bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fundamental role for HIF‐1α in expression of enteric human β defensin‐1
Authors: Kelly Caleb James , Glover Louise E , Campbell Eric L , Ehrentraut Stefan F , Kominsky Doug J , Bowers Brittelle E , Bayless Amanda J , Saeedi Bejan J , Colgan Sean P 
Published: June 2021

Antimicrobial peptides are secreted by the intestinal epithelium to defend from microbial threats. The antimicrobial activity of human β defensin‐1 (hBD‐1) is potentiated by this low‐oxygen environment and the hBD‐1 gene (DEFB1) is constitutively expressed in intestinal epithelial cells (IEC). As previous studies have indicated that hypoxia‐inducible factor (HIF) is active even in healthy intestinal mucosa, we compared the transcriptional profile of IEC in mice lacking IEC HIF‐1α to those of wild‐type mice. This unbiased screen identified a key role for epithelial HIF‐1α in expression of murine defensins. Studies with human IEC revealed that basal HIF‐1α is fundamental for the constitutive expression of hBD‐1 mRNA and protein. While hypoxia did not induce DEFB1 expression, attenuated basal HIF‐1α expression (ascorbate supplementation) repressed DEFB1, suggesting a low threshold for HIF‐1α saturation. DEFB1 promoter studies confirmed HIF‐1α binding to a hypoxia response element. Since DEFB1 is unique to humans, we used 94 human intestinal samples to reveal a strong correlation between DEFB1 and the canonical HIF‐1α target gene GLUT1. Taken together, these findings indicate that basal HIF‐1α is critical for constitutive expression of DEFB1 in the intestine and supports efforts that target HIF in restoration and maintenance of intestinal integrity.Research Support:F30DK096709, TL1RR025778, DK50189, HL60569, DK095491 and by the Crohn's and Colitis Foundation of America.
Cleavage of interleukin‐8 and attenuation of neutrophil chemotaxis by a Giardia cathepsin B
Authors: Cotton James , Bhargava Amol , Ferraz Jose , Hollenberg Morley , Beck Paul , Buret Andre 
Published: June 2021

Parasitic immunomodulatory molecules are currently undergoing investigation for their potential as anti‐inflammatory therapeutics. Children infected with the small intestinal parasite Giardia duodenalis have attenuated inflammatory responses via unknown mechanisms.ObjectiveTo determine if Giardia trophozoites modulate interleukin‐8 (CXCL8) secretion from intestinal epithelial cells (IECs) resulting in attenuated neutrophil (PMN) chemotaxis.ResultsCo‐incubation of Giardia trophozoites with ex vivo small intestinal mucosal biopsy tissues or in vitro monolayers resulted in attenuation of IL‐1β‐ or S. typhimurium‐induced CXCL8 secretion via parasitic cleavage of CXCL8. Giardia‐mediated cleavage of CXCL8 decreased its chemotactic ability for PMNs. Giardia trophozoites secrete cysteine proteases in the presence or absence of in vitro monolayers. Inhibition of Giardia cysteine proteases with a cysteine protease inhibitor (E‐64d) or a cathepsin B‐specific inhibitor (Ca‐074Me) inhibited Giardia‐mediated cleavage of CXCL8.ConclusionGiardia trophozoites release a cathepsin B‐like protease that cleaves CXCL8 and attenuates PMN chemotaxis. Funding provided by NSERC, AIHS, and CCFC.
Exploring underlying reasons of eating patterns among a low‐income adult population in Lake County, Indiana
Authors: Zhao Yanling , Liu Sandra S. , Mc Carthy Órla M. , McCrory Megan A 
Published: June 2021

BackgroundEvidence suggests that eating patterns, including meal skipping and snacking, may impact health outcomes such as obesity and other chronic diseases. However, why people adopt such eating patterns is poorly understood.Objectives and Study DesignWe conducted one‐on‐one semi‐structured interviews about daily eating and other routines among a convenience sample of 20 employees at a community health center in Lake County, IN.ResultsParticipants were aged ≥18 y and mostly African American females. Breakfast was the most commonly skipped meal, followed by lunch and dinner (80%, 60% and 5% of the sample, respectively). In addition, 95% of participants reported ever snacking, and 75% snacked at work or during the day whenever hungry. Only 25% of the sample planned when to eat, and Chi‐square tests indicated this lack of planning may have been related to snacking or skipping breakfast. All participants reported their eating patterns differed on weekends compared to weekdays, with 35% having more time to eat and 30% having different timing of meals on weekends. Overall, being too busy or not having enough time to eat were suggested to be major factors influencing eating patterns.ConclusionNot planning an eating schedule may associate with meal skipping and snacking, and hunger may also relate to snacking. Further investigation about how time management influences eating patterns is needed.Funding: Purdue.
TNFα redistributes ZnT2 to accumulate zinc in lysosomes and activate autophagic cell death in mammary epithelial cells
Authors: Hennigar Stephen R , Lanz Michael C , Kelleher Shannon L 
Published: June 2021

