Molecular Mechanisms of Iron Transport and Homeostasis Regulated by Antarctic Krill-Derived Heptapeptide-Iron Complex.

In this study, the molecular mechanisms of iron transport and homeostasis regulated by the Antarctic krill-derived heptapeptide-iron (LVDDHFL-iron) complex were explored. LVDDHFL-iron significantly increased the hemoglobin, serum iron, total iron binding capacity levels, and iron contents in the liver and spleen to normal levels, regulated the gene expressions of iron homeostasis, and enhanced in vivo antioxidant capacity in iron-deficiency anemia mice (P < 0.05). The results revealed that iron ions within LVDDHFL-iron can be transported via the heme transporter and divalent metal transporter-1, and the absorption of LVDDHFL-iron involved receptor-mediated endocytosis. We also found that the transport of LVDDHFL-iron across cells via phagocytosis was facilitated by the up-regulation of the high mobility group protein, heat shock protein ß, and V-type proton ATPase subunit, accompanied by the regulatory mechanism of autophagy. These findings provided deeper understandings of the mechanism of LVDDHFL-iron facilitating iron absorption.

Iron Complexes with Antarctic Krill-Derived Peptides Show Superior Effectiveness to Their Original Protein-Iron Complexes in Mice with Iron Deficiency Anemia.

Antarctic krill protein-iron complex and peptide-iron complex were acquired to investigate their iron bioavailability, expression of iron-regulated genes, and in vivo antioxidant capacity. Results indicated that the Antarctic krill peptide-iron complex significantly increased the hemoglobin (Hb), serum iron (SI), and iron contents in the liver and spleen in iron-deficiency anemia (IDA) mice (p < 0.05) compared with those of the Antarctic krill protein-iron complex. Despite the gene expressions of the divalent metal transporter 1(DMT1), the transferrin (Tf), and the transferrin receptor (TfR) being better regulated by both Antarctic krill peptide-iron complex and protein-iron complex, the relative iron bioavailability of the Antarctic krill peptide-iron complex group (152.53 ± 21.05%) was significantly higher than that of the protein-iron complex group (112.75 ± 9.60%) (p < 0.05). Moreover, Antarctic krill peptide-iron complex could enhance the antioxidant enzyme activities of superoxidase dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce the malondialdehyde (MDA) level in IDA mice compared with the protein-iron complex, and reduce the cell damage caused by IDA. Therefore, these results indicated that Antarctic krill peptide-iron complex could be used as a highly efficient and multifunctional iron supplement.

Effects of sulforaphane on breast cancer based on metabolome and microbiome.

Sulforaphane (SFN) is a promising phytochemical with a wide range of antitumor activities. A comprehensive understanding of the effects of SFN on breast cancer based on the metabolome and microbiome is limited. Thus, we treated MCF-7 cell-transplanted nude mice with 50 mg/kg SFN. SFN inhibits breast cancer cell proliferation. SFN increased the levels of sulfate-related metabolites and glutathione-related metabolites and decreased tryptophan metabolites and methyl-purine metabolites in urinary metabolic profile. SFN indirectly affected the activation of aryl hydrocarbon receptor by tryptophan metabolism. The ratio of SAM to methionine was decreased by SFN while the global DNA methylation was downregulated in tumor tissue. SFN decreased the sulfate-reducing bacterium Desulfovibrio, which is related to reduced methylation capacity, and increased the genus Lactobacillus related to tryptophan metabolites with antitumor activities. In conclusion, we provide a perspective on the metabolome and microbiome to elucidate the antitumor activities of SFN.

A highly sensitive sensor for carcinoembryonic antigen based on AlGaN/GaN high-electron-mobility transistors.

Carcinoembryonic antigen (CEA) is a well-known biomarker and validated serum biomarker for lung cancer. We introduce a simple label-free method for CEA detection. Specific recognition of CEA was made possible by immobilizing CEA antibodies in the sensing region of AlGaN/GaN high-electron-mobility transistors. The biosensors have a detection limit of 1 fg ml-1in phosphate buffer solution. This approach has advantages of integration, miniaturization, low cost, and rapid detection compared to other testing methods for lung cancer and could be used in future medical diagnostics.

Iron delivery systems for controlled release of iron and enhancement of iron absorption and bioavailability.

Iron deficiency is a global nutritional problem, and adding iron salts directly to food will have certain side effects on the human body. Therefore, there is growing interest in food-grade iron delivery systems. This review provides an overview of iron delivery systems, with emphasis on the controlled release of iron during gastrointestinal digestion, as well as the enhancement of iron absorption and bioavailability. Iron-bearing proteins are easily degraded by digestive enzymes and absorbed through receptor-mediated endocytosis. Instead, protein aggregates are slowly degraded in the stomach, which delays iron release and serves as a potential iron supplement. Amino acids, peptides and polysaccharides can bind iron through iron binding sites, but the formed compounds are prone to dissociation in the stomach. Moreover, peptides and polysaccharides can deliver iron by mediating the formation of ferric oxyhydroxide which is absorbed through endocytosis or bivalent transporter 1. In addition, liposomes are unstable during gastric digestion and iron is released in large quantities. Complexes formed by polysaccharides and proteins, and microcapsules formed by polysaccharides can delay the release of iron in the gastric environment and prolong iron release in the intestinal environment. This review is conducive to the development of iron functional ingredients and dietary supplements.

