Brief Summary of Minutes of Annual Meeting

Brief Summary of Minutes of Annual Meeting

Dr. Roger Coulombe welcomed the assembly and reminded all participants that they should pay their $100 registration fee before the conclusion of the meeting or send directly to him ASAP.

Dr. Michael Harrington, Administrative Advisor, presented an overview of the USDA AFRI and multi-state programs, with several important highlights. These included:

• ESCOP Roadmap for Food and Agriculture
• Updates/changes to the AFRI program
• Key proposal & funding statistics

Participants provided 20-30 minute presentations detailing ongoing research activities and progress for W-3122 relevant objectives.

Business meeting to determine new officers, location of 2014 meeting, and discuss scientific confidentiality of unpublished projects presented.

Objective 1: Determine the mechanisms by which dietary bioactive compounds protect against human diseases.

Pratibha Nerurkar and team (University of Hawaii) have recently demonstrated that bitter melon juice (BMJ) and Morinda citrifolia (noni) improves not only glucose and lipid metabolism, but also prevent weight gain in mice fed high-fat-diet (HFD) containing 58% fat. Mechanistic studies indicate a role for chronic inflammation in pathophysiology of cancer, obesity and T2D.

Meijun Zhu and colleagues (Washington State University) have evaluated the protective effects of grape seed extract (GSE) on inflammatory bowel disease (IBD) symptoms and to further explore the underlying mechanisms using IL10-deficient mice. Though the etiology and pathogenesis of IBD remain poorly defined, the current understanding indicates that the pathogenesis of IBD might involve the defects in intestinal epithelial barrier.  Up to now, pharmacological therapies for IBD long-term management rely on anti-inflammatory drugs, which can result in serious side effects, including secondary infections and immunosuppression. Grape seed extract (GSE) is a by-product of the wine industry, with abundant polyphenolic compounds known for their anti-inflammatory and anti-oxidative effects. They found that dietary GSE supplementation in a wild type and IL10 knockout mouse model did not affect food intake and body weight gain among treatments. GSE supplementation ameliorated IBD disease indices in IL10KO mice. They analyzed gut epithelial barrier function, and found that the colonic goblet cell density of IL10KO mice was numerically lower than that of WT mice, while GSE supplementation increased goblet cell density in both WT and IL10KO mice. Consistently, claudin2, a pore forming tight junction protein, were reduced in both GSE fed WT and IL10KO mice. Compared to WT-CON mice, GSE supplementation also minimized t splenomegaly in IL10KO mice. Concomitantly, GSE supplementation attenuated inflammation and neutrophil infiltration in IL10KO mice. Furthermore, GSE supplementation increased the abundance of Lactobacilli and Bacteroides in gut microbiota of IL10KO mice. In conclusion, results demonstrated that dietary GSE supplementation exerts protective effects in IBD indices of IL10KO mice through multiple mechanisms.

Dave Williams and his team (Oregon State University) continue to research dietary chemoprevention of cancer, specifically protection of the fetus/infant from transplacental carcinogens by dietary supplementation with plant phytochemicals or the whole foods from which they were derived. The emphasis continues to be on phytochemicals from cruciferous vegetables primarily indole-3-carbinol (I3C) and sulforaphane (SFN).

Tiffany Weir, Elizabeth Ryan and colleagues (Colorado State University) have shown that intestinal microbes and their metabolites are an important factor modulating intestinal inflammation and development of CRC. Rice bran has a number of phytochemical components that contribute to its reported anti-inflammatory and anti-carcinogenic bioactivities and has the potential to be incorporated as a dietary component for chemoprevention. Pilot feasibility in a healthy population and initial analysis of a CRC cohort suggest that incorporation of rice bran does not cause a large-scale disturbance in the intestinal ecosystem, but rather induces subtle changes to the microbiota and metabolites detected in stool samples. The changes they observed include increases in certain beneficial commensal bacteria and the introduction of bioactive metabolites reduce inflammation and contribute to CRC chemoprevention. Initial microbiota analysis have revealed that rice bran consumption significantly increased the probiotic bacteria, Bifidobacterium, as well as increasing several butyrate-producing bacterial species such as Paraprevotella and Ruminococcus . This is relevant to chemoprevention as Bifidobacterium is important in modulation of innate and adaptive immune responses and butyrate has been shown to have anti-inflammatory and anti-proliferative effects and feeds colonic epithelium.

