bluuebunny/crossref_metadata_2025_split huggingface dataset:
Body composition metabolic status and definitions of overweight in Guatemalan Children
Authors: Redondo Olga , Villamor Eduardo , Valdés Javiera , Caballero Benjamín , Ramírez Manuel , Franco Manuel 
Published: June 2021

ObjectiveTo examine correlations of body mass index (BMI) or % total body fat (%TF) with metabolic biomarkers of chronic disease risk and to explore differences in prevalence of overweight according to BMI‐based definitions by WHO, CDC, and IOTF criteria.MethodsWe measured anthropometry, %TF (DXA), lipid profile, and insulin resistance in a convenience sample of 95 Guatemalan Ladino children 7–12 y‐old. We compared Spearman correlation coefficients of BMI vs. %TF with metabolic biomarkers. Next, we compared the prevalence of overweight as estimated using WHO, CDC, or IOTF criteria.ResultsCorrelations of %TF with HOMA‐IR (r=0.64), total cholesterol‐to‐HDL ratio (r=0.60), and triglycerides (r=0.55) were higher than those of BMI (r=0.60, 0.54, and 0.50, respectively). The correlation of %TF with BMI was 0.84. Prevalence of overweight according to WHO, CDC, and IOTF criteria was 44%, 38% and 40%, respectively (p < 0.001).ConclusionsPrevalence of overweight varies according to BMI‐based criteria. Since %TF is more strongly related to metabolic parameters than BMI, a formal evaluation of BMI‐based definitions of childhood overweight is warranted in this population.Source of Research Support: Global Health Initiative, Collaborating Centers of Excellence, NHLBI
AIN‐76 and AIN‐93 diets do not provide adequate iron for perinatal development
Authors: Prohaska Joseph , Broderius Margaret 
Published: June 2021

Iron supplementation during pregnancy and neonatal development remains controversial. Rodent models intending to evaluate trace element deficiencies and interactions should rely on an optimal control diet. When the AIN‐93 formulation was developed it dealt primarily with changes in carbohydrate, lipid, and calcium levels; iron recommendations remained the same as its predecessor diet, AIN‐76A, at 35 mg/kg. Increasing the dietary iron to 75 mg/kg (a level recommended by NRC guidelines) to pregnant Sprague Dawley rats, or postweanling males demonstrated that iron status is improved in dams, pups, as well as rapidly growing males. This is based on measurements of hepatic iron, plasma iron, and hemoglobin concentration. Phenotype of copper‐deficient (CuD) dams and pups fed modified AIN‐76A diets were different than CuD rats fed modified AIN‐93G diets with the higher iron level compared to copper‐adequate (CuA) controls. Hepatic iron was no longer augmented in the CuD groups. Additionally plasma and brain iron differences were attenuated. For example, brain iron deficiency evaluated by augmented transferrin receptor expression in CuD rats was not observed in the CuD pups reared by CuD dams fed the modified AIN‐93G diets with extra iron. It may be prudent to reevaluate the composition of standard “control” diets used in rodent models.Supported by International Copper Association.
The expression of Apoc3 mRNA is regulated by HNF4α and COUP‐TFII levels, but not retinoid treatments, in rat primary hepatocytes and hepatoma cells
Authors: Howell Meredith , Li Rui , Zhang Rui , Chen Guoxun 
Published: June 2021

