Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity.
Bottom Line: Enriched fractions resulted in poly-ADP ribose polymerase (PARP) cleavage, suppression of NFκB, induction of IκBα, and reduction in NOS2 mRNA transcript levels.Our results show that human serum extracts enriched with endogenous long-chain hydroxy fatty acids possess anti-inflammatory and anti-proliferative activity.These findings support a hypothesis that the reduction of these metabolites with age may result in a compromised ability to defend against uncontrolled cell growth and inflammation, and could therefore represent a significant risk for the development of CRC.
Affiliation: Phenomenome Discoveries, Inc, Saskatoon, Saskatchewan, Canada. email@example.comShow MeSH
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Mentions: Organic serum extract was next subjected to flash column chromatography as described in the methods, resulting in 12 fractions which were subsequently analyzed by HPLC-MS to determine GTA content. Although other components were present in all the fractions, only fraction 9 out of the 12 was enriched for the C28 GTAs (referred to as the GTA+ve fraction). A GTA negative control fraction (fraction 8, lacking any detectable GTAs) was also selected for the studies described below. Representative total ion chromatograms, extracted mass spectra and selected ion chromatograms of the three C28 GTAs for the GTA-ve and GTA+ve fractions are shown in Figures 2A and 2B, respectively. By comparing the sums of the selected ion chromatograms of the three GTAs to the total ion currents, we estimated that the GTA+ve fraction contained approximately 21% C28 GTAs while the GTA-ve fraction had no detectable levels (bottom panel of Figures 2A and 2B). The non-GTA background components for both fractions were similar, and the most abundant non-GTA components in the GTA+ve fraction were also the most abundant components in the GTA-ve fraction. Therefore, the two fractions were compositionally similar other than the 21% GTA content of the GTA+ve fraction, which represented an approximately 143-fold enrichment of the three C28 GTA metabolites over the crude organic serum extract (as shown in Figure 1A). These fractionations were repeated several times with consistent results. We therefore concluded that the fractions were sufficiently matched for investigating biological activity as described below. For comparison, the relative levels of the three C28 GTAs from 40 pooled CRC patients' serum and serum from 40 matched control subjects is shown in Figure 2C.
Affiliation: Phenomenome Discoveries, Inc, Saskatoon, Saskatchewan, Canada. firstname.lastname@example.org