A neotropical perspective on the uniqueness of the Holocene among interglacials.

Understanding how tropical systems have responded to large-scale climate change, such as glacial-interglacial oscillations, and how human impacts have altered those responses is key to current and future ecology. A sedimentary record recovered from Lake Junín, in the Peruvian Andes (4085 m elevation) spans the last 670,000 years and represents the longest continuous and empirically-dated record of tropical vegetation change to date. Spanning seven glacial-interglacial oscillations, fossil pollen and charcoal recovered from the core showed the general dominance of grasslands, although during the warmest times some Andean forest trees grew above their modern limits near the lake. Fire was very rare until the last 12,000 years, when humans were in the landscape. Here we show that, due to human activity, our present interglacial, the Holocene, has a distinctive vegetation composition and ecological trajectory compared with six previous interglacials. Our data reinforce the view that modern vegetation assemblages of high Andean grasslands and the presence of a defined tree line are aspects of a human-modified landscape.

Mechanisms of Ganweikang Tablets against Chronic Hepatitis B: A Comprehensive Study of Network Analysis, Molecular Docking, and Chemical Profiling.

The hepatitis B virus (HBV) is one of the major viral infection problems worldwide in public health. The exclusive proprietary Chinese medicine Ganweikang (GWK) tablet has been marketed for years in the treatment of chronic hepatitis B (CHB). However, the pharmacodynamic material basis and underlying mechanism of GWK are not completely clear. This study is aimed at investigating the pharmacological mechanism of the GWK tablet in the treatment of CHB. The chemical ingredient information was obtained from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID), and Shanghai Institute of Organic Chemistry of CAS. Ingredients and disease-related targets were defined by a combination of differentially expressed genes from CHB transcriptome data and open-source databases. Target-pathway-target (TPT) network analysis, molecular docking, and chemical composition analysis were adopted to further verify the key targets and corresponding active ingredients of GWK. Eight herbs of GWK were correlated to 330 compounds with positive oral bioavailability, and 199 correlated targets were identified. The TPT network was constructed based on the 146 enriched targets by KEGG pathway analysis, significantly associated with 95 pathways. Twenty-five nonvolatile components and 25 volatile components in GWK were identified in UPLC-QTOF/MS and GC-MS chromatograms. The key active ingredients of GWK include ferulic acid, oleanolic acid, ursolic acid, tormentic acid, 11-deoxyglycyrrhetic acid, dibenzoyl methane, anisaldehyde, wogonin, protocatechuic acid, psoralen, caffeate, dimethylcaffeic acid, vanillin, ß-amyrenyl acetate, formonentin, aristololactam IIIa, and 7-methoxy-2-methyl isoflavone, associated with targets CA2, NFKB1, RELA, AKT1, JUN, CA1, CA6, IKBKG, FOS, EP300, CREB1, STAT1, MMP9, CDK2, ABCB1, and ABCG2.

Effects of food supplementation on cognitive function, cerebral blood flow, and nutritional status in young children at risk of undernutrition: randomized controlled trial.

