bluuebunny/crossref_metadata_2025_split huggingface dataset:
HFE inhibits non transferrin‐bound iron uptake via downregulating Zip14 in HepG2 cells
Authors: Gao Junwei , Zhao Ningning , Knutson Mitchell D. , Enns Caroline A. 
Published: June 2021

Mutations in the Hereditary Hemochromatosis protein, HFE, cause iron overload. Hepatocytes are particularly affected. We investigated how HFE regulates both transferrin (Tf)‐bound and non Tf‐bound iron uptake in HepG2 cells, a human hepatoma cell line. Expression of HFE in this cell line decreased both Tf‐bound (50%) and non Tf‐bound iron uptake (30%). To determine which iron transporter might be involved in iron uptake in HepG2 cells, we measured mRNA levels of two known iron transporters. The mRNA level of Zip14 was five times that of DMT1 (divalent metal transporter 1). Expression of HFE resulted in a decrease in the levels of Zip14 with no change in the mRNA level. Knockdown of Zip14 with siRNA abolished the effect of HFE on non Tf‐bound iron uptake. HeLa cells have no detectable Zip14. When HeLa cells expressing HFE under the tet‐repressible promoter were transfected with Zip14, non‐Tf‐bound iron uptake was inhibited by 40% with the induction of HFE and the levels of Zip14 decreased. These results suggest that HFE controls the stability of Zip14 and therefore the iron loading of hepatocytes.Supported by NIH grants DK054466 (CAE) and DK0655964 (MK)
Skeletal muscle protein synthesis in the elderly: Age, gender, and androgen supplementation
Authors: Henderson Gregory C , Dhatariya Ketan , Ford G. Charles , Klaus Katherine A , Mujeeb Mehrukh , Nair K. Sreekumaran 
Published: June 2021

Skeletal muscle protein synthesis rates decline with age.PURPOSE:We sought to determine if DHEA supplementation in elderly men (EM) and elderly women (EW) and low dose testosterone (T) supplementation in EM would raise protein synthesis rates.METHODS:87 EM (with low bioavailable T and DHEAS) and 57 EW (with low DHEAS) were studied before and after 1 year in which EM received either T (5 mg/d), DHEA (75 mg/d), or placebo (P) and EW received either DHEA (50 mg/d) or P. To assess age effects, 30 young men and 32 young women were studied on a single occasion as controls. [15N]phenylalanine and [2H4]tyrosine tracers were infused and isotopic enrichment was measured in plasma and v. lateralis muscle. Whole body amino acid kinetics were normalized to fat free mass, and mixed muscle protein fractional synthesis rate (FSR) was measured using plasma phenylalanine as the precursor.RESULTS:Despite induction of elevated androgen levels, no significant differences were seen between treated groups and the P group in either EM or EW. Whole body protein synthesis and muscle FSR were lower in elderly than in young (P < 0.05) and were higher in women than men (P < 0.05), with no age‐by‐gender interaction.CONCLUSIONS:Neither DHEA nor T supplementation for one year had any significant impact on age‐related decline in protein synthesis, while both age and gender do impact protein synthesis rates. NIH grants P01 AG14283 and UL1‐RR‐024150‐01.
The impact of three supplements with identical micronutrient content on morbidity in Mexican children
Authors: Leroy Jef L , García‐Guerra Armando , Neufeld Lynnette 
Published: June 2021

The objective of this analysis was to assess the impact of three types of nutrition supplements with identical micronutrient content on morbidity (>3 stools per day, dysentery, fever, severe cough, cough with mucus and/or vomiting) in children.Communities (18 per supplement) were randomly assigned to receive a fortified food (FF), syrup (SY) or Sprinkles (SK). Children 6 to 12 m of age, beneficiaries of the Oportunidades program in Mexico were eligible to participate. Supplements were delivered daily and compliance and morbidity were recorded. Appropriate statistical analyses for cluster randomized trials were used. Data on 480 children (6 to 12 mo at baseline) in the first 6 months of supplementation were analyzed (FF n=137; SY n=159; SK n=184).No statistically significant differences between groups were found at baseline. Children were ill 16 d on average. In unadjusted analysis, there were no statistically significant differences between supplementation groups in morbidity. When adjusting for season, age, sex and height‐for‐age Z‐score at baseline, lagged compliance was associated with lower morbidity (P<0.05). Ensuring adequate compliance with supplementation programs may lower child morbidity.The Oportunidades program funded this study and holds the rights to the data presented.
Treatment with 1,25 dihydroxyvitamin D3 stimulates adipocytic differentiation of porcine mesenchymal stem cells
Authors: Mahajan Avanika , Stahl Chad H. 
Published: June 2021

