Brief Summary of Minutes of Annual Meeting

Annual Meeting was held in person at University of Hawaiʻi at Mānoa (Honolulu, HI) and offered online participation via zoom.

• 0900 – 0915 (day 1): Welcomes and Introduction (Kacie Ho and Walter Bowen)
• 0915 – 0945: David Gang (administrative advisor) briefly talked about the history of multistate program and the importance of interstate collaboration. He updated the project renewal regarding reviewers’ comments and addressed the new report template that should highlight the impacts of research.

0945 – 1015: Station report session 1 (research highlights presented by investigator, 10 min talk + 5 min discussion)

• Mike Giroux, Montana State University - Engineering Crops for Increased Nutrition and Quality
• Janos Zempleni, University of Nebraska-Lincoln - Milk Exosomes in Nutrition and Drug Delivery

1030 – 1200: Station report session 2

• Kacie Ho, University of Hawaiʻi at Mānoa - Leveraging Nutrients and Phytochemicals from Hawaii Commodities and Food Matrices
• Jinzeng Yang, University of Hawaiʻi at Mānoa - Nutrition Studies for Hawaii Specialty Crops and Foods
• Qing Li, University of Hawaiʻi at Mānoa - Medicine and Food Homology: Action Targets of Phytonutrients against Alzheimer’s and Obesity
• Sathish Kumar Natarajan, University of Nebraska-Lincoln - Bioactive Nutrient Interventions to Mitigate Placental Damage During Maternal Obesity
• Jennifer Teske, University of Arizona - Sleep and Obesity: Sex Differences
• Frank Duca, University of Arizona - Role of Prebiotics in Metabolic Homeostasis

1330 – 1500: Field trip to Lyon Arboretum

1530 – 1630: Station report session 3

• Peng Ji, University of California Davis - Role of Iron in Modulating Gut Microbiota and Immunometabolism”
• Yanhong Liu, University of California Davis - Organic Acid Derivatives on Gut Health of Young Pigs
• Urszula Iwaniec, Oregon State University - Diet Composition Influences the Effect of High Fat Diets on one in Growing Male Mice
• Daniel (Dingbo) Lin, Oklahoma State University - Carotenoid Metabolism and Gut Microbiome in Health and Diseases

1645 – 1730: Station report session 4

• Brian Lindshield, Kansas State University - Iron
• Lavanya Reddivari, Purdue University - Physicochemical Properties of Dietary Fibers in Fiber Intolerance

0900 – 0930 (day 2): Lydia Kaume joined meeting online and gave an update on NIFA National Programs and leaders.

0930 – 1015: Station report session 5

• Jaume Amengual Terrasa, University of Illinois at Urbana – role of dietary β-carotene in cardiovascular health
• Pavel Somavat, University of Missouri - Colored Corn Phytochemicals for Novel Applications
• Rich Bruno, The Ohio State University - Gut-level cardiometabolic benefits of green tea polyphenols in metabolic syndrome

1030 – 1430: Business meeting session

• Administrative and executive: David Gang (Advisor), Kacie Ho (Chair), Peng Ji (Secretary)
• Election: Peng Ji was elected as incoming chair and Lavanya Reddivari was elected as incoming secretary.    
• Project renew: David and Kacie shared details of reviewers’ comments and the group discussed and revised accordingly during business meeting. The proposal had been submitted after the annual meeting.
• Collaboration: The group also discussed mechanisms to enhance interstate collaborations.
• Future annual meeting: next annual meeting will be hosted at University of California Davis (CA) with a tentative date in May 2024.
• 1430: Adjourn

Montana State University (Mike Giroux). (Background) Our goal is to create and test increased amylose pasta, prepared from high and normal amylose durum wheat and/or chickpea flour. We have created increased amylose durum by selecting for mutations in individual seed starch synthesis genes.  We will be preparing pasta made from chickpeas blended with normal and high amylose durum semolina.  The pastas nutritional content will be measured and we will then measure the degree to which the increased nutrition pastas can improve human health. (Activities) Creation of high and intermediate amylose durum by identifying unique starch synthase alleles. Field testing of durum isolines varying in amylose content.  Milling and pasta preparation from durum varying in amylose content.  Begin screening chickpea varieties for amylose content and plan experimental approach. (Outcomes) Developed low and high amylose durum that can be used as a breeding parent to select for increased amylose in durum. 

University of Nebraska-Lincoln (Janos Zempleni). (Background) Most cells produce and secrete exosomes (nanoparticles) loaded with cargo such as various species of RNAs, proteins and lipids. Exosomes play essential roles in cell-to-cell communication through regulating gene expression and metabolism of receptor cells. We have made the paradigm-shifting discovery that exosomes do not exclusively originate in endogenous synthesis but may also be obtained from dietary sources such as human and bovine milk. (Activities and outcomes) 1) We demonstrated that milk exosomes select genomic variants in bacteria including pathogens and alter bacterial purine metabolism and the pathogenicity in the murine gut. 2) We demonstrated that the oral bioavailability of cow’s milk exosomes is 50% in mice. 3) We genetically engineered milk exosomes for optimal delivery of therapeutics to diseased tissues. Our protocol used milk exosomes as a vehicle and successfully delivered protein-coding plasmids to the brain when exosomes are administered through nasal spray. 4) We have developed a proprietary technology to make “universal” milk exosomes, which deliver therapeutics to any tissue of choice.

University of Nebraska-Lincoln (Sathish Kumar Natarajan). (Background) Omega-3 and Omega-6 fatty acids are important for neonatal development and health. Dietary derived Omega-3 and Omega-6 fatty acids exert their effects through their metabolites including oxylipins and specialized pro-resolving mediators. (Activities and outcomes) We have demonstrated that diverse panel of oxylipins from the lipoxygenase pathway in the human placenta present at the time of delivery. Omega-3 and omega-6 derived oxylipins levels influenced fetal birth length and weight percentiles. We have also showed Shilajit supplementation (natural tar-like substance found in the mountains ranges of Himalaya) increased gene expression of collagen synthesis in recreationally trained men in our study.

University of Hawaii (Kacie Ho). (Background) Various foods contain both beneficial nutrients and bioactive compounds but may also contain potentially toxic contaminants as well. Our lab investigates both the beneficial and potentially hazardous compounds in food. Additionally, we study encapsulation techniques (e.g. nanoparticles and emulsions) and how these food structures can help to improve nutrient retention, stability, and bioavailability. (Activities) Over the past year, we measured beneficial mineral nutrients and heavy metal toxicants in various edible seaweeds. Additionally, we characterized different nanoparticle/emulsion structures to determine physical and chemical stability. (Outcomes) We found that many seaweeds in Hawaii contain beneficial nutrients, such as Zinc and Magnesium in high quantities. However, we observed that some species were also very high in heavy metals, including Arsenic. These findings indicate the need for heavy metal monitoring for edible seaweeds. Additionally, the question of bioaccessibility and bioavailability from these non-terrestrial edible plants will be addressed in future research.

University of Hawaii (Jinzeng Yang). (Background) Obesity and diabetes are becoming a national health problem worldwide. Skeletal muscles provide the physiological foundation of physical activity and fitness. Active skeletal muscle effectively regulates metabolic activities and energy balance. Preservation of muscle mass in obesity, insulin resistance/type II diabetes is important for effective treatment and prevention of these diseases. Studies from laboratory animal models and complementary medical practices have implied that nutrients from special plants or herbs contain antidiabetic, antioxidant, anti-obese, anti-hypertensive, and anti-inflammatory properties. Seaweed and tropical papaya, which are widely available in Asian and Pacific countries, have been used as home remedies for centuries. There is evidence that C. papaya leaves reduce symptoms of asthma, worming and dysentery.  (Activities) Myostatin propeptide-transgenic mice (MLC-pro) have been maintained by Dr. Yang’s laboratory and used for studying effects of enhanced muscle on diabetes prevention and blood glucose control in prediabetic mice. 40 Animals of both wild-type control and transgenic mice at about 4 months of age were used for high-fat feeding for inducing prediabetic condition, then used for studying the effects of papaya leaf extract on blood glucose control and lipid profiles. (Outcomes) Our study in transgenic mice indicates that depression of myostatin function by its propeptide produces dramatic muscle mass at the growth stage and less fat at older ages. There are effects of the restricted diet alone on weight loss and blood glucose level in diet-induced prediabetic mice. Papaya leaf juice and restricted diet-treated group showed significant improvements in blood glucose level, total cholesterol, LDL-c, and triglyceride levels.

