In Vitro Lipophilic Antioxidant Capacity, Antidiabetic and Antibacterial Activity of Citrus Fruits Extracts from Aceh, Indonesia.

This study reports in vitro lipophilic antioxidant, inhibition of α-amylase and antibacterial activities of extracts of peel and pulp of citrus samples from Aceh, Indonesia. HPLC (high-performance liquid chromatography), phytochemical, and FTIR (fourier transform infrared) analysis detected carotenoids, flavonoids, phenolic acids and terpenoids, contributing to the biological potencies. Most peel and pulp extracts contained lutein and lower concentrations of zeaxanthin, α-carotene, ß-carotene and ß-cryptoxanthin. The extracts also contained flavanone glycosides (hesperidin, naringin and neohesperidin), flavonol (quercetin) and polymethoxylated flavones (sinensetin, tangeretin). L-TEAC (lipophilic trolox equivalent antioxidant capacity) test determined for peel extracts higher antioxidant capacity compared to pulp extracts. All extracts presented α-amylase inhibitory activity, pulp extracts showing stronger inhibitory activity compared to peel extracts. All extracts inhibited the growth of both gram (+) and gram (-) bacteria, with peel and pulp extracts of makin showing the strongest inhibitory activity. Therefore, local citrus species from Aceh are potential sources of beneficial compounds with possible health preventive effects.

Effects of omega-3 PUFA on immune markers in adolescent individuals at ultra-high risk for psychosis - Results of the randomized controlled Vienna omega-3 study.

Alterations of immune function have been reported in ultra-high risk (UHR) for psychosis patients causing expectations in terms of predictive meaningfulness and benefits of anti-inflammatory agents. According to a RCT in UHR-patients supplementation of omega-3 polyunsaturated fatty acids (PUFA) was effective in reducing transition to psychosis risk and to improve symptomatology. Based on preclinical findings, we now investigated state marker properties of and the influence of PUFA on immune markers in a RCT (clinical trials.gov Identifier: NCT00396643). In a longitudinal design we measured plasma levels of the pro-inflammatory interleukin 6 (IL-6), the soluble alpha (Tac) subunit of the interleukin 2 receptor (sIL-2r), and the circulating soluble form of the intercellular adhesion molecule one (sICAM-1), in 79 help-seeking UHR individuals (13-25years of age). Using linear mixed model (LMM) analysis, we investigated the effects of 12weeks supplementation of either 1.2g/d PUFA (n=38) or Placebo (n=41). At baseline, inflammatory markers were not altered in patients who later suffered transition to psychosis within one year (n=12; 11 PUFA-group, 1 PL-group). IL-6 was weakly inverse associated with omega-6 PUFA, and highly increased in nicotine users. In univariate tests of the LMM omega-3 PUFA caused a significant increase of sICAM-1 (p=0.022). PUFA did not significantly influence IL-6 or sIL-2r. The enhancement of sICAM-1 in the PUFA condition is suggestive for supportive effects on vascular immune response and immediate Th1 helper cell mediated immune answer, which was found disturbed in manifest schizophrenia, e.g. by facilitating the leukocyte adhesion and migration across the endothelium.

Polyunsaturated fatty acid biostatus, phospholipase A2 activity and brain white matter microstructure across adolescence.

Adolescence is a period of major brain white matter (WM) changes, and membrane lipid metabolism likely plays a critical role in brain WM myelination. Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential components of cell membranes including oligodendrocytes, and LC-PUFA release and turnover in membranes is regulated by phospholipase A2 enzymes. To investigate the role of membrane lipid metabolism in healthy WM myelination across adolescence, the present study examined the relationship between membrane LC-PUFA biostatus, phospholipase A2 activity, and brain WM microstructure in healthy subjects aged 9-20years (n=30). Diffusion tensor imaging (DTI) was performed to measure average fractional anisotropy (FA) and diffusivity (indices sensitive to WM myelination) of nine major cerebral WM tracts. Blood samples were collected to measure erythrocyte membrane fatty acid concentrations and plasma intracellular phospholipase A2 activity (inPLA2). Plasma inPLA2 activity showed a significant U-curved association with WM radial diffusivity, and an inverted U-curved association with WM FA, independent of age. A significant positive linear correlation was observed between docosahexaenoic acid concentration and axial diffusivity in the corpus callosum. These findings suggest that there may be optimal physiological inPLA2 activity levels associated with healthy WM myelination in late childhood and adolescence. Myelination may be mediated by cleavage of docosahexaenoic acid from membrane phospholipids by inPLA2. These findings have implications for our understanding of the role of LC-PUFA homeostasis in myelin-related neurodevelopmental disorders.

Effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system in individuals at ultra-high risk of psychosis.

BACKGROUND: Oxidative stress and impaired antioxidant defenses are reported in schizophrenia and are associated with disturbed neurodevelopment, brain structural alterations, glutamatergic imbalance, increased negative symptoms, and cognitive impairment. There is evidence that oxidative stress predates the onset of acute psychotic illness. Here, we investigate the effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system (AODS). METHOD: In 64 help-seeking UHR-individuals (13-25 years of age), vitamin E levels and glutathione were investigated before and after 12 weeks of treatment with either 1.2g/d omega-3 (PUFA-E) or saturated fatty acids (SFA-E), with each condition also containing 30.4mg/d alpha-tocopherol to ensure absorption without additional oxidative risk. RESULTS: In multivariate tests, the effects on the AODS (alpha-tocopherol, total glutathione) were not significantly different (p=0.13, p=0.11, respectively) between treatment conditions. According to univariate findings, only PUFA-E caused a significant alpha-tocopherol increase, while PUFA-E and SFA-E caused a significant gamma- and delta-tocopherol decrease. Total glutathione (GSHt) was decreased by PUFA-E supplementation. CONCLUSION: Effects of the PUFA-E condition on the vitamin E and glutathione AODS could be mechanisms underlying its clinical effectiveness. In terms of the vitamin E protection system, PUFA-E seems to directly support the antioxidative defense at membrane level. The effect of PUFA-E on GSHt is not yet fully understood, but could reflect antioxidative effects, resulting in decreased demand for glutathione. It is still necessary to further clarify which type of PUFA/antioxidant combination, and in which dose, is effective at each stage of psychotic illness.

Genomic deletion of MAP3K7 at 6q12-22 is associated with early PSA recurrence in prostate cancer and absence of TMPRSS2:ERG fusions.

6q12-22 is the second most commonly deleted genomic region in prostate cancer. Mapping studies have described a minimally deleted area at 6q15, containing MAP3K7/TAK1, which was recently shown to have tumor suppressive properties. To determine prevalence and clinical significance of MAP3K7 alterations in prostate cancer, a tissue microarray containing 4699 prostate cancer samples was analyzed by fluorescence in situ hybridization. Heterozygous MAP3K7 deletions were found in 18.48% of 2289 interpretable prostate cancers. MAP3K7 deletions were significantly associated with advanced tumor stage (P<0.0001), high Gleason grade (P<0.0001), lymph node metastasis (P<0.0108) and early biochemical recurrence (P<0.0001). MAP3K7 alterations were typically limited to the loss of one allele as homozygous deletions were virtually absent and sequencing analyses revealed no evidence for MAP3K7 mutations in 15 deleted and in 14 non-deleted cancers. There was a striking inverse association of MAP3K7 deletions and TMPRSS2:ERG fusion status with 26.7% 6q deletions in 1125 ERG-negative and 11.1% 6q deletions in 1198 ERG-positive cancers (P<0.0001). However, the strong prognostic role of 6q deletions was retained in both ERG-positive and ERG-negative cancers (P<0.0001 each). In summary, our study identifies MAP3K7 deletion as a prominent feature in ERG-negative prostate cancer with strong association to tumor aggressiveness. MAP3K7 alterations are typically limited to one allele of the gene. Together with the demonstrated tumor suppressive function in cell line experiments and lacking evidence for inactivation through hypermethylation, these results indicate MAP3K7 as a gene for which haploinsufficency is substantially tumorigenic.