Consumer Labels can Convey Polyphenolic Content: Implications for Public Health

Polyphenolics are a large group of related substances. Many of these, in fact much of that found in food, is composed of processing-derived substances too complex for complete identification. Recent studies have suggested likely benefits for diets high in polyphenols, particular in reducing heart disease mortality, but other benefits have also been suggested. A consumer label based on the major polyphenolic classes is both manageable and fairly informative as most foods do not contain all possible classes. Differences between class member can be significant, but data on individual substances is impractical and no data is certainly less informative. Equivalency scales may be useful but may skew content of many foods towards the high-equivalency substances, even while the full beneficial effects of each individual substance is poorly described

Cocoa and health: a decade of research

It has been over 10 years since the first mention in a medical journal about cocoa and chocolate as potential sources of antioxidants for health. During this time, cocoa has been found to improve antioxidant status, reduce inflammation and correlate with reduced heart disease risk; with these results, and its popularity, it has received wide coverage in the press. However, after 10 years of research, what is known about the potential health benefits of cocoa and what are the important next steps in understanding this decadent source of antioxidants

Anthocyanins inhibit tumor necrosis alpha-induced loss of Caco-2 cell barrier integrity

An increased permeability of the intestinal barrier is proposed as a major event in the pathophysiology of conditions characterized by chronic gut inflammation. This study investigated the capacity of pure anthocyanins (AC), and berry and rice extracts containing different types and amounts of AC, to inhibit tumor necrosis alpha (TNFα)-induced permeabilization of Caco-2 cell monolayers. Caco-2 cells differentiated into intestinal epithelial cell monolayers were incubated in the absence/presence of TNFα, with or without the addition of AC or AC-rich plant extracts (ACRE). AC and ACRE inhibited TNFα-induced loss of monolayer permeability as assessed by changes in transepithelial electrical resistance (TEER) and paracellular transport of FITC-dextran. In the range of concentrations tested (0.25–1 μM), O-glucosides of cyanidin, and delphinidin, but not those of malvidin, peonidin and petunidin protected the monolayer from TNFα-induced decrease of TEER and increase of FITC-dextran permeability. Cyanidin and delphinidin acted by mitigating TNFα-triggered activation of transcription factor NF-κB, and downstream phosphorylation of myosin light chain (MLC). The protective actions of the ACRE on TNFα-induced TEER increase was positively correlated with the sum of cyanidins and delphinidins (r2 = 0.83) content in the ACRE. However, no correlation was observed between TEER and ACRE total AC, malvidin, or peonidin content. Results support a particular capacity of cyanidins and delphinidins in the protection of the intestinal barrier against inflammation-induced permeabilization, in part through the inhibition of the NF-κB pathway.Fil: Cremonini, Eleonora. University of California at Davis; Estados UnidosFil: Mastaloudis, Angela. Nu Skin Enterprises; Estados UnidosFil: Hester, Shelly N.. Nu Skin Enterprises; Estados UnidosFil: Verstraeten, Sandra Viviana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Anderson, Maureen. University of California at Davis; Estados UnidosFil: Wood, Steven M.. Nu Skin Enterprises; Estados UnidosFil: Waterhouse, Andrew L.. University of California at Davis; Estados UnidosFil: Fraga, César Guillermo. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Oteiza, Patricia Isabel. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Phenolic composition and antioxidant activity of prunes and prune juice (Prunus domestics

Phenolic compounds in foods have been associated with reduced incidences of heart disease by acting as antioxidants for low-density lipoprotein (LDL). Commercial prune and prune juice extracts (Prunus domestica cv. French) were analyzed for phenolics by reversed phase HPLC with diode array detection and tested for the ability to inhibit the Cu 2+ -catalyzed oxidation of human LDL. The mean concentrations of phenolics were 1840 mg/kg, 1397 mg/kg, and 441 mg/L in pitted prunes, extra large prunes with pits, and prune juice, respectively. Hydroxycinnamates, especially neochlorogenic acid, and chlorogenic acid predominated, and these compounds, as well as the prune and prune juice extracts, inhibited the oxidation of LDL. The pitted prune extract inhibited LDL oxidation by 24, 82, and 98% at 5, 10, and 20 μM gallic acid equivalents (GAE). The prune juice extract inhibited LDL oxidation by 3, 62, and 97% at 5, 10, and 20 μM GAE. These data indicate that prunes and prune juice may provide a source of dietary antioxidants

Use of metabolomics and lipidomics to evaluate the hypocholestreolemic effect of Proanthocyanidins from grape seed in a pig model.