Depending on the species and culture conditions, 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to have pleiotropic effects on the differentiation of mesenchymal stem cells (MSC). In this study, we characterized the effects of 1,25(OH)2D3 on the differentiation of porcine MSC. The MSC were isolated from bone marrow of young pigs and grown in DMEM + 10% fetal bovine serum and antibiotics (BM). Cells received either BM, BM + 10−8 M 1,25(OH)2D3 or BM + 10−7 M 1,25(OH)2D3 with complete media changes every 3d for a total of 12d of culture. On d 3, 6, 9, and 12 cell proliferation was measured using a MTS‐based assay, and samples were collected for gene expression analysis. Regardless of treatment, there was a linear increase in cell numbers over time up to 6d (P < 0.05), after which the cell numbers plateaued. Proliferation was reduced by treatment with 1,25(OH)2D3 in a dose dependent manner (P < 0.05). The concentrations of mRNAs encoding peroxisome proliferator‐activated receptor gamma (PPARG), CCAAT enhancing binding protein (CEBP), lipoprotein lipase (LPL) and adipocyte‐binding protein 2 (AP2) were increased (P < 0.05) by treatment with 1,25(OH)2D3 in a dose‐dependent manner. These changes seen with 1,25(OH)2D3 treatment are suggestive of an increase in adipocytic differentiation.This work was supported in part by the BRDC (Peoria, IL) and the North Carolina Agriculture Research Service.
Long‐term adherence to the 2005 Dietary Guidelines for Americans is associated with lower risk of diabetes: 20‐year findings from the Coronary Artery Risk Development in Young Adults (CARDIA) study
Authors: Zamora Daisy , Gordon‐Larsen Penny , Jacobs David R. , Loria Catherine , Popkin Barry M. 
Published: June 2021

BACKGROUND: Little is known about the long‐term benefits of adherence to current dietary recommendations.OBJECTIVE: To study 20‐year diet quality (DQ) change and 20‐year diabetes mellitus (DM) incidence in black and white adults.METHODS: Data were obtained from the 1985–86 and 2005–6 examinations of the CARDIA study. Participants were 18–30 years old at baseline and were recruited from 4 US cities (n=1838). We used the UNC Diet Quality Index (updated to reflect the 2005 Dietary Guidelines for Americans) to calculate DQ scores (possible range 0–100) at years 0 and 20. Participants were divided into quartiles of 20‐year DQ change. We used logistic regression to calculate odds ratios (OR) for DM (155 cases) adjusted for baseline body mass index (BMI), age, sex, education, race, clinic, and 20‐year changes in physical activity, BMI, smoking, and energy intake.RESULTS: Mean change in DQ score for each quartile was −12 (1st), 4 (2nd), 16 (3rd), and 31 (4th). Compared to people in the 1st quartile, the OR of DM incidence were 0.70 (95% CI: 0.40, 1.20) for those in the 2nd, 0.53 (94% CI: 0.30, 0.95) for those in the 3rd, and 0.47 (95% CI: 0.25, 0.86) for those in the 4th quartile.CONCLUSION: We found a trend of decreased DM risk as DQ improved over 20 years, independently of baseline BMI and its change. Our results are consistent with the idea that adherence to current dietary recommendations may help in the prevention of DM.
Food security status, BMI, and fruit and vegetable consumption amongst Producemobile Users.
Authors: Tangney Christy C , Redfearn Kristin R , Allender Jessica C , Keim Kathryn S 
Published: June 2021