OBJECTIVE: To assess the effects of food supplementation on improving working memory and additional measures including cerebral blood flow in children at risk of undernutrition. DESIGN: Randomized controlled trial. SETTING: 10 villages in Guinea-Bissau. PARTICIPANTS: 1059 children aged 15 months to 7 years; children younger than 4 were the primary population. INTERVENTIONS: Supervised isocaloric servings (≈1300 kJ, five mornings each week, 23 weeks) of a new food supplement (NEWSUP, high in plant polyphenols and omega 3 fatty acids, within a wide variety and high fortification of micronutrients, and a high protein content), or a fortified blended food (FBF) used in nutrition programs, or a control meal (traditional rice breakfast). MAIN OUTCOME MEASUREMENTS: The primary outcome was working memory, a core executive function predicting long term academic achievement. Additional outcomes were hemoglobin concentration, growth, body composition, and index of cerebral blood flow (CBFi). In addition to an intention-to-treat analysis, a predefined per protocol analysis was conducted in children who consumed at least 75% of the supplement (820/925, 89%). The primary outcome was assessed by a multivariable Poisson model; other outcomes were assessed by multivariable linear mixed models. RESULTS: Among children younger than 4, randomization to NEWSUP increased working memory compared with the control meal (rate ratio 1.20, 95% confidence interval 1.02 to 1.41, P=0.03), with a larger effect in the per protocol population (1.25, 1.06 to 1.47, P=0.009). NEWSUP also increased hemoglobin concentration among children with anemia (adjusted mean difference 0.65 g/dL, 95% confidence interval 0.23 to 1.07, P=0.003) compared with the control meal, decreased body mass index z score gain (-0.23, -0.43 to -0.02, P=0.03), and increased lean tissue accretion (2.98 cm2, 0.04 to 5.92, P=0.046) with less fat (-5.82 cm2, -11.28 to -0.36, P=0.04) compared with FBF. Additionally, NEWSUP increased CBFi compared with the control meal and FBF in both age groups combined (1.14 mm2/s×10-8, 0.10 to 2.23, P=0.04 for both comparisons). Among children aged 4 and older, NEWSUP had no significant effect on working memory or anemia, but increased lean tissue compared with FBF (4.31 cm2, 0.34 to 8.28, P=0.03). CONCLUSIONS: Childhood undernutrition is associated with long term impairment in cognition. Contrary to current understanding, supplementary feeding for 23 weeks could improve executive function, brain health, and nutritional status in vulnerable young children living in low income countries. Further research is needed to optimize nutritional prescriptions for regenerative improvements in cognitive function, and to test effectiveness in other vulnerable groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT03017209.

Colistin and tylosin enhances disaccharidase activities, and improves morphology and permeability of the intestine of broilers.

1. The present study focused on the potential effects of antibiotics on intestinal digestion and integrity in broilers in terms of disaccharidase activity, electrophysiological properties and morphology. 2. One-day-old Arbour Acres birds were randomly allocated to one of four treatment groups for 42 days; control, colistin (20 mg/kg), tylosin (55 mg/kg) or chlortetracycline (CTC, 55 mg/kg) groups. Colistin and tylosin supplementation, but not CTC supplementation, caused an increase in body weight gain. 3. Colistin and tylosin elevated the activities of maltase and sucrase in the mucosa of the jejunum on d 42. Age caused a gradual decrease in the short-circuit current (Isc) and conductance (Gt) of the ileum, as a measure of permeability. The Isc and Gt of the ileum were higher in the colistin-supplemented broilers than in the control birds on d 42. Tylosin- and CTC-supplemented birds displayed Isc and Gt values similar to those of the control birds. 4. Colistin supplementation increased the villus area in the jejunum and thinned the muscularis mucosae in the ileum compared with the control group. Tylosin supplementation decreased the thickness of the muscularis mucosae and the depth of crypt in the jejunum. CTC thickened the muscularis mucosae in the jejunum and ileum. 5. Colistin and tylosin exhibited a beneficial effect on intestinal digestion and integrity by enhancing disaccharidase activities and improving gut morphology and permeability.

Efficacy and safety of high-dose vs low-dose leucovorin in patients with colorectal cancer: systematic review and meta-analysis.

AIM: The clinical benefits of a combination of leucovorin and fluorouracil have been established in the treatment of colorectal cancer. Due to a leucovorin shortage in 2008, many institutions revised their protocols to reduce the dose of leucovorin. After the shortage was resolved, some hospitals still maintained their modified protocols. Thus, we conducted a systematic review to evaluate the efficacy and safety of low- vs high-dose leucovorin in the treatment of colorectal cancer. METHOD: The PubMed, Embase and Cochrane databases were searched for studies published before May 2019. The meta-analysis was performed to estimate the pooled effect sizes by using a random effect model. The primary outcomes were median survival time and tumour response rate. Secondary outcomes were haematological and nonhaematological toxicities. RESULTS: Eight randomized controlled trials and four retrospective studies were reviewed. The pooled median survival time was similar between the two dose levels (standard mean difference -0.06, 95% CI -0.19 to 0.08). The pooled tumour response rate was comparatively higher in the high-dose leucovorin regimen (OR 0.81; 95% CI 0.55-1.18). No statistically significant difference was found between the haematological and nonhaematological toxicities of the two groups. However, there were fewer diarrhoea events in the low-dose leucovorin regimen. CONCLUSION: Low-dose leucovorin regimens seemed feasible approaches for colorectal cancer treatment when the shortage happened, because both regimens manifested comparable outcomes in survival time and tumour response rate.

