Targeting macrophagic 17β-HSD7 by fenretinide for the treatment of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and macrophage polarization plays an important role in its pathogenesis. However, which molecule regulates macrophage polarization in NAFLD remains unclear. Herein, we showed NAFLD mice exhibited increased 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7) expression in hepatic macrophages concomitantly with elevated M1 polarization. Single-cell RNA sequencing on hepatic non-parenchymal cells isolated from wild-type littermates and macrophage-17β-HSD7 knockout mice fed with high fat diet (HFD) for 6 weeks revealed that lipid metabolism pathways were notably changed. Furthermore, 17β-HSD7 deficiency in macrophages attenuated HFD-induced hepatic steatosis, insulin resistance and liver injury. Mechanistically, 17β-HSD7 triggered NLRP3 inflammasome activation by increasing free cholesterol content, thereby promoting M1 polarization of macrophages and the secretion of pro-inflammatory cytokines. In addition, to help demonstrate that 17β-HSD7 is a potential drug target for NAFLD, fenretinide was screened out from an FDA-approved drug library based on its 17β-HSD7 dehydrogenase inhibitory activity. Fenretinide dose-dependently abrogated macrophage polarization and pro-inflammatory cytokines production, and subsequently inhibited fat deposition in hepatocytes co-cultured with macrophages. In conclusion, our findings suggest that blockade of 17β-HSD7 signaling by fenretinide would be a drug repurposing strategy for NAFLD treatment.

Features and clinical significance of nutritional metabolism in patients with primary liver cancer / 临床肝胆病杂志

Nutritional metabolism is closely associated with the treatment of tumors and is an important research field in China and foreign countries. On the one hand, the use of nutrient metabolism pathway molecules as therapeutic targets has become a new direction in the field of biomedical research; on the other hand, poor nutritional status in patients with tumors will lead to the fact that the patients cannot be treated or have severe adverse reactions or poor prognosis, and thus it has always been a hot research topic. The liver is a metabolic organ, and the metabolism of liver tumors is different from that of tumors in other parts. Therefore, the research on nutritional metabolism in patients with liver cancer is of particular importance. This article elaborates on the changes in the metabolism of glucose, lipids, proteins, and amino acids and related molecular mechanisms in patients with primary liver cancer, in order to provide thoughts for selecting nutrient metabolism pathways in patients with liver cancer, identifying specific markers for liver cancer, and solving the issue of nutritional support during treatment and provide a reference for the research on nutritional metabolism of liver cancer.

The development of techniques for liquid level detection in auto clinical laboratory analyzers / 生物医学工程学杂志

Liquid level detection (LLD) is necessary for eliminating carry-over of needle's outside by limiting the depth the needle probes into liquid in auto clinical laboratory analyzers. This paper listed various demands of liquid-handling system under different situations; reviewed various LLD techniques, such as capacitive, air pressure, mechanical vibration, ultrasound, light reflection, CCD imaging etc.; briefly introduced the working principles, features, and limitation of the LLDs; and recapitulated the characteristics of contact and non-contact LLDs. Lastly, the next generation technique of LLD is prospected.