Serum levels of lutein and DNA damage in lymphocytes of volunteers upon consumption of lutein-enriched fermented milk.

<p>Values represent “tail DNA” (%) (n = 10).</p>*<p>p<0.001 (Paired T test).</p

Relationships between serum levels (A, TI value; B, TM value) and net increments (C, TI value; D, TM value) of lutein after intervention and DNA damage after 20′ of repair.

<p>Lines represent mean fit lines and 95% regression prediction lines.</p

Diagnostic performance of metabolic biomarkers.

<p>ROC curves were plotted to describe performance characteristics of the indicated metabolites in the 57 subject cohort. The Area under the curve (AUC), 95% range of the interval of confidence (IC) and P values are indicated.</p

Identification of metabolites by co-elution with commercial standards.

<p>Extracted ion chromatograms of selected metabolites in plasma samples (purple lines) and commercial standards (blue lines) are shown. The metabolites are defined by their name, ID number, m/z (M+H), retention time, Human Metabolome Data Base ID number and molecular formula.</p

Protein expression in skin biopsies of CMT1A patients.

<p>Protein expression in skin biopsies of CMT1A patients.</p

Summary of the major changes in the expression of skin and plasma metabolites during progression of CMT1A.

<p>The loss of muscle and nerves is shown during severity of the disease as revealed by the CMT neuropathy score v2. The changes in biomarkers are illustrated by row thicknesses.</p

Scatter plots showing significant correlations between plasma metabolite levels and severity of the disease in CMT1A patients.

<p>Determination of the plasma levels of the metabolites was carried out by UHPLC-MS and its levels correlated with severity of the disease as assessed by CMTNSv2. Healthy controls (blue circles, n = 15), Mild (red squares, n = 15), Moderate (green diamonds, n = 18) and Severe (black triangles, n = 9) groups of CMT1A patients are represented. Metabolites related to (i) protein catabolism (upper row); (ii) mobilization of membrane lipids (middle row) and (iii) muscle biogenesis and the anti-apoptotic function (lower row) are represented. P-value is calculated by analysis of variance; r is the Spearman coefficient.</p

Analysis of plasma metabolome in CMT1A patients.

<p>(A), Representative UHPLC-MS total ion chromatogram of plasma samples. (B), Plot in a two-dimensional Cartesian coordinate system, with the axes (principal components, PC) representing the greatest variations in the data of Control (blue), Mild (red), Moderate (green) and Severe (black) states related to CMT1A. Three quality control (QC) injections per group are also represented in the plot for the four groups of individuals. 95% confidence ellipses are also included. Triplicate outliers of one of the samples in the Moderate group fall out of the ellipse. (C), Plot of distribution of the plasma samples defined by the two canonical variables (CV1 and CV2) obtained by Canonical Variate Analysis considering the 12 selected metabolites after forward stepwise Linear Discriminant Analysis. The 95% canonical ellipses are also included. Control subjects and mild, moderate and severe CMT1A patients are represented by blue circles, red squares, green diamonds and black triangles, respectively. (D), Histogram showing the content of the 12 metabolites in plasma samples of healthy (blue, n = 15) and CMT1A patients (yellow, n = 42). The results shown are the mean values ± S.E.M. *, P<<i>0</i>.<i>05</i> by <i>Student’s t test</i>.</p