The fallacy of enzymatic hydrolysis for the determination of bioactive curcumin in plasma samples as an indication of bioavailability: a comparative study.

BACKGROUND: Numerous health benefits have been demonstrated for curcumin which is extracted from turmeric (Curcuma longa L). However, due to its poor absorption in the free form in the gastrointestinal tract and rapid biotransformation, various formulations have been developed to enhance its bioavailability. Previous studies indicate that the free form of curcumin is more bioactive than its conjugated counterparts in target tissues. Most curcumin pharmacokinetics studies in humans designed to assess its absorption and bioavailability have measured and reported total (free plus conjugated) curcumin, but not free, bioactive curcumin in the plasma because enzymatic hydrolysis was employed prior to its extraction and analysis. Therefore, the bioavailability of free curcumin cannot be determined. METHODS: Eight human subjects (4 male, 4 female) consumed a single dose of 400 mg curcumin in an enhanced absorption formulation, and blood samples were collected over 6 h. Plasma was treated either with or without glucuronidase/sulfatase prior to extraction. Curcumin and its major metabolites were analyzed using HPLC-tandem mass spectrometry. In addition, the literature was searched for pharmacokinetic studies involving curcumin using PubMed and Google Scholar, and the reported bioavailability data were compared based on whether hydrolysis of plasma samples was used prior to sample analysis. RESULTS: Hydrolysis of blood plasma samples prior to extraction and reporting the results as "curcumin" obscures the amount of free, bioactive curcumin and total curcuminoids as compared to non-hydrolyzed samples. As a consequence, the data and biological effects reported by most pharmacokinetic studies are not a clear indication of enhanced plasma levels of free bioactive curcumin due to product formulations, leading to a misrepresentation of the results of the studies and the products when enzymatic hydrolysis is employed. CONCLUSIONS: When enzymatic hydrolysis is employed as is the case with most studies involving curcumin products, the amount of free bioactive curcumin is unknown and cannot be determined. Therefore, extreme caution is warranted in interpreting published analytical results from biological samples involving ingestion of curcumin-containing products. TRIAL REGISTRATION: ClinicalTrails.gov, trial identifying number NCT04103788 , September 24, 2019. Retrospectively registered.

Chronic consumption of a low calorie, high polyphenol cranberry beverage attenuates inflammation and improves glucoregulation and HDL cholesterol in healthy overweight humans: a randomized controlled trial.

PURPOSE: We studied the health benefits of low calorie cranberry beverage consumption on glucoregulation, oxidative damage, inflammation, and lipid metabolism in overweight but otherwise healthy humans. METHODS: 78 overweight or obese men and women (30-70 years; BMI 27-35 kg/m2) with abdominal adiposity (waist: hip > 0.8 for women and > 0.9 for men; waist: height ≥ 0.5) consumed 450 mL placebo or low calorie, high polyphenol cranberry extract beverage (CEB) daily for 8 week in a randomized, double-blind, placebo-controlled, parallel design trial. Blood and urine samples were collected after overnight fast at baseline and after 8 weeks of daily beverage consumption. Blood and urine samples were also collected during 3 oral glucose tolerance test (OGTT) challenges: (1) pre-intervention without the test beverages, (2) following a single dose of placebo or CEB at baseline (week 0), and (3) following a single dose of placebo or CEB at 8 week. RESULTS: Compared to placebo, a single CEB dose at baseline lowered endothelin-1 and elevated nitric oxide and the reduced:oxidized glutathione ratio (P < 0.05). Interferon-γ was elevated (P < 0.05) after a single CEB dose at baseline; however, after 8 week of CEB intervention, fasting C-reactive protein was lower (P < 0.05). CEB consumption for 8 week also reduced serum insulin and increased HDL cholesterol compared to placebo (P < 0.05). CONCLUSIONS: An acute dose of low calorie, high polyphenol cranberry beverage improved antioxidant status, while 8 week daily consumption reduced cardiovascular disease risk factors by improving glucoregulation, downregulating inflammatory biomarkers, and increasing HDL cholesterol.

