bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigallocatechin gallate (EGCG) ‐ loaded nanoparticles decrease cholesterol content in THP‐1 derived macrophages
Authors: Zhang Jia , Nie Shufang , Wang Shu 
Published: June 2021

The aim of this study is to synthesize EGCG‐loaded nanoparticles (Nano‐E) to improve EGCG stability, cellular content, decrease cholesterol accumulation and inflammatory factor production in THP‐1 derived macrophages.Biocompatible and biodegradable Nano–E was prepared by a phase inversion method. The particle size and zeta potential of Nano‐E were measured using Brookhaven analyzer. Encapsulation efficiency (EE), loading content (LC), EGCG release, stability of Nano‐E in different temperatures and pH, cellular EGCG and cholesterol content were measured using a HPLC system. Cellular uptake of fluorescent‐labeled Nano‐E was measured using a fluorescent microscope. Cell viability was measured using a MTT method.Nano‐E were about 45–55nm in diameter. The EE and LC were 90% and 3%, respectively. Nano‐E dramatically improved EGCG stability and increased its uptake by macrophages. The Nano‐E increased cellular EGCG content by 5‐fold compared with native EGCG at 100 μM at 37°C. As compared to 10 μM of native EGCG, Nano‐E at the same concentration significantly decreased cellular total and esterified cholesterol content in macrophages. Both Nano‐E and native EGCG at 10μM didn't decrease macrophage viability.Nano‐E significantly increased EGCG stability, cellular EGCG content, and decreased cholesterol accumulation in THP‐1 derived macrophages.Grant Funding Source: Grant Funding Source: NIH 1R15AT007013–01
Differential effects of whole and refined grains on abdominal adipose tissue depots in an exploratory subgroup analysis of the GRAIN Study
Authors: Harris Kristina , Lemieux Susan , Jonnalagadda Satya , West Sheila , Heuvel Jack Vanden , Kris‐Etherton Penny 
Published: June 2021

Abdominal obesity is associated with insulin resistance, specifically having a higher amount of adipose tissue (AT) in visceral (VAT) rather than abdominal subcutaneous (ASAT) depots. We explored the relationship between ASAT, VAT and metabolic and anthropometric variables in a subgroup (n =28/50) of participants from a 12‐week, randomized, parallel arm, weight‐loss study in overweight/obese individuals comparing whole (WG) and refined grains (RG). Abdominal MRI was performed at 0 and 12 weeks. Axial scans at lumbar vertebrae L4–5 to L3 were manually traced to separate the AT depots. Baseline ASAT correlated with BMI, waist circumference, total and central AT (from DXA), C‐reactive protein, interleukin 6, and leptin (Rs>;0.55, P<0.05); VAT correlated with central AT, insulin and HOMA‐IR (Rs>;0.35, P<0.05). VAT % change correlated inversely with alkylresorcinol % change, a biomarker of whole grain intake (L3 only, R=−0.51, P<0.01). While the between group changes in ASAT and VAT were not significant, VAT decreased significantly from baseline in only the WG group (RG: −14 ± 20 g, P=0.08; WG: −18 ± 20 g, P=0.001). These findings suggest that VAT and insulin are strongly associated, whereas ASAT is more highly correlated with body fatness and inflammatory markers. Consumption of WG in the place of RG during weight loss may elicit a greater reduction in VAT, but more research is warranted.Grant Funding Source: General Mills Bell Institute of Health and Nutrition
Validity of the National Cancer Institute's Automated Self‐ Administered 24‐hour Recall (ASA24): Results of a Feeding Study
Authors: Kirkpatrick Sharon I , Thompson Frances E , Subar Amy F , Douglass Deirdre , Zimmerman Thea P , Kahle Lisa L , George Stephanie M , Potischman Nancy 
Published: June 2021

