bluuebunny/crossref_metadata_2025_split huggingface dataset:
Level of cytoplasmic thioredoxin reductase 1 in prostate tissue is associated with prostate cancer Gleason score, total antioxidant capacity and erythrocyte glutathione peroxidase activity (136.2)
Authors: Vance Terrence , Azabdaftari Gissou , Pop Elena , Lee Sang Gil , Su L. Joseph , Fontham Elizabeth , Bensen Jeannette , Mohler James , Chen Ming‐Hui , Koo Sung , Chun Ock 
Published: June 2021

Thioredoxin reductase 1 (TrxR1) is a member of the thioredoxin system, and a ubiquitous protein disulfide reductase involved in various intracellular inflammatory and oxidative processes. This study was conducted to determine the association between prostate tissue expression of TrxR1 levels and prostate cancer (PCa) Gleason score, dietary total antioxidant capacity (TAC), and erythrocyte glutathione peroxidase (GPx) activity using data from PCaP, a study of incident PCa among African and Caucasian Americans. Cytoplasmic and nuclear TrxR1 levels were measured using immunohistochemical staining of PCa on diagnostic biopsy sections from 55 men and visually scored in a blinded fashion by a pathologist (slides scored 0 to 3, with larger numbers indicating greater intensity of staining). Associations between PCa Gleason score and cytoplasmic TrxR1 levels of benign and malignant cells, and the difference in TrxR1 level between benign and malignant cells (ΔTrxR1), were determined using Fisher’s Exact test, α=0.05. TrxR1 was associated with dietary TAC (p<0.05) in benign cells and GPx (p<0.05) in malignant cells; ΔTrxR1 was found positively associated with Gleason score (p<0.05). These results warrant additional research on oxidative stress and prostate carcinogenesis.Acknowledgement: The authors thank the staff, advisory committees and research subjects participating in the North Carolina‐Louisiana Prostate Cancer Project (PCaP) study for their important contributions.Grant Funding Source: Support by NIH Cancer Epidemiology Small Grant #1R03CA159421‐01A1 and DOD DAMD 17‐03‐2‐0052
CD47 contributes to neutrophil recruitment (146.2)
Authors: Azcutia Veronica , Croce Kevin , Herter Jan , Newton Gail , Mayadas Tanya , Luscinskas Francis 
Published: June 2021

Leukocyte recruitment plays a key role in an inflammatory response. CD47 associates “in cis” with β1, β2 and β3 integrins. CD47 also interacts “in trans” with Signal Regulatory Proteins (SIRP‐α and ‐γ) and thrombospondin (TSP). CD47 plays an important but incompletely understood role in the innate and adaptive immune responses. Neutrophil recruitment in CD47KO mice is reduced in models of peritonitis, lung injury and dermal air pouch inflammation, but the exact contribution(s) of CD47 to neutrophil (PMN) extravasation is unclear. Here we report that in the TNF‐α‐stimulated cremaster muscle microcirculation, PMN rolling velocity is elevated compared to WT (17.8±1.5μm/s vs. 14.3±1.0μm/s, respectively; p<0.05), whereas there was no difference between WT and CD47KO mice in CXCL1‐induced arrest. Also, PMN transendothelial migration (TEM) is reduced by 30% in CD47KO mice compared to WT mice (p<0.05). In vitro flow chamber assays demonstrate reduced adhesion (30% reduction vs. WT; p<0.05) and TEM (60% reduction vs. WT; p<0.05) of CD47KO PMN compared to WT PMN across WT TNF‐activated murine endothelium. We have previously reported that CD47 physically interacts with β2 integrins and regulates integrin affinity on T cells (Azcutia et al., Mol Biol Cell 2013). These previous observations and our current results suggest that CD47 plays a role in PMN recruitment through the regulation of β2 integrin adhesive function.Grant Funding Source: Supported by NIH HL‐36028 and AHA fellowship 11POST7730055.
Is beta‐arrestin related to muscarinic receptor uncoupling in Alzheimer's disease? (153.4)
Authors: Potter Pamela , Bills Matthew , Killpack Luke , Hamada Matthew , Jones Douglas , Sue Lucia , Beach Thomas 
Published: June 2021