Nancy Turner and colleagues (Texas A&M) have demonstrated that butyrate influences histone acetylation and DNA promoter methylation, and through these effects is capable of altering expression of key genes involved in regulating colonocyte physiology. They have also shown that polyphenolic molecules derived from certain varieties of sorghum grain can influence colonic microbiota and metabolism during chronic bouts of inflammatory bowel disease, and by so doing, they reduce the increase in injury caused in an animal model of the disease. Importantly, these effects have been translated into a human study where they have observed alterations in microbial populations and their metabolites found in systemic circulation of overweight subjects.

Dr. Benninghoff and colleagues (Utah State University) in the Applied Nutrition Research Group have developed and are testing a new rodent diet that models typical Western nutrition. Rodent cancer studies typically use defined diets with nutrient profiles optimized for rodent health. However, a defined rodent diet that represents typical American nutrition in all aspects, including calorie sources and macro- and micronutrient composition, was not available. Thus, they used a nutrient density approach to formulate the new Total Western Diet (TWD) based on NHANES data for macro- and micronutrient intakes. The new diet contains more saturated and monounsaturated fats, less polyunsaturated fat, more complex carbohydrates and twice the level of simple sugars.  The TWD includes less calcium, copper, folate, thiamine and vitamins B₆, B₁₂, D and E, but much more sodium.  This newly devised diet that better represents typical American nutrition will be highly useful for studies employing animal models of human disease, including cancer.  As proof of principle, they employed the azoxymethane (AOM) model of colorectal cancer in mice fed either TWD or AIN93G basal diets supplemented with or without green tea extract in the drinking water. Green tea extract reduced body fat percentage in both the TWD and AIN93G groups and decreased fasting glucose levels in mice fed TWD but not AIN93G. Mice fed TWD without green tea had more aberrant crypt foci and a higher total crypt cell count compared to cohorts fed the AIN93G diet and responded better to green tea extract. These results suggest that the Western dietary pattern promotes carcinogenesis and that supplementation with chemopreventive bioactives may be beneficial to populations consuming a poor diet. 

Roger Coulombe and colleagues (Utah State University) showed that dietary indole-3-carbinol (I3C) is an effective transplacental chemopreventive agent in a dibenzo[def,p]chrysene (DBC)-dependent model of murine T-cell lymphoblastic lymphoma. Certain bioactive food components, including I3C and 3,3’-diindolylmethane (DIM) from cruciferous vegetables, have been shown to target cellular pathways regulating carcinogenesis. They extended previous chemoprevention studies in mice to an analogous human neoplasm in cell culture, testing the hypothesis that I3C or DIM may be chemotherapeutic in human T-cell acute lymphoblastic leukemia (T-ALL) cells.  Treatment of several T-ALL cell lines with DIM in vitro significantly reduced cell proliferation and viability at concentrations 8- to 25-fold lower than the parent compound I3C.  DIM arrested CEM and HSB2 cells at the G₁ phase of the cell cycle and significantly increased the percentage of apoptotic cells in all T-ALL lines.  In the CEM cell line, DIM reduced protein expression of cyclin dependent kinases 4 and 6 (CDK4, CDK6) and D-type cyclin 3 (CCND3); DIM also significantly altered expression of eight transcripts related to human apoptosis. Similar anticancer effects of DIM were observed in vivo.  Dietary exposure to 100 ppm DIM significantly decreased the rate of growth of human CEM xenografts in immunodeficient SCID mice, reduced final tumor size by 44% and increased the apoptotic index compared to control-fed mice.  Taken together, our results demonstrate a potential for therapeutic application of DIM in T-ALL.