Post‐lactational involution coincides with increased levels of inflammatory cytokines such as TNFα in the mammary gland (MG). Injection of TNFα into MGs of lactating mice induces involution; however, the role of TNFα in this process is not well understood. Inflammatory cytokines modulate zinc (Zn) transporters to alter subcellular Zn pools in numerous cell types. Therefore, we hypothesized that TNFα redistributes subcellular Zn pools to activate the autophagic cell death observed in mammary epithelial cells (MECs) during involution. Confocal microscopy showed that MECs (HC11) stimulated with TNFα (15 ng/mL, 18 h) redistributed ZnT2 from the secretory compartment and mitochondria to lysosomes. This coincided with significant increases in lysosomal Zn accumulation (~22%, p < 0.05) and activity of the Zn‐dependent lysosomal enzyme, acid phosphatase (19.2 ± 1.1 vs 25.0 ± 0.8 U/mL; p < 0.05). Zn accumulation led to lysosomal swelling, cathepsin D release, and increased cell death (2.8 ± 0.1 vs 1.1 ± 0.1 × 106 cells/mL; p < 0.05). Importantly, siRNA‐mediated ZnT2 knockdown prior to TNFα‐stimulation abrogated these effects. Collectively, this implicates ZnT2 as a requisite component of TNFα‐induced lysosomal Zn accumulation and activation of autophagic cell death in MECs. Moreover, it suggests that factors augmenting TNFα‐induced Zn redistribution in MECs may lead to premature involution and lactation failure.Grant Funding Source: NIH R01 HD058614 to SLK
Objectively measured physical activity in overweight and obese pregnant women can be predicted by self‐efficacy and pre‐pregnancy BMI
Authors: Kong Kai Ling , Welch Amy , Campbell Christina , Peterson Anna , Lanningham‐Foster Lorraine 
Published: June 2021

Research in understanding the relationship between self‐efficacy (SE) and physical activity participation during pregnancy is limited. Our purpose was to examine the relative contribution of pre‐pregnancy body mass index (BMI) and walking SE in predicting physical activity during pregnancy. Walking SE of 37 overweight and obese pregnant women was assessed using barrier self‐efficacy (BSE) and task self‐efficacy (TSE) questionnaires. Walking was quantified by step counts using a StepWatch™ Activity Monitor. Linear and stepwise regression analyses were used to identify the relative contribution of pre‐pregnancy BMI, BSE and TSE to step count prediction at the end of the second (Tri2) and late third trimester (Tri3). At Tri2, TSE (r2 = 0.254, p < 0.003) and BSE (r2 = 0.123, p < 0.049) significantly predicted step count; however TSE explained 23.4% ( p < 0.003) of the variance, which provided the best model to predict step count according to the stepwise regression analysis. At Tri3, TSE (r2 = 0.234, p < 0.003) and pre‐pregnancy BMI (r2 = 0.167, p < 0.015) significantly predicted step count and both variables explained 36% of the variance (p < 0.001), which provided the best model to predict step count. Interventions designed to increase one's self‐efficacy might be an effective strategy to promote more active lifestyles during pregnancy, especially later in gestation for women with higher pre‐pregnancy BMI.Grant Funding Source: Iowa State University
Long‐term feeding of dietary slow release glucose reduces daily caloric food intake in vivo
Authors: Yan Like , Philllips Robert , Powley Terry , Kinzig Kim , Kim Choon Young , Hamaker Bruce 
Published: June 2021

A true dietary slowly digestible starch is not yet available, thus its long‐term effect on food intake has yet to be elucidated.AimExamine the long‐term effect of a dietary slowly digestible starch material on food intake in vivo.MethodsAlginate‐entrapped starch microspheres with different slow digesting rates were incorporated into rodent diets. Diet‐induced obese Sprague Dawley rats were assigned to 5 test groups and fed for 8 wks: 1) 14% low‐fat diet; 2) 45% high‐fat (HF) diet; 3) 45% HF with rapidly digestible starch; 4) 45% HF with slowly digestible microspheres; and 5) 45% HF with more slowly digestible microspheres. Meal patterns were monitored using BioDAQ.ResultsA slowly digestible microsphere group had lower daily food intake compared with the 45% HF rapidly digestible starch group (P < 0.05) and similar food intake as the low fat group. Overall meal size was lower in slow digesting microspheres group and meal frequency decreased over time (P < 0.05). mRNA levels of orexigenic NPY and AgRP lowered in microspheres group to a similar level as low‐fat group.ConclusionChronic dietary slow release glucose reduces daily caloric food intake by changing meal size and meal frequency.
Predictors of Serum 25(OH)D in Elderly African‐Americans in the Health, Aging, and Body Composition (Health ABC) Study
Authors: Hansen J G , Hootman K , Tang W , Brannon P M , Kritchevsky S , Houston D , Harris T , Garcia M , Liu Y , Lohman K , Cassano P A 
Published: June 2021