The Automated Self‐administered 24‐hour dietary recall (ASA24) is a web‐based tool that enables the collection of multiple recalls in large studies at minimal cost. To assess the validity of ASA24, we studied 83 adults, aged 20–70 years, who ate three meals at a study center. True intake was ascertained by inconspicuously weighing foods and beverages offered at a buffet before and after each participant served him/herself, as well as plate waste. Participants were randomly assigned to complete ASA24 or an interviewer‐administered recall using the Automated Multiple‐Pass Method (AMPM) on the following day, and the degree to which reported and true intake matched was examined. Data for one ASA24 participant was excluded because reported intake did not correspond to the previous day. For study center meals, average true energy intake of ASA24 participants (n=40) was 2329 calories compared to an average reported intake of 2138 calories (−191). On average, exact or close matches were reported for 72% of items consumed. Among AMPM participants (n=42), average true energy intake was 2268 calories compared to an average reported intake of 2425 calories (+157). On average, exact or close matches were reported for 78% of items consumed. The average number of items consumed but not reported was 7 for ASA24 and 6 for AMPM. The results support the use of ASA24 as a cost‐effective means of collecting high‐quality dietary data.Grant Funding Source: n/a
The associations between serum antioxidant concentrations and bone mineral density in women aged 50 and over: an analysis of NHANES 2005–6
Authors: Hamidi Maryam Sarah , Cheung Angela Man‐Wei 
Published: June 2021

It has been shown that diets high in antioxidants are associated with high bone mineral density in postmenopausal women. Conversely, some studies suggest that dietary supplements containing antioxidants may have detrimental effects on bone. Serum concentrations of antioxidants can reflect their intakes from both food and supplements. Thus, the objective of our study was to examine the associations between serum concentrations of several antioxidants and femoral neck BMD (FN_BMD) in postmenopausal women aged ≥50 years. We used cross‐sectional data from the NHANES 2005–6. Multiple regression models with adjustments for relevant confounders were used to examine the associations between serum concentrations of vitamins C and E (alpha‐ and gamma‐tocopherol) and alpha and beta‐carotene, and FN_BMD. The study sample included 168 women, with a mean age of 67.5±0.5 years, who were free from diseases and medications that affect bone metabolism, and were fasting >;9 hours prior to examination. In adjusted models, serum concentration of vitamin C had a positive association with FN_BMD (p=0.018), while serum concentration of beta‐carotene had a negative association with FN_BMD (p=0.008). The association between higher serum vitamin C and higher BMD in our study is consistent with findings of other studies. The negative association between serum beta‐carotene and femoral neck BMD needs further investigation.Grant Funding Source: None
Mealtime beverage and food intake to satiation interacts with meal advancement in healthy young men and women
Authors: El Khoury Dalia , Panahi Shirin , Luhovyy Bohdan L. , Goff H. Douglas , Anderson G. Harvey 
Published: June 2021

Thirst, hunger, eating and drinking are closely interrelated. However, their interaction during meal progression and the impact of beverage type on this interrelationship have not been reported. In a randomized controlled study, 29 men and women (22 ± 0.4 years; 22 ± 0.3 kg/m2) consumed to satiation a pizza meal with one of water, 1% milk, regular cola, orange juice and diet cola. Mealtime food and fluid intake were measured within each of three 7‐min phases of the meal. A progressive decline occurred from phase 1 to 3 in fluid intake, averaging 59 ml, and food intake, averaging 268 kcal (P < 0.0001); however, the relative intake of fluid to food increased (P < 0.0001). Beverage type did not alter the overall association of fluid and food intake with meal progression. However, the effect of beverage type on fluid and food intake changed by phases of the meal. Although pizza intake was similar with all beverages averaging 932 kcal, the amount of fluid consumed was higher with orange juice than diet cola during phases 1 (P = 0.01) and 2 (P < 0.001) of the meal. Caloric beverages led to higher mealtime total energy intake compared to water (P < 0.001) and diet cola (P < 0.0001), during all three phases of the meal. Baseline thirst, but not appetite, correlated with fluid (r = 0.277; P = 0.001) and food (r = 0.163; P = 0.050) intake. In conclusion, meal progression was a major determinant of the relationship between mealtime beverage and food intake.Supported by Natural Sciences and Engineering Research Council of Canada‐Collaborative Research and Development, Dairy Farmers of Ontario and Kraft Canada Inc.
Dietary supplement use is associated with positive mood states in US Military and Coast Guard personnel
Authors: Austin Krista Gail , McGraw Susan M , Lieberman Harris 
Published: June 2021