University of Arizona (Frank Duca). (Background) The impact of the diet and intestinal microbiome is vastly understudied in regard to bacterially-derived metabolites that can impact host health. We aim to study the role of both the small and distal intestine microbiota on generating metabolites that can impact energy and glucose homeostasis. (Activities) In healthy chow-fed-, high-fat diet-induced obese-, and high-fat supplemented with oligofructose- rats, we examined the production of short-chain fatty acids (SCFAs) as well as small intestinal metabolites, like bile acids. (Outcomes) We discovered that obesity is associated with decreased postprandial production of SCFAs that is partially rescued with oligofructose treatment. Furthermore, postprandially, obese rats exhibit reduced portal vein levels of butyrate, implicating a potential role of hepatic butyrate signaling in metabolic homeostasis. Additionally, we found that high-fat feeding results in a drastic change in the small intestinal metabolome, especially in bile acids. Supplementation with oligofructose shifts the bile acid profile back towards healthy chow-fed rats.

University of Arizona (Jennifer Teske). (Background) The laboratory focuses on the impact of insufficient sleep on chronic disease and health outcomes, which includes the metabolism of nutrients. We investigate how sleep curtailment due to environmental noise exposure worsens metabolic health and how consumption of Western diets exacerbates disease risk during sleep disruption in rodent models as well as addressing sex differences since women are more sensitive to noise, have worse sleep and a higher prevalence of obesity compared to men. (Activities) Collaborative research grants were submitted that included Dr. Sands from Montana State University. Analysis was conducted to determine the influence of sleep, diet and sex on micronutrient intake and the role of sex hormones on weight gain in male and females rats. (Outcomes) Awarded grants from the National Science Foundation to fund undergraduate research. We provided virtual and hands-on training and determined proficiency for students at all levels (high school, undergraduate and graduate), provided training on anthropometrics, energy expenditure, energy intake and estrous cycle determination and scientific writing and presentation skills training for both oral and poster presentations for students.

University of California Davis (Yanhong Liu). (Background) Emerging evidence suggested that functional amino acids, organic acid derivatives, and a group of non-nutrient bioactives, such as phytochemicals, and pre-and pro-biotics, may provide benefits to animal health and production through different modes of action: regulating nutrient digestibility and absorption, or modulating microbial ecology in the digestive tract and/or immune responses. (Activities) We conducted pig trials to evaluate the effects of probiotics (Bacillus subtilis or Bacillus spp.), a combination of phytochemicals, or glycerides of organic acids on disease resistance and immunity of weaned pigs that were experimentally infected with a pathogenic E. coli. (Outcomes) We observed the beneficial effects of dietary supplementing probiotics and a mixture of phytochemicals on postweaning growth and gut health and resilience to enteric pathogens in weaned pigs. We received a grant from the Novo Nordisk Foundation to explore dietary strategies that could reduce post-weaning diarrhea and the use of antibiotics.

University of California Davis (Peng Ji). (Background) Iron supplementation in the forms of oral drops and fortified formula and complementary food is universally given in infancy without a careful screening of iron status. Previous studies from our lab showed excess iron intake through oral drops increased enteric iron flow and fecal iron concentration. Iron is an essential nutrient for most microorganisms, but few research has evaluated the impact of iron overflow on gut microbiome. (Activities) We use milk replacer-fed piglets to simulate human infants and evaluated the effects of iron-fortified milk replacer on trace mineral homeostasis, growth performance, gut development and microbiome. (Outcomes) The study showed that iron-fortified milk replacer reduced liver zinc concentration, increase iron concentration in colon digesta and feces, increased beta-diversity and relative abundance of potential pathogens (Escherichia-Shigella and Clostridium sensu stricto 1) compared to the low iron milk which significantly increased the abundance of lactobacillus.

University of California Davis (Allison Ehrlich). (Background) Understanding the mechanism of action of how specific nutritional components promote or disrupt intestinal homeostasis can impact dietary recommendations towards improving health. We hypothesized that the immunoregulatory phytochemcial, indole-3-carbinol (I3C) which is found in cruciferous vegetables, will act similarly to non-dietary, high affinity, aryl hydrocarbon receptor ligands AhR ligands and promote immune regulation. During digestion, I3C is metabolized into ligands for the aryl hydrocarbon receptor (AhR), a transcription factor that when systemically activated prevents T1D. (Activities) In NOD mice, we found that an I3C-supplemented diet led to strong AhR activation in the small intestine but minimal systemic AhR activity. Consistent with the compartmentalization of AhR activation, dietary I3C increased a type of proinflammatory cell called Th17 cells, and decreased immunoregulatory CX3CR1+ macrophages in the small intestine. The immune modulation in the gut was accompanied by alterations to the intestinal microbiome. We identified several gut microbes that were correlated with an increase in Th17 cells and a decrease in immunoregulatory macrophages that were influenced by dietary I3C. Using AhR knockout mice both as specific pathogen-free and newly derived as germ free, we found that Th17 cells and CX3CR1+ macrophages are regulated by both dietary ligands and the microbiome via AhR.  (Outcomes) Humans express an AhR with similar ligand sensitivity to the murine AhRd allele, thus the NOD model may be more appropriate for predicting immune modulation in humans in response to dietary AhR ligands. Two manuscripts are currently in preparation on these data demonstrating that genetics, diet, and the host microbiome are important considerations in the outcome of dietary AhR ligands on the gut immune system.    

Oregon State University (Urszula Iwaniec). (Background) Licorice root, either in whole root powder or more concentrated extract form, is often used as an ingredient in dietary supplements, homeopathic remedies, and candies. Licorice root is consumed by older women based, in part, on the belief that, as a natural botanical estrogen, it attenuates common menopausal symptoms, including weight gain and bone loss. Isoliquiritigenin (ILQ) is a phenolic compound found in licorice root that contributes to its activity. (Activities) We performed a dose-ranging study using young estrogen-depleted rats to determine whether dietary ILQ alters bone metabolism and if the effects are associated with estrogen receptor signaling.  Six-week-old ovariectomized rats were fed diets containing 0, 100, 250 or 750 ppm ILQ for 7 days. Gene expression in femur and uterus, biomarkers of bone turnover, body composition, and uterine weight and epithelial morphology were determined. (Outcomes) We observed a dose-dependent increase in serum ILQ but no change in the serum marker of global bone formation. Contrastingly, ILQ administration reduced the serum marker of global bone resorption and tartrate-resistant acid phosphatase expression in osteoclast culture. ILQ treatment and endogenous estrogen production had limited overlap in gene expression in femur and uterus. However, the highest dose of ILQ resulted in uterine epithelial cell hyperplasia in 2 of 5 animals.

