bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Milk Components on the Immune Response to a Pneumonia Vaccine: A Randomized Placebo‐controlled Clinical Trial
Authors: Fischer Laura K. , German J. Bruce , Gershwin M. Eric 
Published: June 2021

Interventions aimed at improving immune function in the elderly could significantly reduce their risk of infectious disease and resulting mortality. The immune benefits of breast milk consumption in human infants are well established and suggest bovine milk components may also help enhance immune function in older populations. The objectives of this study were to evaluate the effects of a milk‐protein supplement on immune function in people at risk of immune senescence (IS). We enrolled 160 subjects over age 50 who were randomized to consume a milk‐based or control supplement for 8 weeks. Immune function was evaluated by measuring the antibody response to a pneumonia vaccine. IgG antibodies were measured before and after vaccine by multi‐analyte immunodetection system. Seroconversion was defined as a 4‐fold increase in titer. Risk of IS was evaluated by measuring a previously described marker of immune function, indolamine 2,3‐dioxygenase (IDO). IDO activity was defined as the ratio of the serum concentration of enzyme product (kynurenine) to substrate (tryptophan), measured by HPLC. Results from this study show a milk intervention significantly (p<0.05) increased the antibody response to 5 vaccine serotypes and the average seroconversion rate. These results highlight the relevance of diet for improving age‐related immune decline in individuals at risk of immune senescence.Grant Funding Source: Dairy Management, Inc, National Dairy Council, the UC Discovery Grant
Acute Angiotensin II Effects On NCC are Dependent on WNK4
Authors: Ko Benjamin , Hansen Lauren , Mistry Abinash , Mallick Rickta , Hoover Robert 
Published: June 2021

Acutely, angiotensin II (AII) is known to affect sodium chloride cotransporter (NCC) abundance and surface expression (SE). A possible role for WNK4 in mediating effects of AII on NCC has been described. To study this in a mammalian cell model, RNAi was used on mDCT15 cells to generate a WNK4 knock‐down cell line (WNK4KD). Thiazide‐sensitive 22Na+ uptake assays in mDCT15 cells showed a dose response to AII, peaking at 10−11M. mDCT15 cells showed a time dependent increase in activity, with peak response at 60 min (40±4%, p<0.01). An angiotensin receptor blocker eliminated this effect. WNK4 knock down in WNK4KD cells was measured via real time PCR to be 50±3%. WNK4KD cells did not show a statistically significant increase in activity with AII. NCC SE as measured by biotinylation and densitometry increased in mDCT15 cells with AII, peaking at 30 min (100±14%, p<0.01). There was a modest but statistically significant increase in SE at 30 min in WNK4KD cells (43±15%, p<0.05). These findings indicate a critical role for WNK4 in mediating acute effects of AII on NCC and provide a foundation to examine the mechanisms by which this occurs.Support K08 DK081728(BK), R01 DK‐085097, VA Research Service (RH)
An Endogenous Activator Protein of H+, K+‐ATPase Regulates Acid Secretion in Isolated Rabbit Gastric Glands
Authors: Nandi Jyotirmoy , Zinkievich J Michael , Ray Tushar 
Published: June 2021