Approximately 60% of armed forces personnel consume a dietary supplement (DS). Therefore, we investigated the association of mood with multiple classes of DS in military (M) and Coast Guard (CG) personnel (N = 5,536). Participants completed a survey of DS use and the Quick Mood Scale to assess wakeful‐drowsiness, relaxed‐anxious, cheerful‐depressed, friendly‐aggression, clearheaded‐confused and well coordinated‐clumsy mood domains. Supplements were categorized as multivitamin/mineral (MVM), individual vitamin/minerals (IVM), protein/amino acids (P), combination products (C), herbals (H), purported steroid analogs (S) and other (O). A one‐way analysis of covariance assessed effects of DS on mood controlling for age. Users of DS, especially MVM and P, reported being more awake (5.23 + 0.03 vs. 5.03 + 0.05), cheerful (5.48 + 0.03 vs. 5.25 + 0.04), friendly (5.58 + 0.03 vs. 5.44 + 0.04), clearheaded (6.01 + 0.03 vs. 5.74 + 0.04), and coordinated (6.02 + 0.03 vs. 5.77 + 0.04), (p<.01). Users of S felt less friendly (more aggressive) (4.79 + 0.18 vs. 5.55 + 0.02, p<.01). As no mechanisms can realistically explain the diverse effects of so many types of DS on different moods, we hypothesize this association is not causal, and DS intake per se does not alter mood. Studies of DS should consider whether mood differences in users vs. non‐users could be a confounding factor.Support: US MRMC/DoD Center Alliance for DS Research
Micronutrient Intakes Vary by Age Group and Ethnicity in Older US Populations
Authors: Bird Julia K , Fulgoni Victor L 
Published: June 2021

Older adults are at greater risk of malnutrition. Causes include reduced food intake, poorer taste and smell, difficulties chewing or preparing food, nutrient malabsorption in the aging digestive tract, and co‐morbidities. In addition, ethnicity may confound nutrient status. Using NHANES, 2003–2008, usual intakes of vitamins, minerals and carotenoids and percentage not meeting the EAR, where available, were determined using the National Cancer Institute method. Statistically significant differences between age groups (51–70, 71+ yrs) were calculated using a Student's t‐test and by linear regression modeling (significance was p<0.05). Defining at risk nutrients as more than 25% of population not meeting the EAR, adults 51+ yrs had lower intakes of at risk nutrients: calcium choline, lycopene, magnesium and vitamin E, and higher intakes of alpha‐ and beta‐carotene, vitamin A, C and D than adults aged 19–50 yrs. Significant differences were found comparing ages 51–70 and 71+ yrs, with lower intakes generally found in the older age group.Ethnicity significantly affected adults’ nutrient intakes for most nutrients with African Americans having the lowest intakes of all nutrients except lutein+zeaxanthin, vitamins A, C and K. In summary, nutrient intakes vary by age group and ethnicity. Adults 71+ yrs and African American seniors are at higher nutritional risk.
Obesity affects short‐term folic acid pharmacokinetics in women of childbearing age
Authors: da Silva Vanessa R. , Hausman Dorothy B. , Kauwell Gail P. , Tackett Randall , Rathbun Stephen , Bailey Lynn B. 
Published: June 2021

Maternal folate status and BMI are independent risk factors for neural tube defects (NTD). Epidemiological studies have identified an inverse association between serum folate and BMI, after adjusting for intake. The objective of this study was to compare the relationship between BMI and the short‐term pharmacokinetic response to an oral dose of folic acid. Healthy obese (BMI ≥ 30.0; n=16) and normal weight (BMI 18.4 – 24.9; n=16) women of childbearing age (18 – 35 y) were administered a single oral dose of folic acid (400 μg). Blood samples were collected over a 10‐h period to evaluate the serum folate response. Fasting baseline serum folate was lower in the obese group (p= 0.005); in contrast, red blood cell folate was higher (p=0.05). Area‐under‐the‐curve for the absorption phase (0–3 h) and peak serum folate were lower in obese vs normal weight women (p<0.005). Overall serum folate response (0–10 h) differed between obese and normal weight women (repeated‐measures ANOVA, p=0.001). Data suggest body distribution of folic acid is significantly affected by obesity and should pregnancy occur may reduce the amount of folate available to the developing embryo. These findings provide additional support for a BMI‐adjusted folic acid intake recommendation for NTD risk reduction.Funded in part by HATCH #GEO00706 and #GEO00707
Maternal dietary Docosahexaenoic acid (DHA) supplementation prevents fetal growth restriction and pulmonary fibrosis caused by perinatal inflammation
Authors: Velten Markus , Britt Rodney D , Heyob Kathryn M , Tipple Trent E , Rogers Lynette K 
Published: June 2021