Oregon State University (David Dallas). (Background) Our lab examines the digestion of milk protein and the release of bioactive peptides in infants and adults. (Activities) We examined the effect of heat treatments on retention of bioactive proteins in common donor human milk and the survival of bovine milk kappa-casein glycomacropeptide within the gastrointestinal tract of adults. We also assessed whether peptides present in intestinal digests from preterm infant could cross the intestinal epithelium in vivo and in vitro (a Caco-2 cell model) and modulate the immune response of macrophage cells (THP1 cells). (Outcomes) We found that vat pasteurization or Holder pasteurization preserved the bioactive proteins in human milk to a much greater extent than ultra-high temperature processing and retort processing. We observed that about 10% of in vivo and in vitro preterm infant human milk intestinal digest-derived peptides could cross the epithelial cell monolayer and modulate the cytokine production of macrophage cells, while digested human milk varied in capacity to regulate intestinal cell immune response and correlated this with specific sets of proteins. We demonstrated that glycomacropeptide does not survive digestion in the adult jejunum, but many fragment forms are created, many of which have potential bioactivity in the gut.

Oregon State University (Emily Ho). (Background) Diet plays an important role in mitigating the development and progression of several cancers, as well as immune dysfunction. This research demonstrates that the microbiome may be a key factor in individual differences in the metabolism and bioactivity of phytochemicals derived from cruciferous vegetables. Secondly, age-related decline in nutritional status may be a critical determinant of healthy aging and susceptibility to infection or other environmental insults. The research program has focused on bioactives derived from cruciferous vegetables and zinc nutrition. (Activities) We have completed investigating the impact of broccoli sprout supplementation on the microbiome and metabolome in healthy human subjects. We have also employed cell culture models and rodent models to understand the impact of zinc status on age-related inflammation and the gut microbiome. (Outcomes) We identified that the gut microbiota could be a critical driving factor in differential responses to cruciferous vegetables, established low dietary zinc as a risk factor for inflammatory processes, DNA damage, and cancer risk, and helped identify new biomarkers for human zinc deficiency and cruciferous vegetable intake. We also established the biological function of zinc and changes in zinc metabolism with immune activation and aging.

Oklahoma State University (Dingbo Lin). (Background) Oxygenized carotenoids, such as zeaxanthin and astaxanthin are fat-soluble pigments rich in colorful diets. The goals of my research focus on further understanding their metabolism and function in human health and diseases. (Activities) In this funding period, we further explored the problems of the absorption efficacy and metabolism of dietary carotenoids in human subjects and mouse models. (Outcomes) The results showed consumption of salmon significantly increased plasma astaxanthin contents. There were three isomers of astaxanthins identified in the human plasma samples. Dietary zeaxanthin enhanced the richness of microbiota populations in tryptophan metabolism.

Kansas State University (Brian Lindshield). (Background) Previously we investigated the rice diets with soy protein isolate and soybean oil was supplemented with a USDA MR24 vitamin/mineral blend and one of four iron fortificants: Ferric phosphate, Ferric pyrophosphate, micronized ferric pyrophosphate, or ferric pyrophosphate with trisodium citrate (TSC) and citric acid (CA) in rats. Unfortunately, the study had to be stopped early because of poor growth with these diets, although hemoglobin concentrations in the ferric pyrophosphate, micronized ferric pyrophosphate, or ferric pyrophosphate were significantly higher than ferric phosphate and AIN93-G Group. We wanted to repeat this study with AIN93-G diets with extruded rice flour to replace the carbohydrates given the limitations of our previous study. (Activities) The only difference in the study was that we chose to add TSC+CA to the ferric phosphate to see if it would improve its bioavailability since hemoglobin concentrations were lower in our previous study. (Outcomes) We just completed the study before the end of this reporting period. The diets were well consumed and there were no significant differences in body weight between groups.

Purdue University (Lavanya Reddivari). (Background) Fiber solubility, fermentation rate and structural complexity affect fiber tolerance, gut barrier function, and gut microbiota. (Activities) We evaluated resistant maltodextrins (RMD), high methoxyl pectin (HMP), inulin (ChIn), and wheat bran (WB) for their impacts on gut fermentation, microbiome and enteric immunity in gnotobiotic IL-10 KO mouse model. (Outcomes) Fecal SCFAs were higher in mice consuming fiber-supplemented diets compared to a control diet. Mice on ChIn and RMD showed intolerance-associated symptoms such as diarrhea and weight loss. ChIn reduced the expression of mucin and tight junction genes, and reduced mucus thickness indicating barrier dysfunction. RMD increased colon, cecum, and spleen weights along with an increase in IL-6 gene expression indicating inflammation. WB did not show any intolerance-associated symptoms or inflammation. HMP supplementation increased SCFAs without any intolerance symptoms, except for increased gut permeability. Overall, structural complexity appears to be the most influential property in fiber tolerance.

University of Illinois Urbana-Champaign (Jaume Amengual). (Background) Carotenoids are rich in fruits and vegetables, and therefore, are major components of healthy diets. Carotenoids can be found in large amounts in humans, and are precursors of vitamin A. (Activities) Over the past year, we utilized preclinical approaches such as cell culture and mouse models to study the metabolism of carotenoids and vitamin A. (Outcomes) We were able to target vitamin A production from carotenoids accumulated in the adipose tissue. As a result, we observed a reduction in adipose tissue size, suggesting that carotenoids accumulated in the adipose tissue could be utilized to reduce obesity.

University of Missouri Columbia (Pavel Somavat). (Background) Colored corn varieties contain disproportionately higher anthocyanin and polyphenolic contents and these varieties, adapted to the midwestern climatic conditions can be utilized for economically extracting value-added phytochemicals, benefitting different agro-industrial sectors supplementing the lower economic value of conventional yellow dent corn. (Activities) Our research aims to evaluate the conventionally bred and colored corn varieties developed by the USDA-ARS colored corn breeding program at the University of Missouri for their milling characteristics and polyphenolic contents with the objective of identifying the most promising varieties for further breeding efforts. We also utilize colored corn varieties for the preparation of shelf-stable natural red colorants using spray and freeze-drying methods and evaluate physiochemical properties of the prepared color extracts. (Outcomes) Although, the commercial maize morado variety contained the highest anthocyanins, total phenols, and condensed tannins, four of the fourteen Missouri grown experimental varieties, namely, HM20, HM21, PBP, and AP were identified to be rich sources of polyphenolic compounds and antioxidant activities. These varieties were identified for subsequent breeding cycles.

The Ohio State University (Richard Bruno). (Background) Obesity-related cardiometabolic disorders are driven by inflammation, oxidative stress, and gut dysbiosis. Green tea catechins protect against cardiometabolic disorders by anti-inflammatory, antioxidant, and prebiotic activities but whether obesity alters catechin bioavailability was unknown. (Activities) To address this knowledge gap, the Ohio Station completed a clinical study examining catechin bioavailability in obese and healthy persons following consumption of a novel catechin-rich green tea extract (GTE) confection. Biospecimens collected from participants up to 24 hours after the consumption of GTE confection were analyzed catechin compounds using LCMS and metagenomics. (Outcomes) Obesity reduced bioavailability of all GTE catechins by 24–27% and their maximum plasma concentrations by 18–36%. Metabolites of GTE catechins, specifically two γ-valerolactones, were unaffected by obesity, and total urinary elimination of these metabolites was approximately doubled that of total catechins regardless of health status. Although α-diversity of gut microbiota was lower in obese persons, Slackia was the only catechin-metabolizing bacteria altered by obesity. These findings indicate that obesity reduces catechin bioavailability without affecting valerolactone generation, urinary catechin elimination, or substantially altered gut microbiota populations, suggesting a gut-level mechanism that limits catechin absorption in obese persons.

