SAES-422 Multistate Research Activity Accomplishments Report

Status: Approved

Basic Information

Participants

Chen, Chi – University of Minnesota; Chicco, Adam – Colorado State University; Coulombe, Roger – Utah State University; Delgado, Efren – New Mexico State University; Harrington, Mike – Colorado State University; Helferich, William – University of Illinois; Majumder, Kaustav– University of Nebraska – Lincoln; Munson-McGee, Stuart – New Mexico State University; Nerurkar, Pratibha – University of Hawaii (through Skype); Pestka, James – Michigan State University; Turner, Nancy – Texas A&M University; Weir, Tiffany – Colorado State University; Williams, David – Oregon State University; Zhu, Meijun – Washington State University

The 2017 Annual Meeting of the W-4122 Multistate Group was called to order by the Chair, Dr. Meijun Zhu in the morning of October 5th. Dr. Mike Harrington (WAAESD) provided an overview of the status of the multi-state program, the current funding priorities identified in the NIFA strategic plan, and budget status at NIFA. Last year, this group was recognized with the Western Region Award of Excellence in Multistate Research. Dr. Harrington would like to resubmit a nomination for W4122 to be considered for the national award again this year. This year, we have five new members attend the meeting. Each member present delivered a presentation to update the group on his/her progress (content summarized in the Annual Group Report). At the business meeting, new officers for 2017-2018 were selected: Chair, Adam Chicco (CSU); Vice-Chair, Stuart Monson (NMSU); and Secretary, Chi Chen (UMn). Also, the dates for the 2017 annual meeting will be October 4-5 and the meeting will be held in Calistoga, CA.

Accomplishments

Objective 1: Examine the effects of phytochemicals and other dietary components on gut microbiota and intestinal function.

MI Station studies environment and diet influence latency/severity of genome-driven autoimmune disease (AD). In female NZBWF1 mice, a model for the prototypical AD lupus, intranasal installation with crystalline silica (cSiO2) triggers premature loss of self-tolerance in the lung as evidenced by robust ectopic lymphoneogenesis thereby accelerating/ exacerbating systemic autoimmunity and glomerulonephritis. Remarkably, dietary supplementation with the ω-3 polyunsaturated fatty acid (PUFA), docosahexaenoic acid (DHA), abrogates cSiO2-accelerated autoimmunity. They assessed the time-dependent effects of DHA consumption on cSiO2-triggered pulmonary autoimmune gene expression. Cohorts (n=8/gp) of 6-wk old female NZBWF1 mice were fed an isocaloric AIN-93G diet containing 0.0, 0.4, or 1.0% DHA (equivalent to human DHA supplement consumption at 0, 2, and 5 g/d, respectively) for 2 wk. Mice were then intranasally instilled with 1.0 mg cSiO2 or vehicle once per week for 4 wk and then maintained on experimental diets for 1,5, 9, or 13 wk. Cohorts were sacrificed, total RNA isolated from lungs, and gene expression levels using an nCounter® PanCancer Immune Profiling module, a multiplexed method for 800 immune-related target genes. cSiO2 induced expression of 48, 90, 106, and 99 autoimmune-related genes by more than 1.5-fold (p>0.05) in the 1, 5, 9, and 13 wk cohorts, respectively. Upregulated genes included interferon-driven proteins, chemokines, cytokines, complement, and macrophage/lymphocyte activation markers. Diets containing low and high DHA concentrations blocked expression of 80-90 % and 100 %, respectively, of the autoimmune genes triggered by cSiO2. These results suggest that DHA supplementation at physiologically relevant doses might be useful in preventing cSiO2 triggering of lupus and other AD.

HI Station demonstrated that Momordica charantia (bitter melon, BM) and Morinda citrifolia (noni) improves glucose and lipid metabolism as well as prevents weight gain in high-fat diet (HFD)-fed mice. These improved metabolic activity by BM and noni was in part due to improvement of intestinal health by ameliorating intestinal inflammation, preserving gut barrier integrity and maintaining a healthy gut microbiome. Similarly, the differential effects of commercial and laboratory-prepared noni juice on glucose metabolism were also associated with improving gut microbial dysbiosis in HFD-fed mice.

OR Station focused on studying dietary chemoprevention of cancer. They are employing a mouse model of transplacental cancer to determine in dietary supplementation of the pregnant mouse can provide protection for the fetus/infant with respect to development of cancer as adults from the in utero exposure. The primary emphasis has been on phytochemicals from cruciferous vegetables primarily indole-3-carbinol (I3C) and sulforaphane (SFN). They are studying the role of Nrf-2 signaling in the chemoprevention due to SFN. In a recent development, they are utilizing zebrafish as a xenograft model for human cancer cells. By pretreating the zebrafish embryos with I3C prior to injection with human leukemia cells from pediatric patients they are assessing the potency and efficacy of I3C in prevention of these cells from proliferation and metastasis.

