bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot study examining the application of plasma alkyresorcinols (AR) and urinary AR metabolites as biomarkers of compliance
Authors: McKeown Nicola M , Marklund Matti , Ma Jiantao , Livingston Kara , Jacques Paul , Blumberg Jeff , Chen C‐Y. Oliver 
Published: June 2021

Alkylresorcinols (AR) are phenolic lipids present in the bran of wheat and rye. Plasma AR and their urinary metabolites can be suitable biomarkers for whole‐grain consumption of these cereals. The objective of this study was to examine plasma AR and urinary AR metabolites in response to whole wheat (WW) consumption. In a randomized crossover study, 19 subjects (10M, 9F; BMI 22.0 kg/m2; age 26 y) incorporated either 3 (LWW) or 6 (HWW) servings of WW daily into their regular diet for 1 wk. Subjects completed a 2‐wk washout period, abstaining from all WW consumption, before each intervention. Fasting blood and 24 h urine were collected before and after each intervention. TFAA‐derivatized plasma AR (C:19, 21, 23) were quantified by GC‐MS after diethyl ether and solid phase extractions. Urinary AR metabolites (3,5‐dihydroxybenzoic acid and 3‐(3,5‐dihydroxyphenyl)‐propanoic acid) were determined using HPLC with electrochemical detection after enzymatic deconjugation and ethyl acetate extraction. Urinary total AR metabolites was significant higher after HWW to LWW (63.9 vs. 35.7 μmol, P <0.001). This dose‐response relationship was independent of age, sex, energy intake, and baseline urinary AR metabolites level. Plasma total AR was higher, but not significantly, after HWW to LWW (58.4 vs. 44.5 ng/ml, P=0.5). The results suggest that urinary AR metabolites may be useful as biomarkers of compliance in intervention studies of whole wheat.Grant Funding Source: the United States Department of Agriculture (USDA agreement No. 58–1950‐7–707) and the General Mills Bell Institute of Health and Nutrition
Tissue distribution of nobiletin and its metabolites in mice after oral administration of nobiletin
Authors: Wang Minqi , Zheng Jinkai , Zhong Zhimei , Song Mingyue , Wu Xian 
Published: June 2021

Nobiletin (NBT), a major citrus polymethoxyflavone, has been shown to have various beneficial bioactivities such as anti‐inflammatory and anti‐carcinogenic effects. However, the in vivo absorption, metabolism, and tissue distribution of NBT is poorly understood. In this study, A/J mice were fed NBT (250, 500, or, 1000 ppm in diet) for 16 weeks, and then the tissue levels of NBT and its major metabolites i.e. 3′‐hydroxylnobiletin (N1), 4′‐hydroxylnobiletin (N2) and 3′,4′‐dihydroxylnobiletin (N3) were determined by HPLC analysis. Our results showed that NBT was extensively metabolized in the small intestine to glucuronide and sulfate conjugates of N1, N2 and N3. In contrast, these conjugates were largely deconjugated in the colon presumably by colonic microflora. It was also evident that considerable amount of N1 and N2 were transformed to N3 in the colon. Moreover, different tissues showed distinct patterns of metabolite accumulation. For example, N2 was dominant in the small intestine and liver, while N3 was dominant in the spleen and colon. Very interestingly, NBT showed high accumulation in the brain, which was even much higher than that in the liver. The plasma levels of total NBT and its metabolites were as high as 25μM. Overall, we revealed detailed information on absorption, metabolism, and tissue distribution of NBT in mice, which is very important for further understanding of bioactivities of NBT.Grant Funding Source: AICR, NIH, NAS and USDA
Association of whole grain intake and longitudinal changes in abdominal adiposity in the Framingham Heart Study
Authors: Wang Huifen , Quatramoni Paula , Fox Caroline S , Jacques Paul F. , McKeown Nicola M. 
Published: June 2021

