bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti‐Retroviral Effects of Modified Sodium Silicate (Alkahydroxy/Alka V6)
Authors: Townsend Deana , White Lauren , Chesnut Troy , Duesler Sandra , Cisneros Ignacio , Richardson C. Reed , Vattem Dhiraj
Published: June 2021

Alkahydroxy/Alka V6, a modified sodium silicate dietary supplement manufactured by Cisne Enterprises Inc. (Odessa, TX) was evaluated for its in vitro anti‐retroviral effects. Assays for inhibition of HIV‐II reverse transcriptase (RT), HIV‐II protease (PR) and glucohydrolase (GH) important for viral replication, coat assembly and virulence respectively, were performed using standard kits. Effects on nitric oxide (NO) dependent antiviral activities were measured in neutrophils using standard assays. Chemical structure determined by nuclear magnetic resonance (NMR) and infra‐red (IR) spectroscopy suggested that the product was a mixture of trimeric sodium silicate and sodium silicate pentahydrate. Results suggest that the product the product significantly decreased HIV‐RT activity in a dose dependent manner (ED50 = 16000 ppm). HIV‐PR activity decreased (ED50 = 20000 ppm) with increasing product concentration. The product also decreased the HIV‐II virulence by inhibiting the GH activity (ED50 = 28500 ppm) which decreased protein glucosylation and glucuronylation. Higher NO was detected in neutrophil medium suggesting an increase NO mediated antiviral activity. We conclude the product has anti‐retroviral activity based on in vitro results. In vivo investigations are imperative to determine its overall anti‐retroviral effectiveness. Funding source: Cisne Enterprises Inc.
The effect of sulfasalazine on homocysteine metabolism in vivo
Authors: Wu Yi‐Ting , Chiang En‐Pei Isabel
Published: June 2021

Sulfasalazine (SSZ) is a disease‐modifying antirheumatic drug (DMARD) commonly used in the treatment of rheumatoid arthritis that inhibits intestine folate absorption and multiple folate‐dependent enzymes. The objective of the present study was to systematically investigate the impacts of long‐term SSZ treatment on homocysteine metabolism in vivo. C57BL/6J mice received either sterile 0.5% cellulose i.p. (vehicle, control group) or SSZ (80 mg/kg/day) for 8 weeks. Folate, S‐adenosyl methionine (adoMet), S‐adenosylhomocysteine (adoHcy) and homocysteine were determined in blood and tissues. Whole blood adoMet levels were significantly elevated compared to subjects on other DMARDs (1807 ± 1346, vs. 330 ± 861, p < 0.001), suggesting that SSZ may increase adoMet synthesis or decrease adoMet utilization. Furthermore, whole blood adoMet levels significantly correlated with the weekly dosage of SSZ (r = 0.34, p = 0.002) in patients receiving SSZ (n = 63).

SSZ did not alter adoMet, adoHcy, methionine adenosyltransferase (MAT) activity and methylated cytidine content of DNA (dMC%) in mice liver or kidney. SSZ treatment increased whole blood adoMet level by induction of the methionine adenosyltransferase activity in erythrocytes in mice. In the present study we demonstrated the novel finding of a direct inducing effect of SSZ treatment on adoMet synthesis and adoMet synthase activity in blood.

Grant Funding Source: ASN
Iodine status of women from selected rural areas of Sidama Zone, Southern Ethiopia
Authors: G‐Egziabher Tafere , Stoecker Barbara J , Mulugeta Afework , Bogale Alemtsehay , Girma Meron , Abebe Yewelsew , Hambidge K Michael
Published: June 2021

Iodine status of a group of women from rural Ethiopia was evaluated. After ethical clearance from the zonal, regional and national levels, 202 nonpregnant volunteers gave informed consent to participate in this cross sectional study. Mean (SD) age was 30.8 (7.9) y. Mean height was 157.3 (6.0) cm and mid upper arm circumference (MUAC) was 24.8 (2.5) cm. Body mass index (BMI) was < 18.5 for 24.8% of the women. BMI was 18.5 to <25 for 73.3% and was ≥ 25 for only 2.0% of women. Thyroid gland enlargement was assessed using palpation and casual urine samples were collected to measure urinary iodine excretion (UIE). UIE was analyzed using the Sandel‐Kolthoff reaction. Median UIE was 37.2 ug/L. Participants with UIE <20 ug/L were 22.8% and were classified as severely iodine deficient; 46.5% had UIE between 20 to <50 ug/L or moderate iodine deficiency, and 27.2 % had UIE in the mild deficiency range of 50 to <100 ug/L. Only 3.5% of the women had UIE ≥ 100 μg/L. The total visible goiter rate was 1.5% and 14.4% of the women had palpable goiter making a total goiter rate of 15.9%. The findings of the present study revealed that current iodine status of the population is a significant public health problem. Hence, there is a need to supply iodized salt in order to achieve the goal of elimination of iodine deficiency disorders in the community. [Supported by NIH Grant R01HD053053 (NICHD & Fogarty International Center)]
Assessment of iron and zinc status of women and their children in Jordan and evaluation of sensitivity and specificity of transferrin receptors in identifying iron deficiency
Authors: Gharaibeh Muna , Stoecker Barbara J
Published: June 2021