The purpose of this study was to characterize the mechanism underlying muscarinic receptor uncoupling in patients with Alzheimer’s disease. We found previously that muscarinic receptors were uncoupled from G‐ proteins in brains of patients with Alzheimer’s disease, as well as in non‐demented controls with substantial β‐amyloid deposition and neuritic plaque formation1. We also have found that as plaque levels and β‐amyloid increased, levels of the G‐protein coupled receptor kinase GRK‐2 were significantly decreased, and Gq/11 protein was shifted from the cytosol to the membrane fraction. In the current study, levels of β‐arrestin, a protein involved in receptor recycling, were examined in four groups: patients diagnosed with Alzheimer’s (AD), age matched controls with many plaques (MP), age matched controls with sparse plaques (SP), and age‐matched controls with no plaques (NP). The amount of plaque formation was correlated with loss of cholinergic neurons as assessed by choline acetyltransferase (ChAT) activity. Levels of signal transduction markers were measured using Western blot. Levels of β‐amyloid were measured using ELISA. We found that β‐arrestin levels were decreased in both non‐demented groups with neuritic plaques as well as in those with Alzheimer’s disease, compared to the control group. It is likely that alterations in GRK, coupled with a decrease in β‐arrestin, could impair muscarinic receptor recycling. Loss of recycling could lead to downregulation or uncoupling of the receptors. Thus, it may be very important to attempt to circumvent impairment of signal transduction by addressing cholinergic dysfunction in treatment of Alzheimer’s disease.1. Potter PE, Rauschkolb PK, Pandya Y, Sue LI, Sabbagh MN, Walker DG, Beach TG. Acta Neuropathol. 122:49‐60, 2011 2. Beach, T.G., Potter, P.E., Kuo, Y.‐M., Emmerling, M.R., Durham, R.A., Webster, S.D., Walker, D.G., Sue, L.I., Scott, S., Layne, K.J. and Roher, A.E. Neurosci. Lett. 283, 9‐12, 2000
Transdifferentiation of hypertrophic chondrocytes during endochondral bone repair by activation of pluripotent stem cell programs (216.1)
Authors: Bahney Chelsea , Hu Diane , Ferro Federico , Taylor Aaron , Miclau Ted , Marcucio Ralph 
Published: June 2021

The majority of bone fractures heal by endochondral ossification, where bone forms secondarily to cartilage. Mechanistically bone repair is presumed to parallel endochondral ossification during development. Dogma holds that chondrocytes mature to hypertrophy, undergo apoptosis, and bone forms by invading osteoprogenitors. However, we have data to suggest chondrocytes transform directly into bone during regeneration. Consequently, we propose an alternate hypothesis where transdifferentiation of chondrocytes into osteocytes plays a direct role in endochondral bone regeneration. Using lineage tracing to follow cartilage transplanted into segmental bone defects created in murine tibiae, we demonstrate the vast majority of osteocytes are cartilage derived. Hypertrophic chondrocytes in the fracture callus are mineralized and express classic bone markers, without significant apoptosis. Instead some “transitioning” chondrocytes express Oct4A and sox‐2, suggesting that activation of the pluripotent programs may facilitate phenotypic transformation. Histologically this process appears coordinated by the invading vasculature and mineralization of cartilage can be fully recapitulated in vitro using endothelial cell conditioned medium. Taken together, these data suggest that there may be significant differences between endochondral ossification during bone development and repair.Grant Funding Source: NIH NRSA F32 (Bahney), MTF Junior Investigator Award (Bahney), NIH #AR053645 & AR057 (TM)
Development of dietary patterns in very young children: food sources of energy (252.3)
Authors: Reidy Kathleen , Deming Denise , Fox Mary Kay , Briefel Ronette 
Published: June 2021

Data from the Feeding Infants and Toddlers Study (FITS) 2008, a national survey of young children, were analyzed to understand the development of dietary patterns in infants, toddlers and preschoolers, focusing on food sources of energy and key nutrients. Twenty four hour dietary recalls were conducted by telephone with parents or primary caregivers of 3200 children age 0‐4 years. The diet transitions during this period from an all milk diet, with milks representing 98% en in the youngest age group ( 0‐3 months) to 15‐17% en by ages 2‐4 years, when children have transitioned to the family table. Data show that problematic dietary patterns, that are quite high in sweets (15% en) and grains (32% en) and low in fruits (7% en) and vegetables (4% en) develop rapidly starting in infancy and are fairly set as early as age 2. Further analysis shows that discretionary calories, energy from solid fats and added sugars, in 2‐4 year olds is 408 calories, more than one third of total energy intake. With over 10% of children ages 2‐5 already obese, it is critically important to lay the foundation for healthful dietary patterns very early in childhood, when eating habits and food preferences are being formed.Grant Funding Source: Supported by Nestle Infant Nutrition
Antenatal multiple micronutrient supplementation and growth in the first two years of life and cognitive function at 24 months in rural Bangladesh (256.5)
Authors: Christian Parul , Shamim Abu , Shaikh Saijuddin , Ali Hasmot , Mehra Sucheta , Lee Wu , Labrique Alain , Schulze Kerry , Klemm Rolf , West Keith 
Published: June 2021