TX Station demonstrated that polyphenol-rich sorghum brans influence the colon microbiota of healthy rats, or those induced to have colitis. The diets included sorghum brans that contain condensed tannins, or deoxyanthocyanins, or a combination of the two. The patterns found in rats consuming a diet without the sorghum brans were reflective of those found in obese individuals or those with inflammatory bowel disease. Importantly, it was possible to protect against this shift by including a single, polyphenol-rich fiber source, and to reduce the colon damage associated with induction of colitis. Beneficial changes in the colon microbiota of rats was observed when a dried plum puree was included in the diet. Alterations in the microbiota contributed to modifications in the fecal metabolome.

WA Station examined roles of AMPK in intestinal epithelial differentiation using in vivo and in vitro system. Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of energy metabolism and recently recognized for its important regulatory role in cell differentiation. The microbial metabolite, butyrate, and polyphenolic compounds enhance barrier function, which were associated with the activation of AMPK. However, the role of AMPK in intestinal epithelial differentiation has not been studied directly. They found that AMPK activation improved the barrier function of Caco-2 cells as indicated by increased transepithelial electrical resistance and reduced paracellular FITC-dextran permeability, which was associated with enhanced epithelial differentiation. They further found that AMPK enhances intestinal barrier function and epithelial differentiation via promoting caudal type homeobox 2 (CDX2) expression, a critical transcription factor governing epithelial differentiation.

CO Station examined whether gut dysbiosis is a causal factor in obesity-related arterial stiffness and endothelial dysfunction. To this end, they determined that obesity-associated vascular dysfubnction was accompanied by global shifts in the gut microbiota and specifically, that three species of Bifidobacterium that were reduced by western diet negatively correlated with multiple measures of vascular dysfunction. To determine whether western diet-induced alterations in the microbiota were causally related to the development of vascular dysfunction, dysbiosis in western diet-fed mice was abated by administration of a broad-spectrum antibiotic cocktail for 8 weeks despite no significant changes to body weight or body fat distribution. Given that bacterial lipopolysaccharide (LPS) has been implicated as a causal role in gut-derived systemic inflammation that leads to cardiometabolic aberrations, they examined LPS as a possible link between vascular function and gut dysbiosis. They observed that five months of western diet feeding caused a marked increase in circulating lipopolysaccharide-binding protein (LBP), a surrogate marker for LPS, and that it was significantly reduced following antibiotic treatment, suggesting that the vascular-protective effects of antibiotics involve reductions in LPS signaling. They also observed downstream inflammatory mediators regulated by LPS (IL-6 and phosphorylated NF-ĸB) were also higher in obese animals and reduced with antibiotics. Finally, to confirm that LPS is capable of inducing vascular dysfunction, and to examine the role of TLR4 in this process, they incubated arteries from control mice and from TLR4-/- mice with LPS for 60 minutes. Acute LPS incubation caused significant endothelial dysfunction in arteries from wild-type mice, but not TLR4-/- mice, confirming that LPS can mediate vascular dysfunction via TLR4 signaling.

Objective 2: Identify cellular mechanisms and host molecular targets of beneficial or adverse dietary components that influence human health.

UT Station is studying possible epigenetic mechanisms for the observed silencing of the GSTA3/A4 genes in domesticated turkey (DT), which potentially underlies the extreme sensitivity to dietary carcinogens lkike aflatoxin B1 (AFB1). By contrast, wild turkeys (WT) have GSTs capable of detoxifying AFB1, and are hence more resistant than DT. Changes in methylation, particularly at CpG sites clustered in the promoter region of a gene, can lead to changes in expression. To identify whether methylation differences may be responsible for GST silencing in domesticated turkeys, they searched for CpG islands "upstream" of the 5' end GSTA3 and GSTA4 genes. CpG sites in the GSTA region occur less frequently than expected by chance, with apparent CpG islands near the 5' ends of most of the GSTA genes, but not GSTA3--the one that are most interested in.They tested for differences between WT and DT livers in the methylation level of the CpG island upstream of GSTA4 and found that methylation levels in this region are low (~1.5%) with no significant difference between these two turkey types. There are only 88 CpGs spread over the 11000bp upstream of GSTA3, but half of those CpGs are concentrated in four 500bp sections within 2500bp of the transcription start site, so they searched for potential methylation differences in those four regions. Preliminary results suggest that methylation in these regions does not differ between WT and DT. Even though these four regions have a higher density of CpGs than the rest of the sequence upstream of GSTA3, it is still a much lower density than the CpG islands upstream of other genes, raising questions about whether these CpG sites are part of a promoter or whether the promoter for GSTA3 is located elsewhere in the genome, potentially shared with another gene. They also looked for differences in the presence or absence of CpG sites in the suspected promoter regions of GSTA3 and GSTA4 due to known SNPs between WT and DT. There are SNPs in these regions but they do not affect CpG sites.

