Liver mechanosignaling as a natural anti-hepatitis B virus mechanism.

The mechanisms underlying the natural control of hepatitis B virus (HBV) infection have long been an intriguing question. Given the wide physiological range of liver stiffness and the growing attention to the role of mechanical microenvironment in homeostasis and diseases, we investigated how physical matrix cues impact HBV replication. High matrix stiffness significantly inhibited HBV replication and activated YAP in primary hepatocyte culture system, a key molecule in mechanosignaling. YAP activation notably suppressed HBV transcription and antigen expression. Several YAP-induced genes exhibited strong anti-HBV effects. Single-cell analysis of liver tissue from male individuals with active HBV replication revealed a strong significant negative correlation between YAP signature activation and HBV transcript levels. Intraperitoneal administration of YAP small molecule agonist potently controls HBV in male mouse models. These findings unveil a mechanism that involves the mechanical environment of hepatocytes and YAP to clear hepatotropic viral infection in the liver, providing new perspectives for HBV cure studies and antiviral development.

Characterization of Three Polysaccharide-Based Hydrogels Derived from Laminaria japonica and Their Hemostatic Properties.

Three Laminaria japonica polysaccharides (LJPs) extracted via water extraction (LJP-W), acid extraction (LJP-A), and enzymatic extraction (LJP-E) were used as raw materials to be cross-linked with chitosan and polyvinyl alcohol to prepare hydrogels. Compared with conventional hydrogel systems, all three types of LJP-based polysaccharide hydrogels exhibited better swelling properties (14 times their original weight) and the absorption ability of simulated body fluid (first 2 h: 6-10%). They also demonstrated better rigidity and mechanical strength. Young's modulus of LJP-E was 4 times that of the blank. In terms of hemostatic properties, all three polysaccharide hydrogels did not show significant cytotoxic and hemolytic properties. The enzyme- and acid-extracted hydrogels (LJP-Gel-A and LJP-Gel-E) demonstrated better whole-blood coagulant ability compared with the water-extracted hydrogel (LJP-Gel-W), as evidenced by the whole blood coagulation index being half that of LJP-Gel-W. Additionally, the lactate dehydrogenase viabilities of LJP-Gel-A and LJP-Gel-E were significantly higher, at about four and three times those of water extraction, respectively. The above results suggested that LJP-Gel-A and LJP-Gel-E exhibited better blood coagulation capabilities than LJP-Gel-W, due to their enhanced platelet enrichment and adhesion properties. Consequently, these hydrogels are more conducive to promoting coagulation and have good potential for wound hemostasis.

Influence of Molecular Weight of Polysaccharides from Laminaria japonica to LJP-Based Hydrogels: Anti-Inflammatory Activity in the Wound Healing Process.

In this study, polysaccharides from Laminaria japonica (LJP) were produced by the treatment of ultraviolet/hydrogen peroxide (UV/H2O2) degradation into different molecular weights. Then, the degraded LJP were used to prepare LJP/chitosan/PVA hydrogel wound dressings. As the molecular weight of LJP decreased from 315 kDa to 20 kDa, the swelling ratio of the LJP-based hydrogels rose from 14.38 ± 0.60 to 20.47 ± 0.42 folds of the original weight. However, the mechanical properties of LJP-based hydrogels slightly decreased. With the extension of the UV/H2O2 degradation time, the molecular weight of LJP gradually decreased, and the anti-inflammatory activities of LJP-based hydrogels gradually increased. LJP that were degraded for 60 min (60-gel) showed the best inhibition effects on proinflammatory cytokines, while the contents of TNF-α, IL-6, and IL-1ß decreased by 57.33%, 44.80%, and 67.72%, respectively, compared with the Model group. The above results suggested that low Mw LJP-based hydrogels showed great potential for a wound dressing application.

Insight into the Double-Edged Role of Ferroptosis in Disease.

Ferroptosis, a newly described type of iron-dependent programmed cell death that is distinct from apoptosis, necroptosis, and other types of cell death, is involved in lipid peroxidation (LP), reactive oxygen species (ROS) production, and mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury, cancer, hepatic fibrosis, Parkinson's disease, and Alzheimer's disease. Therefore, ferroptosis has become one of the research hotspots for disease treatment and attracted extensive attention in recent years. This review mainly summarizes the relationship between ferroptosis and various diseases classified by the system, including the urinary system, digestive system, respiratory system, nervous system. In addition, the role and molecular mechanism of multiple inhibitors and inducers for ferroptosis are further elucidated. A deeper understanding of the relationship between ferroptosis and multiple diseases may provide new strategies for researching diseases and drug development based on ferroptosis.