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The application of curcumin (Cur) in fat-free food is limited due to its poor water solubility, stability, and bioaccessibility. In this study, zein-gum arabic-tannic acid (zein-GA-TA) composite particles with high physical stability were fabricated to deliver Cur (ZGT-Cur). Their stability and in vitro release properties were also evaluated. The results showed that the thermal and photochemical stability of Cur was improved after loading into composite particles. Meanwhile, the retention rate of Cur in ZGT-Cur composite particles was enhanced compared with Z-Cur or ZG-Cur particles. Fourier transform infrared (FTIR) spectroscopy confirmed that the hydrogen bond within the particles was greatly enhanced after the addition of tannic acid (TA). The in vitro antioxidant activity of Cur in ZGT-Cur composite particles was higher in terms of 2,2'-azino-bis (ABTS) (93.64%) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) (50.41%) compared with Z-Cur or ZG-Cur particles. The bioaccessibility of Cur in ZGT-Cur composite particles was 8.97 times higher than that of free Cur. Therefore, the particles designed in this study will broaden the application of Cur in the food industry by improving its stability and bioaccessibility.

Mammary and extramammary Paget's Diseases (PD) are a malignant skin cancer characterized by the appearance of Paget cells. Although easily diagnosed, its pathogenesis remains unknown. Here, single-cell RNA-sequencing identified distinct cellular states, novel biomarkers, and signaling pathways-including mTOR, associated with extramammary PD. Interestingly, we identified MSI1 ectopic overexpression in basal epithelial cells of human PD skin, and show that Msi1 overexpression in the epidermal basal layer of mice phenocopies human PD at histopathological, single-cell and molecular levels. Using this mouse model, we identified novel biomarkers of Paget-like cells that translated to human Paget cells. Furthermore, single-cell trajectory, RNA velocity and lineage-tracing analyses revealed a putative keratinocyte-to-Paget-like cell conversion, supporting the in situ transformation theory of disease pathogenesis. Mechanistically, the Msi1-mTOR pathway drives keratinocyte-Paget-like cell conversion, and suppression of mTOR signaling with Rapamycin significantly rescued the Paget-like phenotype in Msi1-overexpressing transgenic mice. Topical Rapamycin treatment improved extramammary PD-associated symptoms in humans, suggesting mTOR inhibition as a novel therapeutic treatment in PD.

This study aimed to assess the effects of three major SCFAs (acetate, propionate, and butyrate) on NASH phenotype in mice. C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet and treated with sodium acetate, sodium propionate, or sodium butyrate during the 6-week feeding period. SCFA treatment significantly reduced serum levels of alanine aminotransferase and aspartate transaminase, the numbers of lipid droplets, and the levels of triglycerides and cholesterols in livers of the mice compared with control treatment. SCFAs also reduced MCD-induced hepatic aggregation of macrophages and proinflammatory responses. Among the three SCFAs, sodium acetate (NaA) revealed the best efficacy at alleviating MCD-induced hepatic steatosis and inflammation. Additionally, NaA increased AMP-activated protein kinase activation in the liver and induced the expression of fatty acid oxidation gene in both the liver and cultured hepatocytes. In vitro, NaA decreased MCD-mimicking media-induced proinflammatory responses in macrophages to a greater extent than in hepatocytes. These results indicated that NaA alleviates steatosis in a manner involving AMPK activation. Also, NaA alleviation of hepatic inflammation appears to be due to, in large part, suppression of macrophage proinflammatory activation. SCFAs may represent as a novel and viable approach for alleviating NASH.