Food insecurity can affect health, body weight and quality of life. Among food assistance users, the prevalence of food insecurity and its potential impact on body habitus and intake of fruits and vegetables is unclear. In this cross‐sectional study of 191 participants from 8 selected Producemobile sites in Chicago, we describe the demographics, food security status, and fruit and vegetable consumption of Producemobile patrons (18 years of age and older; 6th grade reading level). Weights and heights were measured, and all completed a 35‐item questionnaire containing the USDA 6‐item Core Food Security Module and the NCI All‐Day Fruit and Vegetable Screener.Results:Ethnic composition of the sample surveyed was as follows: 84% African American, 11% Hispanic and 5% Caucasian. Approximately 58% of the households were classified ‘food insecure without hunger’, 24% ‘food insecure with hunger’ and 18% ‘food secure’. More than half (53%) reported using the Producemobile monthly. Two‐thirds of the sample admitted to other forms of food assistance (i.e. food stamps, WIC coupons, school lunch program). BMI for the 46 men was 28.1 ± 6.8 kg/m2 (mean ± SD) and for 144 women, 30.6 ± 6.9. There was no difference in BMI between food secure and food insecure participants (p=0.88). Food insecure patrons reported consuming significantly fewer daily servings of fruit (1.0 ±1.9, p=0.006) and total fruit and vegetable servings (6.8 ± 8.1, p=0.03) when compared to those of food secure individuals (1.6 ± 2.2, 7.4 ± 5.1, respectively).Conclusion:Further research is needed to confirm whether lower intakes of fruits and vegetables are consistently observed amongst adults seeking food assistance and explore the barriers to such behaviors.
Systematic analysis of cell signaling during planarian tissue regeneration, remodeling & homeostasis
Authors: Gurley Kyle Alan , Rink Jochen C , Alvarado Alejandro Sánchez 
Published: June 2021

We have initiated a systematic effort to define the roles of highly conserved signaling pathways in the planarian Schmidtea mediterranea, an organism with astounding regenerative capabilities. Following amputation, freshwater planarians properly regenerate a head or tail from the resulting anterior or posterior wound. The mechanisms that differentiate anterior from posterior and direct the replacement of the appropriate missing body parts are unknown. We report that RNA interference (RNAi) of β‐catenin or dishevelled causes the regeneration of a head instead of a tail at posterior amputations. Conversely, RNAi of the β‐catenin antagonist adenomatous polyposis coli (APC) results in the regeneration of a tail at anterior wounds. The reversal of tissue identity is complete by both anatomical and molecular criteria, it can be observed as early as 12 hours post‐amputation, and it is independent of the angle or location of amputation. However, systematic silencing of known upstream components did not recapitulate these defects. The intracellular components of canonical Wnt signaling may therefore be regulated by an unconventional upstream mechanism in regenerating planarians. In addition, β‐catenin RNAi transforms the tail of uncut adult animals into a head. We suggest that β‐catenin is a molecular switch that specifies and maintains AP identity during planarian regeneration and homeostasis.K.A.G., F32GM082016, T32CA093247. J.C.R., European Molecular Biology Organization. A.S.A., HHMI Investigator and RO‐1 GM57260
The regulation of stem cell self‐renewal
Authors: Morrison Sean J. 
Published: June 2021

The mechanisms that regulate stem cell self‐renewal are fundamental to the formation and maintenance of normal hematopoiesis as well as hematopoietic malignancies. Fetal stem cells differ phenotypically and functionally from adult stem cells in diverse tissues. However, little is known about how these differences are regulated. To address this we compared the gene expression profiles of fetal versus adult hematopoietic stem cells (HSCs) and discovered that the Sox17 transcription factor is specifically and preferentially expressed in fetal and neonatal but not adult HSCs (Cell 130:470). Germline deletion of Sox17 led to severe fetal hematopoietic defects, including a lack of detectable definitive HSCs. Conditional deletion of Sox17 led to the loss of fetal and neonatal but not adult HSCs. Sox17 expression by HSCs was extinguished three to four weeks after birth as HSCs acquired adult properties. During this transition, loss of Sox17 expression by individual cells correlated with slower proliferation and the acquisition of an adult phenotype. Sox17 thus distinguishes the transcriptional regulation of fetal and neonatal HSCs from that of adult HSCs.As HSCs enter the postnatal period, they become dependent upon the polycomb family transcriptional repressor, Bmi‐1. Bmi‐1 is required for the postnatal maintenance of every type of stem cell yet examined including HSCs (Nature 423:302, 2003) and neural stem cells (Nature 425:962, 2003). Bmi‐1‐deficient mice die by early adulthood with stem cell depletion, growth retardation, ataxia, and seizures. These phenotypes correlate with increased expression of the cyclin‐dependent kinase inhibitor p16Ink4a and the p53 agonist p19Arf, which promote cellular senescence. Deletion of Ink4a and/or Arf from Bmi‐1−/− mice partially rescues stem cell self‐renewal and stem cell frequency (G&D 19:1432, 2005). Despite ongoing Bmi‐1 expression, Ink4a expression increases with age, reducing stem cell frequency and function (Nature 443:448). The regulation of stem cell self‐renewal throughout life by networks of proto‐oncogenes and tumor suppressors emphasizes the mechanistic links between stem cell self‐renewal and cancer cell proliferation.
Effects of increased dietary protein and meal patterning on appetite during short‐term energy balance and energy restriction
Authors: Leidy Heather J , Bossingham Mandi J , Carnell Nadine S , Mattes Richard D , Campbell Wayne W 
Published: June 2021