MI Station explored mechanisms of how the common food toxin deoxynivalenol (DON, vomitoxin) evokes anorexia and vomiting can shed new light on in what manner calcimimetics cause problematic side effects in the digestive tract. In prior work, their lab demonstrated that gut enteroendocrine cells (EECs) secrete hormones that mediate DON’s anorectic and emetic effects. Using STC-1 cells, a cloned EEC model, they discovered that DON-induced activation of CaSR and transient receptor ankyrin-1 channel (TRPA1) drives Ca2+-mediated hormone secretion. However, the roles of CaSR and TRPA1 in DON’s anorectic and emetic effects remain unclear. To understand the mechanism of anorexia, they tested the hypothesis that DON-induced food refusal and satiety hormone release in the mouse are linked to activation of CaSR and TRPA1. Oral treatment with selective agonists for CaSR (R-568) or TRPA1 (allyl isothiocyanate, AITC) suppressed food intake in mice and the agonists’ effects were blocked by pretreatment with corresponding antagonists NPS-2143 or ruthenium red (RR), respectively. NPS-2143 or RR inhibited both DON-induced food refusal as well as plasma elevations of the satiety hormones cholecystokinin (CCK) and peptide YY3-36 (PYY3-36) which are well known to mediate reduced appetite and impair food consumption. Co-treatment with both antagonists additively suppressed both anorectic and hormone responses to DON. To elucidate whether similar mechanisms were involved in vomiting, they further tested the hypothesis that DON triggers emesis in mink by activating CaSR and TRPA1. Oral gavage with selective agonists for CaSR (R-568) or TRPA1 (AITC) rapidly elicited emesis in the mink in dose-dependent fashion. Oral pretreatment the animals with their corresponding antagonists NPS-2143 or RR, respectively, inhibited these responses. DON-induced emesis in mink was similarly inhibited by oral pretreatment with NPS-2143 or RR. In addition, these antagonists suppressed concurrent DON-induced elevations in plasma peptide YY3-36 and 5-hydroxytryptamine – hormones previously demonstrated to mediate the toxin’s emetic effects in mink. Furthermore, antagonist co-treatment additively suppressed DON-induced emesis and peptide YY 3-36 release. The major findings of these animal studies along with prior findings by their laboratory support the contention that CaSR and TRPA1 activation contribute to DON-induced food refusal and emesis by mediating hormone exocytosis from EEC. Implicit in these findings, is the suggestion that calcimimetics induce digestive tract side effects in humans by promoting the release of enteroendocrine hormones.

OR Station currently focuses on mechanisms of action and biomarkers associated with an important class (3 of the top 10 ATSDR environmental chemicals of concern), polycyclic aromatic hydrocarbons (PAHs), of food-borne carcinogens as well as the cooked meat mutagens (also known human carcinogens). They have accumulated evidence from the mouse transplacental model and adult rodent colon and prostate cancer models that PAHs and cooked meat mutagens are capable of altering the epigenome including microRNAs and long non-coding RNAs. Currently, they are collaborating with Lawrence Livermore National Laboratory to employ accelerator mass (AMS) spectrometry to determine the fate of orally absorbed benzo[a]pyrene (BaP), a PAH common in food and ranked as a known human carcinogen by the International Agency for Research on Cancer (IARC).

IL Station investigated the effects of inadequate dietary calcium (Ca) on bone turnover, tumor growth, and bone response to tumor in tibia inoculated with 4T1 mammary carcinoma cells using Balb/c mice. Nine-month-old female Balb/c mice were placed on an adequate Ca (5 g/kg diet, n=30) or low Ca (80 mg/kg diet, n=31) diet for 14 days, then injected intratibially with 1,000 4T1 cells (transfected with luciferase for bioluminescence imaging), and sacrificed at 5, 10, or 21 days post-inoculation (n=7-10 mice/group). Control mice (n=6/group) were injected with carrier and sacrificed at 10 days post-inoculation. Tibiae with muscle intact were excised and evaluated by microcomputed tomography and histology. In vivo bioluminescent imaging revealed that 4T1 cells metastasized to lung. Therefore, lungs were further removed for quantification of tumor. Mice fed low Ca exhibited higher bone turnover and higher tibial lesion scores than mice fed adequate Ca. Lesion severity, manifested as cortical osteolysis and periosteal woven bone formation, and tumor cell infiltration to muscle, increased with time, irrespective of diet. However, for most skeletal endpoints the rates of increase were greater in mice consuming low Ca compared to mice consuming adequate Ca. Infiltration of tumor cells into adjacent muscle, but not metastasis to lung, was also greater in mice consuming low Ca diet. The findings suggest that high bone turnover due to Ca insufficiency results in greater local mammary tumor cell growth, cortical osteolysis, woven bone formation, and invasion to muscle in mice.

