Adaptable hydrogel networks with reversible connectivity have emerged as a promising platform for biomedical applications. Synthetic copolymers and low-molecular-weight gelators (LMWG) have been shown to form reversible hydrogels through self-assembly of the molecules driven by self-complementary hydrophobic interaction and hydrogen bonding. Here, inspired by the adhesive proteins secreted by mussels, we found that simply adding natural polyphenols, such as epigallocatechin gallate (EGCG) to amyloid fibrils present in the nematic phase, successfully drives the formation of hydrogels through self-assembly of the hybrid supramolecules. The hydrogels show birefringence under polarized light, indicating that the nematic orientation is preserved in the gel phase. Gel stiffness enhances with incubation time and with an increase in molecular ratios between polyphenol and fibrils, fibril concentration, and pH. The hydrogels are shear thinning and thermostable from 25 to 90 °C without any phase transition. The integrity of the trihydroxyl groups, the gallate ester moiety in EGCG, and the hydrophobicity of the polyphenols govern the interactions with the amyloid fibrils and thus the properties of the ensuing hydrogels. The EGCG-binding amyloid fibrils, produced from lysozyme and peptidoglycans, retain the main binding functions of the enzyme, inducing bacterial agglomeration and immobilization on both Gram-positive and Gram-negative bacteria. Furthermore, the antibacterial mechanism of the lysozyme amyloid fibril hydrogels is initiated by membrane disintegration. In combination with the lack of cytotoxicity to human colonic epithelial cells demonstrated for these hybrid supramolecules, a potential role in combating multidrug-resistant bacteria in biomedical applications is suggested, such as in targeting diseases related to infection of the small intestine.

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We previously reported that the expression of KIAA1199 in human colorectal tumors (benign and malignant) is markedly higher than that in the normal colonic mucosa. In this study, we investigated the functions of the protein encoded by this gene, which are thus far unknown. Immunostaining studies were used to reveal its subcellular localization, and proteomic and gene expression experiments were conducted to identify proteins that might interact with KIAA1199 and molecular pathways in which it might play roles. Using colon cancer cell lines, we showed that both endogenous and ectopically expressed KIAA1199 is secreted into the extracellular environment. In the cells, it was found mainly in the perinuclear space (probably the ER) and cell membrane. Both cellular compartments were also over-represented in lists of proteins identified by mass spectrometry as putative KIAA1199 interactors and/or proteins encoded by genes whose transcription was significantly changed by KIAA1199 expression. These proteomic and transcriptomic datasets concordantly link KIAA1199 to several genes/proteins and molecular pathways, including ER processes like protein binding, transport, and folding; and Ca2+, G-protein, ephrin, and Wnt signaling. Immunoprecipitation experiments confirmed KIAA1199’s interaction with the cell-membrane receptor ephrin A2 and with the ER receptor ITPR3, a key player in Ca2+ signaling. By modulating Ca2+ signaling, KIAA1199 could affect different branches of the Wnt network. Our findings suggest it may negatively regulate the Wnt/CTNNB1 signaling, and its expression is associated with decreased cell proliferation and invasiveness.

The diverse community of microbes present in the human gut has emerged as an important factor for cancer risk, potentially by altering exposure to chemical carcinogens. In the present study, human gut bacteria were tested for their capacity to transform the carcinogenic heterocyclic amine 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx). Eubacterium hallii, Lactobacillus reuteri, and Lactobacillus rossiae were able to convert MelQx to a new microbial metabolite characterized on the basis of high-resolution mass spectrometry and NMR as 9-hydroxyl-2,7-dimethyl-7,9,10,11-tetrahydropyrimido[2′,1′:2,3]imidazo[4,5-f]quinoxaline (MelQx-M1), resulting from conjugation with activated glycerol. Acrolein derived from the decomposition of 3-hydroxypropionaldehyde, which is the product of bacterial glycerol/diol dehydratase activity, was identified as the active compound responsible for the formation of MelQx-M1. A complex human gut microbial community obtained from invitro continuous intestinal fermentation was found to also transform MelQx to MelQx-M1. MelQx-M1 had slightly reduced cytotoxic potency toward human colon epithelial cells invitro, and diminished mutagenic potential toward bacteria after metabolic activation. As bacterially derived acrolein also transformed 2 other HCAs, namely 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3-methylimidazo[4,5-f]quinoline, these results generalize the capacity of gut microbiota to detoxify HCAs in the gut, potentially modulating cancer risk.

Nanotechnology offers new opportunities for providing health benefits in foods. Food fortification with iron phosphate nanoparticles (FePO NPs) is a promising new approach to reducing iron deficiency because FePO NPs combine high bioavailability with superior sensory performance in difficult to fortify foods. However, their safety remains largely untested. We fed rats for 90 days diets containing FePO NPs at doses at which iron sulfate (FeSO), a commonly used food fortificant, has been shown to induce adverse effects. Feeding did not result in signs of toxicity, including oxidative stress, organ damage, excess iron accumulation in organs or histological changes. These safety data were corroborated by evidence that NPs were taken up by human gastrointestinal cell lines without reducing cell viability or inducing oxidative stress. Our findings suggest FePO NPs appear to be as safe for ingestion as FeSO.