Regulating immune homeostasis by targeting liver macrophage polarization is a potential therapeutic strategy for hepatic fibrosis. Chitooligosaccharide (COS) is a bioactive oligosaccharide possessing potent immunomodulatory and hepatoprotective effects. In this study the hepatoprotective effect of COS on hepatic fibrosis was examined in mice and the underlying mechanisms were investigated. Herein, mice were induced to hepatic fibrosis using carbon tetrachloride (CCl₄) and concurrently treated with COS orally. Kupffer cells (KCs) were skewed towards M1 macrophage polarization by lipopolysaccharide (LPS) and towards M2 macrophage polarization by interleukin-4 (IL-4) in vitro, which were utilized for COS treatment. The results showed that mice were rescued from hepatic fibrosis by COS, marked by a reduction in the deposition of the extracellular matrix (ECM) and histological lesions. COS had an inhibitory effect on the polarization of M1 and M2 macrophages both in vivo and in vitro, characterized by the raised biomarker of the M1 and M2 macrophages slipping towards the basal levels. Furthermore, COS inhibited the JAK2/STAT1 pathways on M1 macrophages and the JAK1/STAT6 pathways on M2 macrophages in KCs. In summary, this study revealed a molecular mechanism for the impact of COS effectiveness on the polarization of liver macrophages, suggesting that is could be a possible intervention for hepatic fibrosis.

The aim of this study was to investigate the occurrence of hepatitis E virus (HEV) in sewage samples in Shen Zhen, China. Sewage samples were collected from 152 sewage plants including livestock sewage, domestic sewage and treated sewage from May to July of 2015. Two of 152 samples were HEV positive (1.32%) from the livestock sewage plants. Partial ORF2 fragments of HEV were sequenced and a phylogenetic tree was constructed using MEGA5.1. Blast and phylogenetic analyses showed that both of these two sequences belonged to HEV Genotype 4. To the best of our knowledge, this is the first study on the molecular characterization of HEV in wastewater in China and the first time to detect Genotype 4 in the sewage. Results from this study indicate that the possibilities of sporadic infections of HEV should be emphasized because virus still has the possibility to be circulating in the sewage in China.

Hepatic fibrosis is a classic pathological manifestation of metabolic chronic hepatopathy. The pathological process might either gradually deteriorate into cirrhosis and ultimately liver cancer with inappropriate nutrition supply, or be slowed down by several multifunctional nutrients, alternatively. Herein, we found diet with excessive phenylalanine (Phe) and tyrosine (Tyr) exacerbated hepatic fibrosis symptoms of liver dysfunction and gut microflora dysbiosis in mice. Chitooligosaccharides (COS) could ameliorate hepatic fibrosis with the regulation of amino acid metabolism by downregulating the mTORC1 pathway, especially that of Phe and Tyr, and also with the alleviation of the dysbiosis of gut microbiota, simultaneously. Conclusively, this work presents new insight into the role of Phe and Tyr in the pathologic process of hepatic fibrosis, while revealing the effectiveness and molecular mechanism of COS in improving hepatic fibrosis from the perspective of metabolites.