European journal of clinical investigation
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Eur. J. Clin. Invest. · Dec 2024
The 1400 metabolite-mediated relationship between 91 inflammatory cytokines and migraine: An exploratory two-step Mendelian randomization study.
Inflammatory cytokines and migraines have been associated in previous research, but the underlying mechanisms of action are still elusive. The biological functions of metabolites are crucial in the onset of migraine. Our goals were to clarify the cause-and-effect connection between inflammatory cytokines and migraines and explore the potential mediating function of metabolites. ⋯ Our research findings provide evidence for both a causal connection between inflammatory cytokines and migraines, as well as a metabolite-mediated pathway. These biomarkers facilitate the detection, diagnosis and treatment of migraines while offering fresh perspectives on their underlying mechanisms.
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Eur. J. Clin. Invest. · Dec 2024
Insights into circulating CEACAM1 in insulin clearance and disease progression: Evidence from the Portuguese PREVADIAB2 study.
Type 2 diabetes (T2DM) and obesity are characterized by altered insulin metabolism and action. Reduced hepatic insulin clearance is increasingly recognized as a key contributor to hyperinsulinemia and insulin resistance. CEACAM1 promotes hepatic insulin clearance, and its loss in hepatocytes is associated with reduced insulin clearance in mice and men. This study examines whether CEACAM1 circulating levels reflect compromised insulin metabolism and resistance in the PREVADIAB2 cohort. ⋯ This study demonstrates a progressive increase in insulin resistance and hyperinsulinemia in parallel to elevated BMI and hepatic steatosis prevalence, accompanied by declining circulating CEACAM1 levels. Cluster analysis further linked reduced insulin clearance to lower circulating CEACAM1 levels, suggesting its potential usefulness as a biomarker for metabolic disease progression.
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Eur. J. Clin. Invest. · Dec 2024
The influence of hypoxia-mediated CEACAM6 upregulation on epithelial cell and macrophage response in the context of gastric cancer.
The hypoxic microenvironment is a key component of the gastric tumour niche. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is upregulated in gastric cancer and is considered a novel biomarker for the disease. However, no prior studies have elaborated on the status of CEACAM6 and its role in the hypoxic gastric cancer niche. ⋯ This study established that hypoxia increased CEACAM6 which promoted gastric cancer progression by influencing GCC proliferation and motility as well as macrophage polarization.
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CEACAM1 in leukocytes controls cell activation during inflammation. This and its expression in epithelial cells led to frequent independent appropriation of CEACAM1 as receptor by pathogens in humans and other species to gain host access and to downregulate its immune response. As a countermeasure, decoy receptors with CEACAM1-like pathogen-binding domains evolved. The granulocyte-specific human CEACAM3 endocytic receptor diverts CEACAM1-binding pathogens to neutrophils for internalization and destruction. The role of the glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 which can also bind CEACAM1-targeting pathogens in humans is less clear. ⋯ The glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 are under selection to maintain similarity to the pathogen receptor CEACAM1 in most primate species, indicating a function as decoy receptors.