Objective: This study assessed whether the timing of increased dietary protein intake throughout the day influences the feeling of fullness during energy balance (EB) and restriction (ER). Methods: 9 men (age: 45 ± 5 y; BMI: 32.5 ± 0.6 kg/m2) randomly completed 5 controlled feeding trials consisting of 3 days each of EB and ER (750 kcal/d reduction). The diet was composed of a normal amount of protein (NP) (0.8 g protein·kg−1·d−1) or an additional amount of protein (HP) (+0.6 g protein·kg−1·d−1) given at breakfast (B), lunch (L), dinner (D), or equally divided among all meals (E). Feelings of fullness were assessed over 15 h. Results: No difference in fullness was observed between the EB vs. ER trials; thus, the data were combined. With all HP meals combined, HP led to higher fullness (P<0.05) across the day vs. NP. When comparing the timing of increased protein intake, the 3‐h postprandial, subsequent meal, evening, and overall fullness were not different between HP‐L, HP‐D, or HP‐E vs. NP but were higher for HP‐B vs. NP (p<0.05 for all effects except evening (p=0.1)). Comparing the HP treatments, the HP‐B led to greater overall fullness vs. HP‐L (p<0.005) and HP‐D (p<0.01) but not for HP‐E. Conclusion: Increased dietary protein provided at breakfast leads to immediate and sustained increases in feelings of fullness in overweight men.Support: National Pork Board; American Egg Board; IBRC, Purdue University
Comparison of energy intake and satiety for whole grain barley, wheat and refined rice
Authors: Schroeder Natalia , Gallaher Dan , Arndt Beth , Marquart Len 
Published: June 2021

This study compared the effect of whole grain high‐fiber barley, whole grain wheat and refined rice on energy intake and satiety. Fifty healthy subjects were recruited for this crossover design. Subjects consumed a hot cereal and a snack mix followed by an ad lib lunch once per week. Energy intake was measured through pre and post plate waste as part of the smorgasbord lunch. Through the use of a visual analog scale, hunger and fullness were measured for within and between treatment differences. Data analysis was completed using Proc mixed for between treatment differences and proc t‐test for within treatment differences. Energy intake at lunch did not significantly differ between treatments (p<0.8626). Satiety differed between and within treatments. Subject's felt significantly less hungry on the barley compared to the wheat (p<0.0208). Additionally, the subjects reported significantly less hunger before lunch compared to baseline (p<0.0017) for barley, but not for wheat (p<0.2085) or rice (p<0.0717). The greatest fullness was experienced on the barley compared to the wheat (p<0.0530). Compared to baseline, subjects felt the fullest before lunch on the barley followed by the wheat, and rice. Longer term studies are needed to assess the impact of whole grain foods on energy intake, satiety and weight management.ConAgra Foods Inc.
Dynamics of adolescent and adult beverage intake patterns in Mexico
Authors: Barquera Simon , Hernandez‐Barrera Lucia , Tolentino‐Mayo Maria Lizbeth , Espinosa Juan , Ng Shu Wen , Rivera Juan Angel , Popkin Barry 
Published: June 2021

Objective:To examine the patterns and trends in adolescent and adult beverage intake in Mexico.Design:Use of nationally representative dietary intake, income, and food expenditure surveys.Subjects: For the nationally representative surveys adolescents (aged 12–18y) and adults (aged 19y and older) were studied. For the 1999 and 2006 national nutrition surveys, there were 416 and 7,464 adolescents and 2180 and 21,113 adults, respectively, available in the overall sample.Measurements: Volume (ml) and energy (kcal) per day contributed by all beverages consumed by the subjects was measured.Results:The trends from both the food expenditure and the dietary intake surveys showed large increases in caloric beverages among adolescents and adults over the past decades—particularly 1999–2006. Coupled with very high‐income elasticities, this showed the high likelihood that intakes will increase as Mexican incomes continue to rise. Further, the price elasticities for whole milk and sodas were both greater than 1 and triple those for all other food groups.Conclusion:Mexican adolescents and adults consumed 20.1 and 22.3% of their calories from beverages. Whole milk, sugared‐beverages, fruit juice and alcohol represented the four major categories of beverage intake.
Dietary intake of iron and zinc by urban Guatemalan schoolchildren in the context of food pattern modernization
Authors: Montenegro‐Bethancourt Gabriela , Vossenaar Marieke , Doak Colleen M. , Solomons Noel W. 
Published: June 2021