We previously showed that an endogenous activator protein (HAF) stimulated gastric H+, K+‐ATPase activity in vitro. The present study evaluates the direct role of HAF on intercellular modulation of gastric H+ transport using an HAF‐specific antibody (HAF‐Ab).MethodsCytosolic and membrane fractions of rabbit parietal cells (PC) were analyzed by Western blot using polyclonal HAF‐Ab. The HAF‐Ab was subsequently tested for its effects on H+, K+‐ ATPase activity in PC membrane fractions, and histamine‐stimulated H+ secretion in permeabilized gastric glands (PGG). H+ secretion was measured indirectly using [14C] aminopyrine (AP) uptake ratio.ResultsHAF‐Ab recognized 2 closely apposed bands near the 40 kDa region of the apical and tubulovesicle membranes, and cytosolic fractions. The catalytic α and β subunits of H+, K+‐ ATPase were not recognized by HAF‐Ab. HAF‐Ab dosedependently inhibited HAF‐stimulated membrane H+, K+‐ATPase activity, and decreased AP uptake in histamine‐stimulated PGG. In the latter study, immunofluorescence revealed migration of cytosolic HAF towards the cannelicular plasma membrane, where H+, K+‐ATPase is located.ConclusionsHAF molecules migrate to the secretory plasma membrane following histamine stimulation, and close contact between HAF and H+, K+‐ATPase is essential in the process of gastric acid secretion. HAF‐Ab was found to be specific for HAF, but not for the α and β subunits of H+, K+‐ATPase. Since HAF‐Ab inhibited H+, K+‐ATPase and histamine‐stimulated acid secretion, this suggests, for the first time, evidence for a direct regulatory role of endogenous HAF on gastric H+ transport.
Genetic and Environmental Influences on Body Composition and Obesity in Chinese Children: a Twin Study in China
Authors: Li Ji , Liu Huijuan , Liu Xia , Wang Youfa 
Published: June 2021

IntroductionKnowledge about the genetic influence on body composition (BC) is limited, especially among Asian children.Objectivesto examine the relative contributions of genetic and environmental factors to BC traits among Chinese children, and assess if heritability estimates vary due to puberty.Methods620 twins (161 monozygotic (MZ) pairs, 149 dizygotic (DZ) pairs, 296 boys and 324 girls aged 7–15 y) were enrolled. Heritability was calculated by structural equation models.ResultsIntra‐class correlations for anthropometric and BC indicators were greater among MZ and same sex DZ twins than opposite sex DZ twins. The additive genetic factors were statistically significant in all genetic models, except for fat free mass index and waist‐to‐height ratio (WHtR), while the common environmental components were not significant for BMI. The age‐sex‐adjusted heritability estimates were low or moderate, ranging from 16.3% (WHtR) to 28.4% (BMI), 35.3% (body fat percentage), 68.0% (fat mass (FM)), 51.7% (overweight and obesity), and 22.7% (central obesity). Heritability among pubertal children was lower for waist circumference and WHtR, but greater for FM and FM index than among prepubertal ones.ConclusionsBC including obesity status was significantly influenced by genetic factors in Chinese twins. The estimated proportion of genetic control for anthropometric and BC measures varied considerably.Grant Funding Source: supported by the Johns Hopkins BSPH Faculty Innovation Award, the P&G Fellowship, the NIH/NIDDK (P60 DK0079637), and JMCHCH
Inflammation in postpartum women is inversely related to transferrin saturation, but is not correlated with ferritin or hepcidin
Authors: Jorgensen Josh M , Yang Zhenyu , Lonnerdal Bo , Chantry Caroline J , Allen Lindsay H , Dewey Kathryn G 
Published: June 2021

The relationship of inflammation to indicators of iron status in postpartum women is not well documented. We examined associations between markers of iron status (hemoglobin (Hb), ferritin, hepcidin, and transferrin saturation (TfSat)) and inflammation (C‐reactive protein (CRP) and α‐1‐acid glycoprotein (AGP)) in 114 lactating women enrolled in a randomized placebo controlled trial of iron‐containing prenatal vitamin‐mineral supplements. Blood samples were collected before and after 3 mo of supplementation. At baseline (x̄ = 13.8 d postpartum), 58% of women had CRP > 5 mg/L and 78% had AGP > 1 g/L. At the final study visit (n=95; x̄ = 17.3 wk postpartum), these values dropped to 26% and 29%. There were positive correlations between CRP and AGP at the baseline (r=0.66, P<0.0001) and final (r=0.57, P<0.0001) time points. Neither CRP nor AGP was significantly correlated with ferritin or hepcidin at either baseline or final. CRP and AGP were negatively correlated with TfSat at both baseline (r=−0.45, P<0.0001 and r=−0.32, P<0.001) and final (r=−0.43, P<0.0001 and r=−0.34, P<0.001). Hb was negatively correlated with CRP and AGP at baseline (r=−0.32, P<0.001 and r=−0.20, P=0.03), but not at the final time point. In postpartum women, ferritin and hepcidin were not influenced by inflammation, while TfSat decreased with increasing inflammation. Hb was inversely related to inflammation at 2 wk postpartum, but not at 17 wk.Grant Funding Source : Center for Health and Nutrition Research at UC Davis
Weighting the Factors Associated with Obesity in Children: an International Perspective Toward a Unified Model
Authors: Gregori Dario , Baldi Ileana , Ghidina Marco 
Published: June 2021

