pinecone/core-2020-05-10-deduplication huggingface dataset:
The use of the DR CALUX bioassay and indicator polychlorinated biphenyls for screening of elevated levels of dioxins and dioxin-like polychlorinated biphenyls in eel.

The DR CALUX bioassay is a very suitable screening method for dioxins and dioxin-like-PCBs in feed and food. This was, e. g. demonstrated in a survey in the Netherlands to control the dioxin levels in eel. The DR CALUX assay, but also indicator polychlorinated biphenyls (PCB) were evaluated as a screening method. Based on the limit for polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/F) [at that time 8 pg toxic equivalents (TEQ)/g eel], and the relation between PCDD/F and dioxin-like-PCB, a decision limit of 30 pg TEQ/g eel was used for screening of 153 field samples. Suspected samples (21) and part of the higher contaminated negative samples (35) were analyzed by GC/MS for dioxins, non-ortho, mono-ortho and indicator PCB, revealing 13 samples exceeding the action limit of 30 pg TEQ/g eel. Only one sample slightly exceeded the dioxin level of 8 pg TEQ/g eel. The relatively low sensitivity for mono-ortho PCB was overcome by the use of reference samples, as shown by the correlation of 0.93 between GC/MS and CALUX determined total TEQ levels. The present data show that the DR CALUX assay can be used for screening of total TEQ levels in eel. The use for dioxins only requires a safe, and therefore relatively low, decision limit. The indicator PCB also showed a good correlation with total TEQ levels, mainly due to the large contribution of the mono-ortho PCB at higher concentrations. The relation with dioxins was very poor and as such indicator PCB seem less suitable than the DR CALUX assay for screening for dioxins only. The present study clearly shows that part of the wild eel samples contains high total TEQ levels and will exceed the future European Union limit of 12 pg TEQ/g eel for dioxins and dioxin-like PCB. Especially at high TEQ levels, dioxin-like PCB contribute most to the total TEQ. In practice, wild eel presents only a minor part of the eel consumed
Fungal siderophores function as protective agents of LDL oxidation and are promising anti-atherosclerotic metabolites in functional food

Iron-mediated oxidation of low-density lipoprotein has been implicated in the pathogenesis of vascular disorders such as atherosclerosis. The present investigations were performed to test whether hydrophobic fungal siderophores – hexadentate trihydroxamates desferricoprogen, desferrichrome, desferrirubin, and desferrichrysin – might suppress heme-catalyzed LDL oxidation and the toxic effects of heme-treated LDL on vascular endothelium. Indeed, two of these – desferricoprogen and desferrichrome – markedly increased the resistance of LDL to heme-catalyzed oxidation. In similar dose–response fashion, these siderophores also inhibited the generation of LDL products cytotoxic to human vascular endothelium. When iron-free fungal siderophores were added to LDL/heme oxidation reactions, the product failed to induce heme oxygenase-1, a surrogate marker for the noncytocidal effects of oxidized LDL (not in the case of desferrichrysin). Desferricoprogen also hindered the iron-mediated peroxidation of lipids from human atherosclerotic soft plaques in vitro, and was taken up in the gastrointestinal tract of rat. The absorbed siderophore was accumulated in the liver and was secreted in its iron-complexed form in the feces and urine. The consumption of mold-ripened food products such as aged cheeses and the introduction of functional foods and food additives rich in fungal iron chelators in diets may lower the risk of cardiovascular diseases
Vitamin E analogues as mitochondria-targeting  compounds: From the bench to the bedside?

Despite considerable effort focusing on designing and finding efficient anti-cancer drugs over the last decade, little progress has been achieved, in particular in case of highly recalcitrant malignancies. Also, since there is a trend suggesting that deaths from cancers may be more frequent than from cardiovascular diseases, it is important to look for novel efficient and selective therapeutic approaches to gradually start winning the battle with cancer. Redox-silent vitamin E analogues, epitomised by -tocopheryl succinate, give some hope in the quest for drugs with such properties. Thus far, these agents have been successfully tested in experimental animals with different types of cancer, showing high efficacy against malignancies including HER2-positive breast carcinomas or malignant mesotheliomas. Further research will provide additional, necessary data to launch clinical trials, possibly in near future, translating into development of innovative anti-cancer drugs acting by targeting mitochondria selectively in cancer cells.Full Tex
The cytotoxic effect of Bowman-Birk isoinhibitors, IBB1 and IBBD2, from soybean (Glycine max) on HT29 human colorectal cancer cells is related to their intrinsic ability to inhibit serine proteases

