From farm to fork and beyond! UV enhances Aryl hydrocarbon receptor-mediated activity of cruciferous vegetables in human intestinal cells upon colonic fermentation.

While the "farm to fork" strategy ticks many boxes in the sustainability agenda, it does not go far enough in addressing how we can improve crop nutraceutical quality. Here, we explored whether supplementary ultraviolet (UV) radiation exposure during growth of broccoli and Chinese cabbage can induce bioactive tryptophan- and glucosinolate-specific metabolite accumulation thereby enhancing Aryl hydrocarbon receptor (AhR) activation in human intestinal cells. By combining metabolomics analysis of both plant extracts and in vitro human colonic fermentation extracts with AhR reporter cell assay, we reveal that human colonic fermentation of UVB-exposed Chinese cabbage led to enhanced AhR activation in human intestinal cells by 23% compared to plants grown without supplementary UV. Thus, by exploring aspects beyond "from farm to fork", our study highlights a new strategy to enhance nutraceutical quality of Brassicaceae, while also providing new insights into the effects of cruciferous vegetables on human intestinal health.

Formyl peptide receptor 2 orchestrates mucosal protection against Citrobacter rodentium infection.

Citrobacter rodentium is an attaching and effacing intestinal murine pathogen which shares similar virulence strategies with the human pathogens enteropathogenic- and enterohemorrhagic Escherichia coli to infect their host. C. rodentium is spontaneously cleared by healthy wild-type (WT) mice whereas mice lacking Muc2 or specific immune regulatory genes demonstrate an impaired ability to combat the pathogen. Here we demonstrate that apical formyl peptide receptor 2 (Fpr2) expression increases in colonic epithelial cells during C. rodentium infection. Using a conventional inoculum dose of C. rodentium, both WT and Fpr2-/- mice were infected and displayed similar signs of disease, although Fpr2-/- mice recovered more slowly than WT mice. However, Fpr2-/- mice exhibited increased susceptibility to C. rodentium colonization in response to low dose infection: 100% of the Fpr2-/- and 30% of the WT mice became colonized and Fpr2-/- mice developed more severe colitis and more C. rodentium were in contact with the colonic epithelial cells. In line with the larger amount of C. rodentium detected in the spleen in Fpr2-/- mice, more C. rodentium and enteropathogenic Escherichia coli translocated across an in vitro mucosal surface to the basolateral compartment following FPR2 inhibitor treatment. Fpr2-/- mice also lacked the striated inner mucus layer that was present in WT mice. Fpr2-/- mice had decreased mucus production and different mucin O-glycosylation in the colon compared to WT mice, which may contribute to their defect inner mucus layer. Thus, Fpr2 contributes to protection against infection and influence mucus production, secretion and organization.

Investigation of knee control as a lower extremity injury risk factor: A prospective study in youth football.

This prospective study in youth football examined the relationship between frontal plane knee projection angle (FPKPA) during the single-leg squat and sustaining an acute lower extremity injury or acute non-contact lower extremity injury. Secondly, side-to-side asymmetry in FPKPA and sex as injury risk factors were explored. In addition, we investigated the influence of age, sex, and leg dominance on the FPKPA. A total of 558 youth football players (U11 to U14) participated in the single-leg squat test and prospective injury registration. FPKPA was not found as a risk factor for injuries at this age. There was no difference in the mean FPKPA between sexes. However, FPKPA was associated with age; oldest subjects displayed the smallest FPKPA. Among boys, the frontal plane knee control improved by age. Among girls, the relationship between age and FPKPA was not as clear, but the oldest girls displayed the smallest mean FPKPA in the study (12.2° ± 8.3°). The FPKPA was greater on the dominant kicking leg compared to the non-dominant support leg (P < .001 for boys, P = .001 for girls). However, side-to-side asymmetry in FPKPA was not associated with future injuries. In conclusion, frontal plane knee control in the single-leg squat was not associated with lower extremity injuries among young football players. As the single-leg squat to 90° knee flexion was too demanding for many subjects, easier single-leg squat test procedure or a different movement control test, such as a double-legged squat, could be more suitable for the young football players.