Inadequate vitamin D status is highly prevalent in elderly individuals, and has been associated with adverse health outcomes. This study's objective was to investigate predictors of serum 25(OH)D in approximately 1,000 African‐American Health ABC participants. General linear models were used to evaluate associations between predictor variables and log‐transformed serum 25(OH)D.In a multivariate model, age, gender, study site, height, season of blood draw, physical activity, multivitamin use, vitamin D supplement use, dietary patterns, and body mass index (BMI) explained 22% of the variation in serum 25(OH)D. The main explanatory variable was multivitamin use, which accounted for 11% of serum 25(OH)D variability; multivitamin users had 7.2 ng/mL higher serum concentrations compared to non‐users. BMI was inversely associated, and explained about 1.8% of the variance in serum 25(OH)D. However, the BMI—25(OH)D association was non‐linear, and mainly reflected associations in obese participants (BMI≥30); models including a quadratic BMI term explained more variability than the linear BMI model (R2 2.5% vs. 1.8%).In this elderly population, BMI was negatively associated with serum 25(OH)D and multivitamin use was the primary contributor to variability.Grant Funding Source: NIA: N01‐AG‐6–2101, N01‐AG‐6–2103, N01‐AG‐6–2106, R01‐AG028050; RC1 AG035835; NINR: R01‐NR012459; NRSA T32‐DK‐7158–36 (JGH)
Formate metabolism is altered in riboflavin‐deficient rats
Authors: MacMillan Luke , Lamarre Simon , Andrivon Estelle , Dickie Charlotte , Brosnan Margaret E. , Brosnan John T. 
Published: June 2021

Riboflavin can play an important role in one‐carbon metabolism, particularly as its active forms, FAD and FMN, are used as cofactors in both the production and utilization of formate.Rats were fed either a riboflavin‐replete or a riboflavin‐deficient diet for 13 days at which point blood and tissue samples were taken. Riboflavin deficiency was assessed by the Erythrocyte Glutathione Reductase activation coefficient (EGRac). Total plasma homocysteine (Hcy), hepatic S‐adenosylmethionine (SAM), and S‐adenosylhomocysteine (SAH) concentrations were analyzed by HPLC. Hepatic methylenetetrahydrofolate reductase (MTHFR) was assessed by means of enzyme activity and immunoblot. Plasma formate was analyzed by GC‐MS.EGRac confirmed riboflavin deficiency. Plasma Hcy was elevated in the deficient animals. Hepatic SAM was lower in the deficient animals; there was no difference in SAH. MTHFR was found to be markedly reduced in the deficient group; plasma formate concentration was decreased by about 20%.The increased plasma Hcy and reduced hepatic SAM indicate an impairment in re‐methylation. The decreased plasma formate levels coupled with the defective remethylation suggest that the flavin‐dependent formate production may be decreased. This will be further examined by means of isotopic experiments to measure the endogenous rates of formate production.Grant Funding Source: Canadian Institutes of Health Research & Research Development Corporation of Newfoundland and Labrador
In vivo Effect of 1‐Amino D‐Proline, an Anti‐pyridoxine Factor, on the Metabolism of Vitamin B6‐dependent Enzymes in Moderately Vitamin B6 Deficient Rats
Authors: Mayengbam Shyamchand , Raposo Sara , Aliani Michel , House James D. 
Published: June 2021