Longitudinal studies on the association of whole grain (WG) intake and abdominal adiposity are scarce. We examined the longitudinal association between WG intake and annualized changes in waist circumference (WC) in the Framingham Heart Study (FHS) Offspring adults. WC was measured approximately every 4 years over a median of 14 years of follow‐up. WG intake (g/d) was estimated by FFQ and calculated with and without added bran and germ. Repeated measures models, with data from 4 exam periods (n=11,372 observations), were used to examine associations between WG intake and annualized changes in WC. After adjustment for time‐varying and invariant demographic and lifestyle factors (including WC at the beginning of each exam interval), greater WG intake was associated with less annualized gain in WC. Adults who consumed more whole grains daily (median intake of 39 g/d) gained less abdominal fat per year (0.63 ± 0.04 cm gain in WC) than those who consumed fewer whole grains (median intake of 4 g/d) (0.79± 0.04 cm gain in WC). The inverse association between WG intake and change in WC was stronger in normal weight adults. The association remained significant after further adjusting for lipid‐lowering and blood pressure medications and diabetes. Based on these findings, a randomized trial is warranted to examine whether incorporating WG foods in the diet helps to mitigate gains in abdominal adiposity over time.Grant Funding Source: The National Institute of Health/National Heart, Lung, and Blood Institute (Contract N01‐HC‐25195), the United States Department of Agriculture (USDA agreement No. 58–1950‐7–707) and the General Mills Bell Institute of Health and Nutrition
Race, pregravid BMI and gestational weight gain determine placental fatty acid transfer
Authors: Smither Allison Rose , Durham Holiday A. , Buzhardt Sarah , Moore FA , Cefalu William T. , Lammi‐Keefe Carol J. 
Published: June 2021

Long chain polyunsaturated fatty acids (LCPUFA), arachidonic acid (AA) and docosoahexaenoic acid (DHA), are essential fatty acids for fetal growth (AA) and development (DHA). The fetus relies on maternal stores and placental transfer for LCPUFAs. In our study population of Hispanic and African‐American women, the relationships between maternal and fetal red blood cell (RBC) AA and DHA were examined and predictors of fetal fatty acids such as age, maternal pregavid body mass index (BMI), gestational weight gain, and race were determined. Maternal and venous cord blood and health histories were obtained at delivery (n=9). Gas chromatography was used to assess RBC fatty acids (wt %). Pearson correlations were used to analyze relationships. Stepwise regression determined the most significant predictors of AA and DHA transfer. There was preferential transfer of DHA and AA from mother to fetus over precursor fatty acids. Maternal DHA was positively correlated with fetal DHA (p=0.046), while AA was not. BMI and gestational weight gain were the strongest predictors of AA transfer to the fetus (p=0.045). DHA was less efficiently transferred in Hispanics than in African‐Americans (p=0.036). Future work is needed to better understand how other factors such as maternal diet affect these findings.Funded by a Howard Hughes Medical Institute grant to LSU (ARS); LSU AgCenter; USDA‐AFRI (CJL‐K)
Using Community Readiness Assessment to Inform Environmental Intervention Development in the Children's Healthy Living (CHL) Program in Remote Underserved Minority Populations of the Pacific
Authors: Fialkowski Marie Kainoa , DeBaryshe Barbara , Areta Ropeti , Belyeu‐Camacho Tayna , Bersamin Andrea , Rojas Gena , Vargo Agnes , Nigg Claudio , Guerrero Rachael Leon , Luick Bret , Novotny Rachel 
Published: June 2021

The prevalence of early childhood obesity among Native Hawaiians, Pacific Islanders and Alaska Natives is disproportionately high compared to other US population groups. Sustainable, multi‐strategy, community‐based approaches, rather than individually targeted approaches, are increasingly recognized as effective strategies to obesity prevention. Previous studies, however, have not examined community readiness (CR) as an important facet to obesity prevention interventions. We present results of CR assessments completed in the Children's Healthy Living (CHL) Program that will inform development and implementation of a community‐based intervention to modify the food and physical activity environment to prevent child obesity in 5 jurisdictions: Alaska (AK), American Samoa (AS), Commonwealth of the Northern Mariana Islands (CNMI), Guam (GM) and Hawaii (HI). A survey assessing 6 dimensions of CR was administered to key informants in 4 target communities per jurisdiction. Possible dimension CR scores range from 1 (No Awareness) to 9 (High Level of Community Ownership). Jurisdiction scores ranged from 3 – 4 in AK (n = 23) and CNMI (n = 22), 4 – 5 in HI (n = 24), 5 – 6 in GM (n = 34), and 6 – 7 in AS (n = 39). Results will be used to tailor CHL's community‐based environmental intervention to match each community's level of readiness.Grant Funding Source: Agriculture and Food Research Initiative Grant no. 2011–68001‐30335 from the USDA National Institute of Food and Agricultural Science Enhancement Coordinated Agricultural Program
Maternal high fat diet promotion of mammary tumor risk in adult progeny is associated with early expansion of mammary cancer stem‐like cells and increased maternal oxidative environment
Authors: Montales Maria Theresa E , Melnyk Stepan , Simmen Rosalia CM 
Published: June 2021