TX Station found that radiation altered the proportion of stem cells in the colon crypts, and that a diet containing fish oil and pectin was able to restore the levels to those seen in the non-irradiated mice by 4 and 8 weeks after radiation exposure.

WI Station examined how the iron regulated RNA binding protein and found that iron regulatory protein 1 (IRP1) had the capacity to control the fate of up to 9 mRNA that contain an iron responsive element (IRE) in their 5’ or 3’ untranslated region. Evidence from studies in mice indicated that the transcription factor HIF2alpha was a major regulator of genes encoding divalent metal transporter I (DMT1), the ferric iron reductase DCytB and the iron exporter ferroportin. These 3 proteins control the apical uptake (DMT1, DCytb) and basolateral export (ferroportin) of iron in the duodenum. IRP1 is the key iron mediator of HIF2alpha mRNA translation. IRP1 is a repressor of HIF2alpha synthesis because it binds to the IRE in HIF2alpha mRNA thereby blocking translation of this mRNA. Loss of IRP1 translationally activates HIF2alpha mRNA. Currently, they are examining the impact of IRP1 deficiency on expression of the HIF2alpha gene targets DMT1, DCytB and ferroportin in the duodenum, as well as the role of IRP1 in other aspects of iron metabolism.

NJ Station investigated whether a purified phenolic-enriched raspberry extract would reduce weight gain in a diet-induced obese (DIO) mouse model. For comparison, they used raspberry ketone as a positive control. Eight week-old C57BL/6 male mice were fed high-fat diet (45% fat. 20% protein). Vehicle, raspberry ketone, high and low raspberry extract (REH 2g/kg, REL 0.2mg/kg, respectively) were administered by oral gavage for 24 days, and body weights were recorded daily. They are in the process of analyzing the feeding suppression, meal pattern alterations, and hypothalamic gene expression by phenolic-enriched raspberry extract and raspberry ketone. Their previous experiments found that acute oral dosing of raspberry ketone (200 mg/kg) activates the hindbrain, nucleus of the solitary tract (NTS), as measured by c-fos immunohistochemistry. These findings will provide mechanistic data for uncovering the effects of raspberry ketone and other bioactive phenolic compounds on obesity and related metabolic disorders.

Objective 3: Explore the interaction between dietary components and the host metabolome and epigenome.

TX Station found that dried plums reduced early colon lesions by 50%, and mitigated distal colon microbiota changes in rats induced by carcinogen-injection. They further discovered several compounds endogenous to plums in the luminal metabolome (both proximal and distal), with several of those compounds being demonstrated in the existing literature to suppress proliferation and enhance apoptosis in colon cancer cells. In addition, there were multiple compounds produced from microbial metabolism of phenolic molecules identified in the luminal contents from the proximal and distal colon of rats provided the plum diet. These molecules have also been demonstrated to protect against carcinogenesis. Additional experiments using dried plums, or compounds isolated from plums have demonstrated effects on bone, as well as colon cancer, demonstrating the potential for systemic benefits of dried plum consumption.

Objective 4: Determine how food processing influences chemical composition to affect human health.

WA Station has studied the utilization of grape pomace as a functional food component. Grape pomace is a major byproduct of wine and juice industry, rich in polyphenolics with demonstrated preventive effects against cardiovascular disease, inflammatory bowel disease and others. How to effectively utilize this byproduct is a compelling question with huge economic impact. In the study, grape pomace was examined for its potential application in making healthy corn starch based extrusion snack foods. Extrudates with 5% grape pomace and 16% feed moisture at a selected speed resulted in enhanced expansion with substantial retention of total polyphenolic content and total antioxidant activity in the cornstarch extrudates. Furthermore, the protective effect of grape pomace extrudates against reactive oxygen species production in human colonic epithelial cells was further evaluated using polyphenolic extract prepared from grape pomace raw mixes and extrudates. These studies indicate that grape pomace has a potential to be used an adjunctive ingredient in extruded foods providing enhanced nutritional value without negative impacts on quality characteristics.