Prevalence of iron and zinc deficiency among women and their preschool children was assessed in Jordan in July 2007. Hemoglobin and plasma ferritin, zinc, transferrin receptors and α‐1‐ acid glycoprotein (AGP) were determined in 93 mothers and their children. Measurements of hemoglobin, ferritin, and zinc showed 29% of mothers and 10% of children to be deficient by at least two parameters, and 24% of mothers and 3% of children were deficient by three parameters. Thirty‐eight women (41%) and 24 children (26%) were anemic. Mothers with ferritin <15 μg/L were 54%, and 16% of children had ferritin <12 μg/L; half of children were below 22 μg/L. Mothers body iron (mean ± SD) was estimated to be significantly lower (0.5 ± 4.9) mg/kg than their children (3.5 ± 3.8) mg/kg; 45% of mothers had an iron deficit of 4.0 mg/kg body weight while 18% of children had an iron deficit of 0.71 mg/kg body weight. More than 50% of mothers and 30% of children had AGP≥1.2 g/L. Plasma zinc was 67.2 ± 11.4 μg/dL in mothers and 64.6 ± 9.4 μg/dL in children. More than half of women (58%) and children (56%) were below iZiNCG cut‐offs for zinc deficiency. Zinc was correlated for mothers and children (r=0.33, p<.005). The performance of three parameters: TfR, TfR/ferritin, and TfR/Log10ferritin in detecting iron deficiency among mothers and children was evaluated using receiver operator characteristics (ROC) curves. TfR/ferritin and TfR/Log10ferritin appeared to have better diagnostic efficiency in detecting iron deficiency than the use of TfR alone. In summary, co‐existing micronutrient deficiencies were widespread among mothers and children in northern Jordan. (Supported by Oklahoma State Univ).
Developmental Aspects of Lycopene Action to Disaccharidases Kinetic Parameters of Chicken Jejunal Brush Border
Authors: Bugay Andriy A , Tsvilikhovskii Mykola I
Published: June 2021

Lycopene is known as carotenoid with antioxidant properties associated with gap‐junction formation, prevents apoptosis, atherosclerosis and cancer. This study was undertaken to determine lycopene action to nutrition processes, particularly to ontogenetic kinetic parameters of main disaccharidases of chicken jejunal brush border (BB). Lycopene consumption provide Vmax increasing of sucrase and maltase of chicken jejunal BB from 2nd to 4th week and less significant decreasing of Vmax to 6th week of age. Maximal values of sucrase and maltase Vmax during ontogenesis were stated in 2–3‐weks of chicken in control (127.3 and 12.7 nmol/mg protein per sec) and experimental (154.3 and 17.2 nmol/mg protein per sec) groups respectively. Minimal values of sucrase and maltase Vmax were stated in 6‐weeks of chicken in control (56.4 and 11.3 nmol/mg protein per sec) and experimental (60.1 and 13.2 nmol/mg protein per sec) groups, respectively. Also it is shown significant Km decreasing from 2nd to 6th week of chicken in control and experimental groups for maltase and sucrase, respectively. Maltase and sucrase Ki of control chicken decreased from 75 to 57 mM and from 94 to 59 mM respectively. Maltase and sucrase Ki of experimental chicken decreased from 88 to 57 mM and from 93 to 66 mM respectively. Based on the received data it is concluded that lycopene affects nutrition processes in ontogenetic fashion in chicken jejunal brush border (BB).
Does lycopene or tomato powder impact lipid metabolism in CMO‐I KO and CMO‐II KO mice?
Authors: Elsen Amy Christine , Ford Nikki A. , von Lintig Johannes , Erdman John W.
Published: June 2021

Adult mice lacking the β‐carotene central cleavage enzyme, carotenoid‐15,15′‐oxygenase (CMO‐I), have altered lipid metabolism resulting in fatty liver development [Hessel at JBC 16;282(46):33553‐61]. The objectives of this study were to examine whether diet had any additional effects on lipid metabolism in CMO‐I KO female mice compared with female carotenoid 9′10′‐monooxygenase II knock‐out (CMO‐II KO) and wild type (C57BL/6Jx129x1/SvJ) mice. We fed an AIN‐93G diets consisting of 100mg/kg diet lycopene, 10% tomato powder, or placebo beadlets to knock‐out and wild type mice for 30 days. We evaluated body weights and compared the organ weights as a percentage of total body weight for each genotype. Preliminary data shows that CMO‐I KO uteruses were less than half the size of wild type uteruses and 1.5 times smaller than CMO‐II KO uteruses. Additionally, the effects of lycopene and tomato powder, and/or genotype on hepatic lipids were analyzed. We measured the expression of adipogenic genes, PPAR‐γ, PPAR‐α and Acox1, in liver and adipose tissues. Results and implications of research will be discussed. (Funded in part by NIH grant PHS‐1‐RO1 CA125384.)

Grant Funding Source: NIH
Adjunctive effects of a dietary supplement comprising dried whole fruit, vegetable and berry juice concentrates on clinical outcomes of treatment of periodontitis
Authors: Chapple Iain L. C. , Milward Michael M. , Ling‐Mountford Nicola , Weston Paul , Dallal Gerard E. , Matthews John B.
Published: June 2021

Periodontitis is a prevalent chronic inflammatory disease, a major cause of tooth loss and associates with systemic morbidity and mortality. Biologically, it associates with reduced local and systemic antioxidant defences and elevated levels of oxidative stress secondary to a hyper‐inflammatory neutrophil host response to plaque bacteria. This randomised, placebo‐controlled, double‐blind trial, aimed to assess whether adjunctive benefit could be detected with Juice Plus+® supplementation during and after standard non‐surgical periodontal therapy. Primary outcomes were reduction in periodontal pocket depth (PPD) and gain in connective tissue attachment level (CAL) to teeth, 2‐months post‐therapy. Test interventions were fruit/vegetable (FV, n=16) and FV/berry (FVB, n=15) verses placebo (PL, n=17). Statistical analysis employed 2‐tailed ANCOVA (baseline PPD and CAL as covariates) and interim data on 48 never smokers are reported. Non‐surgical therapy produced significant improvements in PPD (FV = 0.86±0.4mm; FVB = 0.88±0.4mm; PL = 0.81±0.5mm) and for CAL (p<0.0001). Despite such large improvements, additional benefit was seen for PPD with FV (p<0.03) and FVB (p<0.04) supplementation verses PL, and a trend towards additional gains in CAL with FV (p=0.07). Thus, adjunctive Juice Plus+® may offer additional therapeutic benefit to standard non‐surgical periodontal therapy. Support NSA (TN, USA)
Poly‐γ‐glutamate Intake Increases Glutamate and GABA Concentrations of Serum and Brain
Authors: Kim Sun‐Hee , Lee Hye‐Sung , Kim Boram , Chang Moon‐Jeong
Published: June 2021