Exploration of iron-binding mode, digestion Kinetics, and iron absorption behavior of Antarctic Krill-derived heptapeptide-iron complex.

A novel heptapeptide LVDDHFL derived from Antarctic krill was used to assemble an iron complex, of which the iron-binding mode, in vitro digestion kinetics, and iron absorption behavior were explored. Fe2+ bound to one carboxyl oxygen atom of Asp at position 4 and the imidazole group of His at position 5 on the LVDDHFL peptide at a stoichiometric ratio of 1:2, which induced the folding of LVDDHFL to form a more orderly structure. LVDDHFL-iron significantly enhanced the solubility of iron as compared to FeSO4 in the gastroduodenal tract (P < 0.05), making it up to 80.92 ± 3.02% at the end of gastroduodenal digestion. Moreover, iron complexation can enhance the digestive stability of LVDDHFL with the peptide retention rate as 62.26 ± 2.60% and approximately 27.54% of LVDDHFL were degraded to hexapeptide LVDDHF. Nevertheless, the enhancement of LVDDHF - iron on iron absorption was comparable to that of LVDDHFL - iron, but better than that of FeSO4.

Calcium Delivery Systems Assembled using Antarctic Krill Derived Heptapeptides: Exploration of the Assembly Mechanism, In Vitro Digestion Profile, and Calcium Absorption Behavior.

A novel heptapeptide QEELISK derived from Antarctic krill was used to assemble a calcium delivery system, of which the calcium binding mechanism of QEELISK, in vitro digestion kinetics, and calcium absorption behaviors were explored. QEELISK with continuous Glu possessed higher calcium binding capacity than that of QELEISK and QAALISK. Ca2+ bound to the carboxyl oxygen of Glu at position 3 of the QEELISK peptide at a stoichiometric ratio of 1:1 through charge-charge interaction; the formed QEELISK-Ca showed superior stability. Moreover, QEELISK-Ca underwent disaggregation and self-assembly during in vitro digestion reflected by visualization of calcium ions and circular dichroism spectra. QELEISK was partially stable during gastrointestinal digestion, and calcium chelation improved the digestive stability of QELEISK. In addition, a significant enhancement of calcium absorption with QELEISK-Ca occurred in the duodenum and ileum when compared to CaCl2 absorption, which indicated that QEELISK might carry calcium ions through the gastrointestinal tract.

Antarctic krill-derived peptides with consecutive Glu residues enhanced iron binding, solubility, and absorption.

Three peptides containing three glutamic acid (Glu) residues at different positions derived from Antarctic krill were obtained to investigate their iron-binding properties, digestive stability, and effectiveness on enhancing iron solubility and absorption. Results indicated that Fe2+ bound to the carbonyl, carboxyl, or hydroxyl groups of DELEDSLER, EEEFDATR, and DTDSEEEIR at stoichiometric ratios of 0.453, 0.466, and 0.490, respectively. DTDSEEEIR with three consecutive Glu in the middle of the sequence possessed higher iron-binding ability and iron release potential than EEEFDATR with three consecutive Glu in the N-terminal, and DELEDSLER with three discontinuous Glu showed the lowest values. Although EEEFDATR showed remarkably lower digestion stability than DTDSEEEIR, the effect of EEEFDATR-iron on iron solubility and absorption was comparable to that of DTDSEEEIR-iron, but better than that of DELEDSLER-iron and FeSO4. Thus, peptides with consecutive Glu have the potential as an effective iron carrier to improve iron absorption.

Antarctic Krill Derived Nonapeptide as an Effective Iron-Binding Ligand for Facilitating Iron Absorption via the Small Intestine.

A novel nonapeptide DTDSEEEIR identified from Antarctic krill (Euphausia superba) iron-binding peptides was used in this study to analyze its iron-binding sites and structural changes after iron coordination. The enzymatic resistance and transport of DTDSEEEIR-iron during gastrointestinal digestion and absorption as well as the relationship between the DTDSEEEIR stability and the enhancement of iron absorption were further explored. Results revealed that iron ions spontaneously bound to the carboxyl, hydroxyl, and amino groups of the DTDSEEEIR peptide, which induced the folding of DTDSEEEIR to form a more orderly structure. The DTDSEEEIR peptide remained stable to a certain extent (79.60 ± 0.19%) after gastrointestinal digestion and the coordination of iron improved the digestive stability of the DTDSEEEIR peptide (93.89 ± 1.37%). Moreover, the stability of DTDSEEEIR across intestinal epithelium had a positive effect on iron absorption, which implied that DTDSEEEIR might carry iron ions through intestinal epithelial cells.