OR Station has been focused on reducing human health risks from food-borne pathogens and environmental contaminants and to transition from preclinical mouse models to actual human studies employing the incredible sensitivity of AMS (attomole sensitivity; they can detect BaP in blood after dosing humans (protocol approved by FDA) at the low femto (1015) gram levels, equivalent to 1 drop of water in 4000 Olympic-size swimming pools. A pending NIH grant will allow them to use human volunteers to assess how consumption of a cruciferous vegetable (1/2 cup Brussels sprouts) night for a week alters the pharmacokinetics of a subsequent oral dose of 14C-BaP.

Impacts

  1. 1. UT Station identified an appropriate genetic marker for the AFBO-trapping GST allele in wild turkeys, which plan to reintroduce resistance 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.
  2. 2. Characterizing GSTs that are associated with sensitivity to food-borne toxicants at UT Station will allow identification of genomic determinants for resistance in humans and animals, thereby improving animal health and food safety. In addition, diets can be devised to increase resistance of people and animals to dietary and environmental carcinogens and toxicants.
  3. 3. The findings at IL Station show that there is a clear in tumor growth in bone from diets low in calcium versus diets with adequate calcium. These data outline the need for adequate calcium in the diet of breast cancer survivors.
  4. 4. Research at MI Station on understanding how DHA prevents/resolves silica-driven proinflammatory and autoimmune events in the lung will provide low-cost preventative strategies that would empower individuals who are genetically prone to lupus and/or occupationally exposed to respiratory toxicants to reduce their risk for developing this disease as well as delay progression of existing disease by consuming of DHA supplements.
  5. 5. Mechanistic studies on how the common food toxin deoxynivalenol (DON, vomitoxin) evokes anorexia and vomiting at MI Station can shed new light on in what manner calcimimetics cause problematic side effects in the digestive tract. Data obtained will provide novel screening approaches applicable to measuring and eliminating both known and emergent trichothecenes on the farm-to-fork continuum.
  6. 6. TX Station demonstrated that diets containing certain polyphenolic compounds (derived from dried plums or sorghum bran) impact the microbiota and their metabolism, which has significant impacts on epigenetic regulation of gene expression. Importantly, systemic benefits are also derived from consuming these polyphenol-rich fiber sources and their microbial metabolites. They further demonstrated that the adult colon stem cell population is sensitive to radiation exposure, with the impacts being both ion source and dose dependent. These observations suggest the need to protect colon stem cells when individuals are exposed to radiation in order to reduce the risk of future intestinal disease.
  7. 7. Studies at CO Station on identification of microbes and gut-derived mediators of vascular dysfunction will provide new opportunities to prevent or treat a condition that is strongly predictive of overt cardiovascular disease and a comorbidity of diabetes.
  8. 8. The impact of OR Station studies on the absorption, metabolism and excretion of an important dietary carcinogen (found in almost all food) is the first studies in humans. This unique dataset can be used by regulatory agencies such as EPA and FDA to set more accurate safe exposure limits.
  9. 10. Studies at WA Station show that grape pomace has a potential to be use an adjunctive ingredient in extruded foods providing enhanced nutritional value without negative impacts on quality characteristics.
  10. 11. WI Station studies may help identify the mechanisms underlying the regulation of dietary iron absorption by IRP1 and HIF2alpha. By elucidating new ways in which dietary iron absorption is controlled, it may be possible to develop the means to more safely combat the anemia in production animals and humans as illustrated by their experiment using dietary fumarate as a possible means to enhance intestinal HIF2alpha level
  11. 12. NJ Station studies on raspberry ketone in weight loss/gain outcomes will provide an unbiased assessment for natural dietary supplements in the market. It can also facilitate a new red raspberries cultivar selection with enhanced bioactive compounds.