In a cluster‐randomized, controlled trial in rural Bangladesh, antenatal multiple micronutrient (MM) vs. iron‐folic acid (IFA) supplementation enhanced birth weight and length. We assessed the effects of the intervention on growth at 1, 3, 6, 12 and 24 mo of age and cognitive function using Bayley‐III at 24 mo. Children were born with low mean (SD) length for age Z‐score (LAZ) of ‐1.58 (1.20) in the MM and ‐1.69 (1.26) in the IFA group (p<0.001). Linear growth improved over the first 6 months in both groups. MM increased LAZ by mean (SE) 0.06 (0.01), at both 1 and 3 mo of age compared to IFA after adjusting for birth LAZ and design effect (both p<0.001). Stunting prevalence was lower at 1 mo (32.2 vs. 36.0%, RR=0.95, 95% CI:0.92, 0.98) and at 3 mo (24.5 vs. 29.0%, RR=0.91, 95%CI:0.88, 0.94) in the MM vs. IFA group, after adjusting for stunting at birth. The difference between groups was attenuated and not significant by 6 mo and absent by 12 and 24 mo of age, at which time stunting prevalance was 50%. In a substudy (n=750), there was no treatment effect on composite scores of cognition, language, and motor performance or behavior at 24 mo. MM supplementation improved postnatal linear growth beyond birth, but after supplement use had ended at 3 mo postpartum, and around the age of introduction of complementary foods at 6 months, the benefit on growth was no longer apparent, suggesting that infections and inadequate breastfeeding and complementary feeding practices have a strong influence on growth beyond 6 mo in this rural South Asian context.Grant Funding Source: Supported by the Bill & Melinda Gates Foundation Grant 614
Maternal education modifies the association between food insecurity and risk of short IPI among low income women in Massachusetts (268.5)
Authors: Metallinos‐Katsaras Elizabeth , Siu Elizabeth , Colchamiro Rachel 
Published: June 2021

Periconceptional nutrition’s importance has been established through a large body of research, showing adverse effects of poor periconceptional nutritional status on a variety of health outcomes. This study examined the association between food security status during the Inter‐pregnancy interval (IPI) and risk of short IPI among low income women participating in MA WIC (2001‐2009). Women who were on WIC for both 1st and 2nd pregnancies, had singleton full‐term (38‐42 wks) live births, and had complete data on ethnicity, education, age, household (HH) size, pre‐pregnancy weight before 2nd pregnancy, 1st infant’s breastfeeding duration and HH food security status from the 2nd pregnancy were included in these analyses (n=10,625 mothers). IPI= the estimated date of conception for the 2nd pregnancy ‐ the birth date of the first child. Logistic regression was used to examine the association between food security and short IPI (< 12 months), controlling for the aforementioned covariates. Sample characteristics were: mean age of 22.6 years (SD=5.1 yrs), 54.6% non‐white, 23.4% with food insecurity (18.5% low food security (LFS) and 4.9% very low food security (VLFS)), and 28.5% with short IPI. HH food insecurity was associated with a higher risk of short IPI; this varied by maternal education. Among mothers with < 12 years of education, those with VLFS were 56% more likely [OR=1.56, 95%CI=1.1‐2.1] to have short IPI compared to food secure mothers. Those with LFS tended toward increased risk for short IPI [OR=1.20, 95%CI=1.0‐1.4]. Among mothers with > 12 years of education, those with LFS were 28% more likely [OR=1.28, 95%CI=1.0‐1.63] to have short IPI than food secure mothers; there was no association with VLFS risk [OR=1.39, 95%CI=0.9‐2.2]. Among mothers with 12 years of education neither LFS [OR=1.0, 95% CI=0.9‐1.2] nor VLFS [OR=0.8, 95%CI=0.6‐1.1] were associated with short IPI. Food insecurity increased the risk of short IPI in this low income population but the effect varied by maternal education.Grant Funding Source: Supported by UCLA/USDA
Infliuence of age on the absorption, metabolism an excretion of cocoa flavanols (270.4)
Authors: Rodriguez‐Mateos Ana , Cifuentes‐Gomez Tania , Ottaviani Javier , Schroeter Hagen , Heiss Christian , Spencer Jeremy 
Published: June 2021