University of Rhode Island (Brietta Oaks). (Background) Lead exposure is a major public health concern in Rhode Island. There is evidence that omega-3 fatty acid intake may reduce circulating lead concentrations, but research has been limited and has not been explored in pregnant women, who are at a higher risk for adverse effects of lead exposure. In addition, omega-3 fatty acid intake may reduce circulating cortisol, a stress hormone that has negative effects during pregnancy if at chronically high concentrations. (Activities) The study is currently in progress. Pregnant women are actively being recruited from The Women, Infants & Children Program (WIC) offices several times a week. (Outcomes) We have enrolled 11 women and 10 have completed all data and sample collection, including surveys, saliva collection, and blood draw. In our preliminary data, women so far have blood lead concentrations that are within normal limits however fall into the category of vitamin D deficiency or insufficiency.

Cornell University (Elad Tako). (Background) Bioactives from natural food items (e.g. phytochemicals and bioactive peptides) play an important role in modulating gut microbiota, enteric immunity, and gut barrier functions. Our research involves evaluating gut health-promoting effects of chia-derived bioactive peptides, probiotics, black corn extracts (BCE), fractions of Concord grapes (Vitis labrusca L.) and catechin derivatives. (Activities) We conducted separate studies using animal models to evaluate intestinal microbiota, enteric immunity and gut barrier functions in response to dietary supplementation of 1) the effects of the intra-amniotic administration of the hydrolyzed chia protein and the probiotic Lacticaseibacillus paracasei, BCE, grape puree included the grape skin, endocarp, mesocarp, and juice but not the seeds on gut health, and the synthetic catechin pentaacetate and catechin pentabutanoate (two new ester derivatives of catechin). (Outcomes) Results suggest that hydrolyzed chia protein or a probiotic promoted positive changes in terms of intestinal inflammation, barrier, and morphology, improving intestinal health. The BCE promoted positive changes in the cecum microbiome and maintained intestinal morphology and functionality. The grape puree treatment resulted in higher Clostridium numbers and lower Bifidobacterium numbers when compared to all other groups. In contrast, catechin and its synthetic derivatives significantly decreased Clostridium genera and E. coli species density and decreased expression of genes encoding iron and zinc transporter in the duodenum.

University of Connecticut (Ji-Young Lee). (Background) Alcoholic hepatitis (AH) is a progressive form of alcoholic liver disease. Hepatocytes and macrophages play a crucial role in the development of AH. (Activities) We determine the effect of astaxanthin, a xanthophyll carotenoid, and nicotinamide riboside, a NAD+ precursor, on alcohol-induced inflammation and oxidative stress in hepatocytes and macrophages with an elucidation of mechanisms of action. (Outcomes) We found that astaxanthin and NR inhibited inflammation and oxidative stress in hepatocytes and macrophages exposed to alcohol by preventing mitochondrial dysfunctions.

University of Maine (Dorothy Klimis-Zacas). (Background) Wounds occur in over 15 million people with approximately $60 billion spent annually on wound care. Deficient vascularization is a significant factor that promotes chronic and non-healing wounds, ultimately resulting in amputation. Currently, most clinical wound treatments are antibiotics for infection control. Chronic wounds such as diabetic foot ulcers, ischemic limbs, and pressure ulcers lack treatments that promote wound healing and improve tissue remodeling. Thus, there is an urgent need to develop effective, cost-efficient, natural sources-derived therapies that have no deleterious side effects. (Activities) We have completed the preclinical study that aims to determine the efficacy of non-fidelity biomedical prototype(s) composed of wild blueberry extract(s) to promote angiogenesis, re-epithelialization, vascularization, collagen formation, and anti-inflammation related to wound healing. Meanwhile, we developed a second prototype based on nanocarrier technology for effective transdermal delivery of the wild blueberry extract. The product was tested with an animal model. Analyses are taking place in 2023. (Outcomes) Results from animal studies showed that the serum/gel prototype at specific concentrations significantly promoted wound closure by 12% over the control and increased re-epithelialization, vascularization, collagen formation and decreased the inflammatory response compared to the control. The effects are mediated, in part, through regulating gene expression.