Many adult chronic diseases might be programmed during early life by maternal nutritional history. Here, we evaluated effects of maternal high fat diet on mammary gland development and tumor formation in adult progeny. Female Wnt‐1 transgenic mice exposed to high fat (HFD, 45% kcal fat) or control Casein (CAS, 17% kcal fat) diets in utero and during lactation were weaned to CAS diet at postnatal day 21 (PND 21). Relative to the CAS group, offspring exposed to maternal HFD had higher body and mammary tissue weights and elevated blood sugar and serum insulin levels at weaning and at PND110 and greater terminal end bud numbers at PND30. Mammary expression of tumor suppressors PTEN and p53 and pro‐apoptosis Bcl‐2 genes were lower in progeny exposed to maternal HFD. Mammary tumor latency was also lower (P=.01) in HFD (115±21 d) than CAS (190±13 d) offspring but tumor incidence and growth did not differ between groups. Epithelial cells from pre‐neoplastic mammary tissues showed expansion of the CD29highCD24+ (basal) and Thy1+CD29highCD24+ (cancer stem cell) subpopulations with maternal HFD exposure. Dams exposed to HFD had lower serum glutathione (GSH/GSSG) and cysteine (cysteine/cystine) oxidative ratios than CAS dams at weaning, but the two groups did not differ in body weights and insulin levels. Thus, maternal high fat diet, by altering early mammary development, may constitute a major risk factor for adult breast cancer.Grant Funding Source: USDA‐CRIS 6251–51000‐005–004S, Arkansas Breast Cancer Research Program, Arkansas Biosciences Institute
The satiety response to a standard lunch in habitual breakfast eaters and skippers
Authors: Forester Shavawn M. , Witbracht Megan , Horn William , Laugero Kevin , Keim Nancy L. 
Published: June 2021

BackgroundInsulin, Leptin, GLP‐1, and Glucagon are known regulators of food intake and glucose metabolism. Past studies showed a benefit of eating breakfast on satiety but were possibly confounded by disruption of habitual meal patterns. Thus, we conducted a cross‐sectional study of 30 women who were habitual breakfast eaters (Br‐E) or habitual skippers (Br‐S) to assess the hormones Insulin, Leptin, GLP‐1, and Glucagon following a standard lunch meal.MethodsBr‐E ate their typical breakfast meal between waking and 10am, whereas Br‐S followed their normal Br‐S routine. Both Br‐E and Br‐S did not consume any food or caloric beverage after 10am until the standard lunch was served. Blood was drawn 5 min pre‐lunch and 5, 20, 35, 50, 110 min post‐lunch. A multiplexed sandwich immunoassay (MSD) was used to measure hormones.ResultsRepeated measures ANOVA revealed group differences that were time dependent for Insulin (p=0.02), GLP‐1 (p=0.02), and Gluc (p=0.02). GLP‐1 was higher in Br‐E at 5 (p=0.02) and 110 (p=0.03) min.DiscussionClear differences in circulating hormones between Br‐E and Br‐S suggest that the previous breakfast meal influenced the postprandial response, even though all subjects were post absorptive at the start of the protocol. Our data further support the idea that regularly eating breakfast promotes satiety. Funding: USDA CSREES 2009–35215‐05364; USDA Intramural project 5306–51530‐019–00D.Grant Funding Source: USDA CSREES 2009–35215‐05364; USDA Intramural project 5306–51530‐019–00D
Modulations of sirtuin 1 protein levels by nicotine and β‐ cryptoxanthin can be mediated by miR‐34a in A/J mice lung cancer model
Authors: Iskandar Anita R , You Min , Wang Xiang‐Dong 
Published: June 2021

MicroRNAs (miRs) are small endogenous non‐coding RNAs that can regulate gene expression in a post‐transcriptional manner and target important molecules in carcinogenesis. We recently found that nicotine promoted lung tumorigenesis and emphysema in tobacco‐carcinogen (NNK)‐treated male A/J mice. We found that lung levels of sirtuin 1 (SIRT1) protein were decreased in the mice treated with the combination of NNK and nicotine. Moreover, β‐ cryptoxanthin (BCX) supplementation to these mice suppressed both lung tumor and emphysema development, which accompanied by SIRT1 protein restoration to normal levels without sirt1 mRNA alteration. This observation indicated a potential post‐transcriptional regulation of SIRT1. We then conducted real‐time PCR analyses to measure the lung levels of miR‐34a and miR‐217, which have been shown to hinder sirt1 translation. We observed that the levels of miR‐34a were increased in the lungs of the mice treated with the combination of NNK and nicotine, whereas miR‐217 levels were not different among all groups. The levels of miR‐34a in the lungs of the BCX‐supplemented mice were restored to that of the normal levels, indicating an inverse association between the levels of miR‐34a and SIRT1 protein. Our data indicate that the modulation of SIRT1 protein level by nicotine/BCX can be mediated by miR‐34a regulation in the nicotine‐promoted emphysema/lung tumorigenesis in A/J mice.Grant Funding Source: U.S. Department of Agriculture grant 1950–51000‐064S
Astaxanthin inhibits TGF‐β1‐induced fibrogenic gene expression by inhibiting the activation of Smad3 and KLF‐6 pathways in LX‐2 and primary mouse hepatic stellate cells
Authors: Yang Yue , Lee Ji‐Young 
Published: June 2021