Accumulating evidence from dietary intervention studies suggest that regular consumption of foods and beverages rich in flavanols may have cardiovascular benefits. However, such biological effects are dependent on the bioavailability of flavanols, and, as such, individual variations in absorption, metabolism and excretion are highly relevant. The aim of this study was to investigate whether or not the absorption, metabolism an excretion of cocoa flavanols is age‐dependent. A 3‐armed randomized, cross‐over intervention study was performed in 40 healthy, caucasian men aged 18‐35 or 65‐80 years old. The subjects received either 5.3 or 10.7 mg CF/Kg body weight (BW); 1 gram of acetaminophen was used as a control to compare differences in metabolism. Plasma and urine samples were collected over 24 hours post‐consumption, and were analysed by HPLC with UV, fluorescence and electrochemical detection. Our data demonstrate that the intra‐ and inter‐individual variability of flavanol absorption is relatively low, and while small differences in the metabolism and catabolism of flavanols were identified as a function of age, in general, flavanols were absorbed, metabolised and excreted in a similar fashion, thus supporting future efforts to establish population‐level cocoa flavanol intake recommendations.Grant Funding Source: FP7 grant of the European Union entitled FLAVIOLA (FP7‐KBBE‐2008‐2B).
microRNAs in bovine milk are bioavailable in healthy adults and downregulate reporter gene activity in human kidney HEK‐293 cell cultures (271.4)
Authors: Baier Scott , Zempleni Janos 
Published: June 2021

MicroRNAs (miRNA) repress gene expression at the level of transcription and translation. MiRNA are stable and evolutionary conserved. We tested the novel hypothesis that dietary miRNA in bovine milk are bioavailable and affect human gene expression. Milk and miR‐29b were chosen as models because of the large amounts of milk consumed in the U.S., the abundance of miR‐29b in milk, and the role of miR‐29b in bone health. We tested our hypothesis in milk feeding studies in adults using a randomized crossover design, and a reporter gene assay in HEK‐293 cell cultures. Plasma levels of miR‐29b peaked 3 h after milk consumption to 247% above baseline levels (as per qRT‐PCR; P=0.03; n=6; t‐test), consistent with absorption occurring in the upper small intestine. Levels of miR‐200c and miR‐150 (neg. control) in milk are 800% and <1%, respectively, that of miR‐29b. The peak plasma level of miR‐200c increased 383% above baseline, whereas miR‐150 levels did not change, consistent with a dose‐response relationship and assay specificity. Culturing HEK‐293 cells with miRNA from milk decreased the activity of a miR‐200c reporter gene by 24% compared with vehicle controls. We conclude that milk‐borne miRNA alter the expression of human genes, creating a pattern conducive to bone health. Our findings are significant in infant nutrition (miRNA content in formulas vs. breast milk) and the nutrition of postmenopausal women (osteoporosis).Grant Funding Source: Supported by ARD Hatch and NIH.
Hindlimb heating increases vascular access of large molecules to murine tibial growth plates measured by in vivo multiphoton imaging (342.3)
Authors: Serrat Maria , Williams Rebecca 
Published: June 2021

Advances in understanding the molecular regulation of linear growth have led to development of novel drug therapies for growth plate disorders. An unmet challenge is delivering agents to avascular cartilage plates. Dense matrix and lack of penetrating blood vessels create a semi‐permeable vascular‐cartilage “barrier,” which hinders molecular transport. We employed a hindlimb heating model to manipulate bone circulation in 5‐week‐old female mice (N=22). We used in vivo multiphoton microscopy to quantify temperature‐enhanced delivery of large molecules into tibial growth plates. We tested the hypothesis that increasing hindlimb temperature from 22C to 34C increases vascular access of large systemic molecules, modeled using 10‐, 40‐, and 70 kDa dextrans that approximate sizes of physiological regulators. Vascular access was quantified by vessel diameter, velocity, and dextran leakage from vessels and accumulation in growth plates. Growth plate entry of 10 kDa dextrans increased over 150% at 34C. Entry of 40‐ and 70 kDa dextrans increased < 50%, suggesting size‐dependence. Velocity and vessel diameter increased 118% and 31%, respectively, at 34C. Results demonstrate that heat enhances vascular carrying capacity and bioavailability of large molecules around growth plates, suggesting that temperature could be a noninvasive way to enhance therapeutic delivery to impaired growth plates of children.Grant Funding Source: Supported by NSF MRI‐R2 0959012 and 0929997, WV‐NASA, and UK‐CCTS (NIH UL1TR000117)
Associations between change in DASH diet scores and CVD risk factors in the PREMIER Trial (369.1)
Authors: Beasley Jeannette , Viswanathan Shankar , Wylie‐Rosett Judith 
Published: June 2021