Poly‐γ‐glutamic acid (γ‐PGA) is a mucilaginous and biodegradable compound produced by Bacillus subtilis from fermented soybeans and is found in Korean traditional soy product, cheongkukjang. This study was carried out to evaluate the effects of γ‐PGA from food source on the neurotransmitter GABA and its metabolic precursor, glutamate concentrations in diet‐induced obese rats. Eight week old Sprague‐Dawley male rats (n=60) were used in this study. Rats were divided into two groups and induced obesity by providing either 10% control fat or 45% high fat diet for 5 weeks. And then, rats were blocked into 6 groups and fed 0.1% γ‐PGA diet for 4 weeks. After sacrifice of the rats, brain and serum GABA and glutamate concentrations were analyzed by High Performance Liquid Chromatography with fluorometric detector. The rats fed the high fat diet significantly increased their body weights. Glutamate and GABA concentrations in the serum and brain were significantly (p<0.05) increased by 0.1% γ‐PGA intake in the control fat diet groups while those were not in high fat groups. The results indicated that γ‐PGA intake increased GABA concentration in the serum and brain. However, the effects were not shown in the obese rats. 
Cassia cinnamon supplementation before an oral glucose tolerance test in overweight or obese young women
Authors: Gutierrez Jean Lorraine , Cooke Matthew , Lutz Rafer , Rodney Bowden , Kane Robert , Willoughby Darryn
Published: June 2021

Objective

The purpose of this study was to compare the effects Cassia cinnamon and cellulose placebo on oral glucose tolerance test (OGTT) blood glucose (BG) and serum insulin (SI) values and the Matsuda insulin sensitivity index (Mat‐ISI) in young, healthy, overweight or obese and sedentary women.

Methods

On three separate days, 10 women (22.7 ± 4 years, BMI of 35.39 ± 5.36) reported for a fasted, venous blood draw. Participants consumed 5g of cellulose placebo or 5g of Cassia cinnamon bark. Three hours after the initial blood draw, the participants completed an OGTT by consuming a 75g glucose solution within 2 minutes. Venous blood draws were taken 30, 60, 90, and 120 minutes after OGTT to determine changes in BG and SI.

Results

The maximum BG concentration following OGTT was significantly lower in the Cassia group, as compared to the placebo group (P = 0.025). The overall glucose response, glucose and insulin total area under the curve, and Mat‐ISI were not different between the two groups (P > 0.05).

Conclusions

A 5g dose of Cassia cinnamon may reduce maximum post‐OGTT BG and improve glucose tolerance but does not have a significant impact on post‐OGTT insulin response in overweight or obese and sedentary women.
Compound K produces cardiac protection by activating Akt phosphorylation
Authors: Tsutsumi Rie , Mawatari Kazuaki , Katayama Erika , Nakaya Yutaka , Tsutsumi Yasuo M.
Published: June 2021

Ginseng root is one of the most popular herbs throughout the world and it has been used as a medicine to enhance stamina and capacity to cope with fatigue and physical stress. In this study, we focused the cardiac protective effects of Compound K (C‐K; 20‐O‐D‐glucopyranosyl‐20(S)‐protopanaxadiol), which is a protopanaxadiol metabolite derived from ginsenoside Rb1, Rb2, and Rc by the metabolic actions of intestinal bacteria.

Mice were exposed to 30 min ischemia followed by 120 min of reperfusion (control). Some mice were assigned to C‐K, or PI3K inhibitor, wortmannin. C‐K preconditioned significantly reduced infarct size compared to control group (22.4 ± 2.5% [n = 7] vs. 43.2 ± 2.0% [n = 12] respectively, p<0.05) and wortmannin eliminated the protection produced by C‐K (43.3 ± 2.4% [n = 7]). Additionally, the hearts treated with C‐K had a 2‐fold increase in basal phosphorylation of Akt and pretreated with wortmannin completely abolished Akt phosphorylation in response to C‐K treatment.

These results reveal that C‐K produces cardiac protection in mice in association with PI3K/Akt signaling.
Effects of a single high‐fat meal rich in cottonseed oil on lipid profile, insulin sensitivity, and multimeric forms of adiponectin of healthy females
Authors: Sodhani Shradha , Sundaresan Sinju , Makkieh Kay , Imrhan Victorine , Mills Nathaniel , Vijayagopal Parakat , Prasad Chandan
Published: June 2021

This study investigates the effect of consuming a single high‐fat meal rich in cotton seed oil (CSO) on plasma lipid, glucose, insulin, and adiponectin levels. In a randomized cross‐over design, eleven healthy female subjects consumed 1 of 2 iso‐caloric meals consisting of carrot muffin/s and milkshake providing 1 g of fat/kg body weight. Blended palm oil (BPO) served as control and blood drawn at baseline, 3 and 6 hours was analyzed for biochemical assays. One‐way repeated ANOVA was performed followed by post‐hoc tests to determine differences between three time periods and identify groups that were significantly different. Subjects were divided into groups based on the sequence of meal ingested (CSO followed by BPO) to account for carry‐over effects. Consumption of CSO did not show any significant differences (p<0.05) in mean blood glucose levels compared to BPO controls. The serum insulin levels also did not reach significance. No significant differences were observed in plasma levels of total cholesterol, HDL‐c, LDL‐c and triglycerides in CSO compared to BPO. CSO increased the ratio of polymeric to monomeric form of adiponectin compared to BPO (2.05 in CSO vs. 1.34 in BPO); however this increase did not reach statistical significance. A single high‐fat meal rich in CSO altered ratio of multimeric forms of adiponectin with no effect on insulin and lipid profile in healthy females.