• Hogg, A., P. Carr, J. Eberly, C. Chen, C. Kowatch-Carlson, F. Crutcher, P. Lamb, K. McNamara, E. Haney, K. Kephart, V. Smith, L. Dykes, X. Chen, L. Huang, and M.J. Giroux. (2022) Registration of ‘Lustre’ Durum Wheat.   Journal of Plant Registrations 16:576-584. https://doi.org/10.1002/plr2.20214
• Zempleni J. Letter to the editor (regarding Perspective: The role of human breast-milk extracellular vesicles in child health and disease by D. O’Reilly et al., published in Advances in Nutrition on 24 August 2020). Adv Nutr 12:280, 2021.
• Sukreet S, Pereira Braga C, An TT, Adamec J, Cui J, Trible B, Zempleni J. Isolation of extracellular vesicles from byproducts of cheese making by tangential flow filtration yields heterogeneous fractions of nanoparticles. J Dairy Sci 104:9478-9493, 2021.
• Khanam A. Yu J, Zempleni J. Class A scavenger receptor-1/2 facilitates the uptake of bovine milk exosomes in murine bone marrow-derived macrophages and C57BL/6J mice. Am J Physiol Cell Physiol 321:C606-C614, 2021.
• Ogunnaike M, Wang, H, Zempleni J. Bovine mammary alveolar MAC-T cells afford a tool for studies of bovine milk exosomes in drug delivery. Int J Pharm 610:121263, 2021.
• Wang H, Wu D, Sukreet S, Delaney A, Belfort MB, Zempleni J. Quantitation of exosomes and their microRNA cargos in frozen human milk. JPGN Reports 3:e172, 2022.
• Mutai E, Ngu AKH, Zempleni J. Preliminary evidence that lectins in infant soy formula apparently bind bovine milk exosomes and prevent their absorption in healthy adults. BMC Nutr 8:7, 2022.
• Sukreet S, Pereira Braga C, An, TT, Adamec J, Cui J, Zempleni J. Ultrasonication of milk decreases the content of exosomes and microRNAs in an exosome-defined rodent diet. J Nutr 152:961-970, 2022.
• Sadri M,* Wang H,* Kuroishi T,* Li Y, Zempleni J. Holocarboxylase synthetase knockout is embryonic lethal in mice. PLoS One 17:e0265539, 2022.
• Zhou F, Ebea P, Mutai E, Wang H, Sukreet S, Navazesh S, Dogan H, Li W, Cui J, Ji P, Ramirez DMO,* Zempleni J.* Small extracellular vesicles in milk cross the blood-brain barrier in murine cerebral cortex endothelial cells and promote dendritic complexity in the hippocampus and brain function in C57BL/6J mice. Front Nutr 9:838543, 2022.
• Ngu A, Wang S, Wang H, Khanam A, Zempleni J. Milk exosomes in nutrition and drug delivery. Am J Physiol Cell Physiol 322:C865-C874, 2022.
• Munir J, Ngu A, Wang H, Ramirez DMO, Zempleni J. Review: Milk small extracellular vesicles for use in the delivery of therapeutics. Pharm Res (online ahead of print), 2022.
• Li G, Ho KKHY, Zuo YY. Relative dye adsorption method for determining the hydrophobicity of nanoparticles. The Journal of Physical Chemistry C. 2021;126(1):832-7.
• Ho KKHY, Redan BW. Impact of thermal processing on the nutrients, phytochemicals, and metal contaminants in edible algae. Critical reviews in food science and nutrition. 2021;62(2):508-26
• Li G, Cao Z, Ho KKHY, Zuo YY. Quantitative determination of the hydrophobicity of nanoparticles. Analytical Chemistry. 2022;94(4):2078-86.
• Thompson M, Ulu A, Mukherjee M, Yuil-Valdes AG, Thoene M, Van Ormer M, Slotkowski R, Mauch T, Anderson-Berry A, Hanson CK, Nordgren TM, Natarajan SK. Something Smells Fishy: How Lipid Mediators Impact the Maternal-Fetal Interface and Neonatal Development. Biomedicines. 2023 Jan 10;11(1):171. doi: 10.3390/biomedicines11010171. PMID: 36672679. Review.
• Muthuraj PG, Krishnamoorthy C, Anderson-Berry A, Hanson C, Natarajan SK. Novel Therapeutic Nutrients Molecules That Protect against Zika Virus Infection with a Special Note on Palmitoleate. Nutrients. 2022 Dec 27;15(1):124. doi: 10.3390/nu15010124. PMID: 36615782. Review.
• Neltner TJ, Sahoo PK, Smith RW, Anders JPV, Arnett JE, Schmidt RJ, Johnson GO, Natarajan SK, Housh TJ. Effects of 8 Weeks of Shilajit Supplementation on Serum Pro-c1α1, a Biomarker of Type 1 Collagen Synthesis: A Randomized Control Trial. J Diet Suppl. 2022 Dec 22:1-12. doi: 10.1080/19390211.2022.2157522. Online ahead of print. PMID: 36546868
• Ro SH, Bae J, Jang Y, Myers JF, Chung S, Yu J, Natarajan SK, Franco R, Song HS. Arsenic Toxicity on Metabolism and Autophagy in Adipose and Muscle Tissues. Antioxidants (Basel). 2022 Mar 31;11(4):689. doi: 10.3390/antiox11040689. PMID: 35453374. Review.
• Thompson M, Ulu A, Yuil-Valdes AG, Mukherjee M, Thoene M, Van Ormer M, Slotkowski R, Lyden E, Anderson Berry A, Hanson CK, Nordgren TM, Natarajan SK. Omega-6 and Omega-3 Fatty Acid-Derived Oxylipins from the Lipoxygenase Pathway in Maternal and Umbilical Cord Plasma at Delivery and Their Relationship with Infant Growth. Int J Mol Sci. 2022 Jan 9;23(2):708. doi: 10.3390/ijms23020708. PMID: 35054892.
• Meyer RK, Bime MA, Duca FA. Small intestinal metabolomics analysis reveals differentially regulated metabolite profiles in obese rats and with prebiotic supplementation. Metabolomics. 2022, 18(8):60.
• Meyer RK, Lane AI, Weninger SN, Martinez TM, Kangath A, Laubitz D, Duca FA. Oligofructose restores postprandial short-chain fatty acid levels during high-fat feeding. Obesity (Silver Spring). 2022, 30(7):1442-1452.
• Wachsmuth HR, Weninger SN, Duca FA. Role of the gut-brain axis in energy and glucose metabolism. Exp Mol Med. 2022, 54(4):377-392.
• Yue JTY, Duca FA, Lam TKT. Silencing gut CCK cells alters gut reaction to sugar. Nat Neurosci. 2022, 25(2):136-138.
• Howard EJ, Lam TKT, Duca FA. The Gut Microbiome: Connecting Diet, Glucose Homeostasis, and Disease. Annu Rev Med. 2022, 73:469-481.
• Smith KA, Pugh JN, Duca FA, Close GL, Ormsbee MJ. Gastrointestinal pathophysiology during endurance exercise: endocrine, microbiome, and nutritional influences. Eur J Appl Physiol. 2021, 121(10):2657-2674.
• Mattar P, Uribe-Cerda S, Pezoa C, Guarnieri T, Kotz CM, Teske JA, Morselli E, Perez-Leighton C. Brain site specific regulation of hedonic intake by orexin and DYN peptides: Role of the PVN and obesity. Nutr Neurosci, 2022, 25(5)5:1105-1114.
• Jinno, C., X. Li, and Y. Liu. 2022. Dietary supplementation of Bacillus subtilis or antibiotics modified intestinal microbiome of weaned pigs under enterotoxigenic Escherichia coli infection. Frontiers Microbiol. 2022. 1064328.
• Wong, B. T., S. Park, L. Kovanda, Y. He, K. Kim, S. Xu, C. Lingga, M. Hejna, E. Wall, R. Sripathy, X. Li, and Y. Liu. 2022. Dietary supplementation of botanical blends enhanced performance and disease resistance of weaned pigs experimentally infected with enterotoxigenic Escherichia coli F18. J. Anim. Sci. skac353.
• Kim, K., M. Song, Y. Liu, and P. Ji. 2022. Enterotoxigenic Escherichia coli infection of weaned pigs: Intestinal challenges and nutritional intervention to enhance disease resistance. Front. Immunol. doi: 10.3389/fimmu.2022.885253.
• Kim, K., C. Jinno, P. Ji, Y. Liu. 2022. Trace amounts of antibiotic altered metabolomic and microbial profiles of weaned pigs infected with a pathogenic E. coli. J. Anim. Sci. Biotechnol. 13:59-73.
• Kim K, He Y, Jinno C, Kovanda L, Li X, Bravo D, Cox E, Liu Y. 2022. Supplementation of oligosaccharide-based polymer enhanced growth and disease resistance of weaned pigs by modulating intestinal integrity and systemic immunity. J Anim Sci Biotechnol. 13:10-23.