Retinoic acid (RA) treatment induces hyperlipidemia in humans and animals. This has been attributed to the induction of Apolipoprotein CIII (gene, Apoc3), which inhibits lipoprotein lipase activity. We have shown that vitamin A status and retinoid treatment regulate hepatic lipogenic gene expression, suggesting that the induction of lipogenic genes, but not Apoc3, may contribute to hyperlipidemia. To test this, we analyzed the expression levels of Apoc3 mRNA in response to retinoid treatments or adenovirus‐mediated over‐expression of nuclear receptors mediating RA responses in primary rat hepatocytes and HL1C rat hepatoma cells using real‐time PCR. We report that retinoids did not induce Apoc3 mRNA expression in these cells. The over‐expression of HNF4α or COUP‐TFII significantly induced or inhibited the Apoc3 mRNA level, respectively, whereas RXRα or RARα over‐expression had no effect. We conclude that RA treatment could not directly induce Apoc3 mRNA levels in rat hepatocytes. Instead, the hepatic expression of Apoc3 mRNA is regulated by the expression levels of HNF4α and COUP‐TFII. Therefore, RA‐induced hyperlipidemia may not be attributed to the direct induction of Apoc3 mRNA level in hepatocytes.Sponsor: Dr. Guoxun Chen, 1215 W. Cumberland Ave. 229 Jessie Harris Building, Knoxville, TN, 37996
Oral Administration of Retinoic Acid Lowers Brain Serotonin Concentration in Rats
Authors: Smazal Anne Lorraine , Lee Schalinske Kevin 
Published: June 2021

Major depressive disorder has been associated with lowered functionality of serotonin, dopamine, and norepinephrine in the brain. Oral retinoid therapy has been reported to induce sudden and severe depressive symptoms in adolescents and adults. Retinoid compounds have been shown to negatively impact neurotransmitter synthesis and transport in vitro, whereas animal models of retinoid therapy and brain health have traditionally utilized intraperitoneal administration of retinoic compounds and focused on depressive behaviors. To our knowledge, no previous in vivo studies have used oral administration to demonstrate the impact of retinoid compounds on neurotransmitters in the brain. In this study, male Sprague‐Dawley rats received oral administration of either all‐trans‐retinoic acid or vehicle daily. After 9 days, rats were sacrificed and brain tissue was collected for analysis. Rats receiving all‐trans‐retinoic acid had a significant (48%) decrease in brain serotonin concentrations compared to control. Neither norepinephrine nor dopamine levels were impacted by oral dosage of all‐trans‐retinoic acid. To our knowledge, this is the first demonstration of lowered brain serotonin concentrations resulting from oral administration of retinoic acid and represents a potential therapeutic strategy to prevent major depressive disorder owing to retinoid usage. Support: College of Human Sciences, ISU.Grant Funding Source: College of Human Sciences, ISU
The synergistic effect of 1′‐acetoxychavicol acetate and sodium butyrate on cell death of human hepatocellular carcinoma cells
Authors: Kato Rie , Matsui‐Yuasa Isao , Azuma Hideki , Kojima‐Yuasa Akiko 
Published: June 2021

Introduction1′‐Acetoxychavicol acetate (ACA), obtained from alpinia galangal, exhibits chemopreventive effects on chemically induced tumor formation. Sodium butyrate (NaB), one of the major short chain fatty acids, is known to inhibit cancer cell proliferation in tumor cells. The interaction between ACA and NaB is still unclear. Here, we examined the effect of ACA and NaB on cell death of HepG2 cells.MethodsThe cell number was measured by neutral red assay. Intercellular reactive oxygen species (ROS) was measured by DCFH‐DA assay.ResultsThe cell number of HepG2 cells was synergistically decreased with the combined treatment of ACA and NaB, resulting from apoptotic cell death. In ACA and NaB simultaneously treated cells, intercellular ROS also increased significantly. However, the cell number in ACA and NaB treated cells was improved with the treatment of catalase. The increase in intercellular ROS was prevented with DPI, the inhibitor of NADPH oxidase. These events weren't observed in normal cells.ConclusionACA and NaB synergistically induce apoptotic cell death via the activation of NADPH oxidase and the increase in the intercellular ROS, and the effect is specific to carcinoma cells.
Genistein via JAK2 increased the phosphorylation of AMPK independently leptin receptor in C2C12 cells
Authors: Palacios‐Gonzalez Berenice , Flores‐Galicia Isabel , Torres Nimbe , Tovar Armando R 
Published: June 2021