Beside genetic predisposition, several factors have been proposed to promote overweight and eventually obesity in children, from the socio‐ and built‐ environment down to behavioural attitudes. How this model is shared by different cultural settings is unclear and less investigated.Using a unified protocol for data collection, a cross‐sectional study has been performed on 960 children in India, Italy, Germany, France, UK, Argentina, Mexico and Brazil. Children CDC z‐scores for Body Mass Index have been evaluated in association with several known factors influencing overweight and obesity (maternal and neonatal aspects, socio‐economic familiar status, BMI of parents, physical activity, nutrition habits, screening activities). Based on a random‐effect mixed effect model and the Kullback‐Leibler Entropy Measure, the capability to explain variability in BMI of such factors has been computed. Percentages of explained variation are given in the table.Capability of proposed factors to capture variability in BMI is significantly higher in UK (p=0.03) than in other countries, being significantly lower in an emerging country like India (p=0.042): more intense research should be specifically targeted to capture risk factors specific for the cultural setting in addition to the general ones.Bouchard, 2007.
Effects of vitamin A status on the responses of the hepatic genes’ expression to insulin and retinoic acid in primary hepatocytes from Zucker lean and fatty rats
Authors: Chen Wei , Chen Guoxun 
Published: June 2021

Insulin‐mediated regulation of hepatic gene expression plays a key role in glucose and lipid homeostasis. This study was aimed to examine the hepatic gene expression in response to insulin and retinoic acid (RA) treatments in primary hepatocytes from Zucker rats of different vitamin A (VA) status. Primary hepatocytes were isolated from Zucker lean (ZL) or fatty (ZF) rats fed either vitamin A sufficient (VAS) or deficient diet (VAD) for 8 weeks after weaning. The mRNA levels of Gck, Pck1, Srebp‐1c and Pklr after insulin and RA stimulation for 6 hours were determined using real‐time PCR. In hepatocytes of ZL rats on either diet, insulin synergized with RA to induce the expression of Gck and Srebp‐1c. This was impaired in hepatocytes of ZF rats on VAS, but partially recovered in those on VAD diet. In lean hepatocytes, the Pck1 expression was suppressed by insulin and induced by RA respectively. The insulin‐suppressed Pck1 expression was impaired in hepatocytes from ZF rats fed VAS diet and partially restored in that fed VAD diet. The RA‐induced Pck1 expression was normal in hepatocytes from ZF rats fed VAS, and was enhanced in that fed VAD. The Pklr expression was similar between ZL and ZF and not affected by VA status. We conclude that VA status modulate the insulin‐ and RA‐regulated hepatic gene expression in hepatocytes of ZF rats. It suggests that micronutrients contribute to the hepatic insulin response.Grant Funding Source: AHA
Genistein‐mediated inhibition of mammary stromal adipocyte differentiation limits expansion of mammary stem/progenitor cells by paracrine signaling
Authors: Montales Maria Theresa E. , Scanlon Samantha , Nakatani Hajime , Matsuda Tsukasa , Simmen Rosalia C.M. 
Published: June 2021