Scope:This work aims to evaluate changes in the fecal metabolomic profile due to grapeseed extract (GSE) intake by untargeted and targeted analysis using high resolution massspectrometry in conjunction with multivariate statistics.Methods and results:An intervention study with six crossbred female pigs was performed. Thepigs followed a standard diet for 3 days, then they were fed with a supplemented diet containing1% (w/w) of MegaNaturalR©Gold grape seed extract for 6 days. Fresh pig fecal samples werecollected daily. A combination of untargeted high resolution mass spectrometry, multivariateanalysis (PLS-DA), data-dependent MS/MS scan, and accurate mass database matching wasused to measure the effect of the treatment on fecal composition. The resultant PLS-DAmodels showed a good discrimination among classes with great robustness and predictability.A total of 14 metabolites related to the GSE consumption were identified including biliary acid,dicarboxylic fatty acid, cholesterol metabolites, purine metabolites, and eicosanoid metabolitesamong others. Moreover, targeted metabolomics using GC-MS showed that cholesterol andits metabolites fecal excretion was increased due to the proanthocyanidins from grape seedextract.Conclusion:The results show that oligomeric procyanidins from GSE modifies bile acid andsteroid excretion, which could exert a hypocholesterolemic effect

A Randomized, Double-Blinded, Phase II Trial of Gemcitabine and Nab-Paclitaxel Plus Apatorsen or Placebo in Patients with Metastatic Pancreatic Cancer: The RAINIER Trial.

Lessons learnedThe addition of the heat shock protein 27 (Hsp27)-targeting antisense oligonucleotide, apatorsen, to a standard first-line chemotherapy regimen did not result in improved survival in unselected patients with metastatic pancreatic cancer.Findings from this trial hint at the possible prognostic and predictive value of serum Hsp27 that may warrant further investigation.BackgroundThis randomized, double-blinded, phase II trial evaluated the efficacy of gemcitabine/nab-paclitaxel plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 (Hsp27) mRNA, or placebo in patients with metastatic pancreatic cancer.MethodsPatients were randomized 1:1 to Arm A (gemcitabine/nab-paclitaxel plus apatorsen) or Arm B (gemcitabine/nab-paclitaxel plus placebo). Treatment was administered in 28-day cycles, with restaging every 2 cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and on treatment. The primary endpoint was overall survival (OS).ResultsOne hundred thirty-two patients were enrolled, 66 per arm. Cytopenias and fatigue were the most frequent grade 3/4 treatment-related adverse events for both arms. Median progression-free survival (PFS) and OS were 2.7 and 5.3 months, respectively, for arm A, and 3.8 and 6.9 months, respectively, for arm B. Objective response rate was 18% for both arms. Patients with high serum level of Hsp27 represented a poor-prognosis subgroup who may have derived modest benefit from addition of apatorsen.ConclusionAddition of apatorsen to chemotherapy does not improve outcomes in unselected patients with metastatic pancreatic cancer in the first-line setting, although a trend toward prolonged PFS and OS in patients with high baseline serum Hsp27 suggests this therapy may warrant further evaluation in this subgroup

Cyanidin and delphinidin modulate inflammation and altered redox signaling improving insulin resistance in high fat-fed mice

Consumption of diets high in fat and/or fructose content promotes tissue inflammation, oxidative stress, and insulin resistance, activating signals (e.g. NF-κB/JNK) that downregulate the insulin cascade. Current evidence supports the concept that select flavonoids can mitigate obesity and type 2 diabetes (T2D). This work investigated if supplementation with the anthocyanidins (AC) cyanidin and delphinidin could attenuate the adverse consequences of consuming a high fat diet (HFD) in mice. Consumption of an AC-rich blend mitigated HFD-induced obesity, dyslipidemia and insulin resistance (impaired responses to insulin and glucose). HFD-fed mice were characterized by increased liver lipid deposition and inflammation, which were also attenuated upon AC supplementation. HFD caused liver oxidative stress showing an increased expression of NADPH oxidases, generators of superoxide and H2O2, and high levels of oxidized lipid-protein adducts. This was associated with the activation of the redox sensitive signals IKK/NF-κB and JNK1/2, and increased expression of the NF-κB-regulated PTP1B phosphatase, all known inhibitors of the insulin pathway. In agreement with an improved insulin sensitivity, AC supplementation inhibited oxidative stress, NF-κB and JNK activation, and PTP1B overexpression. Thus, cyanidin and delphinidin consumption either through diet or by supplementation could be a positive strategy to control the adverse effects of Western style diets, including overweight, obesity, and T2D. Modulation of inflammation, oxidative stress, and NF-κB/JNK activation emerge as relevant targets of AC beneficial actions.Fil: Daveri, Elena. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados UnidosFil: Cremonini, Eleonora. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados UnidosFil: Mastaloudis, Angela. Nse Products, Inc.; Estados UnidosFil: Hester, Shelly N.. Nse Products, Inc.; Estados UnidosFil: Wood, Steven M.. Nse Products, Inc.; Estados UnidosFil: Waterhouse, Andrew L.. University of California; Estados UnidosFil: Anderson, Mauri. University of California; Estados UnidosFil: Fraga, César Guillermo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analitica y Fisicoquímica. Cátedra de Fisicoquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Oteiza, Patricia Isabel. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Evaluation of the potential of total proanthocyanidin content in feces as an intake biomarker.

