Pregnancy triggers well-known alterations in maternal glucose and lipid balance but its overall effects on systemic metabolism remain incompletely understood. Detailed molecular profiles (87 metabolic measures and 37 cytokines) were measured for up to 4260 women (24–49 years, 322 pregnant) from three population-based cohorts in Finland. Circulating molecular concentrations in pregnant women were compared to those in non-pregnant women. Metabolic profiles were also reassessed for 583 women 6 years later to uncover the longitudinal metabolic changes in response to change in the pregnancy status. Compared to non-pregnant women, all lipoprotein subclasses and lipids were markedly increased in pregnant women. The most pronounced differences were observed for the intermediate-density, low-density and high-density lipoprotein triglyceride concentrations. Large differences were also seen for many fatty acids and amino acids. Pregnant women also had higher concentrations of low-grade inflammatory marker glycoprotein acetyls, higher concentrations of interleukin-18 and lower concentrations of interleukin-12p70. The changes in metabolic concentrations for women who were not pregnant at baseline but pregnant 6 years later (or vice versa) matched (or were mirror-images of) the cross-sectional association pattern. Cross-sectional results were consistent across the three cohorts and similar longitudinal changes were seen for 653 women in 4-year and 497 women in 10-year follow-up. For multiple metabolic measures, the changes increased in magnitude across the three trimesters. Pregnancy initiates substantial metabolic and inflammatory changes in the mothers. Comprehensive characterisation of normal pregnancy is important for gaining understanding of the key nutrients for fetal growth and development. These findings also provide a valuable molecular reference in relation to studies of adverse pregnancy outcomes.

The type of tumor‐infiltrating macrophages may be decisive in tumor immunity, lymphangiogenesis and in the clinical outcome of cancer. Here, we elucidated the prognostic significance of lymphatic vessels, different types of macrophages and the balance between different macrophage types in colorectal cancer. We analyzed the impact of density, type and location of macrophages on the clinical behavior of 159 primary colorectal carcinomas using CD68 as a pan‐macrophage marker and CLEVER‐1/Stabilin‐1 as a marker for regulatory/suppressive macrophages. Podoplanin was used as a pan‐lymphatic vessel marker. A high number of CLEVER‐1/Stabilin‐1⁺ peritumoral macrophages positively correlated with survival (p = 0.04). However, in more advanced disease (Stage IV), the patients with a high number of peritumoral or intratumoral CLEVER‐1/Stabilin‐1⁺ macrophages had a shorter disease‐specific survival (p = 0.05, and p = 0.008, respectively). Moreover, a low number of suppressive intratumoral CLEVER‐1/Stabilin‐1⁺ macrophages among high numbers of CD68⁺ macrophages correlated with a low number of distant recurrences (p = 0.01) and to fewer disease relapses exclusively in the liver as well (p = 0.006). A high number of intratumoral lymphatics correlated with poor survival (p = 0.03). The results of this work suggest that the type of macrophages, number of lymphatic vessels and their location contribute to the clinical behavior of colorectal cancer in a disease stage‐specific manner.

Ectoenzymes with a catalytically active domain outside the cell surface have the potential to regulate multiple biological processes. A distinct class of copper‐containing semicarbazide‐sensitive monoamine oxidases, expressed on the cell surface and in soluble forms, oxidatively deaminate primary amines. Via transient covalent enzyme–substrate intermediates, this reaction results in production of aldehydes, hydrogen peroxide and ammonium, which are all biologically active substances. The physiological functions of these enzymes have remained unknown, although they have been suggested to be involved in the metabolism of biogenic amines. Recently, new roles have been proposed for these enzymes in regulation of glucose uptake and, even more surprisingly, in leukocyte–endothelial cell interactions. The emerging functions of ectoenzymes in signalling and cell–cell adhesion suggest a novel mode of molecular control of these complex processes.