Mammary adiposity may contribute to breast cancer development and progression by releasing cytokines and other inflammatory mediators that promote mammary epithelial proliferation. We evaluated the effects of soy isoflavone genistein (GEN) on the adipogenic differentiation of a SV40‐immortalized mouse mammary stromal fibroblast like cells (MSF) treated with differentiating agents insulin, hydrocortisone and troglitazone (DM). MSF cultured in DM with and without extracellular matrix for 14 days showed reduced differentiation (2–3 fold) into mature adipocytes with 40nM but not 2uM GEN, as evaluated by Oil Red O staining. Addition of sera from GEN‐fed adult mice to MSF similarly reduced adipogenic differentiation (4–5 fold), relative to sera from casein‐fed mice. Lipid accumulation was decreased by GEN (40nM>2uM). Expression levels of lipogenic enzyme genes fatty acid synthase and PPAR‐γ were down‐regulated by 40nM GEN. Estrogen receptor (ER)‐β, an inhibitor of PPAR‐γ transcriptional activity, but not ER‐α transcript levels were increased by 40 nM GEN. Conditioned media from GEN‐treated MSF reduced anchorage‐independent mammosphere formation of human breast cancer cells MCF‐7. Thus, dietary factor control of mammary adiposity, possibly mediated by ER‐β, may limit mammary stem/progenitor cell expansion and protect against breast cancer.Grant Funding Source: USDA‐CRIS 6251‐5100002‐06S; CUMG/ACHRI
Polyphenol‐rich Aronia melanocarpa (chokeberry) extract regulates expression of cholesterol and lipid metabolism genes in Caco‐2 cells
Authors: Kim Bohkyung , Park Youngki , Taheri Rod , Kimball Kerilyn , Roto Anna , Lee Jiyoung , Bolling Bradley 
Published: June 2021

Chokeberry, Aoronia melanocarpa, is a rich source of polyphenols. We investigated the effect of an anthocyanin‐rich chokeberry extract (CBE) on the expression of genes involved in intestinal lipid metabolism in Caco‐2 cells, a human intestinal cell line. CBE had a Total Phenols value of 745 mg gallic acid equivalents/g and contained 12% anthocyanins. Cells were incubated with 50 or 100 μg/mL of CBE for 24 h and gene expression was measured by quantitative realtime PCR. ATP binding cassette transporter (ABC) A1, scavenger receptor class B, type 1, Niemann‐Pick C1 Like 1, and HMG‐CoA reductase mRNA abundance was significantly reduced by CBE. In contrast, CBE induced LDL receptor (LDLR) and ABCG8 to levels 2.5‐ and 1.5‐fold of controls. Western blot analysis confirmed increased LDLR protein level. Expression of genes involved in lipid metabolism and chylomicron assembly, including sterol regulatory element binding protein 1c, fatty acid synthase, and acyl‐CoA oxidase and microsomal triglyceride transfer protein, was significantly decreased by CBE in a dose‐dependent manner. Our data suggest that CBE may play an important role in the flux of cholesterol as well as lipid metabolism in the intestine. Supported by College of Agriculture and Natural Resources and Research Foundation at the University of Connecticut.Grant Funding Source : College of Agriculture and Natural Resources and Research Foundation at the University of Connecticut.
Role of General Control Nonderepressible 2 (GCN2) kinase in mediating responses to dietary methionine restriction
Authors: Plaisance Eric P , Van Nancy , Orgeron Manda , McDaniel Alexandra N , Behrens Phillip H , Gettys Thomas W , Anthony Tracy G 
Published: June 2021

Restriction of dietary methionine from normal levels (0.86%) to 0.17% produces a coordinated series of biochemical and physiological responses that improve biomarkers of metabolic health, limit fat accretion, and enhance insulin sensitivity. GCN2 kinase serves as a sensor to detect reductions in essential amino acids and initiates integrated behavioral and transcriptional responses that mediate metabolic adaptation. The role of GCN2 in mediating the responses to dietary methionine restriction (MR) was assessed using GCN2−/− mice. Dietary MR for 8 wks produced a comparable reduction in hepatic triglyceride and increase in food consumption in wild type (WT) and GCN2−/− mice, while the normal diet‐induced increase in plasma adiponectin was actually enhanced in GCN2 nulls. The transcriptional responses produced by dietary MR in brown adipose tissue did not differ between WT and GCN2 null mice. In contrast, the diet‐induced increase in energy expenditure and reductions in fasting insulin and hepatic SCD‐1 expression observed in WT mice were partially compromised in GCN2 nulls, and the normal reductions in adiposity, plasma leptin and glucose were absent in GCN2−/− mice. The present findings suggest that GCN2 is an important component of the nutrient sensing mechanism(s) linking restriction of dietary methionine to the metabolic adaptations produced by the diet. Work supported by NIH: 2 P20 RR021945 (TWG), 2 U24 DK076169 (TWG), 1 F32 DK088513 (EPP), 1 RO1 HD070487 (TGA).Grant Funding Source: NIH
Leucine Pulse Increases Skeletal Muscle Protein Synthesis during Continuous Feeding in Neonatal Pigs
Authors: Boutry Claire , Suryawan Agus , El-Kadi Samer W , Wheatley Scott M , Orellana Renan A , Nguyen Hanh V , Davis Teresa A 
Published: June 2021