Supported by Texas Department of Agriculture
Chocolate matrix factors modulate pharmacokinetic behavior of cocoa flavan‐3‐ols following oral consumption by Sprague‐Dawley rats
Authors: Neilson Andrew Peter , Sapper Teryn N. , Janle Elsa M , Mattes Richard D , Rudolph Ralf , Matusheski Nathan V , Ferruzzi Mario G
Published: June 2021

Little data exists on modulation of phase‐II metabolism of catechin (C)/epicatechin (EC) from chocolate by carbohydrate and milk. The objective of this study was to assess the impact of the matrix on profiles of plasma C/EC metabolites following administration of commercially relevant chocolate. Sprague‐Dawley rats were fed 1.5 g confection (ref. dark, high sucrose, or milk chocolate) by gavage; plasma was collected over 8 h. HPLC‐MS indicated that major metabolites of EC were EC‐5‐O‐β‐glucuronide, 3′‐O‐Me‐EC‐5‐O‐β‐glucuronide, and 4′‐O‐Me‐EC‐5‐O‐β‐glucuronide; major metabolites of C were C‐5‐O‐β‐glucuronide and 3′‐O‐Me‐C‐5‐O‐β‐glucuronide. Plasma metabolite concentrations were generally highest for high sucrose trt and lowest for milk treatment, while ref. dark treatment generally resulted in intermediate levels over 8 h. AUC of 4′‐O‐Me‐EC‐5‐O‐β‐glucuronide was significantly higher for high sucrose trt (2325 nM*h) vs. milk trt (1300 nM*h). Additionally, CMAX values for EC‐5‐O‐â‐glucuronide, 4′‐O‐Me‐EC‐5‐O‐β‐glucuronide, and 3′‐O‐Me‐EC‐5‐O‐β‐glucuronide were significantly higher for high sucrose trt (4012, 518, and 2518 nM, respectively) vs. milk trt (2590, 240, and 1670 nM, respectively). Milk and sucrose appear to modulate the metabolism and pharmacokinetics, and to a lesser extent overall bioavailability, of catechins from chocolate confections.

Grant Funding Source: Kraft Foods research, Development, and Quality
Regulation of sterol transporter expression by plant sterols in HepG2 cells
Authors: Park Young‐Ki , Carr Timothy P.
Published: June 2021

Intake of plant sterols has long been shown to reduce cholesterol absorption and subsequently plasma cholesterol concentrations. However, it has not been fully elucidated whether plant sterols can alter the expression of cholesterol transporters by functioning as a signaling molecule to elicit responses at the cellular sterol level. This study tested the hypothesis that plant sterols can modulate the expression of transporters including Niemann‐Pick C1‐Like 1 (NPC1L1) and scavenger receptor class B, type I (SR‐BI) in liver. HepG2 cells, a human hepatoma cell line, were used as a model of hepatocytes. The cells were treated with 25α‐hydroxycholesterol (10 μmol/L) or 100 μmol/L of cholesterol, sitosterol and stigmasterol for 24 h to measure genes involved in cholesterol transport using quantitative realtime PCR. All sterols significantly reduced the mRNA expression levels of hydroxy‐3‐methyl glutaryl CoA reductase (HMG‐CoA reductase), NPC1L1, SR‐BI and LDL receptor. Importantly, sitosterol and stigmasterol reduced the mRNA levels of genes to a similar extent of cholesterol. Our findings indicate that plant sterols can modulate expression of cholesterol‐related genes by functioning as a signaling molecule in HepG2 cells. [Research supported by USDA‐NRI competitive grant no. 2007‐35200‐18298]
Phytosterols and fatty acids, but not phytosterol esters, affect cholesterol micellarization in vitro
Authors: Brown Andrew William , Hang Jiliang , Dussault Patrick H , Carr Timothy P
Published: June 2021

The mechanisms by which consumption of phytosterols and their fatty acyl esters decreases LDL cholesterol, an atherosclerotic risk factor, are incompletely characterized. To test the hypothesis that phytosterols, phytosterol esters, and simulated hydrolysis products of the esters differentially affect micellarization of cholesterol (a necessary step in efficient cholesterol absorption), we measured the influence of these compounds on cholesterol incorporation in model mixed‐bile micellar systems. We found that sterols and fatty acids independently altered cholesterol incorporation: oleic acid increased cholesterol micellarization as compared with palmitic and stearic acids; phytosterols resulted in an almost 50% reduction in cholesterol micellarization in a dose‐dependent manner, with no differences among phytosterols. Phytosterol esters did not incorporate into the micelles, nor did they result in a change in cholesterol micellarization. We conclude that phytosterols decrease micellarization by competition, and that fatty acids can differentially affect cholesterol micellarization.

Grant Funding Source: Research supported by USDA‐NRI competitive grant no. 2007‐35200‐18298
Antioxidative Activities of Isoflavones Metabolites Generated by Fermentation with Bacillus species Isolated from Cheonggukjang, a Traditional Korean Fermented Soyfood
Authors: Kim Jon‐Sang , Nam Dae Hwan , LIM Ji Sun , Park Jia , Hong Ye Seul , Seo Ji Yeon , Han Min Young , Kim Hyo Jung
Published: June 2021

Soybean is major source of isoflavones such as genistein and daidzein. Cheonggukjang, one of the most popular Korean fermented soyfoods, has been produced by fermenting steamed soybean with Bacillus strains that is usually present in rice straw. In our previous study it has been found that an extensive metabolism of isoflavones was occurring during the preparation of cheonggukjang. This study was aimed to evaluate the antioxidative potential of isoflavone metabolites produced by fermenting purified genistein, daidzein, and glycitein with various Bacillus species isolated from traditional cheonggukjang. Isoflavone metabolites produced during fermentation showed a significant change in the antioxidant capacity from the parent compounds as revealed by radical scavenging assay (DPPH), ferric reducing antioxidant power (FRAP) assay, and analysis of intracellular ROS level using dichlorofluorescin diacetate(DCFDA). The strongest antioxidant activity was observed when isoflavones were fermented with B. amiloliquefacienes 51 strain and B. lichenniformis 17.
Cranberry phytochemicals act as non‐microbial antigens for different types of human peripheral blood mononuclear cells
Authors: Rowe Cheryl A. , Montero Cindy , Nantz Meri P. , Khoo Christina , Percival Susan S.
Published: June 2021