Liver fibrosis, a condition defined by excessive accumulation of extracellular matrix, is triggered by the activation of hepatic stellate cells (HSCs). Astaxanthin (ASTX), a xanthophyll carotenoid, has multiple protective properties against nonalcoholic steatohepatitis (NASH). To investigate anti‐fibrogenic functions of ASTX, we used LX‐2, a human HSC cell line, and primary HSCs isolated from C57BL/6J mice in this study. Increases in the production of reactive oxygen species by transforming growth factor β 1(TGF‐β1) or tert‐butyl hydroperoxide was significantly attenuated by 25 μM ASTX in LX‐2 cells. Pretreatment with ASTX significantly decreased TGF‐β1‐induced mRNA abundance of α‐smooth muscle actin (α‐SMA) and collagen 1 α1 (Col1α1) and Western blot confirmed the reduction in α‐SMA expression by ASTX in LX‐2 cells. The nuclear translocation of major transcription factors transducing TGF‐β1 signal, i.e., Smad‐3 and Krueppel‐like factor 6 (KLF‐6), was noticeably inhibited by ASTX in LX‐2 cells. ASTX also significantly repressed the expression of α‐SMA and restored superoxide dismutase 2 expression in activated primary mouse HSCs. In conclusion, our study demonstrates that ASTX exerts anti‐fibrogenic and antioxidant effects in HSCs in vitro by repressing the activation of Smad‐3 and KLF6 by TGF‐β1, suggesting a potential role of ASTX in the prevention of NASH.Grant Funding Source: USDA AFRI 2012–67018‐19290
Consumption of Different Sources of Omega‐3 Fatty Acids Alters Lipogenic Gene Expression in Growing Rats
Authors: Mock Kaitlin , Tou Janet , Benedito Vagner , Gigliotti Joseph 
Published: June 2021

Currently, there is an increased intake of omega‐3 (n‐3) polyunsaturated fatty acids (PUFA) through diet and supplementation. The objective of this study was to determine if the n‐3 PUFA source plays a role in de novo lipid metabolism by altering gene expression. Female Sprague‐Dawley rats were assigned to one of six diets: corn oil (CO), flaxseed oil (FO), krill oil (KO), menhaden oil (MO), salmon oil (SO), or tuna oil (TO). Most n −3 PUFA sources had decreased expression of hepatic lipogenic genes. Stearoyl CoA Desaturase 1 expression decreased in TO (P=0.04) and MO (P=0.008) compared to CO. Fatty Acid Synthase expression decreased in TO (P=0.006), SO (P=0.001), MO (P=0.001), and FO (P=0.01) compared to CO. Sterol Regulatory Element Binding Protein 1c expression decreased in MO (P=0.007) compared to CO. Peroxisome Proliferator‐Activated Receptor Alpha (PPAR α) was used as a measure of hepatic lipolysis, however, no differences were found. There were no significant changes in expression of lipogenic genes in gonadal tissue of n‐3 PUFA groups when compared to CO. In the gonadal tissue, PPARγ increased in FO (P=0.04) compared to CO, and Hormone Sensitive Lipase had no differences in expression compared to CO. These values suggest that n‐3 fatty acids may be altering de novo lipid metabolism by decreasing expression of lipogenic genes in liver tissue, and increasing expression of a lipolytic gene in gonadal tissue.Grant Funding Source: NIFA #1004489 and WVU Hatch Grant H459
Quercetin aglycone up‐regulates antioxidant response genes and proteins in osteoblast‐like fetal rat calvarial cells
Authors: Messer Jonathan G. , Hopkins Robin G. , Kipp Deborah E. 
Published: June 2021