Dave Pagliarini and colleagues (University of Wisconsin) has continued to investigate the effects of iron deprivation on the cellular control of mitochondrial biogenesis. The discovered, using microarray and quantitative mass-spectrometry approaches, that depriving mouse myotubes of iron, through treatment with the iron chelator deferoxamine (DFO) leads to a global decrease in the transcript abundance of mitochondrial- and nuclear-encoded mitochondrial genes and mitochondrial proteins. They have found that this response to iron chelation is universal across a broad range of cell types, rapid and dose-dependent. Additionally, they discovered that the effect on cellular gene expression and respiratory capacity can be fully reversed upon the reintroduction of iron, indicating that the response to iron deprivation is an adaptive cellular response rather than irreversible cellular damage. Lastly, they showed that this process is independent of well-established regulators of mitochondrial biogenesis, including PGC-1α, PGC-1β and HIF-1α. They have continued to elucidate the molecular basis of this adaptive cellular response by performing detailed timecourse measurements of mitochondrial transcript and protein levels following iron deprivation, and found that the decrease in oxidative phosphorylation proteins preceded the decrease in their corresponding transcripts. These results suggest that the changes in mitochondrial transcript and protein levels occur though two separate mechanisms or that the changes in transcript abundance are in response to the protein changes.

Objective 2: Elucidate mechanisms of action of dietary toxicants and develop biomarkers for human risk assessment and disease prevention.

Dave Williams and colleagues (Oregon State University) currently focuses on mechanisms of action and biomarkers associated with an important class of environmental chemicals of concern, polycyclic aromatic hydrocarbons (PAHs), of food-borne carcinogens. Their research has included identification of molecular biomarkers such as alterations in levels of tumor suppressor genes, DNA adductions, etc., in addition to biological endpoints.

Roger Coloumbe and colleagues (Utah State University) focused his efforts on identifying which GST gene(s) are responsible for protection against AFB₁. Unlike their more susceptible counterparts, wild turkeys possess functional hepatic GSTs with AFB₁ detoxification activity.  Given that alpha-class GSTs are the likely candidates from rodent models, they expressed, cloned and functionally characterized six GSTA genes from the livers of wild and domestic turkeys.  In contrast to their hepatic forms, all E. coli-expressed recombinant GSTAs from both domestic and wild turkeys, had AFBO-detoxification activity. This implies that hepatic GSTs in domestic turkeys are downregulated by one or more genetic or epigenetic mechanisms.  Focused sequencing of the hepatic transcriptome revealed significantly more hepatic GSTAs are expressed in wild than domestic birds, a difference more marked for two genes - GSTA3 and GSTA4. As in isolated populations of people with cancer susceptibility due to GST polymorphisms, loss of protective GST alleles in domestic turkeys is the likely mechanism for their extreme sensitivity compared to wild birds, fulfilling predictions that genetic improvement, domestication, and industry consolidation of commercial poultry result in the loss of genetic diversity, species fitness, and often, enhanced susceptibility to pathogens and environmental agents.

Mendel Friedman and colleagues (USDA-California) developed quantitative methods for the detection of biologically active aflatoxin B₁ (AFB1) in Vero cells. Aflatoxin-producing fungi contaminate food and feed during storage and processing periods. Once consumed, aflatoxins (AFs) accumulate in tissues, causing illnesses in animals and humans. The policy of blending and dilution of grain containing higher levels of aflatoxins with uncontaminated grains for use in animal feed implicitly assumes that the deleterious effects of low levels of the toxins are linearly correlated to concentration. This assumption may not be justified, since it involves extrapolation of these nontoxic levels in feed, which are not of further concern. To develop a better understanding of the significance of low dose effects, they developed quantitative methods for the detection of aflatoxin B₁ (AFB1) by two independent assays: the green fluorescent protein (GFP) assay, as a measure of protein synthesis by the cells, and the microculture tetrazolium (MTT) assay, as a measure of cell viability. The results demonstrate a non-linear dose-response relationship at the cellular level. AFB1 at low concentrations has an opposite biological effect to higher doses that inhibit protein synthesis.