Consumption of soy protein in Zucker fa/fa rats increase the expression of genes involved in fatty acid oxidation as well as the phosphorylation of AMPK and ACC in skeletal muscle. Previous studies have shown that incubation of C2C12 with genistein, induces the expression of genes involved in fatty acid oxidation and phosphorylation of AMPK. The aim of the study was to determine whether genistein can increase the gene expression and phosphorylation of AMPK in cells silenced for the leptin receptor (ObR). Regardless of the leptin receptor, genistein increased the phosphorylation of AMPK and the expression of CPT1, UCP3, PCG1α, PPARδ. The AMPK phosphorylation induced by genistein was partially repressed when cells were incubated with the inhibitor of the kinase activity of JAK2. Interestingly in Zucker fa/fa rats which have a mutation of the leptin receptor and that consumed soy protein showed also an increased phosphorylation of JAK2 in skeletal muscle. These results indicate that genistein stimulates JAK2 phosphorylation, which in turn stimulates AMPK phosphorylation and expression of genes involved in fatty acid oxidation.Grant Funding Source: CONACYT
Variations in Milk Carotenoids from Jersey Cows fed Pasture versus Total Mixed Ration
Authors: Beliveau Amy Rose , Smith Jillian M , Wenzel Adam James , Curran‐Celentano Joanne 
Published: June 2021

Interest in organic dairy production is rising. According to the USDA Certified Organic standards, producers are required to feed their cows on pasture for a minimum of 120 days. Research indicates that factors such as diet have the potential to impact milk composition. The objective of this experiment was to determine the changes in concentrations of milk carotenoids over a pasture season from cows under two different feeding systems. Individual milk samples were collected biweekly from 9 cows fed on pasture at an organic dairy and from 9 cows fed total mixed ration (TMR) at a conventional dairy. Components were extracted from the milk and separated via High Performance Liquid Chromatography. Data were analyzed using SPSS® version 19.0. Results showed that total carotenes, total xanthophylls, lutein, β‐cryptoxanthin, α‐ and β‐carotene and 13cis β‐carotene were significantly higher in milk from cows fed on pasture. These components also varied significantly over the season. In milk from cows fed TMR, only total xanthophylls and lutein changed significantly over time. Results indicate that pasture feeding affects carotenoid concentration in milk, suggesting that both diet and season can influence milk composition. Potential variations should be reflected in the National Nutrient Database.Grant Funding Source: NH Agriculture Experiment Station
Ontogenic expression of retinoid homeostatic genes in principal vitamin A storage organs
Authors: Owusu Sarah A , Ross Catharine 
Published: June 2021

Vitamin A (VA) is essential for proper lung development in early life. The combination of VA and 10% all‐trans retinoic acid (VARA) works synergistically to increase total retinyl ester storage and retinol uptake in neonatal rat lung. To confirm the necessity of VA for lung maturation and septation, VA metabolism during neonatal development must be understood. In the present study, we determined the effects of VA nutritional status and VARA supplementation during ontogeny on expression of retinoid homeostatic genes. Rat dams and their post‐weaning offspring were fed a VA‐marginal or supplemented diet, while pups received an oral dose of oil (placebo) or VARA on post‐natal day (P) P0/1, P4, P7, and P10. Tissues were collected 6 hr later. Gene expression was determined by qRT‐PCR in liver, lung, and kidney. VA‐supplemented diet and VARA treatment upregulated LRAT, Cyp26A1/B1, and STRA6, retinoid homeostatic genes important for VA storage, RA terminal oxidation, and retinol uptake, respectively. However, VARA did not regulate VA trafficking genes (RBP in liver and megalin in kidney). Cyp26a1 expression in liver decreased throughout development in rats fed marginal diet, but increased on the supplemented diet. No apparent difference was observed in RALDH1/2/3 expression with VARA treatment. Our results advance the understanding of neonatal VA metabolism and catabolism in principal VA storage organs.Grant Funding Source: NIH HD006892
1,25‐dihydroxyvitamin D regulation of pyruvate carboxylase and glucose addiction in MCF10A‐ras human breast epithelial cells
Authors: Zheng Wei , Teegarden Dorothy 
Published: June 2021