To determine whether specific families of phytochemicals are able to interact with human peripheral blood mononuclear cell (PBMC) receptors and initiate an immune response, isolated human PBMC were incubated with three different extracts of cranberries representing anthocyanins, proanthocyanidins, or polyphenols. Proliferation of cells upon ex vivo stimulation and surface marker expression were measured by flow cytometry. The fraction containing mainly proanthocyanidins caused proliferation and activation of ãä T cells, as well as the activation of B cells. The fraction containing mainly anthocyanins slightly activated NK cells detected as an increased expression of NKG2D on NK cell surfaces. The polyphenol fraction increased B cell proliferation, and markedly increased expression of VLA‐1, about 10 fold, on monocytes. VLA‐1 is a cell adhesion molecule. PBMC secreted a number of cytokines in response to incubation with the cranberry fractions; the proanthocyanidin‐containing fraction having the greatest stimulatory effect. These results suggest that cranberry phytochemicals have the potential to immuno‐modulate in a variety of ways. Supported by Ocean Spray Cranberries, Inc and FAES
Genistein stimulates nitric oxide synthesis in human vascular endothelial cells via activation of cAMP‐response element binding protein
Authors: Liu Dongmin , Si Hongwei
Published: June 2021

We previously reported that genistein, a phytoestrogen, up‐regulates endothelial nitric oxide synthase (eNOS) expression nitric oxide (NO) release in human vascular endothelial cells (ECs), an effect that is not related to its potential estrogenic action. In the present study, we further investigated the underlying mechanism by which genistein stimulates eNOS expression in ECs. Inhibition of the mitogen‐activated protein kinase, phosphatidylinositol 3‐OH kinase/Akt or protein kinase C had no effect on the enhanced NO synthesis by genistein. However, pharmacological or molecular intervention of PKA activation completely abolished PKA activity and the genistein‐stimulated eNOS expression and NO production, suggesting that genistein acts through a PKA‐dependent pathway. Furthermore, genistein increased intracellular cAMP concentration and PKA activity and subsequently activated the phosphorylation of CREB at ser‐133. Transfection of ECs with siRNA targeting CREB abolished genistein‐induced phosphorylation of CREB, eNOS expression and NO synthesis. These findings reveal for the first time an important signaling pathway in vascular ECs that is activated by genistein and suggest that this plant‐derived compound may play a beneficial role in vascular function through targeting cAMP/PKA/CREB/eNOS/NO signaling. This work was supported by grants from NCCAM/NIH (1R21AT004694‐01, 1R21AT002739).
Modulation of Redox/Nitric Oxide Signaling by Lamiaceae Herbs in Seminal Vesicles of Lumbricus terrestris
Authors: DeLeon Robert Corey , Lester Christen , Maitin Vatsala , Vattem Dhiraj
Published: June 2021

Health benefits of Lamiaceae herbs are attributed to the presence of antioxidant phytochemicals. However, their in vivo mechanism of action is not well understood. We determined the effect of dietary Lamiaceae herbs on modulating redox/nitric oxide (NO) signaling and sperm quality in oxidation prone environment of seminal vesicles. Animals fed ad libitum on Lumbricus growth medium supplemented with 0% (control), 0.1% or 0.5% (w/v) of different herbs. The seminal vesicles from the animal were dissected out on day 2 and day 6, and gently disrupted. Levels of malondialdehyde (MDA), DNA fragmentation (DNAF), glutathione (GSH), nitrates/nitrites (NOx), superoxide dismutase (SOD) and catalase (CAT) were determines using standard assays. Sperm maturity and deformation (DFO) was quantified microscopically. Transcriptional changes relevant to redox/NO signaling were quantified using Real time qPCR. Overall, the herb treatments decreased MDA levels by 60–90%, increased SOD activity (15–50%) and NOx (6–15%) and decreased DNAF (6–11%) and DFO (20–50%). Treatments with basil and oregano at 0.1 % (w/v) were most effective. Preliminary data analysis suggests modulation of redox response via protein kinase C, ARE‐Nrf2 and AP‐2 mediated expression of SOD, glutathione peroxidase and Nitric oxide synthase. Funding source: Texas State University.
Influence of maternal hypothyroidism in fetal cardiac Renin‐Angiotensin System (RAS)
Authors: Lino Caroline Antunes , Shibata Caroline Emy Rodrigues , Barreto‐Chaves Maria Luiza
Published: June 2021

Objective

Thyroid hormones (TH) are critical for organogenesis and fetal development. Similarly, the RAS has also been implicated in embryogenesis. However, the possible influence exerted by maternal hypothyroidism during the pregnancy in cardiac RAS of embryos is unknown. The aim of this study was to analyze the maternal hypothyroidism effect in the expression of some RAS components in fetal heart at embryonic day 20 (ED 20).

Methods

Females Wistar rats were mating with 12 weeks of age. At gestational day 9, the dams were divided into 2 groups. The control received water and hypothyroid (hypo) group received water with Metimazol (0.02%). Dams and offspring were killed at ED20. Total body, heart, lung and renal weights of fetuses were evaluated. Western Blotting was used to evaluate AT1, AT2 and Ang I/II expression levels in fetal heart. Data were expressed as mean±SD and were analyzed using analysis of variance. Values of P<0.05 were considered statistically significant (n=5).

Results

Total body, lung and renal weights were decreased in embryos of hypo group. However, AT1, AT2 and Ang I/II expression levels in fetal heart in hypo group were not different compared to that observed in control.