Publications

  1. Aleksic B, Bailly S, Draghi M, Pestka JJ, Oswald IP, Robine E, Bailly JD, Lacroix MZ. Production of four macrocyclic trichothecenes by stachybotrys chartarum during its development on different building materials as measured by uplc-ms/ms. Building and Environment 2016, 106, 265-273.
  2. Bates MA, Brandenberger C, Langohr II, Kumagai K, Lock AL, Harkema JR, Holian A, Pestka JJ. Silica triggered autoimmunity in lupus-prone mice blocked by docosahexaenoic acid consumption. Plos One 2016, 11: e0160622.
  3. Bates MA, Gilley KN, Jackson-Humbles DN, Harkema JR, Holian A, Pestka JJ. Silica-triggered multi-organ autoimmune gene expression in lupus-prone mice is ablated by docosahexaenoic acid consumption. FASEB Journal 2017, 31.
  4. Beaver LM, Kuintzle R, Buchanan A, Wiley MW, Glasser ST, Wong CP, Johnson GS, Chang J, Löhr CV, Williams DE, Dashwood RH, Hendrix DA, Ho E. Long Non-Coding RNAs and Sulforaphane: A Target for Chemoprevention and Suppression of Prostate Cancer. Journal of Nutrition Biochemistry 2017, 42:72-83.
  5. Bibi S, de Sousa Moraes LF, Lebow N, Zhu MJ. Dietary green pea protects against DSS-induced colitis in mice challenged with high-fat diet. Nutrients 2017, 9: 509
  6. Bibi S, Kowalski RJ, Zhang S, Ganjyal GM, Zhu MJ. Stability and functionality of grape pomace Used a nutritive additive during extrusion process. Journal of Food Processing & Technology 2017, 8:680.
  7. Bibi S, Kang Y, Du M, Zhu MJ. Maternal high-fat diet consumption enhances offspring susceptibility to DSS-induced colitis in mice. Obesity 2017, 25: 901-908
  8. Borresen E, Brown DG, Harbison G, Taylor L, Fairbanks A, O’Malia J, Bazan M, Rao S, Baily S, Wdowik M, Weir TL, Brown RJ, Ryan EP. A randomized-controlled trial to increase navy bean or rice bran consumption in colorectal cancer survivors. Nutrition & Cancer 2016, 68:1269-1280
  9. Brown DG, Rao S, Weir TL, O’Malia J, Bazan M, Brown RJ, Ryan EP. Metabolomics investigation of tumors, adjacent colonic mucosa and stool from colorectal cancer patients. Cancer & Metabolism 2016, 4:11.
  10. Chen YS, Wang R, Dashwood WM, Löhr C, Williams DE, Ho E, Mertens-Talcott S, Dashwood R. A miRNA signature for an environmental heterocyclic amine defined by a multi-organ carcinogenicity bioassay in the rat. Archives of Toxicology 2017, 91:3415-3425.
  11. Doerge DR, Woodling KA, Churchwell MI, Fleck SC, and Helferich WG. Pharmacokinetics of isoflavones from soy infant formula in neonatal and adult rhesus monkeys. Food Chemical Toxicology 2016: S0278-6915.
  12. Foster MT, Gentile CL, Cox-York K, Wei Y, Wang D, Estrada A, Reese L, Miller T, Pagliassotti MJ, Weir TL. Fuzhuan tea consumption imparts hepatoprotective effects and alters intestinal microbiota in high saturated fat diet-fed rats. Molecular Nutrition and Food Research 2016, 60:1213-12
  13. Gotthardt JD, Bello NT. Meal pattern alterations associated with intermittent fasting for weight loss are normalized after high-fat diet re-feeding. Physiology & Behavior 2017,174: 49-56.
  14. Housley L, Hsu A, Beaver LM, Wong CP, Stevens JF, Choi J, Jiang Y, Bella D. Williams DE, Shannon J, Dashwood RH, Ho E. Untargeted metabolic screen reveals changes in human plasma metabolite profiles following consumption of fresh broccoli sprouts. Molecular Nutrition and Food Research. In press.
  15. Johnson NB, Deck KM, Nizzi CP, Eisenstein RS. A synergistic role of IRP1 and FBXL5 in coordinating iron metabolism during cell proliferation. Journal of Biology Chemistry 2017, 292: 15976-15989
  16. Kang Y, Xue Y, Du M, Zhu MJ. Preventative effects of Goji berry in dextran sulfate sodium-induced colitis. Journal of Nutritional Biochemistry 2017, 40: 70-76.
  17. Kunde DA, Chong WC, Nerurkar PV, Ahuja KD, Just J, Smith, JA, Guven, N and Eri, RD Bitter melon extract protects against ER stress in LS174T colonic epithelial cells. BMC Complement Alternative Medicine. 2017, 17: 2.
