Activation of Kupffer cells (KCs) by gut-derived lipopolysaccharide (LPS) instigates nuclear factor-κB (NF-κB)-mediated inflammatory responses in alcohol-associated liver diseases (ALD). Here, we utilized a novel optogenetically engineered exosome technology called ‘exosomes for protein loading via optically reversible protein–protein interactions (EXPLOR)’ to efficiently deliver the super-repressor IκB-loaded exosomes (Exo-srIκB) to the liver and examined its therapeutic potential in acute-on-chronic alcohol-associated liver injury. We detected enhanced uptake of DiI-labeled Exo-srIκB by LPS-treated inflammatory KCs, which suppressed LPS-induced inflammatory gene expression levels. In animal experiments, a single intravenous injection of Exo-srIκB prior to alcohol binge drinking significantly attenuated alcohol-associated hepatic steatosis and infiltration of neutrophils and macrophages but not a liver injury. Notably, three consecutive days of Exo-srIκB injection remarkably reduced alcohol-associated liver injury, steatosis, apoptosis of hepatocytes, fibrosis-related gene expression levels in hepatic stellate cells, infiltration of neutrophils and macrophages, and inflammatory gene expression levels in hepatocytes and KCs. In particular, the above effects occurred with inhibition of nuclear translocation of NF-κB in liver tissues, and these beneficial effects of Exo-srIκB on ALD were shown regardless of doses. Our results suggest an exosome-based modulation of NF-κB activity in KCs by Exo-srIκB as a novel and efficient therapeutic approach in ALD.

Although tremendous research has reported the protective effects of natural compounds in nonalcoholic fatty liver disease (NAFLD), there is still no approved drug. This study aimed to examine the efficacy of Panax ginseng in NAFLD in preclinical studies. A total of 41 studies were identified by searching the PubMed, Web of Science, and Cochrane Library databases. The methodological quality was assessed by the risk of bias tool from the Systematic Review Center for Laboratory Animal Experimentation. The standardized mean difference (SMD) with a 95% confidence interval was calculated, and the random effects model was used to examine overall efficacy or heterogeneity. The publication bias was analyzed by Egger’s test. The results showed that Panax ginseng treatment significantly reduced the systemic levels of alanine aminotransferase (SMD: −2.15 IU/L; p < 0.0001), aspartate aminotransferase (SMD: −2.86 IU/L; p < 0.0001), triglyceride (SMD: −2.86 mg/dL; p < 0.0001), total cholesterol (SMD: −1.69 mg/dL; p < 0.0001), low-density lipoprotein (SMD: −1.46 mg/dL; p < 0.0001), and fasting glucose (SMD: −1.45 mg/dL; p < 0.0001) while increasing high-density lipoprotein (SMD: 1.22 mg/dL; p = 0.0002) in NAFLD regardless of animal models or species. These findings may suggest that Panax ginseng is a promising therapeutic agent for NAFLD treatment.

Long-lived wild rodents closely related to laboratory mice on the evolutionary scale may allow identification of dormant pathways that resist aging. Spiny mice ( Acomys ) are known for their exceptional regenerative capacity, but their resilience to aging is unknown. Here, we report that aged golden spiny mice ( Acomys russatus ), reared in a non–pathogen-free environment, resist functional decline, have a greater repair capacity with reduced senescence in immune-metabolic organs compared to their sister species, eastern spiny mice ( Acomys dimidiatus ). Aged A. russatus maintains transcriptional integrity akin to young mice, highlighting experimental checkpoints for inflammation and mortality. We identified that elevated levels of clusterin in A. russatus macrophages restrain inflammaging and enhance health span in aged mice. Thus, A. russatus biology reveals therapeutically actionable targets that may enhance or maintain function during aging.