Research progress on ginger polysaccharides: extraction, purification and structure-bioactivity relationship.

Ginger is a widespread source of herbal medicine and traditional spices. Among its various bioactive components, ginger polysaccharides (GPs) have attracted the attention of researchers worldwide because of their significant bioactivity. Recent studies have demonstrated the antioxidant, antitumour, anti-inflammatory, immunomodulatory, hypoglycaemic, cough suppressant and thrombotic anticoagulant effects of GPs. However, the structure-bioactivity relationship of GPs has yet to be comprehensively investigated. This review aims to explore all the current published studies on GPs. It further examines various aspects, including the extraction and purification methods, structure, bioactivity, application and structure-bioactivity relationship of GPs. Thus, this review intends to provide a reference for future GP-related research and development.

Yes-associated protein promotes the proliferation and differentiation of liver progenitor cells during liver fibrosis.

Liver fibrosis is closely related to the proliferation and differentiation of liver progenitor cells (LPCs). Yes-associated protein (YAP) is a key effector molecule of the Hippo signaling pathway and plays an important role in regulating cell proliferation and liver homeostasis. However, its role in LPCs proliferation and differentiation during liver fibrosis are not well understood. Using immunohistochemistry, immunofluorescence staining, quantitative PCR and Western blotting, we discovered that LPCs expansion and enhanced YAP expression in LPCs in either choline-deficient, ethionine-supplemented (CDE) diet or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-induced fibrotic mice, as well as in patients with liver fibrosis. By injecting adeno-associated virus vectors under the transcriptional control of Lgr5 promoter, we found that targeted knockdown of YAP in LPCs attenuated the CDE/DDC diet-induced ductular reaction and liver fibrosis. Using EdU incorporation and Cell Counting Kit-8 assays, we demonstrated that YAP can modulate LPCs proliferation. Importantly, spleen transplantation of YAP-overexpressing LPCs improved their ability to differentiate into hepatocytes and alleviated carbon tetrachloride-induced liver fibrosis. Collectively, our findings indicate that LPCs expansion and differentiation during liver fibrosis could be modulated by YAP, further suggesting the possibility of manipulating YAP expression in LPCs as a potential treatment for chronic liver diseases.

Exosomes derived from hepatitis B virus-infected hepatocytes promote liver fibrosis via miR-222/TFRC axis.

Exosomal miRNAs activates hepatic stellate cell (HSC) and promote fibrosis. miR-222 was found to be increased in hepatitis B virus (HBV)-infected hepatocytes, and ferroptosis was reported to ameliorate liver fibrosis (LF). Although miR-222 and ferroptosis have been implicated in LF, the association between miR-222 and ferroptosis and how they coordinate to regulate LF are still not explicit. This study investigates the roles of miR-222 and transferrin receptor (TFRC) in LF. Lipid reactive oxygen species (ROS) level was analyzed by flow cytometry. FerroOrange staining was used to measure intracellular iron level. Luciferase reporter assay was adopted to confirm the binding of miR-222 and TFRC. Real-time quantitative PCR and immunoblots were applied to analyze gene and protein expression. The results showed that supplementation of exosomes derived from HBV-infected LO2 cells remarkably enhanced LX-2 cell activation, evidenced by elevated hydroxyprolin (Hyp) secretion and α-SMA and COL1A2 expression. miR-222 was significantly increased in HBV-Exo. Overexpressing miR-222 upregulated cell viability, secretion of Hpy, and expression of α-SMA and COL1A2, which were all blocked by overexpression of TFRC. Further study showed that TFRC was a target of miR-222, and miR-222 promoted LX-2 cell activation through suppressing TFRC-induced ferroptosis in LX-2 cells. Exosomal miR-222 derived from HBV-infected hepatocytes promoted LF through inhibiting TFRC and TFRC-induced ferroptosis. This study emphasizes the significance of miR-222/TFRC axis in LF and suggests new insights in clinical decision making while treating LF. Exosomes derived from HBV-infected LO2 cells promote LX-2 cell activation and liver fibrosis in mouse Exosomal miR-222 derived from HBV-infected LO2 cells promotes LX-2 cell activation TFRC is a target of miR-222 and inhibits LX-2 cell activation induced by miR-222 miR-222 promotes LX-2 cell activation through inhibiting TFRC-induced ferroptosis.

Specific knockdown of Y-box binding protein 1 in hepatic progenitor cells inhibits proliferation and alleviates liver fibrosis.

The proliferation of hepatic progenitor cells (HPCs) contributes to liver regeneration and fibrogenesis during chronic liver injury; however, the mechanism modulating HPC proliferation remains unknown. Y-box binding protein-1 (YB-1) is a transcription factor that regulates the transcription of several genes and is highly expressed in liver injury. We explored the role of YB-1 in HPC proliferation and liver fibrosis. We detected increased expansion of HPCs and elevated levels of YB-1 in HPCs from patients with hepatitis B virus-related fibrosis and choline-deficient ethionine-supplemented or 5-diethoxycarbonyl-1,4-dihydrocollidine diet-induced mice compared with those in control groups. HPC-specific deletion of YB-1 using YB-1flox/flox; Foxl1-Cre+/- mice led to reduced HPC expansion and less collagen deposition in the liver tissues compared with that in Cre-/- mice. In cultured primary HPCs, YB-1 knockdown inhibited HPC proliferation. Further experiments indicated YB-1 negatively regulated p53 expression, and silencing of p53 blocked YB-1 knockdown-mediated inhibition of HPC proliferation. Collectively, YB-1 negatively regulates HPC proliferation and alleviates liver fibrosis by p53.

TGF-ß/YB-1/Atg7 axis promotes the proliferation of hepatic progenitor cells and liver fibrogenesis.

Hepatic fibrosis is characterized by excessive extracellular matrix deposition and ductular reactions, manifested as the expansion of hepatic progenitor cells (HPCs). We previously reported that the Y-box binding protein 1 (YB-1) in HPCs is involved in chronic liver injury. In this study, we constructed YB-1f/f Foxl1-Cre mice and investigated the role of YB-1 in HPC expansion in murine choline-deficient, ethionine-supplemented (CDE), and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) models. Liver injury and fibrosis were measured using hematoxylin and eosin (HE), Masson, and Sirius Red staining. HPC proliferation was detected using EdU and immunofluorescence (IF). Autophagic flow was measured by mCherry-GFP-LC3B staining and transmission electron microscopy (TEM). YB-1 expression was measured by immunofluorescence and western blotting. CUT & Tag analysis, chromatin immunoprecipitation, and RT-PCR were performed to explore the regulation of autophagy-related protein 7 (Atg7) transcription by YB-1. Our results indicated that liver injury was accompanied by high expression of YB-1, proliferative HPCs, and activated autophagy in the CDE and DDC models. YB-1f/f Cre+/- mice displayed less liver injury and fibrosis than YB-1f/f Cre-/- mice in the CDE and DDC models. YB-1 promoted proliferation and autophagy of HPCs in vitro and in vivo. Transforming growth factor-ß (TGF-ß) induced YB-1 nuclear translocation and facilitated the proliferation and autophagy of HPCs. YB-1 nuclear translocation promoted the transcription of Atg7, which is essential for TGF-ß/YB-1 mediated HPCs expansion in vitro and in vivo. In summary, YB-1 nuclear translocation induced by TGF-ß in HPCs promotes the proliferation and autophagy of HPCs and Atg7 participates in YB-1-mediated HPC-expansion and liver fibrosis.