Antioxidative Hyaluronic Acid-Bilirubin Nanomedicine Targeting Activated Hepatic Stellate Cells for Anti-Hepatic-Fibrosis Therapy.

Liver fibrosis is a life-threatening and irreversible disease. The fibrosis process is largely driven by hepatic stellate cells (HSCs), which undergo transdifferentiation from an inactivated state to an activated one during persistent liver damage. This activated state is responsible for collagen deposition in liver tissue and is accompanied by increased CD44 expression on the surfaces of HSCs and amplified intracellular oxidative stress, which contributes to the fibrosis process. To address this problem, we have developed a strategy that combines CD44-targeting of activated HSCs with an antioxidative approach. We developed hyaluronic acid-bilirubin nanoparticles (HABNs), composed of endogenous bilirubin, an antioxidant and anti-inflammatory bile acid, and hyaluronic acid, an endogenous CD44-targeting glycosaminoglycan biopolymer. Our findings demonstrate that intravenously administered HABNs effectively targeted the liver, particularly activated HSCs, in fibrotic mice with choline-deficient l-amino acid-defined high-fat diet (CD-HFD)-induced nonalcoholic steatohepatitis (NASH). HABNs were able to inhibit HSC activation and proliferation and collagen production. Furthermore, in a murine CD-HFD-induced NASH fibrosis model, intravenously administered HABNs showed potent fibrotic modulation activity. Our study suggests that HABNs have the potential to serve as a targeted anti-hepatic-fibrosis therapy by modulating activated HSCs via CD44-targeting and antioxidant strategies. This strategy could also be applied to various ROS-related diseases in which CD44-overexpressing cells play a pivotal role.

Survival of Staphylococcus aureus in dried fish products as a function of temperature.

We evaluated the survival ability of Staphylococcus aureus and the production of Staphylococcal enterotoxin A (SEA) in dried filefishes and julienned squid at 10°, 24°, and 35 °C for 5 months. S. aureus survived longer at 10 °C than 24° and 35 °C, and better in dried julienned squid than dried filefishes. At 35 °C, the populations of S. aureus were rapidly diminished and undetectable in dried filefishes and julienned squid after 14 and 19 days, respectively. SEA production did not increase during the 5-month storage period, regardless of the temperature and type of dried fish products. Although it is advised to store dried fish products at 10 °C for quality control in retail markets, refrigerated temperature is more likely to facilitate the survival of S. aureus in dried fish products. Thus, dried fish products should be produced and stored under hygienic conditions.