Bowman-Birk inhibitors (BBI) from soybean and related proteins are naturally occurring protease inhibitors with potential health-promoting properties within the gastrointestinal tract. In this work, we have investigated the effects of soybean BBI proteins on HT29 colon adenocarcinoma cells, compared with non-malignant colonic fibroblast CCD-18Co cells. Two major soybean isoinhibitors, IBB1 and IBBD2, showing considerable amino acid sequence divergence within their inhibitory domains, were purified in order to examine their functional properties, including their individual effects on the proliferation of HT29 colon cancer cells. IBB1 inhibited both trypsin and chymotrypsin whereas IBBD2 inhibited trypsin only. Despite showing significant differences in their enzyme inhibitory properties, the median inhibitory concentration values determined for IBB1 and IBBD2 on HT29 cell growth were not significantly different (39.9+/-2.3 and 48.3+/-3.5 μM, respectively). The cell cycle distribution pattern of HT29 colon cancer cells was affected by BBI treatment in a dose-dependent manner, with cells becoming blocked in the G0-G1 phase. Chemically inactive soybean BBI had a weak but non-significant effect on the proliferation of HT29 cells. The anti-proliferative properties of BBI isoinhibitors from soybean reveal that both trypsin-and chymotrypsin-like proteases involved in carcinogenesis should be considered as potential targets of BBI-like proteins.This work was carried out with the financial support of grants AGR 2006-00706 and AGL 2007-60007/ALI from Junta de Andalucía and Spanish CICYT, respectively. Alfonso Clemente acknowledges receipt of a Ramon and Cajal contract.Peer Reviewe
Vitamin D Status: UV-exposure, Obesity and Cancer

Sun is the main vitamin D source for humans. Sun exposure during the summer may provide large amounts of vitamin D3, which is stored in the fat tissue and released during the winter. Serum 25(OH)D levels > 80 nmol/L at the end of the summer are considered necessary in order to avoid vitamin D deficiency during the winter. However, it is not clear how much sun exposure is needed to achieve this concentration. In this study we simulated a Norwegian summer by using commercially available tanning equipment. We found that moderate exposures given during 5-7 weeks may raise serum 25(OH)D concentrations from typical winter values to typical summer values. A UV dose equal to a whole body sun exposure of 5 - 10 MED at sunny summer midday increased serum 25(OH)D by 15-23 nmol/L. The increase was dependent on the initial vitamin D status: persons with the lowest baseline 25(OH)D concentrations got the largest increase. However, for persons with vitamin D deficiency (25(OH)D < 50 nmol/L) the mentioned UV exposure was not large enough to reach the threshold of vitamin D sufficiency (25(OH)D   75 nmol/L). Moreover, a daily whole body sun exposure of ~0.2 MED seems to be almost equal to an oral vitamin D intake of 2,000 IU.<br>
Body composition and BMI are important predictors of vitamin D status. Our earlier investigations suggested that serum 25(OH)D levels decrease proportionally with increasing BMI. The key mechanism behind is possibly increased sequestration of fat-soluble vitamin D in a large volume of fat tissue. However, other factors, such as low sun exposure and inadequate vitamin D intake, may also contribute to the low vitamin D status in overweight and obese persons. In this study we have investigated the impact of excess body weight on serum 1,25(OH)2D concentrations. According to our results high BMI and adiposity in adults were associated with decreased serum 1,25(OH)2D. Serum 25(OH)D was the strongest predictor of 1,25(OH)2D values. A decrease in 25(OH)D by 1 nmol/L was associated with a decrease in 1,25(OH)2D concentrations by 0.4 pmol/L (P<0.001). There was no correlation between serum concentrations of 25(OH)D and 1,25(OH)2D in obese children and adolescents, although the prevalence of vitamin D deficiency and insufficiency in adolescents was high (58 %).<br>
Low vitamin D status as a consequence of low sun exposure and/or high BMI may play a role in cancer development and prognosis. Our calculations suggest that a low vitamin D status may explain at least 20% of the cancer risk attributable to high BMI. It also seems that the contribution of low 25(OH)D to the increased cancer risk with increasing BMI may be different for different cancer types being highest for colorectal and breast cancers.
A panel of 25 world leaders in vitamin D research recommended that the serum 25(OH)D concentrations should be at least   75 nmol/L (30 ng/ml) in order to provide optimal health outcomes. These values may be achieved by moderate UV exposure or by high vitamin D intake. The dose of vitamin D supplementation and UV exposure should be adjusted according to BMI
Curcumin induces heme oxygenase-1 in normal human skin fibroblasts through redox signaling: relevance for anti-aging intervention