Pyridoxal 5′‐phosphate (PLP) serves as an important cofactor in numerous metabolic pathways, including the transsulfuration pathway which converts homocysteine (Hcy) to cysteine (Cys). While overt deficiency is rare, marginal deficiency is common, and may be exacerbated by anti‐pyridoxine factors in the food supply. To this end, a study was conducted to examine the in vivo effect of 1‐amino D‐proline (1ADP), an anti‐pyridoxine factor found in flaxseed, on indices of sulphur amino acid metabolism in moderately B6‐deficient rats. Male weaning rats (n=6/treatment) received a semi‐purified diet (AIN‐93G) containing either 7 (control; C) or 0.7 mg/Kg diet PN·HCl (moderately deficient; MD), each with one of 4 levels of 1ADP, viz. 0, 0.1,1 and 10 mg/Kg, diet for 5 weeks. For rats receiving the C diet, final body weight was not affected by 1ADP, however rats consuming the highest 1ADP levels in the MD group were significantly lighter (p<0.001). Plasma biomarkers are given in Table 1. The data provide evidence that the consumption of an anti‐pyridoxine factor linked to flaxseed does not pose challenges for subjects who are vitamin B6‐replete. However, this may not be the case for subjects with marginal B6 status, as supported by dose‐dependent reductions in plasma PLP and increases in plasma Hcy.Grant Funding Source: Natural Sciences and Engineering Research Council of Canada (NSERC).
Early life exposure to soy isoflavones in combination with an adequate but not supplemental level of folic acid improves bone development of CD‐1 mice by suppressing expression of neuropeptide Y
Authors: Kaludjerovic Jovana , Ward Wendy E 
Published: June 2021

Early life exposure to soy isoflavones (ISO) improves bone health of female mice at adulthood. This benefit may be mediated by methylation of CpG sites that regulate transcription of genes involved in bone formation. The objective was to examine if early life exposure to ISO and supplemental folic acid (FA), a methyl donor, induces permanent changes in bone‐specific gene expression that result in stronger bones at adulthood in female CD‐1 mice. Mice were randomized to adequate (2 mg/kg diet) or supplemental (8 mg/kg diet) FA during pregnancy and lactation. Offspring received corn oil or ISO (7 mg/kg body weight/day) from day 1 to 10 of life and adequate FA diet until age 4 months. Contrary to our hypothesis, exposure to ISO + supplemental FA had a modest effect on lumbar spine (higher bone mineral density (BMD)) with no effect on femurs. This may be due to higher expression of bone resorption genes, i.e. beta‐catenin and parathyroid hormone receptor 1. In contrast, females exposed to adequate FA + ISO had higher BMD, improved trabecular connectivity and greater strength at the femur and lumbar spine that may be explained by lower expression of neuropeptide Y – a neurotransmitter that is inversely associated with bone formation. Early life exposure to ISO has contrasting effects on adult bone health, depending on the level of FA in the diet. Benefits to BMD, bone structure as well as bone strength were only observed with adequate FA.Grant Funding Source: Canadian Institutes of Health Research (funding number 89941) and a Frederick Banting and Charles Best Canada Graduate Scholarship
An epigenetic perspective on pharmacologic ascorbate in colon cancer
Authors: Kaiser Matthew Carl , Rajendran Praveen , Dashwood Mohaiza W , Levine Mark A , Michaels Alexander , Frei Balz , Dashwood Roderick H 
Published: June 2021

AimThere is growing interest in pharmacologic ascorbate (Asc) and its therapeutic properties (Levine et al. Adv Nutr 2011;2:78). We examined cell viability, histone deacetylase (HDAC) expression, and related protein modifications in cancer versus noncancer colon epithelial cells following exposure to Asc.MethodsMTT assays were conducted in HCT116 colon cancer and CCD841 non‐transformed colonic epithelial cells treated with 0.25 to 16 mM Asc or ascorbate‐2‐phosphate (AAp), in the presence and absence of catalase (CAT, 280 U/mg), or with 5 to 160 μM H2O2. Cell lysates obtained 6 h and 24 h post‐treatment were immunoblotted as reported by Rajendran et al. Mol Cancer 2011;10:68.ResultsIn MTT assays, IC50 data were as follows: 8 mM Asc (CCD841); 3 mM Asc (HCT116), >;50mM AAp (HCT116), and 65 μM H2O2 (HCT116). CAT protected against both Asc‐ and H2O2‐ induced cytotoxicity. At 6 h, Asc and H2O2 altered the expression of HDACs (HDAC4, HDAC6, SIRT3) and enhanced the acetylation of histone (H3, H4) and non‐histone proteins (tubulin, p53).ConclusionsAsc was more cytotoxic to colon cancer cells than non‐cancer cells. Findings with the non‐H2O2 producing compound AAp, and with CAT, implicated H2O2 in Asc‐induced cytotoxicity. Asc was shown, for the first time, to alter epigenetic end‐points related to HDAC changes in colon cancer cells.Grant Funding Source: CA090890, CA090890, AT002034
Pomegranate Polyphenols Suppress Colorectal Aberrant Crypt Foci (ACF) and Inflammation: Possible role of miR126 in vitro and in vivo
Authors: Banerjee Nivedita , Kim Hyemee , Talcott Stephen , Talcott Susanne U Mertens 
Published: June 2021

