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Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine (GEM) with the molecular-targeted drug erlotinib (Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuli-responsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment

This work evaluated the anionic polysaccharides to improve the functional properties and antioxidant activities, and compared the effects on covalently-linked the soy protein isolate (SPI)- (–)-epigallocatechin-3-gallat (EGCG) binary complexes. The increasing molecular weight via covalent insertion of (–)-epigallocatechin-3-gallat (EGCG) into the soy protein isolate (SPI) was verified by SDS-PAGE. The addition of polysaccharides had no obvious effects on the molecular weight, indicating noncovalent insertion by adsorption. Fourier transform infrared spectroscopy (FT-IR) analysis suggested that SPI-EGCG complexes mixed with polysaccharides changed the secondary structures of SPI with a decrease in α-helix and an increase in β-turn. The emulsions exhibited better stability index (ESI) by adding polysaccharides than the binary complexes emulsion, with decreased particle sizes and increased absolute ζ-potential values, while the value of ESI for the pectin mixed increased more. The 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•) scavenging capacity of SPI-EGCG complexes with the addition of polysaccharides were both greater than 70 %. These findings indicated that anionic polysaccharides could be potentially used as a natural and safe alternative for regulating covalently-linked SPI-EGCG emulsion stability and improving emulsion oxidation resistance.

High-fat diet (HFD) promotes lung pre-metastatic niche formation and metastasis. Thus, there is an urgent need to identify the underlying mechanisms and develop strategies to overcome them. Here we demonstrate that glycyrrhizic acid (GA) prevents HFD-enhanced pre-metastatic niche formation and metastasis through gut microbiota. GA reduced HFD-enhanced myeloid-derived suppressor cell recruitment, pro-metastatic protein S100A8/A9 expression and metastasis burden of 4T1 breast cancer and B16F10 melanoma, accompanied by gut microbiota alteration and colonic macrophage polarization far away the M1-like phenotype. These parameters were greatly decreased by treatment with antibiotics, recolonization of Desulfovibrio vulgaris and Clostridium sordellii, and administration of lipopolysaccharide or deoxycholic acid. Macrophage depletion attenuated HFD-enhanced pre-metastatic niche formation and metastasis, but failed to further affect the effects of GA. Mechanistically, counteraction of HFD-enhanced gut microbiota dysbiosis by GA inhibited Gr-1+ myeloid cell migration and S100A8/A9 expression through decreasing the proportion of M1-like macrophages and their production of CCL2 and TNF-α in the colons via LPS/HMGB1/NF-κB signaling inactivation. Together, targeting the gut microbiota by GA to modulate colonic macrophages could be a novel strategy for the prevention of HFD-enhanced pre-metastatic niche formation and metastasis.

The aim of this work was to study the stability of oil-in-water emulsions formed by corn oil with rice bran protein and rice bran protein-catechin complexes, at a (+)-catechin concentration of 0.05%–0.25% (w/v). The experimental results showed that the addition of (+)-catechin decreased the α-helix and β-sheet content to 10.15% and 36.68%, respectively. The surface hydrophobicity increased, and the oil-water interfacial tension decreased to 11.52 mN/m. The emulsions using the rice bran protein-catechin complex (0.15%, w/v) showed the smallest droplet size and the best emulsifying properties. However, a (+)-catechin concentration above 0.20% (w/v) negatively affected the emulsion stability, with increasing droplet size and decreasing absolute ζ-potential values due to protein aggregation. Rheological behavior analyses suggested that the rice bran protein-catechin complex emulsion had higher viscosity and viscoelasticity than the emulsion formed with the control rice bran protein.