OBJECTIVE: To measure associations between changes in the Dietary Approaches to Stop Hypertension (DASH) dietary indices and changes in blood pressure (BP), weight, and waist circumference (CVD risk factors) in PREMIER, a randomized, controlled trial of behavioral intervention for hypertension with and without the DASH dietary pattern.METHODS: DASH diet scores were derived based upon nutrient (9 nutrients, DASH_Nutrient) and food‐based (8 food groups, DASH_Food) targets using two 24‐h recalls administered at baseline, 6 months, and 18 months. Generalized estimating equations (GEE) were used to assess associations between CVD risk factors per SD change in the two DASH indices after accounting for confounders and randomization group.RESULTS: At baseline (n=807), lower DASH scores were associated with higher BMI, African‐American race, and younger age for both indices. Spearman correlations between the indices were 0.36. Mean DASH scores at baseline and 18 months were 2.7 (SD=1.4) and 3.7 (SD 1.4) for DASH_Nutrient (range 0 to 9) and 36.2 (SD=10.5) and 40.0 (SD 11.8) for DASH_Food (range 0‐80). Each SD increase in DASH_Nutrient was associated with a ‐1.26 (95% CI: ‐1.91 to ‐0.61) mmHg decrease in systolic BP versus a ‐0.87 (95% CI: ‐1.44 to ‐0.30) mmHg per SD change in DASH_Food. Each SD increase in DASH_Nutrient score was associated with a ‐0.50 (‐0.95 to ‐0.06) unit decrease in diastolic BP. Changes in the DASH_Food score were not significantly associated with changes in diastolic BP.INTERPRETATION: The DASH dietary pattern defined by nutrient, rather than food, intake is more closely associated with reduction in CVD risk factors.Table. Longitudinal associations (Mean (95% CI)) between changes from baseline in DASH Diet Scores and CVD risk factors

CVD Risk Factor
DASH_Nutrient (derived based on Mellenâ€™s DASH Index), per SD
DASH_Food (derived based on Guntherâ€™s DASH Index), per SD

Systolic Blood Pressure, mmHg
‐1.26 (‐1.91 to ‐0.61)
‐0.87 (‐1.44 to ‐0.30)

Diastolic Blood Pressure, mmHg
‐0.50 (‐0.95 to ‐0.06)
‐0.32 (‐0.75 to 0.11)

Weight, lb
‐1.94 (‐2.80 to ‐1.17)
‐1.10 (‐1.71 to ‐0.49)

Waist Circumference, cm
‐0.89 (‐1.29 to ‐0.48)
‐0.75 (‐1.10 to ‐0.40)

GEE models with unstructured correlation matrix adjusted for baseline CVD risk factor, baseline DASH score, sex, race, age, education, smoking (current, former, never), physical activity, energy intake, BMI, and randomization assignment.
Effects of high‐protein weight loss diets on fat‐free mass changes in older adults: a systematic review (371.5)
Authors: Kim Jung Eun , Sands Laura , Slebodnik Mary , O’Connor Lauren , Campbell Wayne 
Published: June 2021

With advancing age, many adults experience increased body weight (BW) and fat mass (FM) but decreased fat‐free mass (FFM). Purposeful moderate dietary energy restriction (ER) (500‐750 kcal/d E deficits) reduces BW and FM, but also FFM. High protein (HP) vs. normal protein (NP) intake during ER may more effectively retain FFM, but this issue requires systematic evaluation in older adults. We conducted a systematic review of randomized control trials (RCT) to assess the effects of protein intake on ER‐induced changes in FFM in adults mean age 50+ years. Eighteen RCT were systematically evaluated with HP defined as either 1) > 25% of the total E from protein; or 2) > 1 g protein/(kg[[Unsupported Character ‐ Symbol Font ř]]d). The median protein intakes of the HP and NP groups were 30 and 18 % of the total E intake (ranges: 25‐40 and 15‐20), respectively, and 1.53 and 0.87 g protein/(kg[[Unsupported Character ‐ Symbol Font ř]]d) (ranges: 1.04‐1.89 and 0.66‐0.99), respectively. With dietary protein expressed as % of E intake, fewer HP vs. NP groups lost 蠅 30% of BW as FFM (20 vs. 44 % of groups) and more HP vs. NP groups lost < 20 % of BW as FFM (40 vs. 17 % of groups). Similarly, using g protein/(kg[[Unsupported Character ‐ Symbol Font ř]]d), fewer HP vs. NP groups lost 蠅 30% of BW as FFM (19 vs. 44 % of groups) and more HP vs. NP groups lost < 20 % of BW as FFM (44 vs. 12 % of groups). These findings indicate that old adults can more effectively retain FFM during weight loss when they consume a high‐protein diet.Grant Funding Source: Support by Purdue Univ Ingest Behav Res Ctr