The mechanism and biological consequence of 1,25‐dihydroxyvitamin D (1,25D) regulation of glucose metabolism in progression to cancer (Warburg effect) was investigated. Our previous studies show that 1,25D shifts glucose metabolism towards reduced glycolysis and lactate production and reduced flux through the TCA cycle in ras‐oncogene transfected MCF10A (ras) cells, a model of early breast cancer progression. In the current studies, 1,25D reduced the mRNA (by 55%) and protein (by 35%) expression of pyruvate carboxylase (PC), a key enzyme for the anaplerosis of the TCA cycle, suggesting 1,25D may regulate glucose metabolism via PC. 1,25D inhibited growth, reducing ras cell number by 44% in media containing 5 mM glucose. Glucose restriction to 1 mM further reduced ras cell number by 39% compared to 5 mM glucose, indicating the ras cell dependence on glucose (addiction). However, 1,25D prevented the reduction in cell number at 1 mM glucose, suggesting 1,25D may reduce ras cell glucose addiction. Consistent with these results, flow cytometry analysis showed 1,25D treatment prevented the increase in G1 cell cycle arrest at 1 mM glucose noted in ras cells, further supporting that 1,25D reduces glucose addiction. These results suggest 1,25D regulation of glucose metabolism during early cancer progression has important biological consequences which may be mediated via PC.Grant Funding Source: NIH R25CA128770
α‐linolenic acid reduces growth in four breast cancer cell lines with varying receptor expression in high and low estrogen environments
Authors: Wiggins Ashleigh K.A. , Kharotia Shikhil , Mason Julie K. , Thompson Lilian U. 
Published: June 2021

Breast cancer differs in cell receptors which then determines effective treatments. Alpha‐linolenic acid (ALA)‐rich flaxseed oil reduced estrogen receptor (ER)+ cell growth at low and high estrogen (E2) but its effect is unclear in cells with varying ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Our objective was to determine in vitro the ALA and E2 effect on growth and membrane lipids of four breast cancer cell lines with varying ER, PR and HER2 status. Cells were treated with 0 – 200uM ALA ± 1nM E2 and tested for growth by trypan blue exclusion method and fatty acids by gas chromatography. Receptor status confirmed by Western Blot: MCF7‐ER+PR+low HER2; BT474‐ER+PR+HER2+, MDA MB 231‐ER‐PR‐low HER2; MDA MB 468‐ER‐PR‐HER2‐. Compared to –E2 control, MCF7 had a significant E2, ALA and interaction effect on growth; other cell lines only had an ALA effect. 50uM and 75uM ALA significantly decreased growth by 14, 48, 31 and 63% and 38, 77, 80 and 78% in MCF7, BT 474, MDA MB231 and MDA MB468, respectively. E2 significantly increased (91.8%) MCF7 growth. Cells showed significant increases (9–25 fold) in % ALA which related to growth. Thus ALA reduces breast cancer cell growth ± E2 at doses as low as 50uM, likely through alteration of lipid composition. It is effective regardless of ER, PR and HER2 status which may be of importance in difficult to treat cancers such as triple negative. Funded by NSERC.Grant Funding Source: NSERC
Conjugated Linoleic Acid Reduces Adiposity and Increases Markers of Browning and Inflammation in White Adipose Tissue of Mice
Authors: Shen Wan , Chuang Chia‐Chi , Martinez Kristina , Reid Tanya , Brown J. Mark , Xi Lin , Hixson Lindsay , Starnes Joe , McIntosh Michael 
Published: June 2021