• He Y, Jinno J, Li C, Johnson SL, Xue H, Liu Y, Ji P. 2022. Effects of a blend of essential oils, medium-chain fatty acids and a toxin-adsorbing mineral on diarrhea and gut microbiome of weanling pigs experimentally infected with a pathogenic E. coli. J Anim Sci. 100:skab365.
• Qi M, Tan B, Wang J, Liao S, Deng Y, Ji P, Song T, Zha A, Yin Y. The microbiota-gut-brain axis: A novel nutritional therapeutic target for growth retardation. Crit Rev Food Sci Nutr. 2022;62(18):4867-4892. doi: 10.1080/10408398.2021.1879004. Epub 2021 Feb 1. Review. PubMed PMID: 33523720.
• Qi M, Tan B, Wang J, Liao S, Li J, Cui Z, Shao Y, Ji P, Yin Y. Postnatal growth retardation is associated with deteriorated intestinal mucosal barrier function using a porcine model. J Cell Physiol. 2021 Apr;236(4):2631-2648. doi: 10.1002/jcp.30028. Epub 2020 Aug 27. PubMed PMID: 32853405.
• Perng V, Navazesh SE, Park J, Arballo JR, Ji P. Iron deficiency and overload modulate the inflammatory responses and metabolism of alveolar macrophages. Nutrients. 2022 Jul 28;14(15):3100.
• Perng V, Li C, Klocke CR, Navazesh SE, Pinneles DK, Lein PJ, Ji P. Iron deficiency and iron excess differently affect dendritic architecture of pyramidal neurons in the hippocampus of piglets. The Journal of nutrition. 2021 Jan;151(1):235-44.
• Kebreab E, Mendez J, Ji P, Lee JJ, Seo S. Supplementation of exogenous β-mannanase to low-protein diets improves feed conversion efficiency in lactating dairy cows. Animal Production Science. 2022 Sep 16;63(1):70-7.
• McMillen SA, Dean R, Dihardja E, Ji P, Lönnerdal B. Benefits and Risks of Early Life Iron Supplementation. Nutrients. 2022 Oct 19;14(20):4380.
• Martin SA, Riordan RT, Wang R, Yu Z, Aguirre-Burk AM, Wong CP, Olson DA, Branscum AJ, Turner RT, Iwaniec UT, Perez VI. Rapamycin impairs bone accrual in young adult mice independent of Nrf2. Exp Gerontol. 2021, 154:111516. doi: 10.1016/j.exger.2021.111516. PMID: 34389472. Reported and described in last year’s report (manuscript was in press).
• Joyce KM, Wong CP, Scriven IA, Olson DA, Doerge DR, Branscum AJ, Sattgast LH, Helferich WG, Turner RT, Iwaniec UT. Isoliquiritigenin decreases bone resorption and osteoclast differentiation. Mol Nutr Food Res. 2022, 66(11):e2100974. doi: 10.1002/mnfr.202100974. PMID: 35319818
• Liang, N., Koh, J., Kim, B. J., Ozturk, G., Barile, D., Dallas, D. C. (Accepted August 22, 2022). Structural and functional changes of bioactive proteins in human milk treated by vat-pasteurization, retort sterilization, ultra-high temperature pasteurization, freeze-thawing and homogenization. Front Nutr. https://doi.org/10.3389/fnut.2022.926814
• Koh, J., Kim, B. J., Qu, Y., Dallas, D. C. (2022) Mass spectral profiling of caseinomacropeptide extracted from feeding material and jejunal fluid using three methods–ethanol precipitation, perchloric acid precipitation, and ultrafiltration. Food Chemistry. https://doi.org/10.1016/j.foodchem.2022.133864
• Demers-Mathieu, V., Underwood, M. A., Dallas, D. C. (Accepted July 20, 2022). Premature delivery impacts the concentration of plasminogen activators and a plasminogen activator inhibitor in human milk. Frontiers in Pediatrics. Neonatology. DOI: 10.3389/fped.2022.917179
• Liang, N., Kim, B. J., Dallas, D. C. (Accepted May, 2022). Bioavailability of peptides derived from the in vitro digestion of human milk assessed by Caco-2 cell monolayers. Journal of Agricultural and Food Chemistry. https://doi.org/10.1021/acs.jafc.2c01246
• Koh, J., Kim, B. J., Qu, Y., Dallas, D. C. (Nov 2021). Top-down glycopeptidomics reveal intact glycomacropeptide is digested to a wide array of peptides in the human jejunum. Journal of Nutrition. DOI: 10.1093/jn/nxab400
• Liang, N., Beverly, R., Gorton, M., Scottoline, B. P., Dallas, D. C. (Nov 2021). Peptides derived from in vitro and in vivo digestion of human milk are immunomodulatory in THP-1 human macrophages. Journal of Nutrition. DOI: 10.1093/jn/nxab350
• Chen, Y., Kim, B. J., Dallas, D. C. (Oct 2021). Proteomics analysis reveals digestion-resistant proteins from colostrum are associated with inflammatory and cytotoxic responses in intestinal epithelial cells. Journal of Parenteral and Enteral Nutrition. https://doi.org/10.1002/jpen.2285
• Ho E, Wong CP, King JC. Impact of zinc on DNA integrity and age-related inflammation. Free Radic Biol Med. 2022 Jan;178:391-397.
• Bauman, J. E., Hsu, C. H., Centuori, S., Guillen-Rodriguez, J., Garland, L. L., Ho, E., Padi, M., Bageerathan, V., Bengtson, L., Wojtowicz, M., Szabo, E., & Chow, H. S.. Randomized Crossover Trial Evaluating Detoxification of Tobacco Carcinogens by Broccoli Seed and Sprout Extract in Current Smokers. Cancers, 2022, 14(9), 2129.
• Eggersdorfer, M., Berger, M. M., Calder, P. C., Gombart, A. F., Ho, E., Laviano, A., & Meydani, S. N.. Perspective: Role of Micronutrients and Omega-3 Long-Chain Polyunsaturated Fatty Acids for Immune Outcomes of Relevance to Infections in Older Adults-A Narrative Review and Call for Action. Advances in nutrition (Bethesda, Md.), 2022, 13(5), 1415–1430.
• Lee, B. Y., Ordovás, J. M., Parks, E. J., Anderson, C., Barabási, A. L., Clinton, S. K., de la Haye, K., Duffy, V. B., Franks, P. W., Ginexi, E. M., Hammond, K. J., Hanlon, E. C., Hittle, M., Ho, E., Horn, A. L., Isaacson, R. S., Mabry, P. L., Malone, S., Martin, C. K., Mattei, J., Martinez, M. F. Research gaps and opportunities in precision nutrition: an NIH workshop report. The American journal of clinical nutrition, (2022) 16(6):1877-1900.
• Beaver LM, Song Y, Philbrick KA, Wong CP, Olson DA, Branscum AJ, Turner RT, Ho E, Iwaniec UT. Severe Zinc Deficiency Impairs Accrual of Bone in Rapidly Growing Rats That Is Partially Corrected Following Short-term Zinc Repletion. Biol Trace Elem Res. (2022) doi: 10.1007/s12011-022-03456-4. Epub ahead of print. PMID: 36348174.
• Bouranis JA, Beaver LM, Jiang D, Choi J, Wong CP, Davis EW, Williams DE, Sharpton TJ, Stevens JF, Ho E. Interplay between Cruciferous Vegetables and the Gut Microbiome: A Multi-Omic Approach. Nutrients. (2022) 22;15(1):42. doi: 10.3390/nu15010042. PMID: 36615700.
• Dingbo Lin, Denis M Medeiros. The microbiome as a major function of the gastrointestinal tract and its implication in micronutrient metabolism and chronic diseases. Nutr Res. 2023 Apr;112:30-45. doi: 10.1016/j.nutres.2023.02.007.
• Sanmi E Alake, Stanley Lightfoot, Karen Wozniak, Dingbo Lin, Winyoo Chowanadisai, Brenda J Smith, Edralin A Lucas. 2023. Wheat germ supplementation reduces inflammation and gut epithelial barrier dysfunction in female interleukin-10 knockout mice fed a pro-atherogenic diet. J Nutr 2023 Mar;153(3):870-879. doi: 10.1016/j.tjnut.2023.01.008.
• Babajide A Ojo, Sanmi E Alake, Amritpal Kaur, Siau Yen Wong, Bryant Keirns, Jerry W Ritchey, Winyoo Chowanadisai, Dingbo Lin, Stephen Clarke, Brenda J Smith, Edralin A Lucas. 2023. Supplemental wheat germ modulates phosphorylation of STAT3 in the gut and NF-κB p65 in the adipose tissue of mice fed a Western diet. Current Developments in Nutrition