Continuous orogastric tube feeding is used for infants unable to maintain an oral diet. Orogastric bolus feeding has a greater stimulatory effect on muscle protein synthesis than continuous feeding in neonatal pigs. Leucine administration stimulates protein synthesis, but its effects during continuous feeding have not been investigated. Twenty piglets (8‐d‐old) received formula for 24h continuously (CON) or by bolus (BOL), i.e., every 4h for 15min. For the CON+LEU group, leucine was administered parenterally (800μmol•kg−1•h−1) every 4h for 1h. The leucine pulse increased circulating leucine (P<0.0005), but had no effect on isoleucine and valine concentrations. Circulating insulin, glucose, and most other essential amino acids increased 15min after the BOL meal (P<0.05) and returned to baseline by 2h, but were unchanged in CON and CON+LEU groups. Protein synthesis rates in longissimus dorsi, gastrocnemius and soleus muscles were greater in the CON+LEU and BOL than in the CON group (P<0.005). In the BOL and CON+LEU groups, there was an increase in the phosphorylation of ribosomal protein S6 kinase 1 and the formation of active eIF4E.eIF4G complex in skeletal muscle (P<0.05). In conclusion, administration of a leucine pulse during continuous orogastric feeding increases skeletal muscle protein synthesis in neonatal pigs by stimulating translation initiation (NIH AR444474 and USDA/ARS 6250‐51000‐055).Grant Funding Source: NIH‐USDA/ARS
Pre‐ and Post‐weaning diets with low omega‐6 to omega‐3 fatty acid ratio reduced plasma lipid levels and increased cholesterol efflux capacity in the offspring of C57BL/6 mice
Authors: Balogun Kayode Adeniyi , Randunu Raniru Sergaevna , Cheema Sukhinder Kaur 
Published: June 2021

We investigated whether maternal and post‐weaning dietary ratios of omega (n)‐6 to n‐3 PUFA alter lipid metabolism of the offspring and whether the effects are gender specific. Female C57BL/6 mice were fed semi‐purified diets (20% w/w fat) containing n‐6 to n‐3 PUFA ratios of 5:1, 15:1 or 30:1 before mating, during pregnancy, and until weaning. Offspring were continued on their mothers’ diets for 4 months. Plasma lipid profile of the offspring was measured at weaning and at 4 months. HDL cholesterol efflux capacity of plasma was assayed using J774 cells. Male offspring from 5:1 group had a relatively lower plasma cholesterol at weaning and at 4 months (p<0.05). At weaning, the male offspring showed no difference in plasma triglyceride (TAG) and nonesterified fatty acids (NEFA) however there was a relative reduction at 4 months in the 5:1 group (p<0.001). Females in the 5:1 group had a relatively lower TAG and NEFA at weaning and at 4 months (p<0.05). The 15:1 females had lower LDL‐cholesterol at weaning and at 4 months; 5:1 males had lower levels at weaning with no differences at 4 months. HDL‐cholesterol was the same in all the groups; however plasma from the 5:1 males showed higher cholesterol efflux compared to 30:1 (p < 0.05). Our data suggest that maternal diets low in n‐6 to n‐3 PUFA ratio reduce plasma lipid levels, the effect is enhanced if the post‐weaning diet is the same and there are gender differences. Supported by NSERCGrant Funding Source: NSERC
The Experimental Therapy of Brain Injury by Tissue Engineering with Hyaluronic Acid Based Scaffold
Authors: Qunyuan Xu , Ying Wang , Shaoping Hou , Weiming Tian , Fuzhai Cui 
Published: June 2021