The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat. Mice were fed three combinations of fatty acids at three doses (0.06%, 0.2%, and 0.6%, w/w) for 7 wk. The types of fatty acids were linoleic acid (control), an equal mixture of 10,12 CLA plus linoleic acid, or an equal mixture of 10,12 plus 9,11 CLA. Mice receiving the 0.2% and 0.6% dose of 10,12 CLA or the CLA mixture had decreased white adipose tissue (WAT) and brown adipose tissue (BAT) mass and increased incorporation of CLA isomers in epididymal WAT, liver, and muscle compared to controls. Food intake, glucose tolerance, and liver triglycerides were not affected by 0.2% CLA. Notably, in mice receiving 0.2% of both CLA treatments, the mRNA levels of genes associated with browning including uncoupling protein1 (UCP1), UCP1 protein levels, cytochrome c oxidase (CCO) activity, and the appearance of multilocular lipid droplets were most robustly increased in epididymal WAT compared to controls. CLA‐induced browning was accompanied by increases in mRNA levels of markers of low‐grade inflammation. Muscle CCO activity and BAT UCP1 protein levels were not affected by either CLA treatment. Collectively, these data suggest a linkage between decreased adiposity, browning in WAT, and low‐grade inflammation due to consumption of 10,12 CLA. Supported by NIH NIDDK/ODS 5R01‐DK063070‐09.Grant Funding Source: NIH NIDDK/ODS 5R01‐DK063070‐09
Effects of Cfh genotype and dietary glycemic index on age‐related macular degeneration in mice
Authors: Rowan Sheldon , Weikel Karen , Chang Min‐Lee , Nagel Barbara , Thinschmidt Jeffrey , Grant Maria , Fliesler Steven , Taylor Allen 
Published: June 2021

Age‐related macular degeneration (AMD) is a leading cause of visual impairment in aging Americans. Both genetics and diet contribute to the risk for developing AMD. For example, common variants in the Complement Factor H (Cfh) gene confer major susceptibility to‐ or protection from‐ developing AMD. Similarly, consuming diets with higher glycemic index (GI) foods is associated with increased risk of AMD. Understanding genetic/diet interactions will reveal individualized nutritional approaches to modulate the risk for AMD.The objective of this study was to explore, in the Cfh null mouse, whether modulation of the dietary GI would alter the incidence of AMD. Wildtype or Cfh null 12‐week mice were fed high or low GI diets for 9‐months and were then evaluated for abnormalities in the retina or retinal‐pigmented epithelium (RPE). Wildtype mice showed no abnormalities on either diet. Surprisingly, Cfh null mice showed distinct abnormalities in the RPE when fed a low GI diet. Electron microscopy revealed the presence of vacuoles, disruption of the basal infoldings, and increased numbers of basal laminar deposits – all hallmarks of early AMD.Conclusiona Cfh/GI interaction led to development of AMD‐like features, paradoxically involving a low GI diet. This work was supported by intramural funds from the HNRCA and NEI RO1 21212.
Natural killer cell cytotoxicity is reduced in aged female mice fed a high folic acid diet
Authors: Sawaengsri Hathairat , Wang Junpeng , Desautels Nellie , Steluti Josiane , Histed Alex , Smith Donald , Wu Dayong , Meydani Simin N , Selhub Jacob , Paul Ligi 
Published: June 2021