  18. Lee DM, Battson ML, Jarrell, Cox-York K, Foster MT, Weir TL, Gentile CL. Fuzhuan tea reverses arterial stiffening following modest weight gain in mice. Nutrition 2017, 33:266-270.
  19. Lemas DJ, Young BE, Baker PR, Tomczik A, Soderborg TK, Hernandez TL, de la Houssaye BA, Robertson CE, Rudolph MC, Ir D, Patinkin ZW, Krebs NF, Santorico SA, Weir TL, Barbour LA, Frank DN, Friedman JE. Alterations in human milk leptin and insulin impact early changes in the infant gut microbiome. American Journal Clinical Nutrition 2016, 103:1291.
  20. Madeen EP, Löhr CV, You H, Siddens LK, Krueger SK, Dashwood RH, Gonzalez FJ, Baird WM, Ho E, Bramer L, Waters KM and Williams DE. Dibenzo[def,p]chrysene Transplacental Exposure in Wild-Type, Cyp1b1 Knockout, and CYP1B1 Humanized Mice. Molec. Carcinogenesis 2017, 56:163-171.
  21. Monson MS, Cardona CJ, Coulombe RA, Reed KM. Hepatic transcriptome responses of domesticated wild turkey embryos to aflatoxin B1. Toxins 2016, 8: 16.
  22. Monson M S, Coulombe RA, Reed KM. Sensitivity and response of poultry to aflatoxin B1 exposure. Agriculture 5 (3) 742-777. 2016, doi:10.3390/agriculture50x000x.
  23. Oni EN, Halikere A, Li G, Toro-Ramos AJ, Swerdel MR, Verpeut JL, Moore JC, Bello NT, Bierut LJ, Goate A, Tischfield JA, Pang ZP, Hart RP. Increased nicotine response in iPSC-derived human neurons carrying the CHRNA5 N398 allele. Scientific reports 2016, 6: 34341.
  24. Palmoera-Sanchez Z, Watson GW, Wong CP, Beaver LM, Williams DE, Dashwood RH, Ho E. The Phytochemical 3, 3’-Diindolylmethane Decreases Expression of AR-Controlled DNA Damage Repair Genes Through Repressive Chromatin Modifications and is Associated with DNA Damage in Prostate Cancer Cells. Journal of Nutritional Biochemistry 2017, 47:113-119.
  25. Pestka JJ, Clark ES, Schwartz-Zimmermann HE, Berthiller F. Sex is a determinant for deoxynivalenol metabolism and elimination in the mouse. Toxins 2017, 9.
  26. Reed KM, Mendoza KM Abrahante J, Coulombe RA. Response of the Hepatic Transcriptomes of Domesticated and Wild Turkey to Aflatoxin B1. Presented at International Society of Animal Genetics, Dublin, IR. July 2017.
  27. Rendeiro C, Sheriff A, Bhattacharya TK, Gogola JV, Baxter JH, Chen H, Helferich WG, Roy EJ, Rhodes JS. Long-lasting impairments in adult neurogenesis, spatial learning and memory from a standard chemotherapy regimen used to treat breast cancer. Behavioral Brain Research 2016, 315:10-22.
  28. Riggs PK, Tedeschi LO, Turner ND, Braga-Neto U, Jayaraman A. The role of “omics” technologies for livestock sustainability. Archive Latinioam Production Animal 2017 25:147-153.
  29. Ritchie LE, Taddeo SS, Weeks BR, Carroll RJ, Dykes L, Rooney LW, Turner ND. Impact of novel sorghum bran diets on DSS-induced colitis. Nutrients 2017, 9: E330.
  30. Schwartz-Zimmermann HE, Hametner C, Nagl V, Fiby I, Macheiner L, Winkler J, Danicke S, Clark E, Pestka JJ, Berthiller F. Glucuronidation of deoxynivalenol (don) by different animal species: Identification of iso-don glucuronides and iso-deepoxy-don glucuronides as novel don metabolites in pigs, rats, mice, and cows. Archives of Toxicology 2017. In press.
  31. Seidel DV, Azcarate-Peril MA, Chapkin RS, Turner ND. Shaping functional microbiota using dietary bioactives to reduce colon cancer risk. Seminars in Cancer Biology 2017, 46:191-204.
  32. Sheflin AM, Borresen EC, Kirkwood J, Boot C, Whitney AK, Lu S, Brown RJ, Broeckling CD, Ryan EP, Weir TL. Dietary Supplementation with Rice Bran or Navy Bean Alters Gut Bacterial Metabolism in Colorectal Cancer Survivors. Molecular Nutrition and Food Research 2017, 61:1500905.
  33. Sheflin AM, Melby C, Carbonero F, Weir TL. Linking dietary patterns with gut microbial composition and function, Gut Microbes, 2017. 8:113-129
  34. Sun X and Zhu MJ. AMP-activated protein kinase: a therapeutic target in intestinal diseases. Open Biology 2017, 7: 170104.