Scope: Curcumin, a component of the spice turmeric, was tested for its potential hormetic anti-aging effects as an inducer of mild stress. Methods and results: Early passage young human skin fibroblasts treated with low doses of curcumin (below 20μM) showed a time- and concentration-dependent induction of heme oxygenase-1 (HO-1), followed by compensatory increase in glutathione-S-transferase activity, GSH levels and GSH/GSSG ratio. These effects were preceded by induction of oxidative stress (increased levels of reactive oxygen species and DNA damage) and impairment of cells' GSH redox state. Curcumin also induced nuclear factor-erythroid-2-related factor 2 accumulation in the nuclei. The use of the antioxidant N-acetyl cysteine prevented the induction of HO-1 by curcumin. Pharmacological inhibition of phosphatidylinositol 3-kinase, but not other kinases, significantly prevented curcumin-induced HO-1 levels, which was corroborated by the induction of phospho-Akt levels by curcumin. Late passage senescent cells already had higher HO-1 levels, and further induction of HO-1 by curcumin was considerably impaired. The induction of stress responses by curcumin in human cells led to protective hormetic effects to further oxidant challenge. Conclusion: Curcumin induces cellular stress responses in normal human skin fibroblasts through phosphatidylinositol 3-kinase/Akt pathway and redox signaling, supporting the view that curcumin-induced hormetic stimulation of cellular antioxidant defenses can be a useful approach toward anti-aging intervention.União Europeia. Fundo Europeu de Desenvolvimento Regional (FEDER) - programa COMPETE (QREN)Fundação para a Ciência e a Tecnologia (FCT) - bolsa PTDC/QUI-BIQ/101392/2008 (NaturAge)
Rosmarinic acid, major phenolic constituent of Greek sage herbal tea, modulates rat intestinal SGLT1 levels with effects on blood glucose

Scope: Previous results suggested that the effects of Salvia fruticosa tea (SFT) drinking on glucose regulation might be at the intestinal level. Here we aim to characterize the effects of SFT treatment and of its main phenolic constituent – rosmarinic acid (RA) – on the levels and localization of the intestinal Na+/glucose cotransporter-1 (SGLT1), the facilitative glucose transporter 2 and glucagon-like peptide-1 (GLP-1).
Methods and results: Two models of SGLT1 induction in rats were used: through diabetes induction with streptozotocin (STZ) and through dietary carbohydrate manipulation. Drinking water was replaced with SFT or RA and blood parameters, liver glycogen and the levels of different proteins in enterocytes quantified. Two weeks of SFT treatment stabilized fasting blood glucose levels in STZ-diabetic animals. The increase in SGLT1 localized to the enterocyte brush-border membrane (BBM) induced by STZ treatment was significantly abrogated by treatment with SFT, without significant changes in total cellular transporter protein levels. No effects were observed on glucose transporter 2, Na+/K+-ATPase or glucagon-like peptide-1 levels by SFT. Additionally, SFT and RA for 4 days significantly inhibited the carbohydrate-induced adaptive increase of SGLT1 in BBM.
Conclusion: SFT and RA modulate the trafficking of SGLT1 to the BBM and may contribute to the control of plasma glucose.We thank NANTA, Fábrica de Moagem do Marco S.A., Portugal, for offering the Soybean meal 47.5 (LC diet). M. F. A. was supported by the
Foundation for Science and Technology, Portugal, through the grant SFRH/BD/12527/2003. This work was supported by the Foundation for Science and Technology, Portugal, through the research grant POCI/AGR/62040/2004
Vitamin C modulates the interaction between adipocytes and macrophages