Unmetabolized folic acid in plasma, which is indicative of high folic acid intake, is associated with reduced natural killer (NK) cell‐mediated cytotoxicity in elderly (>;60y) women. In this study, we determined if high folic acid intake affects NK cytotoxicity in aged female mice. Aged (16 months) female C57BL/6 mice were fed a control diet (1× RDA folic acid; 2mg/kg) or a high folic acid (HF) diet (20× RDA folic acid;HF 40mg/kg) for 3 months. Folate concentration and splenic NK activity were evaluated. Mice on HF diet had significantly higher unmetabolized folic acid (29.0 pmol/mL versus 0.6 pmol/mL) and formylated folate (19.0 pmol/mL versus 3.1 pmol/mL) (P<0.01). Spleen NK activity was determined as percent dead target cells at multiple effector: target (E:T) cell ratios, where the dead (not lysed) target cells were identified by flow cytometry. In HF mice, percent dead target cells were lower by 14% and 23% for (E:T) cell ratio 25:1 (P=0.03) and 12.5:1 respectively (P=0.036) than the control mice. Percent NK cell was lower by 21% in the spleen of the HF mice when compared to the control mice (P<0.01), but not percent of NKT cells, suggesting that the decrease in cytotoxicity of HF mice might be due to the reduction in the number of spleen NK cells. Further studies are required to understand the mechanism that underlies the HF‐induced reduction in NK cell number and cytotoxicity.Grant Funding Source: HNRCA Pilot grant
Modulating Myeloperoxidase‐Induced Endothelial Permeability by a Carbon Monoxide‐Releasing Molecule, CORM‐3
Authors: Patterson Eric K , Serizawa Fukashi , Capretta Alfredo , Fraser Douglas D , Potter Richard F , Cepinskas Gediminas 
Published: June 2021

Previous work has demonstrated that CORM‐derived carbon monoxide (CO) supresses inflammation. However, the mechanisms are not well understood. Neutrophil (PMN)‐derived myeloperoxidase (MPO) is known to play a significant role in the pathophysiology of numerous inflammatory disorders through: 1) direct peroxidation and 2) producing hypohalous acids, particularly hypochlorous acid. Thus, an overwhelming MPO‐dependent production of oxidants in the sub‐endothelial space after PMN degranulation, contributes to tissue damage and propagating inflammation.We hypothesized that CORM‐3‐derived CO interferes with MPO's catalytic activity, and thereby mitigates endothelial inflammatory damage.In vitro assays were used to study the inhibition of MPO's catalytic activity. Further, live cell in vitro assays were used to investigate endothelial damage through measuring reactive oxygen species (ROS) and cellular permeability.Our results indicate that CORM‐3 inhibits total MPO activity as well as MPO's peroxidation and halogenation cycles. Cellular assays determined that ROS production and cellular permeability are decreased when extracellular MPO is treated with CORM‐3. In all assays inactivated CORM‐3 (iCORM‐3) was significantly less effective than CORM‐3.We conclude that CO may mitigate inflammatory damage partly through inhibition of MPO activity. Support: HSFO‐393 and LHRI IRF‐025–09
Post‐translational protein modification in autoimmune epithelitis
Authors: Rodriguez‐Rodriguez Mayra , Pérez‐Pérez Maria Elena , Badillo‐Soto Adriana , Bollain y Goytia Juan José , Pacheco‐Tovar Deyanira , Avalos‐Díaz Esperanza , Herrera‐Esparza Rafael 
Published: June 2021

Sjögren's syndrome is an autoimmune epithelitis of salivary and lachrymal glands that results in Sicca syndrome. Citrulline is synthesised by the conversion of ornithine to arginine during urea formation, exists as free citrulline produced by NOS enzymes, and another form produced by post‐translational modification of proteins at arginine residues by peptidylarginine deiminases (PADs), which is important in autoimmunity. We investigate post‐translational reactions in salivary gland biopsies from 24 patients with primary Sjögren's syndrome and 24 controls using immunohistochemistry and a tag‐purified anti‐cyclic citrullinated protein CCP antibody to detect citrullinated peptides, PAD2 also was assessed. The present work demonstrated the weak presence of the PAD2 in some normal salivary ducts (10%), although PAD2 expression was increased considerably in Sjögren's patients. The presence of citrullinated proteins in the salivary tissues of Sjögren's patients strongly supports the in situ post‐translational modification of proteins in this setting. The mutual expression of CCP and PAD2 (70%) suggests that this post‐translational modification is enzyme‐dependent. In conclusion, patients with Sjögren's syndrome expressed the catalytic machinery to produce post‐translational reactions that may result in auto‐antigen triggering.Grant: P/PIFI 2011–32MSU0017H‐06–01