Elucidation of the relationships between genotype, diet, and health requires accurate dietary assessment. In intervention and epidemiological studies, dietary assessment usually relies on questionnaires, which are susceptible to recall bias. An alternative approach is to quantify biomarkers of intake in biofluids, but few such markers have been validated so far. Here we describe the use of metabolomics for the discovery of nutritional biomarkers, using citrus fruits as a case study. Three study designs were compared. Urinary metabolomes were profiled for volunteers that had (a) consumed an acute dose of orange or grapefruit juice, (b) consumed orange juice regularly for one month, and (c) reported high or low consumption of citrus products for a large cohort study. Some signals were found to reflect citrus consumption in all three studies. Proline betaine and flavanone glucuronides were identified as known biomarkers, but various other biomarkers were revealed. Further, many signals that increased after citrus intake in the acute study were not sensitive enough to discriminate high and low citrus consumers in the cohort study. We propose that urine profiling of cohort subjects stratified by consumption is an effective strategy for discovery of sensitive biomarkers of consumption for a wide range of foods.

Rationale Adoptive transfer of cardiac progenitor cells (CPCs) has entered clinical application despite limited mechanistic understanding of the endogenous response following myocardial infarction (MI). Extracellular matrix (ECM) undergoes dramatic changes after MI and therefore might be linked to CPC-mediated repair. Objective Demonstrate the significance of Fibronectin (Fn), a component of the ECM, for induction of the endogenous CPC response to MI. Methods and Results This report shows that presence of CPCs correlates with expression of Fn during cardiac development and after MI. In vivo, genetic conditional ablation of Fn blunts CPC response measured 7 days after MI through reduced proliferation and diminished survival. Attenuated vasculogenesis and cardiogenesis during recovery was evident at the end of a 12 week follow-up period. Impaired CPC-dependent reparative remodeling ultimately leads to continuous decline of cardiac function in Fn knockout animals. In vitro, Fn protects and induces proliferation of CPCs via β1-Integrin-FAK-Stat3-Pim1 but Akt-independent mechanism. Conclusion Fn is essential for endogenous CPC expansion and repair needed for stabilization of cardiac function after MI.

The fibrinolytic pathway could play a critical role in TAA progression, via direct or indirect impact on ECM and consecutive modulation of TGF-β bioavailability.