Scope: Increased adiposity is related with monocyte infiltration into the adipose tissue that accentuates inflammation. Antioxidant treatments emerge as approaches to counteract this phenomenon. Methods and results: Cocultures of differentiated 3T3-L1 adipocytes and RAW264.7 macrophages were incubated for 24-72 h with/without 100 nM insulin and/or 200 μM vitamin C (VC). Nitric oxide (NO) secretion (24 h) was measured. Also, expression (24 h) and secretion (72 h) of MCP-1, leptin and apelin were analyzed. NO secretion was significantly inhibited by insulin and VC only in cocultures. MCP-1 expression/secretion was enhanced in cocultures. Insulin incubation reduced MCP-1 expression in both cultures and VC only in controls. Both treatments inhibited MCP-1 secretion in cocultures. Apelin gene expression was induced in cocultures. Insulin induced apelin mRNA expression, but VC inhibited its expression in cocultures under insulin treatment. Apelin secretion was notably induced by insulin and inhibited by VC in cocultures. Leptin expression was decreased in coculture, while presented no effects by VC. Conclusion: VC importantly modulates the established pro-inflammatory state in the interaction between adipocytes and macrophages
Genetic variations involved in interindividual variability in carotenoid status.

International audienceAs shown in most clinical studies dedicated to carotenoids, there is a huge interindividual variability in absorption, and blood and tissue responses, of dietary carotenoids. The recent discovery that several proteins are involved in carotenoid metabolism in humans has prompted a possible explanation for this phenomenon: genetic variants in genes encoding for these proteins may affect their expression or activity, and in turn carotenoid metabolism and carotenoid status. The proteins clearly identified so far are (i) the carotene oxygenases β,β-carotene-15,15'-monooxygenase (BCMO1) and β,β-carotene-9',10'-oxygenase (BCDO2), which are involved in carotenoid cleavage, (ii) scavenger receptor class B type I (SR-BI), cluster determinant 36 (CD36), and Niemann Pick C1-like 1 (NPC1L1), which are involved in carotenoid uptake by cells, and (iii) glutathione S-transferase Pi 1 (GSTP1) and human retinal lutein-binding protein (HR-LBP), which are involved in the transport of xanthophylls in the retina. Other proteins, such as ATP-binding cassette subfamily G member 5 (ABCG5) and the fatty acid-binding proteins (FABPs) are also apparently involved although firmer evidence is still required. A genome-wide association study, as well as several candidate gene association studies, has shown that groups of subjects bearing different alleles in single nucleotide polymorphisms located in or near several of the above-mentioned genes display different blood and/or tissue concentrations of carotenoids. Further studies are needed to identify all the proteins involved in carotenoid metabolism and assess whether other types of genetic variation, e.g. copy number variants and epigenetic modifications, can modulate carotenoid status. One potential application of such research could be personalized dietary guidelines for carotenoids according to individual genetic characteristics
Masked mycotoxins: a review

The aim of this review is to give a comprehensive overview of the current knowledge on plant metabolites of mycotoxins, also called masked mycotoxins. Mycotoxins are secondary fungal metabolites, toxic to human and animals. Toxigenic fungi often grow on edible plants, thus contaminating food and feed. Plants, as living organisms, can alter the chemical structure of mycotoxins as part of their defence against xenobiotics. The extractable conjugated or non-extractable bound mycotoxins formed remain present in the plant tissue but are currently neither routinely screened for in food nor regulated by legislation, thus they may be considered masked. Fusarium mycotoxins (deoxynivalenol, zearalenone, fumonisins, nivalenol, fusarenon-X, T-2 toxin, HT-2 toxin, fusaric acid) are prone to metabolisation or binding by plants, but transformation of other mycotoxins by plants (ochratoxin A, patulin, destruxins) has also been described. Toxicological data are scarce, but several studies highlight the potential threat to consumer safety from these substances. In particular, the possible hydrolysis of masked mycotoxins back to their toxic parents during mammalian digestion raises concerns. Dedicated chapters of this article address plant metabolism as well as the occurrence of masked mycotoxins in food, analytical aspects for their determination, toxicology and their impact on stakeholders
Cocoa flavonoids improve insulin signalling and modulate glucose production via AKT and AMPK in HepG2 cells