Ron Riley and team (USDA-Georgia) conducted a second human study (HS2) that indicated a significant correlation between urinary FB1 (UFB1) and elevation in the blood sphinganine 1-phosphate/sphingosine 1-phosphate ratio, a result consistent with the conclusion that FB exposure led to disruption of sphingolipid metabolism in humans. A Human Study 3 (HS3) was begun with a survey of fumonisin contamination in maize across Guatemala which was initiated in May 2012 and completed in October 2012.  A total of 640 maize samples from all 22 departments were analyzed for both fumonisin and aflatoxins. Very high levels of aflatoxins and fumonisin were detected in maize from the Department of Petén.  High levels of fumonisin, but not aflatoxins, were also detected in the Departments of Chiquimula and Santa Rosa and very low levels of fumonisin and aflatoxin were detected in the highland Department of Sacatepéquez.  An additional low and two high FB exposure departments were also selected based on the results of the maize survey, Sacatepequez (low fumonisin exposure), Chiquimula (high fumonisin exposure) and Santa Rosa (high fumonisin exposure). Human blood (n=390), urine (n=390) and corn (n=30) for human consumption were collected in February and March 2013 and analyzed for UFB1, sphingoid base 1-phosphates and FB, respectively.  The FB analysis of the maize and the UFB1 levels confirm low exposure in Sacatepequez and high exposure in Chiquimula and Santa Rosa.  The ratio of sphinganine 1-phosphate/sphingosine 1-phosphate and the levels of sphinganine 1-phosphate in the blood are significantly correlated with the UFB1 levels. Results thus far are consistent with the conclusion that FB exposure can led to elevation in sphinganine 1-phosphate in blood as a consequence of fumonisin inhibition of ceramide synthase in tissues.  The UFB1 and blood sphingoid base-1-phosphate data that we have accumulated should allow us to predict a window of UFB1 that increases the relative risk for fumonisin exposure-induced disruption of sphingolipid metabolism in humans.

Objective 3: Discover and characterize novel dietary compounds that have beneficial or adverse effects on human health.

Marie Louise Ricketts and colleagues (University of Nevada) has extended their investigation into the modulation of FXR-target genes in the small intestine and liver by a grape seed procyanidin extract (GSPE). Studies initially focused on the effects of GSPE on known intestinal FXR target genes in Caco2 cells, namely apical sodium dependent bile acid transporter (ASBT), ileal bile acid binding protein (IBABP), fibroblast growth factor 15/19 (FGF15/19) and organic solute transporters alpha and beta. They have expanded their studies in vivo using C57BL/6 wild type mice. Their results show that GSPE differentially modulates FXR-target genes ultimately altering enterohepatic bile acid recirculation in both the intestine and liver. GSPE-mediated alterations in gene expression result in impairment of intestinal BA up-take and decrease the amount of BA that return to the liver via the portal circulation; an observation supported by a significant reduction in serum bile acid levels following GSPE administration. They hypothesize that the impairment in bile acid absorption caused by GSPE administration may represent another mechanism involved in its’ hypotriglyceridemic effect.

Mendel Friedman and colleagues (USDA-California) examined the antitumor effects of dietary black and brown rice brans in tumor-bearing mice. Black and brown rice brans from Oryza sativa LK1-3-6-12-1 and Chuchung cultivars each contained 21 compounds characterized by GC/MS. Mice fed diets with added rice brans for 2 weeks were intracutaneously inoculated with CT-26 mouse cancer cells and fed the same diet for two additional weeks. Tumor mass was 35% and 19% lower in the black and brown bran-fed groups, respectively. Tumor inhibition was associated with increases in cytolytic activity of splenic natural killer (NK) cells; partial restoration of nitric oxide production and phagocytosis in peritoneal macrophages; increases in released tumor necrosis factor-α, IL-1β, and IL-6 from macrophages; increases in infiltration of leukocyte into the tumor; and reduction in angiogenesis inside the tumor. Proangiogenic biomarkers vascular endothelial growth factor, cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) were also reduced in mRNA and protein expression. ELISA of tumor cells confirmed reduced expression of COX-2 and 5-LOX. Reduced COX-2 and 5-LOX expression downregulated vascular endothelial growth factor and inhibited neoangiogenesis inside the tumors. Induction of NK activity and macrophages and inhibition of angiogenesis seem to contribute to tumor regression.