What formyl peptide receptors, if any, are triggered by compound 43 and lipoxin A4?

In this study, we determined receptor preferences for compound 43, a nitrosylated pyrazolone derivative, and the eicosanoid lipoxin A(4) (LXA(4)), potent anti-inflammatory mediators in many experimental in vivo models. Their effects have been suggested to be mediated through binding to formyl peptide receptor (FPR)2 [earlier known as formyl peptide receptor-like 1 or the lipoxin A(4) receptor (ALXR)], one of the two members of the FPR family expressed in neutrophils. Compound 43 activates all neutrophil functions investigated, whereas LXA(4) induces a unique inhibiting pathway suggested to involve ß-arrestin binding as an early signalling step, but not a transient rise in intracellular Ca(2+). We show that compound 43 can activate not only FPR2 but also FPR1, the other neutrophil receptor in the FPR family, and FPR1 is actually the preferred receptor in human neutrophils and possibly also in the murine equivalent. LXA(4) analogues from two commercial sources were used, and neither of these induced any translocation of ß-arrestin as measured in an enzyme fragment complementation assay. The conclusions drawn from these experiments are that neither compound 43 nor LXA(4) works as FPR2 agonists in neutrophils, findings of importance for a proper interpretation of results obtained with these compounds as regulators of inflammation.

Lipoxin A(4) metabolites/analogues from two commercial sources have no effects on TNF-alpha-mediated priming or activation through the neutrophil formyl peptide receptors.

The eicosanoid lipoxin A(4) (LXA(4)) is a potent anti-inflammatory mediator in many in vivo experimental models, and it has been proposed that the effects of this molecule are mediated through binding to FPR2 (also termed FPRL1 or ALXR), a member of the formyl peptide receptor family. Research has shown that LXA(4) inhibits neutrophil function, which has been suggested to be an important mechanism in the anti-inflammatory activity of this lipoxin. However, experiments demonstrating such an impact of LXA(4) have not always been convincing. In this study, we examined the influence of metabolically stable LXA(4) analogues on the biological activities induced by a previously characterized FPR2 agonist (WKYMWM) and a commonly used FPR1 agonist (fMLF). We also investigated the analogues regarding their direct effect on TNFalpha-mediated neutrophil mobilization of the complement receptor 3 (CR3) and their indirect effect on cytokine-dependent priming of the cells. The LXA(4) analogues we used came from two commercial sources. In our experiments, they did not induce any direct neutrophil response, nor did they affect the increase in the number of CR3 molecules on the neutrophil surface or the primed response. Therefore, we conclude that these LXA(4) analogues do not have an impact on TNF-alpha induced signalling in neutrophils. We also applied a recently described technique that has proven to be a valuable tool for identifying selective FPR1 and FPR2 agonists and antagonists. We found that the lipoxin analogues did not induce any changes in the neutrophil response, which implies that LXA(4) does not act through FPR2 in these cells.

Process indicators from ten centres in the Finnish breast cancer screening programme from 1991 to 2000.

The aim of this study was to evaluate the quality of the Finnish mammography programme by assessing process indicators from 10 screening centres using data from the first and subsequent screens. We compared these screen-specific indicators with European standards and results from countries with similar screening protocols. Ten Finnish centres invited approximately 1,000,000 women from 1991-2000. Women were mainly 50-64 years old. Mean compliance amongst this age group was 90% at the first and 93% at subsequent screens. The corresponding recall rates were 4.6% and 2.3%, respectively. The average breast cancer detection rates were 0.44% and 0.36%, respectively. The positive predictive values (PPVs) of mammography at the first and subsequent screens were 10% (range 7-20%) and 16% (range 12-31%), and the corresponding benign to malignant (B:M) biopsy ratios were 1:1 (range 0.5-1.8:1) and 0.4:1 (range 0.3-0.8:1). The PPV of mammography increased significantly during the study period, and the average process indicators fulfilled the criteria of the European community for the most part. However, the variation in PPVs was wide, as has been seen for other European mammography programmes, indicating meaningful differences in diagnostic criteria and potential adverse effects.