• Rui Wang, Julianna Maria Santos, Jannette M. Dufour, Emily Stephens, Jonathan M Miranda, Rachel L. Washburn, Taylor Hibler, Gurvinder Kaur, Dingbo Lin, Chwan-Li Shen. 2022. Ginger root extract improves intestinal health in diabetic rats via improving intestinal integrity and mitochondrial function and suppressing oxidative stress and inflammation. Nutrients 2022 Oct 19;14(20):4384. doi: 10.3390/nu14204384.
• Urbizo-Reyes U, Liceaga AM, Reddivari L, Li S, Kim K-H, Cox, AD, Anderson JM. 2022. Canary seed (Phalaris canariensis L.) peptides prevent obesity and glucose intolerance in mice fed a Western Diet. Int J Mol Sci 23(23), 14927.
• Li S, Jin Y, Cox AD, Lee D, Reddivari L. 2022. Intermittent antibiotic treatment accelerated the development of colitis in IL10-KO mice. Biomed Pharmacotherapy 146, 112486
• Urbizo-Reyes U, Kim K-H, Reddivari L, Anderson JM, Liceaga AM. 2022. Oxidative stress protection by canary seed (Phalaris canariensis L.) peptides in Caco-2 cells and Caenorhabditis elegans. Nutrients 14 (12), 2415.
• Elango D, Wang X, Bhatnagar RS, Tan Q, Gaffoor I, Hu Z, Xue W, Roth GW, Morris GP, Reddivari L, Chopra S. 2022. Association genetics of early season cold and late season frost tolerance in Sorghum bicolor. Crop Sci 62:1844–1865
• Urbizo-Reyes U, Reddivari L, Kim K-H, Anderson JM, Liceaga AM. 2022. Enzyme kinetics, molecular docking, and in silico characterization of canary seed (Phalaris canariensis L.) peptides with ACE and pancreatic lipase inhibitory activity. J Funct Foods 88, 104892.
• Zinati G, Reddivari L, Kan J. 2022. Variation in phytonutrient levels in Butternut Winter squash with storage period, management practices, and cropping system in the Vegetable Systems Trial at Rodale Institute. https://rodaleinstitute.org/science/articles/variation-in-phytonutrient-levels-in-butternut-wintersquash-with-storage-period-management-practices-and-cropping-systems-in-the-vegetable-systems-trial-vst-at-rodale-institute/
• Miller AP, Black M, Amengual J. Fenretinide inhibits vitamin A formation from β-carotene and regulates carotenoid levels in mice. Biochim Biophys Acta Mol Cell Biol Lipids. 2022; DOI: 10.1016/j.bbalip.2021.159070.
• Acharya P, Black M, Blessner G, Amengual J. Development and validation of a method to deliver vitamin A to macrophages. Meth Enzymol. 2022; 674:363-389
• Coronel J, Yu J, Pilli N, Kane MA, Amengual J. The conversion of β-carotene to vitamin A in adipocytes drives the anti-obesogenic effects of β-carotene in mice. Mol Metab. 2022; DOI: 10.1016/j.molmet.2022.101640.
• L Chen, S Zhang, X Sun, JD McDonald, RS Bruno, J Zhu. Application of comparative lipidomics to elucidate postprandial metabolic excursions following dairy milk ingestion in individuals with prediabetes. J Proteome Res, 2021; 20(5):2583-2595. doi: 10.1021/acs.jproteome.0c01009.
• MT Goodus, KE Carson, AD Sauerbeck, P Dey, AN Alfredo, PG Popovich, RS Bruno, DM McTigue. Liver inflammation at the time of spinal cord injury enhances intraspinal pathology, liver injury, metabolic syndrome and locomotor deficits. Exp Neurol. 2021;342:113725. doi: 10.1016/j.expneurol.2021.113725
• RS Bruno, A Pokala, M Torres-Gonzalez, CN Blesso. Cardiometabolic Health Benefits Of Dairy Milk Polar Lipids. Nutr Rev, 2021;79(Suppl 2):16-35. doi: 10.1093/nutrit/nuab085
• S Cao, EN Shaw, W Quarles, GY Sasaki, P Dey, JK Hodges, A Pokala, M Zeng, RS Bruno. Daily inclusion of resistant starch-containing potatoes in a Dietary Guidelines for Americans dietary pattern does not adversely affect cardiometabolic risk or intestinal permeability in adults with metabolic syndrome: A randomized controlled trial. Nutrients, 2022; 14(8):1545. doi: 10.3390/nu14081545
• KR Weinhold, RR Andridge, JA Bomser, GY Sasaki, RS Bruno, TS Orchard. Sugars measured enzymatically in a fasting overnight urine sample are not sensitive biomarkers of dietary added sugar intake in postmenopausal women. Nutr Health, 2022; 2601060221106819. doi: 10.1177/02601060221106819.
• X Sun, P Dey, RS Bruno, J Zhu. EGCG and catechin relative to green tea extract differentially modulate the gut microbial metabolome and liver metabolome to prevent obesity in mice fed a high-fat diet. J Nutr Biochem, 2022; 109:109094. doi: 10.1016/j.jnutbio.2022.109094.
• L Chen, R Xu, J McDonald, RS Bruno, F Choueiry, J Zhu. Dairy milk casein and whey proteins differentially alter the postprandial lipidome in persons with prediabetes: A comparative lipidomics study. J Agric Food Chem, 2022; 70(33):10209-10220. doi: 10.1021/acs.jafc.2c03662.
• H-Y Chen, A Almonte-Loya, F-Y Lay, M Hsu, E Johnson, E Gonzalez-Avalos, J Yin, RS Bruno, Q Ma, HE Ghoneim, DJ Wozniak, FE Harrison, C-WJ Lio. Epigenetic remodeling by vitamin C potentiates plasma cell differentiation. eLife, 2022; 11:e73754. doi: 10.7554/eLife.73754.
• GY Sasaki, Y Vodovotz, Z Yu, RS Bruno. Catechin bioavailability following consumption of a green tea extract confection is reduced in obese persons without affecting gut microbial-derived valerolactones. Antioxidants, 2022, 11(12):2490. doi: 10.3390/antiox11122490.
• Oaks BM, Adu-Afarwuah S, Ashorn P, Lartey A, Laugero KD, Okronipa H, Stewart CP, Dewey KG. Increased risk of preterm delivery with high cortisol during pregnancy is modified by fetal sex: a cohort study. BMC Pregnancy and Childbirth. 2022 Sep;22:727.
• Davis JN, Williams A, Arnold CD, Rohner F, Wirth JP, Addo Y, Flores-Ayala RC, Oaks BM, Young MF, Suchdev PS, Engle-Stone R. The relationship between ferritin and body mass index is mediated by inflammation among women in higher-income countries, but not in most lower-income countries nor among young children a multi-country analysis. Current Developments in Nutrition. 2022 Sep 9;6(10):nzac139.
• Akseer N, Keats EC, Thurairajah P, Cousens S, Bétran AP, Oaks BM, Osrin D, Piwoz E, Gomo E, Ahmed F, Friis H, Belizán J, Dewey KG, West K, Huybregts L, Zeng L, Dibley MJ, Zagre N, Christian P, Kolsteren PW, Kaestel P, Black RE, Arifeen SE, Ashorn U, Fawzi W, Bhutta ZA, The Global Young Women’s Investigators Group. Characteristics and birth outcomes of pregnant adolescents compared to older women: an analysis of individual level data from 140,000 mothers from 20 RCTs. EClinicalMedicine. 2022 Feb 26;45:101309.
• Adu-Afarwuah S, Arnold CD, Lartey A, Okronipa H, Maleta K, Ashorn P, Ashorn U, Fan YM, Matchado A, Kortekangas E, Oaks BM, Jackson KH, Dewey KG. Small-quantity lipid-based nutrient supplements increase infants' plasma essential fatty acid levels in Ghana and Malawi: a secondary outcome analysis of the iLiNS-DYAD randomized trials. Journal of Nutrition. 2022 Jan 11;152(1):286-301.
• Keats EC, Akseer N, Thurairajah P, Cousens S, Bhutta ZA, The Global Young Women’s Nutrition Investigators Group. Multiple micronutrient supplementation in pregnant adolescents in low- and middle-income countries: a systematic review and a meta-analysis of individual participant data. Nutrition Reviews. 2022 Jan 10;80(2):141-156.