Scope: Cocoa and (-)-epicatechin (EC), a main cocoa flavanol, have been suggested to exert beneficial effects in diabetes, but the mechanism for their insulin-like effects remains unknown. In this study, the modulation of insulin signalling by EC and a cocoa phenolic extract (CPE) on hepatic HepG2 cells was investigated by analysing key proteins of the insulin pathways, namely insulin receptor, insulin receptor substrate (IRS) 1 and 2, PI3K/AKT and 5′-AMP-activated protein kinase (AMPK), as well as the levels of the glucose transporter GLUT-2 and the hepatic glucose production. Methods and results: EC and CPE enhanced the tyrosine phosphorylation and total insulin receptor, IRS-1 and IRS-2 levels and activated the PI3K/AKT pathway and AMPK in HepG2 cells. CPE also enhanced the levels of GLUT-2. Interestingly, EC and CPE modulated the expression of phosphoenolpyruvate carboxykinase, a key protein involved in the gluconeogenesis, leading to a diminished glucose production. In addition, EC- and CPE-regulated hepatic gluconeogenesis was prevented by the blockage of AKT and AMPK. Conclusion: Our data suggest that EC and CPE strengthen the insulin signalling by activating key proteins of that pathway and regulating glucose production through AKT and AMPK modulation in HepG2 cells. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.This work was supported by the grants AGL2010–17579 and CSD2007-00063 from the Spanish Ministry of Science and Innovation (MICINN).Peer Reviewe
Phenolic metabolites of anthocyanins following a dietary intervention study in post-menopausal women

Scope Numerous studies feeding anthocyanin-rich foods report limited bioavailability of the parent anthocyanins. The present study explores the identity and concentration of the phenolic metabolites of anthocyanins in humans. Methods and results Anthocyanin metabolites were quantified in samples collected from a previously conducted 12-wk elderberry intervention study in healthy post-menopausal women. Individual 1-, 2- and 3-h post-bolus urine samples and pooled plasma samples following acute (single bolus) and chronic (12-wk supplementation) anthocyanin consumption (500 mg/day) were analysed using HPLC-ESI-MS/MS. Twenty-eight anthocyanin metabolites were identified in urine and 21 in plasma (including sulfates of vanillic, protocatechuic and benzoic acid). Phenolic metabolites reached peak concentrations of 1237 nM in plasma, while anthocyanin conjugates only reached concentrations of 34 nM. Similarly, in urine, phenolic metabolites were detected at concentrations of 33 185 ± 2549 nM/mM creatinine, while anthocyanin conjugates reached concentrations of 548 ± 219 nM/mM creatinine. There was no evidence that chronic exposure had any impact on either the profile or quantity of metabolites recovered relative to acute exposure. Conclusion An extensive range of phenolic metabolites of anthocyanin was identified following elderberry consumption in humans, including 11 novel metabolites, which were identified at much higher concentrations than their parent compounds
Accumulation of promutagenic DNA adducts in the mouse distal colon after consumption of heme does not induce colonic neoplasms in the western diet model of spontaneous colorectal cancer

Author version made available in accordance with Publisher copyright policy.Scope: Red meat is considered a risk factor for colorectal cancer (CRC). Heme is considered\ud
to promote colonic hyperproliferation and cell damage. Resistant starch (RS) is a food that\ud
ferments in the colon with studies demonstrating protective effects against CRC. By utilizing\ud
the western diet model of spontaneous CRC, we determined if feeding heme (as hemin chloride)\ud
equivalent to a high red meat diet would increase colonic DNA adducts and CRC and whether\ud
RS could abrogate such effects.\ud
Methods and results: Four groups of mice: control, heme, RS and heme + RS were fed\ud
diets for 1 or 18 months. Colons were analyzed for apoptosis, proliferation, DNA adducts\ud
“8-hydroxy-2-deoxyguanosine” and “O6-methyl-2-deoxyguanosine” (O6MeG), and neoplasms.\ud
In the short term, heme increased cell proliferation (p < 0.05). Changes from 1 to 18\ud
months showed increased cell proliferation (p<0.01) and 8-hydroxy-2-deoxyguanosine adducts\ud
(p < 0.05) in all groups, but only heme-fed mice showed reduced apoptosis (p < 0.01) and increasedO6MeGadducts\ud
(p<0.01). The incidence of colon neoplasms was not different between\ud
any interventions.\ud
Conclusion: We identified heme to increase proliferation in the short term, inhibit apoptosis\ud
over the long term, and increase O6MeG adducts in the colon over time although these changes\ud
did not affect colonic neoplasms within this mouse model