BackgroundEpidemiological data suggest that maternal inflammation contributes to intrauterine growth restriction, preterm birth, and adult‐onset pulmonary diseases. DHA has anti‐inflammatory properties but responsible mechanisms are not defined.ObjectiveWe hypothesized that perinatal inflammation and oxidative stress induce a fibrotic phenotype by EMT induction and that this phenotype can be rescued by dietary DHA administration.MethodsPregnant C3H/HeN mice were injected on E 16 with LPS or saline and placed on control or DHA diets. Pups were exposed to 85% (O2) or RA for 2 weeks than returned to room air (RA). Protein, RNA, histological, and pulmonary function analyses were performed.ResultsLPS/O2 exposure reduced birth weight, decreased alveolarization, impaired pulmonary function, induced inflammation, matrix remodeling, EMT, and collagen deposition. Maternal DHA supplementation attenuated deleterious effects on birth weight, alveolarization, pulmonary mechanics, matrix remodeling, collagen deposition, and EMT in lung tissues of LPS/O2 mice.ConclusionsOur data indicate that pulmonary morbidities at 8 weeks are due to maternal inflammation and neonatal oxidative stress. Perinatal DHA supplementation improves outcome by attenuating fibrotic response and improving alveolarization. These strategies would be straightforward to implement in pregnancy/lactationGrant Funding Source: NIH: LKR R01AT006880, DFG: MV, VE 614/1–1
Genome‐wide transcriptome analysis of the effects of sulforphane on normal and prostate cancer cells
Authors: Beaver Laura Michelle , Buchanan Alex , Sokolowski Elizabeth I , Chang Jeff H , Wong Carmen P , Williams David E , Dashwood Roderick H , Ho Emily 
Published: June 2021

Sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, induces anti‐proliferative and pro‐apoptotic responses in prostate cancer cells, but not normal prostate cells. The mechanisms responsible for these specific chemopreventive properties remain unclear. We utilized RNA sequencing (RNA‐seq) to test the hypothesis that SFN modifies patterns of gene expression that are critical in prostate cancer progression. Normal prostate epithelial cells and prostate cancer cells were treated with 15 uM SFN and the transcriptome was determined at 6 and 24h time points. SFN alters the mRNA expression levels of ~3,000 genes in each sample and the transcriptional response is highly dynamic over time. SFN treatment also alters the expression of non‐coding RNAs including lincRNAs. SFN targets multiple pathways in normal and prostate cancer cells that are critical in cancer including proliferation, apoptosis, angiogenesis, DNA damage response, and cell migration. Network analysis suggests that the transcription factor Sp1 may be a major mediator by which SFN treatment induces changes in gene expression. Studies evaluating the effect of SFN on Sp1 are ongoing and Sp1 mRNA levels are significantly decreased by SFN treatment. Together, this information can be leveraged to help develop intervention strategies to significantly reduce the incidence and severity of prostate cancer. Funding: P01CA090890Grant Funding Source: National Institute of Health
Impact of development and genetic variation on human hepatic CYP2B6 expression and activity.
Authors: Gaedigk Andrea , Twist Greyson P , Gaedigk Roger , Dai Hongying , Riffel Amanda K , Leeder J Steven , Pearce Robin E 
Published: June 2021

CYP2B6 metabolizes many drugs that are used clinically in children and adults. To better understand the developmental expression and variability in CYP2B6 activity, we characterized a large panel of human liver samples (24 fetal, 141 pediatric, 36 adult) for RNA and protein expression and activity (microsomal buproprion hydroxylation). Genotyping included six CYP2B6 SNPs and one SNP each for P450 oxidoreductase and PPARα. RNA expression was correlated with immunoreactive protein, activity and age (r=0.29, 0.79 and 0.27, respectively). A piece‐wise regression indicated a strong correlation above a defined cut‐off point between activity and expressed protein (r=0.74), but no significant correlation when activity and protein expression were low. In fetal samples, low levels of CYP2B6 mRNA were detected, but little or no protein or activity were observed. Levels of RNA, protein and activity increased markedly after birth. No gender effects were observed. A trend was seen between CYP2B6 rs3745274 (associated with CYP2B6*6 and *9) and decreased RNA expression, but not for any of the other SNPs tested. This study confirms that CYP2B6 expression and activity develops over the first months of life. Although a large range of CYP2B6 activity (>;500‐fold) was observed in this cohort, CYP2B6 allelic variation does not appear to be a predictor of CYP2B6 activity.Supported by a grant from the Tom Keaveny Foundation.
Performance 2012: Engaging the public with the physiology and pharmacology of sporting success
Authors: Lewis David Ian , Mills Dan , Haigh Charlotte 
Published: June 2021