Quercetin (QRC), a flavonol found in fruits and vegetables, has been shown to up‐regulate antioxidant response genes and proteins in a variety of cell types, but little is known about the effects of QRC on these genes and proteins in osteoblasts. The purpose of this study was to determine the extent that QRC alters expression of antioxidant genes and proteins in primary cultures of fetal rat calvarial cells, a well‐described model of osteoblast differentiation. Cells were treated up to 48 h starting at confluence with 0 or 20 μM QRC aglycone. Antioxidant gene and protein expression were analyzed using real‐time quantitative PCR and Western blotting, respectively. Quercetin significantly up‐regulated heme oxygenase 1 (HO‐1), catalase, and gamma‐glutamate‐cysteine ligase catalytic subunit (GCLC) (p < 0.05), but did not up‐regulate peroxiredoxins 3 and 5, and NADPH:quinone oxidoreductase (p >; 0.05). Protein expression was generally congruent with gene expression, with HO‐1 being the most markedly up‐regulated in response to 20 μM QRC. These data suggest that QRC up‐regulates some genes and proteins associated with the antioxidant response in osteoblasts. Since evidence suggests that oxidative stress may contribute to osteoporosis, QRC may have protective effects on bone health.Grant Funding Source: USDA Agricultural Research Services
Lean Gain Is Enhanced by a Leucine Pulse during Long‐Term Continuous Feeding in Neonatal Pigs
Authors: Boutry Claire , El‐Kadi Samer W. , Suryawan Agus , Steinhoff‐Wagner Julia , Stoll Barbara , Orellana Renán A. , Nguyen Hanh V. , Davis Teresa A. 
Published: June 2021

Infants who are unable to maintain oral feeding can be nourished continuously by orogastric tube. We have previously shown in neonatal pigs that a leucine pulse administered during continuous feeding enhanced protein synthesis in skeletal muscle compared to continuous feeding alone for a 24 h period. Twenty‐three piglets (7‐d‐old) were fed continuously a milk replacement formula via orogastric tube for 21 d with an additional parenteral infusion of either leucine (800 μmol•kg−1•h−1, LEU) or alanine (ALA) for 1 h every 4 h. At 21 d, the body weight was higher and the weight gain greater in LEU than in ALA pigs. The lean gain, determined by dual‐energy X‐ray absorptiometry (DEXA), was higher and the fat gain lower in the LEU than ALA group. Longissimus dorsi (LD), gastrocnemius and soleus muscle and kidney weights were heavier in LEU than ALA with no effect of treatment on liver, small intestine and heart weights. Fractional protein synthesis rate and formation of the active eukaryotic initiation factor (eIF) eIF4E•eIF4G complex in LD were greater in the LEU than ALA group. In conclusion, administration of a leucine pulse during 21 d of continuous feeding decreases fat gain and increases lean gain by stimulating the translation initiation pathway leading to protein synthesis in skeletal muscle in neonates. (NIH AR444474 and USDA/ARS 6250–51000‐055)Grant Funding Source: NIH AR444474 and USDA/ARS 6250–51000‐055
Maternal anemia modifies the effect of multiple micronutrient supplements on birth weight and infant mortality in Indonesia
Authors: Sebayang Susy Katikana , Pierce Marcella , Harefa Benyamin , Aditiawarman Aditiawarman , Apriatni Mandri S. , Shankar Anita V. , Dibley Michael , Kelly Patrick J. , Tjiong Roy , Anwar Khaerul , Shankar Anuraj H. 
Published: June 2021

ObjectiveTo assess effects of maternal anemia on the impact of maternal multiple micronutrient (MMN) supplementation compared to iron & folic acid (IFA) in a double blind RCT in Indonesia (ISRCTN34151616).MethodsWe analyzed 14611 singleton births with data on maternal hemoglobin (Hb), height, parity, education, gestational age at birth, sex, season of birth & household wealth. Mortality was analyzed with Cox proportional hazards models; birth weight (BW) & maternal Hb with linear models; low birth weight (LBW), small for gestational age (SGA) & preterm‐LBW with logistic models.ResultsIn anemic women MMN reduced early infant mortality (< 90 days of birth) by 39% [Adj HR 0.61; 95%CI 0.49–0.78 p<0.001; interaction (int) p=0.04] and neonatal mortality by 36% (Adj HR 0.64; CI=0.47–0.86 p=0.003; int p=0.18). MMN improved BW by 37g (CI −1 to 74 p=0.056; int p=0.01), and reduced LBW by 17% (aRR 0.83; CI 0.66–1.05 p=0.11; int p=0.04) and preterm‐LBW by 40% (aRR 0.60; CI 0.42–0.87 p=0.007; int p=0.002), and improved Hb by 0.28g/dl (CI −0.031 to 0.59 p=0.08) in anemic women.ConclusionsMaternal MMN supplements, as compared to IFA, have greater benefits on infant survival and birth weight in anemic than in non‐anemic women.Funding:Turner Foundation, UNICEF, CHHD, USAID Indonesia grant # 497G00010000100. AusAID supported SKS's PhD at U of Sydney.