Mendel Friedman and colleagues (USDA-California) also explores how Hericium erinaceus (Lion's Mane) mushroom extracts inhibit metastasis of cancer cells to the lung in CT-26 colon cancer-transplanted mice.  They investigated the antimetastatic activity of four Hericium erinaceus edible mushroom extracts using CT-26 murine colon carcinoma cells as an indicator of inhibition of cell migration to the lung. Hot water (HWE) and microwaved 50% ethanol (MWE) extracts of H. erinaceus strongly elicited cancer cell death through apoptosis and inhibited metastasis of cancer cells to the lungs by 66% and 69%, respectively. HWE and MWE reduced the expression of matrix metalloproteinases MMP-2 and MMP-9 in cells and their activities in culture media. Urokinase-type plasminogen activator (u-PA), another extracellular matrix (ECM)-degrading proteinase, also showed decreased protein expression. In CT-26 cells, HWE and MWE down-regulated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) phosphorylations. The reduced phosphorylations seem to cause reduction of activity of the MMPs, thereby blocking migration and invasion of cells. Dietary administration of HWE and MWE reduced the formation of tumor nodules in the lung by about 50% and 55%, respectively, and prevented increases in lung weight caused by cancer cell metastasis. These results demonstrate the effectiveness of HWE and MWE as beneficial antimetastatic agents, targeting their upstream signaling molecules for mediating the expression of the ECM-degrading proteinases.

Objective 4: Increase beneficial or decrease adverse effects of bioactive constituents and microbes in food.

Mendel Friedman and colleagues (USDA-California) investigated the combined effect of three internal temperatures and different concentrations of sodium chloride (NaCl) and apple polyphenols (APP), individually and in combination, on the heat-resistance of a five-strain cocktail of Listeria monocytogenes in ground beef. Mathematical models were used to quantitate the combined effect of these parameters on heat resistance of the pathogen. The theoretical analysis shows that compared with heat alone, the addition of NaCl enhanced and that of APP reduced the heat resistance of L. monocytogenes. By contrast, the protective effect of NaCl against thermal inactivation of the pathogen was reduced when both additives were present in combination, as evidenced by reduction of up to ~68%. The observed high antimicrobial activity of the combination of APP and low salt suggests that commercial and home processors of meat could reduce the salt concentration by adding APP to the ground meat. The influence of the combined effect allows a reduction of the temperature of heat treatments as well as the salt content of the meat.

This research team (Friedman, USDA-California) also evaluated the effectiveness of oregano and cinnamon essential oils and powdered olive and apple extracts against different types of Salmonella bacteria that can present as food contaminants. All tested plant compounds showed efficacy against Salmonella under different conditions and may be suitable to enhance the microbial safety of ground pork, leafy green vegetables, and other food products that are susceptible to contamination with this pathogen.

Dave Williams (Oregon State University) has focused on reducing human health risks from food-borne pathogens and environmental contaminants. Indole -3 carbinol (I3C) is especially potent in reducing the risk to the fetus from exposure in utero to chemical carcinogens ingested in food. 

Impact Statements:

1. W3122 researchers are identifying appropriate genetic markers for the AFBO-trapping GST allele in wild turkeys. Once identified resistance can be reintroduced into domestic turkeys by backcrossing. An AFB1-resitant turkey would help save the poultry industry millions of dollars lost each year due to contaminating aflatoxins in feeds. For additional information contact Roger Coloumbe (roger@usu.edu)
2. W3122 researchers are looking at unique whole food, food component and phytochemical profiles to reduce food-borne pathogen loads and improve health. For additional information contact Mendel Friedman (Mendel.Friedman@ARS.USDA.GOV)
3. W3122 researchers have identified bitter melon juice as a culturally appropriate dietary intervention to control breast cancer and T2D among ethnic minorities in Hawaii. For more information contact Pratibha Nerurkar (Pratibha@hawaii.edu)
4. W3122 researchers are looking for new ways to combat iron deficiency by examining molecular mechanisms that regulate mitochondrial biogenesis during iron deprivation. Moreover, elucidating mechanisms of mitochondrial alteration may provide valuable insight into disease pathogenesis, as mitochondrial dysfunction occurs in diabetes, cancer, and age-related disorders. For more information contact Dave Pagliarini (Pagliarini@wisc.edu)
5. W3122 researchers are unraveling the complexities underlying the molecular actions of bioactive dietary components by providing evidence of a new molecular mechanism contributing to the triglyceride-lowering ability of this grape seed extract. For more information contact Marie-Louise Ricketts (mricketts@cabnr.unr.edu)
6. W3122 have shown in human studies that Fumosin B (FB) exposure (based on the UFB1), is significantly correlated with the Sa1P/So1P ratio and the increased level of Sa1P in blood spots, supporting the hypothesis that exposure to high levels of FB in humans disrupts sphingolipid metabolism through inhibition of ceramide synthase. This is a significant finding because every animal disease known to be caused by FB is closely correlated with evidence of disruption of sphingolipid metabolism. Being able to predict the level of FB intake that is likely to result in disruption in sphingolipid metabolism is an important first step for defining any possible role for FB as a contributing factor to the increased neural tube defect risk in areas where maize is a dietary staple. For more information contact Ron Riley (ron.riley@ars.usda.gov)
7. W3122 researchers have demonstrated that butyrate influences histone acetylation and DNA promoter methylation, and through these effects is capable of altering expression of key genes involved in regulating colonocyte physiology. They have also shown that polyphenolic molecules derived from certain varieties of sorghum grain can influence colonic microbiota and metabolism during chronic bouts of inflammatory bowel disease, and by so doing, they reduce the increase in injury caused in an animal model of the disease. These effects have been translated into a human study where they have observed alterations in microbial populations and their metabolites found in systemic circulation of overweight subjects. For more information contact Nancy Turner (n_turner@tamu.edu)
8. W3122 researchers have identified rice bran as a feasible dietary intervention for the prevention of recurrence of colorectal cancer. They are also identifying external (total diet intake) and intrinsic (genetic make-up, microbial community structure) host factors that can be used in predicting individual response to diet interventions. For more information contact Tiffany Weir (Tiffany.weir@colostate.edu)
9. W3122 researchers have garnered national and international media attention for studies on dietary chemoprevention of cancer by phytochemicals and determination of mechanisms of action. For more information contact Dave Williams (dave.williams@orst.edu)
10. W3122 researchers have demonstrated that dietary grape seed extract supplementation exerts protective effects in IBD indices of IL10KO mice through multiple mechanisms and may have importance as a human therapeutic for IBD. For more information contact Meijun Zhu (mzhu@uidaho.edu)

Publications:

Kim, J.E., Bunderson, B., Croasdell, A., Reed, K.M, and R.A. Coulombe, Jr. (2013) Alpha-class glutathione S-transferases in Wild Turkeys: Characterization and Role in Resistance to the Carcinogenic Mycotoxin Aflatoxin B1. PLOS One 8(4): e60662. doi:10.1371/journal.pone.0060662

Bunderson, B., Kim, J.E., Croasdell, A., Mendoza, K, Reed, K.M, and R.A. Coulombe, Jr. (2013) Heterologous Expression and Functional Characterization of Avian Mu-Class Glutathione S-Transferases. Comp. Biochem. Physiol. C – Toxicol Pharmacol. 158: 109-116. DOI: 10.1016/j.cbpc.2013.05.007.

Wu, Y., McEwen, G.D., Tang, M., Yu, T., Dimmick, Zhou, A., Gilbertson, T.A., Coulombe, Jr., R.A., and J.R. Stevens. (2013) Sensing Biophysical Alterations of Human Lung Cells (A549) in the Context of Toxicity Effects of Diesel Exhaust Particles. Cell Biochem Biophys May 28 (epub ahead of print) DOI: 10.1007/s12013-013-9618-4

Watterson, T.L., Hamilton, B., Martin, R., and R.A. Coulombe, Jr. (2012) Urban Particulate Matter Activates Akt in Human Lung Cells. Archives of Toxicology 86:121-135 DOI: 10.1007/s00204-011-0739-5

Benninghoff, A.D.* and Williams, D.E. (2013) The role of estrogen receptor beta (ERβ) in transplacental cancer prevention by indole-3-carbinol.  Cancer Prevention Research 6(4): 339-348.

Chen CH, Ravishankar S, Marchello J, Friedman M. 2013. Antimicrobial activity of plant compounds against Salmonella Typhimurium DT104 in ground pork and the influence of heat and storage on the antimicrobial activity. J Food Prot 76(7):1264-9.

