating effect on the relationship between depression and quality of life in patients with dysphagia. Thus, to improve the quality of life of patients with dysphagia, nurses should apply interventions to help them find meaning in life. Relevance to clinical practice Meaning in life can be used as a nursing intervention strategy to improve the quality of life for patients living with dysphagia and depression.

Ceramide metabolism is known to be an essential etiology for various diseases, such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main ceramide metabolism pathway in mammalian cells. In this article, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The reaction products, C8-GlcCer for GCS, could be separated on a C18 column by reverse-phase high-performance liquid chromatography (HPLC). Quantification was conducted using the multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 588.6 → 264.4 for C8-GlcCer at positive ionization mode. The calibration curve was established over the range of 0.625–160 ng/mL, and the correlation coefficient was larger than 0.999. This method was successfully applied to detect GCS in the human hepatocellular carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells. We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved that this method could be successfully applied to GCS inhibitor screening of preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic dermatitis and Gaucher disease.