Ubiquinol is superior to ubiquinone to enhance Coenzyme Q10 status in older men.

Coenzyme Q10 (CoQ10) exerts its functions in the body through the ability of its benzoquinone head group to accept and donate electrons. The primary functions are to relay electrons for ATP production in the electron transport chain and to act as an important lipophilic antioxidant. Ubiquinone, the oxidized form of CoQ10, is commonly formulated in commercial supplements, and it must be reduced to ubiquinol to exert CoQ10's functions after consumption. Thus, we aimed to examine whether as compared to ubiquinone, ubiquinol would be more effective to enhance the CoQ10 status in older men. We conducted a double-blind, randomized, crossover trial with two 2-week intervention phases and a 2-week washout between crossovers. Ten eligible older men were randomized to consume either the ubiquinol or ubiquinone supplement at a dose of 200 mg d-1 with one of the main meals. A total of 4 blood samples were collected after an overnight fast for the determination of ubiquinone and ubiquinol in plasma and PBMC and the assessment of FRAP, total thiol, and malondialdehyde (MDA) in plasma and ATP in PBMC. After 2 weeks of the supplementation, the ubiquinol supplement significantly increased plasma ubiquinone 1.7 fold from 0.2 to 0.6 µmol L-1 and total CoQ10 (the sum of 2 forms) 1.5 fold from 1.3 to 3.4 µmol L-1 (p < 0.05) and tended to increase the plasma ubiquinol status 1.5 fold from 1.1 to 2.8 µmol L-1, but did not alter the ratio of ubiquinol to total CoQ10. The ubiquinone supplement insignificantly increases plasma ubiquinol, ubiquinone, and total CoQ10 and did not affect the ratio. Of 10 subjects, six were more responsive to the ubiquinol supplement and 2 were more so to the ubiquinone. The supplementation of both CoQ10 forms did not alter the CoQ10 status in PBMC. FRAP, total thiol, and MDA in plasma and ATP in PBMC were not changed during the intervention. The significant increase in plasma CoQ10 status observed after the 2-week supplementation suggested that ubiquinol appeared to be a better supplemental form to enhance the CoQ10 status than ubiquinone in older men. Neither ubiquinol nor ubiquinone supplement affected the measured biomarkers of oxidative stress.

Non-Provitamin A and Provitamin A Carotenoids as Immunomodulators: Recommended Dietary Allowance, Therapeutic Index, or Personalized Nutrition?

Vegetables and fruits contain non-provitamin A (lycopene, lutein, and zeaxanthin) and provitamin A (ß-carotene, ß-cryptoxanthin, and α-carotene) carotenoids. Within these compounds, ß-carotene has been extensively studied for its health benefits, but its supplementation at doses higher than recommended intakes induces adverse effects. ß-Carotene is converted to retinoic acid (RA), a well-known immunomodulatory molecule. Human interventions suggest that ß-carotene and lycopene at pharmacological doses affect immune functions after a depletion period of low carotenoid diet. However, these effects appear unrelated to carotenoids and retinol levels in plasma. Local production of RA in the gut-associated lymphoid tissue, as well as the dependency of RA-induced effects on local inflammation, suggests that personalized nutrition/supplementation should be considered in the future. On the other hand, the differential effect of RA and lycopene on transforming growth factor-beta suggests that lycopene supplementation could improve immune functions without increasing risk for cancers. However, such preclinical evidence must be confirmed in human interventions before any recommendations can be made.

