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Human monocyte-derived dendritic cells (DCs) exposed to pathogen-associated molecular patterns (PAMPs) undergo bioenergetic changes that influence the immune response. We found that stimulation with PAMPs enhanced glycolysis in DCs, whereas oxidative phosphorylation remained unaltered. Glucose starvation and the hexokinase inhibitor 2-deoxy-d-glucose (2-DG) modulated cytokine expression in stimulated DCs. Strikingly, IL23A was markedly induced upon 2-DG treatment, but not during glucose deprivation. Since 2-DG can also rapidly inhibit protein N-glycosylation, we postulated that this compound could induce IL-23 in DCs via activation of the endoplasmic reticulum (ER) stress response. Indeed, stimulation of DCs with PAMPs in the presence of 2-DG robustly activated inositol-requiring protein 1α (IRE1α) signaling and to a lesser extent the PERK arm of the unfolded protein response. Additional ER stressors such as tunicamycin and thapsigargin also promoted IL-23 expression by PAMP-stimulated DCs. Pharmacological, biochemical, and genetic analyses using conditional knockout mice revealed that IL-23 induction in ER stressed DCs stimulated with PAMPs was IRE1α/X-box binding protein 1-dependent upon zymosan stimulation. Interestingly, we further evidenced PERK-mediated and CAAT/enhancer-binding protein β-dependent trans-activation of IL23A upon lipopolysaccharide treatment. Our findings uncover that the ER stress response can potently modulate cytokine expression in PAMP-stimulated human DCs.

Brewer's spent grain (BSG) was dried via infra-red drying (IRD) or hot-air drying (HAD) and milled into fine powders. Proximate analysis (moisture, protein, fat, ash, carbohydrates by difference), water activity, dietary fiber, total soluble phenolics, and antioxidant capacity analyses were performed to characterize and compare both types of BSG powders. Mice feeding of the two types of dried BSG, each at three different concentrations, was conducted to compare the effects of the two types of dried BSG on health indicators and to determine evidence of dose response. Weights of body, feed intake, adipose tissue, kidney, and liver were recorded; blood plasma, cholesterol, liver fat, and fecal fat and protein were also measured.Significant differences were observed for liver and adipose tissue, cholesterol, and fecal protein between mice fed diets with different concentrations of BSG compared to the control diet. The analysis of hormones related to type II diabetes and metabolic syndrome did not show differences between the hormones examined, except for ghrelin and leptin, which are directly correlated with increased white adipose tissue in mice consuming high fat diets. No differences in health indicators were found in mice fed with the two different types of BSG. Mice fed with HAD and IRD BSG diets increased the relative abundance of Firmicutes and Bacteroidetes phylum microbiota compared to control diet, with no differences due to the type and concentrations of BSG in mice diets. The present results suggest that increasing levels of BSG incorporated into human foods may impart health benefits.

The cyclophanes 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10, 24,27,30,33-octaaza-17,40-dioxa[10.1.10.1]paracyclophane (PO) and 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10,24,27,30,33-octaaza[10.1.10.1]paracyclophane (PC) were coordinated with iron to form cationic binuclear Fe(III) Fe2PO and Fe2PC complexes, respectively. Their antioxidant capacity, superoxide dismutase and peroxidase mimetic activity, as well as their toxicity toward peripheral blood mononuclear cells (PBMCs) were evaluated. Both Fe2PO and Fe2PC are interesting biomimetics with antioxidant capacity similar to that of ascorbic acid that prevent mortality in cultured PBMCs, with the potential to have bioactive and protective functions in disease animal models.