The anti‐tumorigenic efficacy of polyphenols ellagitannins and anthocyanins extracted from pomegranate has been extensively studied in various cancer models. The objective of this study was to investigate the role of post‐transcriptional regulation of apoptotic and inflammatory biomarkers by specific microRNAs treated with pomegranate polyphenols (PP).mRNA, microRNA expression were measured by RT‐PCR, protein by western blotting and multiplex bead assay. In vivo studies were performed with Sprague Dawley rats.PP juice suppressed the number of high multiplicity aberrant crypts foci (HMACF >; 4 ACF) by 42% (P<0.05) and lowered Ki67 antigen. Cell proliferation was also inhibited by PP (5–25 μg/mL) in colon cancer cells HT‐29. In vitro and vivo results were accompanied by a downregulation of expression including NF‐κB, inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2), vascular adhesion molecule‐1 (VCAM‐1), insulin growth factor (IGF) and PI3K/Akt/mTOR signaling pathways. miRNA 126 is frequently lost in colon cancer and targets VCAM‐1 and PI3K. PP increased miR126 expression. In vitro, the involvement of miR‐126 was confirmed using the antagomir for miR‐126, where PP reversed the effects of the antagomir.In summary Pg inhibited HT29 cell proliferation, suppressed the number of HMACF formation and colon tumorgenesis where microRNA 126‐regulated pathways seem to be involved.Grant Funding Source: Vegetable and Fruit Improvement Center, Texas AandM University
Pomegranate Polyphenolics reduce inflammation in Intestinal Colitis ‐ Potential Involvement of the miR‐145/p70S6K/HIF1α Pathway
Authors: Kim Hyemee , Banerjee Nivedita , Pfent Catherine , Talcott Stephen , Mertens‐Talcott Susanne 
Published: June 2021

Pomegranate polyphenolics have previously been demonstrated effective in the prevention of inflammation and carcinogenesis. To determine the anti‐inflammatory effects and possible mechanisms of pomegranate polyphenolics in colitis, the mRNA and protein levels were assessed in colonic mucosa by RT‐PCR, western blotting and multiplex bead assay.Compared to the control, pomegranate suppressed cell proliferation (37.5%), and protected against DSS‐induced colon inflammation and injury (50% and 66.7%). Pomegranate significantly down‐regulated phosphorylation of p70S6K, and decreased HIF1α expression. p70S6K is the direct target of miR‐145. Induction of miR‐145 by pomegranate juice (2.0 fold) compared to control juice corresponds to the down‐regulation of p70S6K. Pomegranate significantly attenuated the expresison of pro‐inflammatory cytokines (TNF‐α, Il‐1β and Il‐10), COX‐2 and iNOS. The involvement of miR‐145/p70S6K/HIF1α was additionally investigated in CCD18Co colon‐myofibroblastic cells, where the involvement of this pathway was confirmed using the specific antagomiR of miR‐145, where the effects of pomegranate polyphenolics were in part reversed by the antagomir.These results suggest that pomegranate intake attenuated DSS‐induced colitis by modulating the miR‐145/p70S6K/HIF1α pathway and inhibiting inflammatory responses, and it may be a potential therapeutic for colitis.Grant Funding Source: Vegetable & Fruit Improvement Center (TAMU)
The effect of eggs on satiety in children and adolescents
Authors: Liu Ann , Puyau Renee S , Han Hongmei , Johnson William D , Greenway Frank L , Dhurandhar Nikhil V 
Published: June 2021

Consumption of an egg breakfast may aid in body weight regulation through promotion of satiety. Dietary interventions are particularly relevant for children since the use of drugs and bariatric surgery are not commonly recommended. In a randomized crossover trial, we evaluated the effects of an egg breakfast vs. an isocaloric bagel breakfast on subsequent food intake in children (age 4–6 years, n=13) and adolescents (age 14–17 years, n=15). There were no differences in lunch time food intake between the two breakfast treatments for either age group. Visual analog scale ratings of hunger and satiety were also not different between the two treatments in adolescents. Consumption of the egg breakfast led to a significant increase in serum PYY levels (P = 0.0001) in adolescents. However, increased levels of PYY were not correlated with decreased food intake. These data demonstrate that egg consumption does not alter short‐term food intake in children, and they suggest that adolescents may not be as responsive to changes in appetite hormones as adults. This work is registered at ClinicalTrials.gov NCT01530061.Grant Funding Source: American Egg Board