Yacon (Smallanthus sonchifolius) Leaf Extract Attenuates Hyperglycemia and Skeletal Muscle Oxidative Stress and Inflammation in Diabetic Rats.

The effects of hydroethanolic extract of Yacon leaves (HEYL) on antioxidant, glycemic, and inflammatory biomarkers were tested in diabetic rats. Outcome parameters included glucose, insulin, interleukin-6 (IL-6), and hydrophilic antioxidant capacity (HAC) in serum and IL-6, HAC, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in soleus. The rats (10/group) were divided as follows: C, controls; C + Y, HEYL treated; DM, diabetic controls; and DM + Y, diabetic rats treated with HEYL. Diabetes mellitus was induced by administration of streptozotocin. C + Y and DM + Y groups received 100 mg/kg HEYL daily via gavage for 30 d. Hyperglycemia was improved in the DM + Y versus DM group. Insulin was reduced in DM versus C group. DM rats had higher IL-6 and MDA and lower HAC in the soleus muscle. HEYL treatment decreased IL-6 and MDA and increased HAC in DM rats. DM + Y rats had the highest CAT activity versus the other groups; GPx was higher in C + Y and DM + Y versus their respective controls. The apparent benefit of HEYL may be mediated via improving glucoregulation and ameliorating oxidative stress and inflammation, particularly in diabetic rats.

Gigantol from Dendrobium chrysotoxum Lindl. binds and inhibits aldose reductase gene to exert its anti-cataract activity: An in vitro mechanistic study.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium. chrysotoxum Lindl is a commonly used species of medicinal Dendrobium which belongs to the family of Orchidaceae, locally known as "Shihu" or "Huangcao". D. chrysotoxum Lindl is widely known for medicinal values in traditional Chinese medicine as it possesses anti-inflammatory, anti-hyperglycemic induction, antitumor and antioxidant properties. STUDY AIM: To characterize the interaction between gigantol extracted from D. chrysotoxum Lindl and the AR gene, and determine gigantol's efficacy against cataractogenesis. MATERIALS AND METHODS: Human lens epithelial cells (HLECs) were induced by glucose as the model group. Reverse transcription polymerase chain reaction (RT-PCR) was used to assess AR gene expression. Then, the mode of interaction of gigantol with the AR gene was evaluated by UV-visible spectroscopy, atomic force microscope (AFM) and surface-enhanced Raman spectroscopy (SERS). The binding constant was determined by UV-visible. RESULTS: Gigantol depressed AR gene expression in HLECs. UV-visible spectra preliminarily indicated that interaction between the AR gene and gigantol may follow the groove mode, with a binding constant of 1.85×103L/mol. Atomic force microscope (AFM) data indicated that gigantol possibly bound to insert AR gene base pairs of the double helix. Surface-enhanced Raman spectroscopy (SERS) studies further supported these observations. CONCLUSION: Gigantol extracted from D. chrysotoxum Lindl not only has inhibitory effects on aldose reductase, but also inhibits AR gene expression. These findings provide a more comprehensive theoretical basis for the use of Dendrobium for the treatment of diabetic cataract.

Silkworm pupae oil exerts hypercholesterolemic and antioxidant effects in high-cholesterol diet-fed rats.

BACKGROUND: Silkworm pupae is a good resource of edible oil that is especially rich in unsaturated fatty acids and is considered to be an excellent dietary supplement for hyperlipidemia. RESULTS: Groups fed a high-cholesterol diet (HCD) with silkworm pupae oil (SPO) supplementation (1, 2, or 4 mL kg-1 day-1 ) orally had significantly lower levels of serum total cholesterol (P < 0.05) and low-density lipoprotein cholesterol (P < 0.05) compared to the HCD group. With regard to antioxidant parameters, except for levels of glutathione peroxidase (GSH-Px) in the liver, 2 and 4 mL kg-1 day-1 of SPO supplementation leaded to higher total antioxidant capacity (P < 0.05), superoxide dismutase (P < 0.05) and GSH-Px levels (P < 0.05), as well as lower malondialdehyde levels (P < 0.05), both in serum and liver compared to the HCD group. CONCLUSION: The results of the present study indicate that supplementation with SPO can improve lipid profiles and alleviate oxidative stress in high-cholesterol diet-fed rats. © 2016 Society of Chemical Industry.