  35. Sun X, Yang QY, Rogers CJ, Du M, Zhu MJ. AMPK regulate intestinal differentiation via histone modification of CDX2. Cell Death and Differentiation 2017, 24: 819-831.
  36. Tinder AC, Puckett RT, Turner ND, Cammack JA, Tomberlin JK. Bioconversion of sorghum and cowpea by black soldier fly (Hermetia illucens (L.)) larvae for alternative protein production. Journal of Insects as Food and Feed 2017, 3:121-130.
  37. Turner ND and Lloyd SK. Association between red meat consumption and colon cancer: A systematic review of experimental results. Experimental Biology & Medicine 2017, 242:813-839.
  38. Wang B, Fu X, Zhu MJ, Du M. Retinoic acid inhibits white adipogenesis by disrupting GADD45A mediated Zfp423 DNA demethylation. Journal of Molecular Cell Biology 2017, 9:338-349.
  39. Wang B, Fu X, Liang X, Deavila JM, Wang Z, Zhao L, Tian Q, Zhao J, Gomez NA, Trombetta SC, Zhu MJ, Du M. Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFRa+ adipose progenitors. Cell Discovery 2017, 3:17036.
  40. Wang S, Liang X, Yang Q, Fu X, Zhu MJ, Rodgers BD, Jiang Q, Dodson MV, Du M. Resveratrol enhances brown adipocyte formation and function by activating AMP-activated protein kinase (AMPK) a1 in mice fed high-fat diet. Molecular Nutrition and Food Research 2017, 61: 1600746.
  41. Whitney AK and Weir TL. Inhibitory activity of Fuzhuan tea fractions against Salmonella enterica and enteric pathogens. Current Topics in Phytochemistry 2016, 13:17-27.
  42. Wu W, Zhou H-R, Bursian SJ, Link JE, Pestka JJ. Calcium-sensing receptor and transient receptor ankyrin-1 mediate emesis induction by deoxynivalenol (vomitoxin). Toxicological Sciences 2017, 155:32-42.
  43. Wu W, Zhou H-R, Pestka JJ. Potential roles for calcium-sensing receptor (casr) and transient receptor potential ankyrin-1 (trpa1) in murine anorectic response to deoxynivalenol (vomitoxin). Archives of Toxicology 2017, 91:495-507.
  44. Xue Y, Du M, Zhu MJ. Quercetin suppresses NLRP3 inflammasome activation in epithelial cells triggered by Escherichia coli O157:H7. Free Radical Biology and Medicine 2017, 108:760-769
  45. Xue Y, Zhang D, Du M, Zhu MJ. Dandelion extract suppresses reactive oxidative species and inflammasome in intestinal epithelial cells. Journal of Functional Food 2017 29: 10-18.
  46. Xue Y, Du M, Sheng H, Hovde CJ, Zhu MJ. Escherichia coli O157:H7 suppress host autophagy and promote bacterial adhesion via Tir-mediated and cAMP-independent activation of protein kinase A. Cell Death and Discovery 2017, 3, 17055.
  47. Xue Y, Zhang H, Sun X, Zhu MJ. Metformin improves ileal epithelial barrier function in interleukin-10 deficient mice. PloS ONE 2016, 11: e0168670
  48. Yang G, Bibi S, Du M, Suzuki T, Zhu MJ. Regulation of the intestinal tight junction by natural polyphenols: a mechanistic perspective. Critical Reviews in Food Science and Nutrition 2017, 595: 3830-3839.
  49. Yin Q, Tang L, Cai K, Tong R, Sternberg R, Yang X, Dobrucki LW, Borst LB, Kamstock D, Song Z, Helferich WG, Cheng J, Fan TM. Pamidronate Functionalized Nanoconjugates for Targeted Therapy of Focal Skeletal Malignant Osteolysis. Proc Natl Acad Sci U S A. 2016, 113:E4601-9.
  50. Zhang X, Cook KL, Warri A, Cruz IM, Rosim M, Riskin J, Helferich W, Doerge D, Clarke R, Hilakivi-Clarke L. Lifetime genistein intake increases the response of mammary tumors to tamoxifen in rats. Clinical Cancer Research 2017. 23: 814-824.
  51. Zhao J, Yang Q, Zhang L, Liang X, Sun X, Wang B, Chen Y, Zhu MJ, Du M. AMPKa1 deficiency suppresses brown adipogenesis in favor of fibrogenesis during brown adipose tissue development. Biochemical and Biophysical Research Communications 2017 491: 508-514.
  52. Zou T, Yang Q, Wang B, Zhu MJ, Nathanielsz PW, Du m. Resveratrol supplementation to high fat diet-fed pregnant mice promotes brown and beige adipocyte development and prevents obesity in male offspring. Journal of Physiology 2017, 595:1547-1562.
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