There is considerable public interest in sport, with a significant upsurge following major international competitions. The 2012 Olympic Games therefore provided an ideal opportunity to explore, with the public, biomedical aspects of sport. Our aim was to provide them with knowledge and understanding of exercise physiology and pharmacology, and promote debate on the ethical issues which may arise.Three events were organised. The first, targeted at young people gave them the opportunity to act as scientists in a mock drug testing laboratory followed by a debate on the use of gene doping in sport. The second, for individuals who provide sporting opportunities for young people, was a facilitated debate in which their roles and responsibilities towards their athletes was explored. The final event was a two‐day interactive exhibition for the general public which combined “have a go” sporting activities such as wheelchair basketball with those which focused more on the science or ethics of performance enhancement e.g. an interactive mind‐map where the public could contribute their ideas on the harms and benefits of gene doping.Performance 2012 successfully engaged the public with the physiology and pharmacology of performance enhancement in sport. All resources are available via the project website www.fbs.leeds.ac.uk/performance2012/index.phpThe support of the Wellcome Trust is gratefully acknowledged.
The novel zebrafish mutant fantome/wdr43 as a human craniofacial ribosomopathy model
Authors: LaBonty Melissa , Zhao Chengtian , McCann Kathleen , Andreeva Viktoria , Baserga Susan J , Yelick Pamela C 
Published: June 2021

IntroductionThe zebrafish mutant fantome(fan) exhibits severe pharyngeal arch cartilage defects. Positional cloning was used to map the fan allele to a premature stop codon in wdr43, which encodes a t‐Utp ribosomal protein characterized in yeast to function in rRNA biogenesis. The objective of this study is to use the fantome/wdr43 mutant to define roles for wdr43 in craniofacial development.MethodsWISH, Alcian blue stain, Y2H, IF histochemistry, shRNA targeted knock‐down, qRT‐PCR, antisense morpholino oligomer (MO), mRNA injections, Western and Northern blot analyses.ResultsThe fan/wdr43 mutation was confirmed by rescue with single cell wdr43 mRNA injections, and by anti‐sense wdr43 MO phenocopy. WISH analyses revealed reduced neural crest cell populations, and qRT‐PCR revealed upregulated p53 signaling in fan mutants. In vitro subcellular localization studies showed that full length Wdr43 localized to nucleoli, while truncated fan mutant Wdr43 did not. Stable cell lines expressing shRNAs targeting wdr43 are being used to examine the subcellular localization of other nucleolar phosphoproteins including t‐Utps and Tcof1/Treacle, commonly mutated in Treacher Collins Syndrome.ConclusionsThe fantome/wdr43 mutant exhibits features similar to TCS, and may be an informative model for human neurocristopathies, including TCS.Support:NIH/NIDCR R01 DE018043 (PCY).Grant Funding Source: n/a
Structural and functional studies of mRNA processing and quality control
Authors: Tong Liang 
Published: June 2021

Eukaryotic mRNA precursors (pre‐mRNAs) must undergo extensive maturational processing, including 5′‐end capping, splicing and 3′‐end cleavage and polyadenylation. Turnover of mature mRNAs is mediated by exoribonucleases that function in the 5′→3′ or 3′→5′ direction (as well as other enzymes), which are important for the degradation of defective mRNAs as well (mRNA quality control). A nuclear 5′→3′ exoribonuclease (XRN2, Rat1 in yeast) also couples pre‐mRNA 3′‐end processing and Pol II transcription termination.We have been studying the structure and function of various components of the 3′‐end processing machinery as well as the 5′→3′ exoribonucleases. For example, we showed that Ssu72, a Pol II C‐terminal domain (CTD) pSer5 phosphatase, binds a pSer5 peptide with the pSer5‐Pro6 peptide bond in the cis configuration. Moreover, Ssu72 also recognizes the CTD phosphorylated at Ser7, but a pSer7 peptide is bound in the opposite direction as compared to the pSer5 peptide.Unexpectedly, our studies on a protein factor (Rai1) that stimulates the 5′→3′ exoribonuclease Rat1 led to the discovery of a novel quality control mechanism for mRNA 5′‐end capping. Studies in yeast and mammalian cells confirm that mRNAs with incomplete 5′‐end caps are produced under physiological conditions, and that Rai1 and its mammalian homolog (DXO) have important roles in the detection and degradation of such defective mRNAs.