Investigation of synergistic mechanism and identification of interaction site of aldose reductase with the combination of gigantol and syringic acid for prevention of diabetic cataract.

BACKGROUND: Gigantol and syringic acid (SA) have been shown to synergistically prevent formation of diabetic cataract (DC). However, the exact mechanism of this effect is unknown. Here, we investigate the effect of these compounds on the activity of aldose reductase (AR) and cataract formation. METHODS: We examined the synergistic anti-cataract efficacy of gigantol and SA in the high glucose- and streptozotocin -induced DC rat model; synergism was evaluated using Jin's formula. We investigated possible mechanisms of action by measuring AR expression and activity and levels of sorbitol using enzyme kinetics, Western blot, and RT-PCR. Finally, we examined binding interaction between AR and both compounds using a combination of site-directed mutagenesis, recombinant expression of wild-type and mutant proteins, and enzyme kinetics. RESULTS: Combination treatment of gigantol and SA synergistically protected both HLECs(human lens epithelial cells) grown in vitro and DC formation in STZ-induced rats in vivo. Synergism was attributed to inhibition of AR activity, downregulation of AR expression via impaired transcription, and decreased sorbitol levels. Enzyme kinetics studies showed that the activity of an AR Asn160Ala mutant protein was significantly decreased compared to wild-type AR, confirming that Asn160 is a key residue for interaction between AR and both compounds. CONCLUSION: Combined administration of gigantol and SA synergize to enhance anti-cataract efficacy. The synergistic effect is mainly attributed to disruption of the polyol pathway and inhibition of AR activity.

Early enteral and parenteral nutrition on immune functions of neurocritically ill patients.

This study was designed to investigate the influence of early enteral and parenteral nutrition on immune functions of neurocritically ill patients. Patients who were admitted to the neurological intensive care unit (ICU) of The Second Affiliated Hospital of Zhengzhou University between May 2014 and January 2016 were selected. They had been hospitalized for more than one week and received enteral nutrition (EN) via nasogastric tube, with a gross energy of 25 kcal/(Kg • d). Patients were divided into EN group, EN + early PN (EPN) group and EN + supplemental PN (SPN) group according to the time of PN support. Differences in patients’ general information and changes in serum protein and immune indexes were compared between the three groups. On admission, patients’ Glasgow coma scale (GCS), age, immune functions and protein indexes had no obvious differences between the three groups. After nutritional support, serum protein level reduced in the EN group while prealbumin (PALB) and retinol binding protein (RBP) increased in the EN + EPN group and EN + SPN group after one week of admission to hospital, and the differences were statistically significant (p less than 0.05). Total protein (TP), albumin (ALB), PALB and transferrin (TRF) increased significantly in the EN + EPN group and EN + SPN group compared with the EN group (p < 0.05); before and after treatment, an increase was found in ALB in the EN + EPN group in comparison with EN + SPN group, with a notable difference (p < 0.05); C3, C4, immunoglobulin M (IgM) and immunoglobulin A (IgA) increased in the EN + SPN group after nutritional support compared with before treatment, and the difference was statistically significant (p < 0.05). Moreover, immunoglobulin G (IgG) and IgA in the EN + EPN group increased after nutritional support comparing to prior to nutritional support, and the difference was statistically significant (p < 0.05). After nutritional treatment, IgA and IgG increased markedly in the EN + EPN group, and there was a statistical significance between the groups (p < 0.05); the EN + EPN group and EN + SPN group exceeded the EN group in total lymphocyte count (TLC), and the difference had a statistical significance (p less than 0.05). These results demonstrate that neurocritically ill patients achieving the target energy can avoid malnutrition and immunodeficiency; serum protein decrease can cause malnutrition after one week of EN support; and enteral and parenteral nutrition can improve nutritional and immune indicators of neurocritically ill patients in the acute phase. In addition, EPN is more likely to improve malnutrition and immune functions of critical patients than SPN.