Conclusion

Although RAS is modulated during the embryogenesis period, the induction of maternal hypothyroidism was not able to promote alteration on fetal cardiac expression levels of RAS components at ED 20.
Fructose consumption during gestation alters glucose metabolism and placental expression of TNF‐α and SNAT2
Authors: Lineker Christopher William , Patel Nikhil , Dunichand‐Hoedl Abha , Bell Rhonda C.
Published: June 2021

Increased fructose (FR) consumption has been associated with obesity and insulin resistance, which, if present during gestation, may increase the risk of metabolic disease in the offspring. Alterations in placental transport may mediate these effects. This study examined the effect of FR consumption during gestation on placental mRNA expression of nutrient transporters (GLUT3, CD36, SNAT2) and the pro‐inflammatory cytokine TNF‐α. Female rats received either 10% FR solution (n=18) or tap water (CNTL) (n=17) during gestation. Maternal blood was collected before gestation, and on gestational days (GD) 12 and 19; pregnancies were terminated on GD 20. Fetuses and placentas were weighed. Placental mRNA expression was quantified using real‐time PCR. Maternal weight, placental weight, fetal weight and GLUT3 and CD36 expression were not different between FR fed rats and CNTL rats. Maternal glucose (mmol/L) was elevated on GD 19 in FR vs. CNTL rats (6.26 ± 1.2 vs 5.18 ± 0.7; p<0.05). Insulin (ng/ml) was increased at mid‐gestation (FR: 2.74 ± 1.5; CNTL: 1.41± 0.5; p<0.05) and on GD 19 (FR: 2.11 ± 1.3; CNTL: 1.07 ± 0.4; p<0.05). Placental expression of SNAT2 (FR: 1.61 ± 0.1; CNTL: 0.90 ± 0.3; p<0.05) and TNF‐α (FR: 1.38 ± 0.2; CNTL: 0.82 ± 0.2; p<0.05) was increased in FR rats compared to CNTLs. Although overall fetal growth appeared to be unaffected, further studies examining changes in offspring metabolism are warranted. NSERC
Maternal consumption of soy protein affects lipid metabolism in the offspring of rats
Authors: Kwon Young Hye , Won Sae Bom , Han Anna
Published: June 2021

Previous studies suggest that nutrition during the fetal and neonatal periods may program susceptibility in the offspring to later development of chronic diseases, such as obesity, hypertension, CVD and diabetes. We investigated the effect of the early life consumption of soy protein and genistein on gene expression involved in metabolic syndrome phenotype. SD rats were fed a casein diet (CAS: 200 g casein/kg diet), a soy protein diet (SPI: 200 g soy protein isolate/kg), or a casein + genistein diet (GEN: 200g casein + 250 mg genistein/kg) throughout 2 week before pregnancy, pregnancy and lactation. There was no significant difference in the weights of the dams among groups throughout study periods. Male offspring were studied at 21 d after birth. The male SPI offspring had significantly lower body weight and body fat than the other groups. Serum total cholesterol concentration was significantly lower in the SPI group. The fasting serum glucose and insulin concentrations were not different among groups. Expressions of 15 genes involved in lipid, fatty acid, steroid metabolism were significantly altered in the SPI group compared to those in CAS group (|fold change| ≥ 2.0) as determined by microarray analysis. Therefore, in the present study, we observed that maternal consumption of soy protein during pre‐pregnancy, pregnancy and lactation affects lipid metabolism in the offspring of rats. This work was supported by a grant from Korea Research Foundation.
Total and high molecular weight adiponectin levels in mice with altered GH signaling
Authors: Lubbers Ellen , Miles Donald Bailey , List Edward O. , Kopchick John J. , Berryman Darlene E.
Published: June 2021

Adiponectin, which negatively correlates to fat mass and insulin resistance, associates into high molecular weight (HMW) and low molecular weight forms. The HMW form possesses the predominate insulin sensitizing bioactivity, yet most mouse studies have reported only total levels. This study evaluates total and HMW adiponectin concentrations in giant bovine GH transgenic (bGH), dwarf GH receptor gene disrupted (GHR−/−), dwarf GH antagonist (GHA) transgenic mice fed either a high fat (HF) or low fat (LF) diet as compared to littermate controls. The bGH and GHR−/− strains represent opposites in GH signaling, with GHR−/− mice being highly insulin sensitive, obese and long‐lived in the absence of GH signaling and with bGH mice being insulin resistant, lean and short‐lived with excess GH signaling. GHA mice have repressed GH signaling are dwarf and obese, like GHR−/− mice, but do not have increased longevity or improved insulin sensitivity. GHR−/− mice on a HF and LF diet and GHA females have increased HMW, total and HMW/total adiponectin levels. Total adiponectin levels are increased in GHA males and decreased in bGH males, but there is no difference in HMW or HMW/total ratio as compared to littermate controls. The increase in total, HMW, and HMW/total adiponectin levels in the long‐lived male GHR−/− mice suggests that elevated adiponectin concentrations could contribute to their improved lifespan.

Research was supported via funds from NIDDK (DK064905, DK075436), NIA (AG031736, AG19899), State of Ohio's Eminent Scholar Program that includes a gift from Milton and Lawrence Goll, DiAthegen, Diabetes Research Initiative at Ohio University, and AMVETS.

Grant Funding Source: DEB was supported in part by funds from NIDDK (DK064905) and NIA (AG031736). EOL is supported by funds from NIA (AG031736) and NIDDK (DK075436). JJK is supported by funds from NIA (AG19899 and AG031736), NIDDK (DK075436), the State of Ohio's Eminent Scholar Program that includes a gift from Milton and Lawrence Goll, and a grant from DiAthegen LLC. All work was further supported by the Diabetes Research Initiative at Ohio University and by a grant from AMVETS.
Sodium selenate inhibits adipogenesis in vitro
Authors: Wiacek Julie Lynn , Kim Kee‐Hong
Published: June 2021