• Bentil HJ*, Abreu AM*, Adu-Afarwuah S, Rossi JS, Tovar A, Oaks BM. Associations between dietary magnesium intake and glycemic markers in Ghanaian women of reproductive age: a pilot cross-sectional study. Nutrients. 2021 Nov 19;13(11):4141.
• Hong BV, Zhu C, Wong M, Sacchi R, Rhodes CH, Kang JW, Arnold CD, Adu-Afarwuah S, Lartey A, Oaks BM, Lebrilla CB, Dewey KG, Zivkovic AM. Maternal and infant supplementation with small-quantity lipid-based nutrient supplements increases child HDL cholesterol efflux capacity and is associated with changes in the HDL glycoproteome. ACS Omega. 2021 Nov 18;6(47):32022-32031.
• Kolba N, Zarei A, Cheng J, Agarwal N, Dadmohammadi Y, Khazdooz L, Abbaspourrad A, Tako E. Alterations in Intestinal Brush Border Membrane Functionality and Bacterial Populations Following Intra-Amniotic Administration (Gallus gallus) of Catechin and Its Derivatives. Nutrients. 2022 Sep 22;14(19):3924. doi: 10.3390/nu14193924.
• Agarwal N, Shukla V, Kolba N, Jackson C, Cheng J, Padilla-Zakour OI, Tako E. Comparing the Effects of Concord Grape (Vitis labrusca L.) Puree, Juice, and Pomace on Intestinal Morphology, Functionality, and Bacterial Populations In Vivo (Gallus gallus). Nutrients. 2022 Aug 27;14(17):3539. doi: 10.339
• Cheng J, Kolba N, Sisser P, Turjeman S, Even C, Koren O, Tako E.Intraamniotic Administration (Gallus gallus) of Genistein Alters Mineral Transport, Intestinal Morphology, and Gut Microbiota. Nutrients. 2022 Aug 24;14(17):3473. doi: 10.3390/nu14173473.
• Kolba N, Zarei A, Cheng J, Agarwal N, Dadmohammadi Y, Khazdooz L, Abbaspourrad A, Tako E. Alterations in Intestinal Brush Border Membrane Functionality and Bacterial Populations Following Intra-Amniotic Administration (Gallus gallus) of Nicotinamide Riboside and Its Derivatives. Nutrients. 2022 Jul 29;14(15):3130. doi: 10.3390/nu14153130.
• Knez M, Pantovic A, Tako E, Boy E. FADS1 and FADS2 as biomarkers of Zn status - a systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2022 Jul 26:1-19. doi: 10.1080/10408398.2022.2103790.
• Agrizzi Verediano T, Stampini Duarte Martino H, Kolba N, Fu Y, Cristina Dias Paes M, Tako E. Black corn (Zea mays L.) soluble extract showed anti-inflammatory effects and improved the intestinal barrier integrity in vivo (Gallus gallus). Food Res Int. 2022 Jul;157:111227. doi: 10.1016/j.foodres.2022.111227.
• Gomes MJC, Martino HSD, Kolba N, Cheng J, Agarwal N, Rocha MM, Tako E. Zinc Biofortified Cowpea (Vigna unguiculata L. Walp.) Soluble Extracts Modulate Assessed Cecal Bacterial Populations and Gut Morphology In Vivo (Gallus gallus). Front Biosci (Landmark Ed). 2022 Apr 25;27(5):140. doi: 10.31083/j.fbl2705140.
• Agrizzi Verediano T, Agarwal N, Juste Contin Gomes M, Martino HSD, Tako E. Effects of dietary fiber on intestinal iron absorption, and physiological status: a systematic review of in vivo and clinical studies. Crit Rev Food Sci Nutr. 2022 Apr 9:1-16. doi: 10.1080/10408398.2022.2060933.
• Agarwal N, Kolba N, Khen N, Even C, Turjeman S, Koren O, Tako E. Quinoa Soluble Fiber and Quercetin Alter the Composition of the Gut Microbiome and Improve Brush Border Membrane Morphology In Vivo (Gallus gallus). Nutrients. 2022 Jan 20;14(3):448. doi: 10.3390/nu14030448.
• Agarwal N, Kolba N, Jung Y, Cheng J, Tako E. Saffron (Crocus sativus L.) Flower Water Extract Disrupts the Cecal Microbiome, Brush Border Membrane Functionality, and Morphology In Vivo (Gallus gallus). Nutrients. 2022 Jan 5;14(1):220. doi: 10.3390/nu14010220.
• Beasley JT, Bonneau JP, Moreno-Moyano LT, Callahan DL, Howell KS, Tako E, Taylor J, Glahn RP, Appels R, Johnson AAT. Multi-year field evaluation of nicotianamine biofortified bread wheat. Plant J. 2022 Mar;109(5):1168-1182. doi: 10.1111/tpj.15623.
• Kim M-.B. Pham TX, Vanluling M, Kostour V, Kang H, Corvino O, Jang H, Odell W, Park Y-K, Lee J-Y. Nicotinamide riboside supplementation exerts anti-obesity effect and prevents inflammation and fibrosis in white adipose tissue of female diet-induced obesity mice. J Nutr Biochem. 2022, 107:109058.
• Kim M-B, Bae M, Lee Y, Kang H, Hu S, Pham TX, Park Y-K, Lee J-Y. Consumption of low dose fucoxanthin does not prevent hepatic and adipose inflammation and fibrosis in mouse models of diet-induced obesity. Nutrients. 2022, 14:2280.
• Mostofa MG, Tran M, Gilling S, Lee G, Fraher O, Jin L, Kang H, Park Y-K, Lee J-Y, Wang L, Shin D-J. miR-200c coordinates HNF1 homeobox B and Apolipoprotein O functions to modulate lipid homeostasis in alcoholic fatty liver disease. J Biol Chem. 2022, 298:101966.
• Miller CL, Anto L, Garcia C, Kim M-B, Jain A, Provatas AA, Lee J-Y, Nichols FC, Blesso CN. Gut microbiome-derived glycine lipids are diet-dependent modulators of hepatic injury and atherosclerosis. J Lipid Res. 2022, 63:100192.
• Bae M, Kim M-B, Lee J-Y. Fucoxanthin attenuates the changes in energy metabolism during the activation of hepatic stellate cells. Nutrients. 2022, 4:1902.
• Li Y, Kim M-B, Park Y-K, Lee J-Y. Fucoxanthin metabolites exert anti-fibrogenic and antioxidant effects in hepatic stellate cells. J Ag Food Res. 2022, 6:100245.
• Special Issue Co-Editor of “Genes and Metabolism”, Current Opinion in Clinical Nutrition and Metabolic Care, volume 24, Number 4. 2021.
• Vendrame S, Adekeye TE, Klimis-Zacas D (2022). The role of berry consumption on blood pressure regulation and hypertension: an overview of the clinical evidence. Nutrients, https://www.mdpi.com/2072-6643/14/13/2701
• Natalie E. VandenAkker, Stefano Vendrame, Panagiotis Tsakiroglou, Marissa McGilvrey, and Dorothy Klimis-Zacas.Whole Red Raspberry (Rubus idaeus)-Enriched Diet Is Hepatoprotective in the Obese Zucker Rat, a Model of the Metabolic Syndrome. Journal of Medicinal Food. 2021.817-824. http://doi.org/10.1089/jmf.2020.0130
• VandenAkker, N., Tsakiroglou, P., Vendrame S., Klimis-Zacas D., Red raspberry (Rubus idaeus) consumption restores the impaired Phenylephrine-induced vasoconstriction and Acetylcholine-induced vasorelaxation in the aorta of the obese Zucker rat, a model of the Metabolic Syndrome, J. Berry Res. 11 (2021) 89–101 DOI:10.3233/JBR-200567
• Pon Velayutham Anandh Babu and Dorothy Klimis-Zacas, (2022), Mechanisms of Action of Berry Bioactives on the Vascular System, In: Berries and Berry bioactive compounds in promoting health, Ed. Dorothy Klimis-Zacas and Ana Rodriquez-Mateos, Royal Society of Chemistry, Chapter 6, 166-184.
• Del Bo’, S. Vendrame, D. Martini, P. Riso and D. Klimis-Zacas, (2022), The role of berries and their bioactive compounds in obesity-induced inflammation, In: Berries and Berry bioactive compounds in promoting health, Ed. Dorothy Klimis-Zacas and Ana Rodriquez-Mateos, Royal Society of Chemistry, Chapter 11, 306-334.
• Co-editor of the Book “Berries and Berry Bioactive Compounds in Promoting Health”, Dorothy Klimis-Zacas and Ana Rodriguez-Mateos, Royal Society of Chemistry (2022)
• Nyakundi BB, Yang J. 2023. Uses of Papaya Leaf and Seaweed Supplementations for Controlling Glucose Homeostasis in Diabetes. Int J Mol Sci. 24:6846. doi: 10.3390/ijms24076846.