Choi S-H, Ahn J-B, Kim H-J, Im N-K, Kozukue N, Levin CE, Friedman M. 2012. Changes in free amino acid, protein and flavonoid content in jujube (Ziziphus jujube) fruit during eight stages of growth and antioxidative and cancer cell inhibitory effects by extracts. J Agric Food Chem 60(41):10245-55.

Choi SP, Kim SP, Nam SH, Friedman M. 2013. Antitumor effects of dietary black and brown rice brans in tumor-bearing mice: Relationship to composition. Mol Nutr Food Res 57(3):390-400.

Du W-X, Avena-Bustillos RJ, Woods RD, Breksa A, McHugh TH, Friedman M, Levin CE, Mandrell R. 2012. Sensory evaluation of baked chicken wrapped with antimicrobial apple and tomato edible films formulated with cinnamaldehyde and carvacrol. J Agric Food Chem 60(32):7799-804.

Friedman M. 2013. Review of the anticarcinogenic, cardioprotective, and other health benefits of tomato compounds lycopene, a-tomatine, and tomatidine in pure form and in fresh and processed tomatoes. J Agric Food Chem. 2013, Online; DOI.org/10.1021/jf402654e

Friedman M, Henika PR, Levin CE. 2013. Bactericidal activities of health-promoting, food-derived powders against the foodborne pathogens Escherichia coli, Listeria monocytogenes, Salmonella enterica, and Staphylococcus aureus. J Food Sci 78(2):M270-M5.

Friedman M, Rasooly R. 2013. Review of the inhibition of biological activities of food-related selected toxins by natural compounds. Toxins 5(4):743-75.

Juneja VK, Altuntas EG, Ayhan K, Hwang C-A, Sheen S, Friedman M. 2013. Predictive model for the reduction of heat resistance of Listeria monocytogenes in ground beef by the combined effect of sodium chloride and apple polyphenols. Int J Food Microbiol 164(1):54-9.

Juneja VK, Gonzales-Barron U, Butler F, Yadav AS, Friedman M. 2013. Predictive thermal inactivation model for the combined effect of temperature, cinnamaldehyde and carvacrol on starvation-stressed multiple Salmonella serotypes in ground chicken. Int J Food Microbiol 165(2):184-99.

Kim SP, Nam SH, Friedman M. 2013. Hericium Erinaceus (Lion's Mane) mushroom extracts inhibit metastasis of cancer cells to the lung in CT-26 colon cancer-transplanted mice. J Agric Food Chem 61(20):4898-904.

Moore-Neibel K, Gerber C, Patel J, Friedman M, Jaroni D, Ravishankar S. 2013. Antimicrobial activity of oregano oil against antibiotic-resistant Salmonella enterica on organic leafy greens at varying exposure times and storage temperatures. Food Microbiol 34(1):123-9.

Rasooly R, Hernlem B, Friedman M. 2013. Low levels of aflatoxin B1, ricin, and milk enhance recombinant protein production in mammalian cells. PLoS ONE 8(8):article no. e71682; doi:10.1371/journal.pone.0071682.

Rasooly R, Hernlem B, He X, Friedman M. 2013. Non-linear relationships between aflatoxin B1 levels and the biological response of monkey kidney Vero cells. Toxins 5(8):1447-61.

Rounds L, Havens CM, Feinstein Y, Friedman M, Ravishankar S. 2013. Concentration-dependent inhibition of Escherichia coli O157:H7 and heterocyclic amines in heated ground beef patties by apple and olive extracts, onion powder and clove bud oil. Meat Sci 94(4):461-7.

Todd J, Friedman M, Patel J, Jaroni D, Ravishankar S. 2013. The antimicrobial effects of cinnamon leaf oil against multi-drug resistant Salmonella Newport on organic leafy greens. Int J Food Microbiol 166(1):193-9.

Rajamoorthi A, Shrivastava S, Steele R, Nerurkar P, Gonzalez JG, Crawford S, Varvares M and Ray RB. Bitter Melon Reduces Head and Neck Squamous Cell Carcinoma Growth by Targeting c-Met Signaling. PLoS One. 2013 Oct 17;8(10):e78006. doi: 10.1371/journal.pone.0078006.