Adipogenesis refers to the differentiation of predadipocytes into mature adipocytes. This process is a potential target to treat or prevent obesity. Adipogenesis not only increases fat accumulation, but also elevates inflammation and oxidative stress. Selenium, an essential micromineral, has been shown to have potent anti‐oxidative and anti‐inflammatory properties. We therefore hypothesized that selenium can serve as a potential anti‐adipogenic agent. Sodium selenate was chosen over sodium selenite due to its relatively low toxicity in 3T3‐L1 cells. We found that selenate significantly inhibits adipogenesis in vitro in a dose dependent manner. Complete inhibition was observed at 50 microM, at which there were no negative effects on cell viability. We revealed that selenate's inhibitory action is limited to the early stage (day 0 to 2) of adipogenesis. Furthermore, we found that selenate reduced mRNA expression levels of adipogenic transcription factors, such as, peroxisome proliferator‐activated receptor‐gamma (PPAR‐gamma). More importantly, selenate was likely to maintain preadipocyte factor‐1 (Pref‐1), a preadipocyte marker gene expression, during adipogenesis. Taken together, our results support selenate's anti‐adipogenic properties in vitro. These effects are likely due to selenate‐mediated alteration of the adipogenic transcriptional program in the early stage of differentiation. This project is partially funded by the USDA‐AFRI grant and The Showalter Trust Fund Award.

Grant Funding Source: USDA‐AFRI and The Showalter Trust Fund Award
Characterization of the H4K16bio Mark in Human Lymphoid Cells
Authors: Rios‐Avila Luisa , Wijeratne Subhashinee Samudra K. , Pestinger Valerie , Zempleni Janos
Published: June 2021

Holocarboxylase synthetase (HCS) catalyzes the covalent binding of biotin to lysine (K) residues in histones. Histone biotinylation is biologically important for gene regulation in humans. For example, biotinylation of the K‐12 in histone H4 (H4K12bio) represses the transcription of genes coding for transposable elements, interleukin‐2, and the sodium‐dependent multivitamin transporter. Mass spectrometry studies provided preliminary evidence for the existence of a novel biotinylation site, H4K16bio, in addition to the 11 known biotinylation sites in histones H2A, H3 and H4. In this study we developed a new antibody to H4K16bio and conducted an extensive series of tests to confirm specificity. Bulk extracts of human histones tested positive for H4K16bio, using the novel antibody as a probe. Currently, we are using ChIP/qRT‐PCR to obtain first insights into potential biological functions of H4K16bio. (Supported by ARD, NIH DK063945, DK077816, DK082476 and ES015206, USDA CSREES 2006‐35200‐17138, and NSF EPS 070189).
Anti‐inflammatory and metabolic mechanisms by which omega‐3 fatty acids improve insulin resistance in high fat diet‐induced obese mice
Authors: Kalupahana Nishan Sudheera , Claycombe Kate , Stewart Taryn , Hadidsaz Rachael , Booker Suzanne , Siriwardhana Nalin , Moustaid‐Moussa Naima
Published: June 2021

In this study, we investigated the effects of eicosapentaenoic acid (EPA) on prevention (P) and reversal (R) of high‐fat (HF) diet‐induced obesity and metabolic alterations. Male C57BL/6J mice were fed low‐fat (LF), HF or a HF‐EPA‐P diet for 11 weeks. A fourth group was initially fed HF for 6 weeks followed by HF‐EPA‐R diet for 5 weeks. As expected, mice fed HF diet developed obesity and glucose intolerance. In contrast, mice fed HF‐EPA‐P diet maintained normal glucose tolerance despite weight gain when compared to the LF group. While the HF group developed fasting hyperglycemia and hyperinsulinemia, both HF‐EPA groups (P and R)‐R exhibited normal glycemia and insulinemia, demonstrating EPA's ability to prevent and improve insulin resistance associated with high fat feeding. Analysis of adipokines revealed that plasma adiponectin levels were lower in the HF group, but were comparable between LF and HF‐EPA groups, regardless of the high fat content of the diet. Further analysis of adipose tissue adipokine levels and proteomic studies in cultured adipocytes demonstrated that EPA reduces adipose inflammation (MCP‐1 and PAI‐1) and lipogenesis, while increasing fatty acid oxidation and mitochondrial content. These studies demonstrate that beneficial effects of EPA in improving insulin resistance are in part mediated by EPA's lipid oxidizing and anti‐inflammatory effects.

Grant Funding Source: UT‐ORC, AHA and USDA‐NRI
Effects of Riboflavin Deficiency on Hepatic Gene Expression of Rats
Authors: Shih Yi‐Ting , Yang Feili Lo
Published: June 2021

The prevalence of impaired riboflavin status has been around 15% to 20% across various age groups in Taiwan. In order to explore the influence of riboflavin deficiency on hepatic biochemical indices and gene expression, 60 male weanling SD rats were randomly assigned to riboflavin adequate‐ad lib, adequate‐pair fed, deficient‐ad lib and deficient‐high fat AIN‐93G diet for 3, 6 and 12 weeks after 1 week of acclimation. Riboflavin status of animals was confirmed by erythrocyte glutathione reductase activity coefficient (EGRAC) every other week. In addition to suppressed growth, riboflavin deficiency significantly reduced the liver contents of cofactors FAD and FMN, thus the enzyme activities of PMP oxidase and succinate dehydrogenase, but not glutathione reductase. Six weeks of riboflavin deficiency also resulted in changes in expression of clusters of genes responsible for energy metabolism, nutrient metabolism (methionine, iron and pyridoxine), cell cycle, apoptosis and detoxification (Cytochrome P450, family 2b and 4a, FMO, GST and UGT), analyzed by Agilent Rat Whole Genome Oligo. Therefore many changes in physiological functions of liver due to riboflavin deficiency may be regulated at transcriptional level. [Sponsored by Fu Jen University Research Grant 109631060991‐1]
A Forward Genetics Approach to Identify Genetic Regulators of Liver Mineral Accumulation in Mice
Authors: McCreedy Rebecca , Wang Libo , Zhang Min , Jones Byron C. , Beard John , Fleet James C
Published: June 2021