Stroke causes death and severe disability highly and often result in cavity formation in the brain. The complexity of the CNS makes efforts to repair injuries very difficult. Tissue engineering in combination with stem cell transplantation has the potential to fill such a cavity and replace lost neurons. In our study, a three dimensional hyaluronic acid (HA) based hydrogel was created as a biodegradable tissue engineering scaffold to mimic the structure and components of the extracellular matrix (ECM) in the brain. The molecules of poly‐L‐lysine (PLL) were immobilized on the backbone of the hydrogel for improving cell adherence and compatibility with brain tissue. In addition, a pH sensitivity antibody releasing system was developed by covalently attaching the antibody of Nogo receptor (Ab‐NgR) to the hyaluronic acid (HA) hydrogel, delivering the antibody to the injured brain, which can bind to multiple inhibitory myelin proteins, such as Nogo‐66, and promote neural regeneration. The modified hydrogel would be suitable for the acidosis in the brain tissue after injury. The antibody delivery system or the modified hydrogel was shown to have strong action to induce the growth of axons from the dorsal root ganglia in vitro, in addition to helping the cell adherence and survival. After implanting to the adult rat model of ischemia with occlusion of the middle cerebral artery, this antibody delivery system showed to have promotion function with regard to regeneration of neural cells in the host brain and improvement of behavior in those ischemic models. After implantation of this polymer hydrogel into the injured area of the brain of rat models, it was clearly shown that the hydrogel had good compatibility with the brain tissue and inhibitory action for genesis of glial scar. Also, the hydrogel could correctly bridge the tissue defects and form a permissive interface with the host tissue to favour axonal ingrowth and angiogenesis. The HA hydrogel scaffolds modified by ab‐NgR and PLL are therefore appealing for cell delivery and tissue development in the brain following stroke.The work was supported by the National Natural Science Foundation of China (Grant Nos. 30700210, 30670656, 30570578), the National Basic Research Program of China (Grant No. 2007CB947704), and the Beijing Committee of Science and Technology (No. Z0005187040311).
Effect of breakfast cereals with varying doses of oat fiber on appetite and satiety
Authors: Rebello Candida Joan , Johnson William D , O'Shea Marianne , Kurilich Anne , Greenway Frank L 
Published: June 2021

ObjectiveTo compare the satiety impact of Quaker Oatmeal and Quaker Oatmeal Squares with Honey Nut Cheerios.Methods96 healthy individuals, ≥18 years were enrolled in a randomized controlled crossover trial. Half the participants were given Quaker Oatmeal (QO) {6.7g fiber or Honey Nut Cheerios (HN) {4.5g fiber)}, and half received Quaker Oatmeal Squares (OS) {6g fiber} or HN. All breakfasts contained 355kcals (250kcals cereal and 105kcals milk). Visual analogue scales of hunger and satiety were completed at baseline, 30, 60, 120, 180 and 240 minutes. Subjects repeated the breakfast test at least a week later. Responses were analyzed as area under the curve (AUC) and significant differences from baseline.ResultsThe AUC for fullness (p=0.005) and stomach fullness (p=0.0073) was greater with QO than HN. Hunger (p=0.0009), desire to eat (p=0.0002), and prospective intake (p=0.0012) decreased with QO as compared with HN. In a comparison between OS and HN greater fullness (p=0.0133) and stomach fullness (p=0.0245) was observed with OS at 240 minutes.ConclusionsQO suppressed appetite and increased satiety when compared with HN. OS provided greater fullness than HN, at the final time point. The content of oat fiber and the vehicle of delivery are important components affecting the satiety process.Study was funded by PepsiCo