Background:Meeting iron (Fe) and zinc (Zn) needs is related to foods consumed and nutrient bioavailability.Objective:To estimate the dietary intake of Fe and Zn and their adequacy among 3rd and 4th grade schoolchildren in Quetzaltenango, Guatemala.Methods:Data were obtained in a cross‐sectional study of 449 students, boys and girls, stratified by SES in private (n=230) or public (n=219) schools. Intake estimation comprised a single 24‐h pictorial self‐recording, supplemented by a dietitian interview to quantify amounts. Adequacy reference was the 2004 WHO recommended nutrient intakes (RNI).Results:Median intake of Fe, 12.9 mg, represented 145% of its RNI. Its 5 main sources were: fortified cornflakes; sweet rolls; fortified Incaparina gruel; beefsteak; and fried eggs. Median intake of Zn, 7.9 mg, represented 141% of RNI. Its 5 main sources were: beefsteak; fortified Incaparina gruel; corn tortilla; ground beef; and fried eggs. The leading repast for Fe was breakfast (36.5% of total), whereas lunch led for Zn (35.2%). Intake of Fe (p<0.001), but not of Zn (p=0.851), was higher in the private school sample.Conclusions:Intakes of Fe and Zn are generally adequate in this western highlands city, and supported, in part, by fortified foods.
Analysis of gene expression patterns of hepatocyte‐like cells derived from human bone marrow mesenchymal stem cells
Authors: Stock Peggy , Staege Martin S , Müller Lutz P , Volkmer Ines , Lützkendorf Jana , Christ Bruno 
Published: June 2021

The aim of the study was to determine the degree of differentiation of hepatocyte‐like cells derived from human mesenchymal stem cells (hMSC) by comparing global gene expression patterns of differentiated and undiffentiated hMSC from bone marrow (hBM‐MSC), adult liver and fetal hepatocytes.hMSC were isolated from bone marrow and differentiated into hepatocyte‐like cells. Microarray analysis was performed using the HG‐U133A array from Affymetrix. For comparative analysis of expression patterns published datasets and results obtained from this study were combined. All datasets were analysed by Microarray Suite 5.0 and Genesis software.In comparison to undifferentiated hBM‐MSC, hepatocyte differentiated hBM‐MSC showed a dramatic change of the gene expression profile. We found approximately 1000 genes upregulated and 1400 genes were downregulated in differentiated MSC with a fold change ≥3. Among these, around 60% and 40% showed similar expression levels as in adult liver, respectively. Expression of glutamine synthetase and ribonuclease 4 is significantly upregulated in hepatocyte differentiated MSC, typical for adult hepatocytes in the perivenous area of the liver lobule. Thus, hepatocyte‐like cells derived from hBM‐MSC feature human hepatocyte gene expression patterns, which encourages to step forward to use hBM‐MSC as a novel source for cell therapy of liver diseases.
Effect of citrulline on cultured macrophages from Zucker Diabetic Fatty (ZDF) rats
Authors: Bonhomme Sandra , Kohler Josephine , Dumez Celine , Breuillard Charlotte , Leplenier Servane , Couderc Remy , Cynober Luc , Darquy Sylviane 
Published: June 2021

Obese and type 2 diabetic patients present metabolic and immune impairments that weaken response to aggression and infectious complications. Arginine (Arg), which level is depressed in diabetes, has immune properties and is essential in situations of stress. In particular, it is the precursor of nitric oxide (NO). Since administration of Arg is associated with adverse effects, the use of citrulline (Cit) as an indirect progenitor for NO is of particular interest.Objectives:To evaluate the effect of Cit on macrophages from ZDF control fa/+ and diabetic‐obese fa/fa rats.Peritoneal macrophages (5105 cells) from fa/+ and fa/fa rats were cultured with 0.5, 1 and 2 mmol/l Cit concentrations for 24 h (n=12/group). NO and TNFα were measured in the supernatant. In cell extracts, iNOS protein expression was evaluated by Western blot.Results:In the fa/+ rats NO production was related to Cit concentration, and TNFα concentration remained constant. In fa/fa rats NO production increased with 1 mmol/l of Cit, and TNFα production decreased with high Cit concentration.Conclusions:Cit can act as a precursor for Arg in macrophage NO production. Like arginine, Cit has an anti‐inflammatory effect by decreasing TNFα production and is able to restore NO production in inflammatory situations such as diabetes and obesity. Cit administration can be considered as an alternative to arginine supplementation in clinical use.