We integrated ionomic profiling of mouse liver with quantitative trait loci (QTL) analysis using a panel of recombinant inbred lines (RIL) resulting from a cross of C57BL/6J (B6) and DBA/2J (DBA) inbred mouse lines (BXD). Following acid digestion, the levels of 13 elements (Na, Mg, P, K, Ca, Mn, Fe, Co, Cu, Zn, Se, Mo, and Cd) were determined by ICP‐MS in 400 samples from 27 RIL. Bayesian mapping using gender and analytical run as covariates and incorporating two stages of marker selection based on probabilities amongst prior distributions was used to identify QTL. 37 QTL were located and 12 strong peaks with a Bayes Factor (BF) >10 affected liver Fe (3 QTL), Mg (1), P (1), Mn (2), Cu (2), Mo (1), and Cd (2). Few of these loci contained genes known to regulate the mineral metabolism, demonstrating the value of this approach for gene discovery. The peaks controlling liver iron level on Chr 16, 17 and 18 each contain >100 candidate genes. The Chr 16 QTL peak (BF>4.5e+15) included the transferrin receptor (Tfrc) gene and polymorphisms between B6 and DBA mice were found within the 3′ UTR that normally regulates mRNA stability. However, transcript‐level QTL analysis revealed no difference in Tfrc mRNA levels between the BXD lines and suggests a Tfrc‐independent mechanism. Our data highlight the potential of coupling ionomics and forward genetics to identify natural genetic variants controlling mineral metabolism.
Reproducibility of 24 hour energy expenditure measured by whole‐room indirect calorimetry in lean and obese males
Authors: Corbin Karen D , Knab Amy M , Shanely R. Andrew , Nieman David C , Zeisel Steven H
Published: June 2021

To understand the effects of extrinsic and intrinsic factors on metabolism, it is essential to reproducibly measure 24 hour energy expenditure (EE). We aimed to determine the reproducibility of 24 hour EE in our new metabolic chamber, which has a floor space of 10′11″ X 8′0.5″, in lean vs. obese subjects. The subjects were 10 healthy males, age 22–33, BMI 18.6–39.8. Prior to chamber stays, they were asked to fast overnight, follow a food list, and avoid exercise, alcohol, and caffeine. Whole room indirect calorimetry measurements were obtained on two non‐consecutive days. The chamber diet contained 34% (+/− 0.4%) (mean +/− standard error of the mean, SEM) fat, 49% (+/− 0.5%) carbohydrate, and 17% (+/− 0.3%) protein. Calories were assigned to each subject based on calculated resting metabolic rate times 1.4 with prediction algorithms used to ensure energy balance. This resulted in subjects receiving a diet that was within 88.4 kcal (+/− 27.9 kcal) of their measured EE. The EE difference between the two chamber stays was 68.9 kcal/day (+/− 22.2 kcal). The EE difference in lean (BMI ≤ 24.9; n = 6) vs. obese (BMI ≥ 30; n = 3) individuals was 33.2 kcal/day (+/− 9.2 kcal) and 158 kcal/day (+/− 35.2 kcal), respectively. Our results suggest that with minimal control of pre‐measurement conditions, our metabolic chamber is able to reproducibly measure EE in individuals of various body weights.
The effect of dietary macrocomposition on weight loss and nonalcoholic fatty liver disease (NAFLD) in bariatric surgery candidates.
Authors: Uhley Virginia Ellen , Neidert Adam , Birkmeyer John , Finks Jonathan F , Burant Charles , Oral Elif Arioglu
Published: June 2021

Most bariatric surgery programs use a conventional low fat, calorie restricted diet during the preparation phase for surgery. However, no systematic comparison of diets with different macronutrient compositions have been performed. We are investigating the clinical effects of a low carbohydrate versus a low fat diet in patients that are preparing for bariatric surgery. Enlarged steatotic livers increase the operative risk of bariatric surgery and weight loss prior to bariatric surgery has been shown to reduce operative risk. We hypothesize that the use of a 1000–1200 kcalorie low carbohydrate diet (< 15% of total kcaloric intake) during the preparation phase for bariatric surgery will cause a greater reduction in weight, hepatic fat content and hepatic volume compared to a “conventional” 1000–1200 kcalorie low‐fat diet (30% fat, 60% carbohydrates of total kcaloric intake) and offer clinical advantages by making the technical aspects of surgery easier. Here we present preliminary data on 8 patients that have finished the study. Our results will provide a basis to help identify the optimal dietary intervention to make bariatric surgery safe and effective for the increasing numbers of patients opting for this aggressive therapy for morbid obesity.
The effects of cocaine use on dietary intake and BMI changes in HIV+ adults
Authors: Lin Olivia , Campa Adriana , Johnson Paulette , Stewart Tiffanie , Sales Sabrina , Baum Marianna K
Published: June 2021

Objective

Cocaine use has been shown to affect appetite. This study examines the effects of cocaine use on caloric and macronutrient intake in a cohort of HIV+ drug users over a 6‐month period.

Methods

After consenting 231 HIV+ participants, 24‐hour recalls were administered and anthropometries determined for BMI calculation at baseline, 3 and 6 months. Use, frequency and route of consumption of illicit drugs were assessed through a questionnaire and confirmed by urine toxicology.

Results

Mean age was 42.7±7 years and 73.2 % were male. At baseline, use of cocaine (74.7%) was confirmed and was inversely correlated with BMI (r=−0.207, p=0.004), remaining significant over time (r= −0.202, p=0.006). Protein (z= −.904, p=0.046) and carbohydrate (z= −1.904, p=0.05) intakes significantly decreased in cocaine users over time. Changes in energy and fat intake were not significant over 6 months. Protein intake was significantly higher in those who were not using drugs compared to those using either cocaine alone or in combination with other drugs (÷2= 11.4, p=0.01).

Conclusion

These findings support a significant association of sustained cocaine use with adverse changes in BMI that seems to be mediated by decreased intake of protein and carbohydrate over time, without significant changes in total energy. Further studies are needed to determine dietary recommendations for HIV+ cocaine users.

Funded by NIDA

Grant Funding Source: NIDA