Nutritional quality of eggs from hens fed distillers dried grains with solubles.

A feeding trial was conducted with laying hens where either 10% or 20% regular-fat distiller's dried grains with solubles (R-DDGS) or low-fat DDGS (L-DDGS) were incorporated into the feed. Production parameters and the effect of DDGS on egg nutritional quality, focusing on yolk lipids, were evaluated. Neither R-DDGS nor L-DDGS at up to 20% of laying hen feeds had a statistically significant impact on hen weight gain, egg production, feed intake, feed efficiency, egg mass, or egg weight. Specific gravity was slightly lower for eggs from hens fed 10% R-DDGS or 20% L-DDGS. Eggs from layers fed DDGS had enhanced levels of tocopherols, tocotrienols, and xanthophylls in the yolk, as well as also increased yolk yellow and red color. Eggs from L-DDGS diet had higher tocopherol content, but eggs from R-DDGS diets had higher xanthophylls. Fatty acid composition in eggs was slightly altered by DDGS, but the ratio of saturated to unsaturated fatty acids was very similar. Feeding DDGS to layer hens had no effect on lecithin or cholesterol content of the eggs. Thus, inclusion of DDGS in the diet of laying hens resulted in increases of several beneficial lipophilic nutrients in egg yolks with no apparent detrimental effects.

Hyperglycemia and Anthocyanin Inhibit Quercetin Metabolism in HepG2 Cells.

A high glucose (Glu) milieu promotes generation of reactive oxygen species, which may not only cause cellular damage, but also modulate phase II enzymes that are responsible for the metabolism of flavonoids. Thus, we examined the effect of a high Glu milieu on quercetin (Q) metabolism in HepG2 cells. HepG2 cells were grown for 3 days in Glu ranging from 5.5 to 50 mmol/L and/or cyanidin-3-glucoside (C3G) ranging from 0 to 25 µmol/L. Subsequently, the capacity of HepG2 cells to metabolize Q was assessed for up to 16 h. Q metabolites were analyzed by high-performance liquid chromatography. Four major Q metabolites were observed in the culture medium and inside the HepG2 cells. Three of these metabolites appear to be sulfated forms of Q or methylated Q, and one was a methylated Q. These metabolites and Q itself were reduced or tended to be reduced in cells grown in a high Glu compared to a normal Glu medium. Addition of C3G or superoxide dismutase plus catalase did not prevent or enhance reduction of Q metabolites. In vitro, a hyperglycemic milieu decreases the production of the principal Q metabolites in HepG2 cells, mediated through mechanisms independent of oxidative stress.

Liquid chromatography with tandem mass spectrometry quantification of urinary proanthocyanin A2 dimer and its potential use as a biomarker of cranberry intake.

The lack of a biomarker for the consumption of cranberries has confounded the interpretation of several studies investigating the effect of cranberry products, especially juices, on health outcomes. The objectives of this pilot study were to develop a liquid chromatography tandem mass spectrometric method for the quantification of the proanthocyanin dimer A-2 in human urine and validate urinary proanthocyanin dimer A-2 as a biomarker of cranberry intake. Five healthy, nonsmoking, premenopausal women (20-30 years of age, body mass index: 18.5-25 kg/m(2) ) were assigned to consume a cranberry beverage containing 140 mg proanthocyanin and 35 kilocalories at 237 mL/day, according to a weekly dosing schedule for 7 weeks. Eleven 24 h and morning spot urine samples each were collected from each subject. A reliable, sensitive method for the detection of proanthocyanin dimer A-2 in urine using liquid chromatography with tandem mass spectrometry was developed with a limit of quantitation of 0.25 ng/mL and a relative standard deviation of 7.26%, precision of 5.7%, and accuracy of 91.7%. While proanthocyanin dimer A-2 was quantifiable in urine, it did not appear to be excreted in a concentration that corresponded to the dosing schedule and intake of cranberry juice.