Rensvold JW, Ong SE, Jeevananthan A, Carr SA, Mootha VK and Pagliarini DJ, Complementary RNA and Protein Profiling Identifies Iron as a Key Regulator of Mitochondrial Biogenesis. Cell Reports, 2013, 3(1): 237-245.

Caiozzi G, Wong BS, Ricketts ML. Dietary modification of metabolic pathways via nuclear hormone receptors.Cell Biochem Funct. (2012) 30(7):531-51. doi: 10.1002/cbf.284

Bondy, G.S., Mehta, R., Caldwell, D., Coady, L., Armstrong, C., Savard, M., Miller, J. D., Chomyshyn, E., Bronson, R., Zitomer, N.C., Riley, R.T. (2012) Effects of long term exposure to the mycotoxin fumonisin B₁ in p53 heterozygous and p53 homozygous transgenic mice. Food and Chemical Toxicology. 50 (10), 3604-3613. (reported last year but without volume and pages)

Gelineau-van Waes, J., Rainey, M.A., Maddox, J. R., Voss, K. A., Sachs, A. J., Gardner, N. M., Wilberding, J. D. and Riley, R. T. (2012) Increased sphingoid base-1-phosphates and failure of neural tube closure after exposure tofumonisin or FTY720. Birth Defects Research Part A: Clinical and Molecular Teratology 94(10), 790-803. (reported last year but without volume and pages)

Pitt, J.I., Wild, C.P., Gelderblom, W.C.A., Miller, J.D., Riley, R.T., Wu, F. and Baan, R.A. (Eds). (2012).  Management Of Mycotoxins In Foods And Feeds For Improving Public Health.  165 pp., International Agency for Research on Cancer Scientific Publication No 158, Lyon, France.

Van der Westhuizen, L., Shephard, G. S., Gelderblom, W. C. A., Torres, and Riley, R.T. (2013) Fumonisin biomarkers in maize eaters and implications for human disease. World Mycotoxin Journal 6(3):223-232.

Voss, K.A., Riley, R.T., Moore, N.D., Burns, T.D. (2013) Alkaline cooking (Nixtamalization) reduced the in vivo toxicity of fumonisin-contaminated corn in a rat feeding bioassay. Food Additives and Contaminants. 30, 1415-1421.

Cho, Y., N.D. Turner, L.A. Davidson, R.S. Chapkin, R.J. Carroll, and J.R. Lupton.  2012.  A chemoprotective fish oil/pectin diet enhances apoptosis via Bcl-2 promoter methylation in rat azoxymethane-induced carcinomas.  Experimental Biology & Medicine 237:1387-1393.

Turner, N.D., L.E. Ritchie, R.S. Bresalier, and R.S. Chapkin.  The microbiome and colorectal neoplasia – environmental modifiers of dysbiosis.  Current Gastroenterology Reports 15(9):346.

Weir TL*, Manter DK, Sheflin AM, Barnett BA, Heuberger AH, Ryan EP (2013) Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS One. PLoS One 8(8): e70803. doi:10.1371/journal.pone.0070803

Keller AC, Weir TL*, Broeckling CD, Ryan EP (2013) Antibacterial activity and phytochemical profile of fermented Camellia sinensis (Fuzhuan tea). Food Research International. dx.doi.org/10.1016/j.foodres/2013.04.023

Borresen EC, Henderson AJ, Kumar A, Weir TL, Ryan EP (2012) Fermented foods: Patented approaches and formulations for nutritional supplementation and health promotion. Recent Patents on Food, Nutrition & Agriculture. 4,134-140.

Xu X, Hu Y, Xiao W, Huang J, He X, Wu J,  Ryan EP, Weir TL* (2012) Effects of fermented Camilla sinensis, Fuzhuan tea, on egg cholesterol and production performance in laying hens. J. Int. Food and Agric. Res. 1:6-10.

Parasramka, M.A., Dashwood, W.M., Wang, R., Saeed, H.H., Williams, D.E., Ho, E. and Dashwood, R.H. (2012) A Role for Low-Abundance miRNAs in Colon Cancer: the miR-206/Krüppel-Like Factor 4 (KLF4) Axis.  Clin. Epigenetics. 4:16 DOI: 10.1186/1868-7083-4-16.

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