Due to the health benefits associated with proanthocyanidins (PAs), it is useful to identify dietary PA biomarkers that can be determined by simple methods. Since increased levels of circulating PA metabolites are associated with increased fecal PA content, this study explores the spectrophotometric measurement of fecal PA content and its use as a biomarker of PA intake. To this end, fecal PA content was measured using an adaptation of Porter’s spectrophotometric method in samples from a preclinical study and an observational study. In the former, excretion of 250–400 mg PA polymer equivalents/100 g feces was observed during supplementation and the day after, together with a significant association (p < 0.05) between PA intake and the excretion of both intact PAs and some PA metabolites, i.e., (+)-catechin, (−)-epicatechin and syringic acid. No relationship between intake and excretion was found in the observational study, either for the entire group (mean excretion of 240 ± 226 mg PA polymer equivalents/100 g feces) or after stratification into tertiles of consumption. In conclusion, the spectrophotometric determination of total PA content in feces proved to be a valid compliance marker in a preclinical study, but it was not associated with PA intake in free-living subjects. The potential of total PA excretion in observational studies, determined in fecal samples collected the day before dietary recall or in several fecal samples from the same subject, remains to be elucidated, as does a complete validation of the method proposed here.post-print552 K

Submesoscale processes at shallow salinity fronts in the Bay of Bengal : observations during the winter monsoon

Author Posting. © American Meteorological Society, 2018. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 48 (2018): 479-509, doi:10.1175/JPO-D-16-0283.1.Lateral submesoscale processes and their influence on vertical stratification at shallow salinity fronts in the central Bay of Bengal during the winter monsoon are explored using high-resolution data from a cruise in November 2013. The observations are from a radiator survey centered at a salinity-controlled density front, embedded in a zone of moderate mesoscale strain (0.15 times the Coriolis parameter) and forced by winds with a downfront orientation. Below a thin mixed layer, often ≤10 m, the analysis shows several dynamical signatures indicative of submesoscale processes: (i) negative Ertel potential vorticity (PV); (ii) low-PV anomalies with O(1–10) km lateral extent, where the vorticity estimated on isopycnals and the isopycnal thickness are tightly coupled, varying in lockstep to yield low PV; (iii) flow conditions susceptible to forced symmetric instability (FSI) or bearing the imprint of earlier FSI events; (iv) negative lateral gradients in the absolute momentum field (inertial instability); and (v) strong contribution from differential sheared advection at O(1) km scales to the growth rate of the depth-averaged stratification. The findings here show one-dimensional vertical processes alone cannot explain the vertical stratification and its lateral variability over O(1–10) km scales at the radiator survey.S. Ramachandran acknowledges support from the National Science Foundation through award OCE 1558849 and the U.S. Office of Naval Research, Grants N00014-13-1-0456 and N00014-17- 1-2355. A. Tandon acknowledges support from the U.S. Office of Naval Research, Grants N00014-13-1-0456 and N00014-17-1-2355. J. T. Farrar and R. A. Weller were supported by the U.S. Office of Naval Research, Grant N00014-13-1-0453, to collect the UCTD data and process theUCTD and shipboard meteorological data. J. Nash, J. Mackinnon, and A. F. Waterhouse acknowledge support from the U. S. Office of Naval Research, Grants N00014-13-1-0503 and N00014-14-1-0455. E. Shroyer acknowledges support from the U. S. Office of Naval Research, Grants N00014-14-10236 and N00014-15- 12634. A. Mahadevan acknowledges support fromthe U. S. Office of Naval Research, Grant N00014-13-10451. A. J. Lucas and R. Pinkel acknowledge support from the U. S. Office of Naval Research, Grant N00014-13-1-0489.2018-08-2

Proteomic identification of putative microRNA394 target genes in <em>Arabidopsis thaliana</em> identifies major latex protein family members critical for normal development

Expression of the F-Box protein Leaf Curling Responsiveness (LCR) is regulated by microRNA, miR394, and alterations to this interplay in <i>Arabidopsis thaliana</i> produce defects in leaf polarity and shoot apical meristem organization. Although the miR394-LCR node has been documented in Arabidopsis, the identification of proteins targeted by LCR F-box itself has proven problematic. Here, a proteomic analysis of shoot apices from plants with altered LCR levels identified a member of the Latex Protein (MLP) family gene as a potential LCR F-box target. Bioinformatic and molecular analyses also suggested that other MLP family members are likely to be targets for this post-translational regulation. Direct interaction between LCR F-Box and MLP423 was validated. Additional MLP members had reduction in protein accumulation, in varying degrees, mediated by LCR F-Box. Transgenic Arabidopsis lines, in which MLP28 expression was reduced through an artificial miRNA technology, displayed severe developmental defects, including changes in leaf patterning and morphology, shoot apex defects, and eventual premature death. These phenotypic characteristics resemble those of Arabidopsis plants modified to over-express LCR. Taken together, the results demonstrate that MLPs are driven to degradation by LCR, and indicate that MLP gene family is target of miR394-LCR regulatory node, representing potential targets for directly post-translational regulation mediated by LCR F-Box. In addition, MLP28 family member is associated with the LCR regulation that is critical for normal Arabidopsis development