bluuebunny/crossref_metadata_2025 huggingface dataset:
Methanol extract of gromwell has anti‐obesty effect in obese (DIO, ob/ob) mice
Authors: Park Jin Kyung , Chon Jeong Woo , Lee Mi Ae , Hwang Eun‐Joo , Park Yoo Kyoung
Published: June 2021

The effect of methanol extract of gromwell in inducing weight loss in obese mice was assayed. DIO mice were induced with a high fat diet (45%) for 10 weeks. After 10 weeks of dietary manipulation, gromwell extracts [LGR (100 mg/ kg/day) and HGR (300 mg kg/day)] was administered by gavages for 10 weeks. After 10wks, the body weight of gromwell groups was reduced LGR (16.21%), HGR (11.46%) as compared with the control. Leptin of gromwell groups were significantly decreased compared with the control. The mRNA level of PPARγ, SREBP‐1c, SCD‐1 and NPY of gromwell groups was significantly increased than control. Second, ob/ob mice were treated gromwell extract with 100 (LGR) or 300 mg/kg/day (HGR) as previously described. Body weight gain was reduced in gromwell groups (18.65%, 19.36%) as compared with the control. Also gromwell groups were significantly reduced liver, epididymal adipose tissue weight than control. In fasted serum and level of total cholesterol (TC), triglyceride (TG), glucose and hepatic TC, TG on gromwell groups were significantly lower compared with the control, while HDL‐c were significantly higher than control (p<0.05). Gromwell improved positive energy state for homeostasis in genetically obese mice. Further research will be focused on exploring the detailed mechanisms by which extract of gromwell exerts effect on lipolysis pathways in obese mice.
Diet‐induced hepatocellular carcinoma in genetically‐predisposed mice
Authors: Buchner David , Hill‐Baskin Annie E , Markiewski Maciej , Shao Haifeng , DeSantis David , Hsiao Gene , Subramaniam Shankar , Berger Nathan A , Croniger Colleen , Lambris John D , Nadeau Joseph H
Published: June 2021

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, with ~70% of cases resulting from hepatitis B and C infections, aflatoxin exposure, chronic alcohol use, or genetic liver diseases. The remaining ~30% of cases are associated with obesity, type 2 diabetes, and related metabolic diseases although a direct link has not been established. We tested the long‐term (~500 days) effects of high‐fat and low‐fat diets on two inbred strains of mice and discovered that C57BL/6J but not A/J males were susceptible to NASH (non‐alcoholic steatohepatitis) and HCC on a high fat but not low fat diet. Susceptible mice showed characteristics of NASH (steatosis, hepatitis, fibrosis and cirrhosis), dysplasia, and HCC. mRNA profiles of HCCs versus livers showed involvement of two networks, one centered on Myc and the other on NFKB, a result that is consistent with the two major classes of HCC in humans. miRNA profiles revealed dramatically increased expression of a cluster of miRNAs on the X chromosome without amplification of the chromosomal segment and differential expression of miR‐146 that is involved in NFKB signaling. A switch from high‐fat to low‐fat diet reversed the outcomes, with switched C57BL/6J males being lean rather than obese and without evidence for NASH or HCCs at the end of the study. This demonstrates that diet modification has important implications for the prevention of HCC.
Absence of Inhibitor of Nuclear Factor κ B Kinase‐Mediated Suppression of Vascular Endothelial Function in Middle‐Aged/Older Adults Who Exercise
Authors: Walker Ashley E , Pierce Gary L , Lesniewski Lisa A , Lawson Brooke R , Magerko Katherine A , Seals Douglas R
Published: June 2021

We determined if reduced bioactivity of the inhibitor of nuclear factor κ B kinase (IKKB) contributes to enhanced vascular endothelial function in habitually exercising (EX) vs. sedentary (SED) middle‐aged and older adults. BMI was lower (P < 0.05) in EX (n = 5 [5 m], 63 ± 3 y) than in SED (n = 7 [5 m], 61 ± 2 y), but other coronary risk factors did not differ. EX and SED were studied after 4 d of oral treatment with placebo or salsalate (3000‐4500 mg/d), an inhibitor of IKKB (randomized double‐blind crossover). During placebo, brachial artery flow‐mediated dilation (FMD), a measure of endothelium‐dependent dilation, was ~150% greater in EX vs. SED (%Δ: 6.16 ± 0.59 vs. 2.46 ± 0.62; mmΔ: 0.24 ± 0.02 vs. 0.10 ± 0.02; both P = 0.001). Salsalate increased FMD in SED (5.76 ± 0.49 %Δ and 0.23 ± 0.01 mmΔ, P < 0.001 vs. SED placebo) to levels not different from EX placebo (P > 0.30), but had no effect on EX (6.55 ± 1.21 %Δ and 0.24 ± 0.03 mmΔ). Infusion of the antioxidant vitamin C increased FMD by ~80% (P < 0.05) in SED during placebo, but had no effect in SED during salsalate or in EX during either conditions (all P > 0.10). Endothelium‐independent dilation (sublingual nitroglycerin) did not differ between groups or conditions (all p > 0.05). An absence of IKKB bioactivity and reduced oxidative stress contribute to enhanced vascular endothelial function in middle‐aged/older adults who exercise.

NIH AG031617, AG006537, AG013038, AG022241, RR00051; AHA 0715735Z
Propolis, a product of the bee hive, has an antagonistic affect on quorum‐sensing regulated bioluminescence, gene transcription and motility
Authors: Bulman Zack , Hudson Andre , Savka Michael A
Published: June 2021

Propolis or ‘bee hive glue’ is collected by bees from local flora and has been used to protect against virus, bacteria, inflammation and ulcers. The purpose of our study was to examine the effect of propolis on a bacterial gene regulatory process called quorum sensing (QS). QS regulatory activity of six samples of propolis was examined using five QS N‐acyl‐homoserine lactone (AHL)‐dependent bacterial biosensors. Concentrations of propolis that do not affect biosensor growth were exposed to the biosensors with inducing concentrations of the cognate AHL. Propolis antagonized the QS bacterial signaling system in liquid‐ and agar‐based bioassays and in C18 reverse‐phase thin‐layer chromatography assays. Using RT‐PCR, genes involved in QS signaling in pathogen Pectobacterium carotovorum were repressed by propolis. Pseudomonas aeruginosa, uses QS to conduct its swarming motility behavior. When propolis is added to P. aeruginosa, swarming motility is reduced up to 58.5%. Together, we present evidence that propolis samples contain compounds that suppress QS responses. In this regard, propolis could be the starting point for the discovery of novel anti‐pathogenic compounds to disrupt QS signaling systems.
Treatment with the SIRT1 activator SRT1720 reduces large elastic artery stiffness, superoxide production and inflammation in old mice
Authors: Gano Lindsey B , Donato Anthony J , Henson Grant D , Hearon Christopher M , Hamza Muhammad , Seals Douglas R
Published: June 2021

Aortic pulse wave velocity (aPWV), the gold‐standard measure of large elastic artery stiffness, is a strong independent predictor of incident cardiovascular disease in older adults. We hypothesized that chronic activation of the protein deacetylase sirtuin‐1 (SIRT1) would reduce aPWV in old mice and that this would be associated with reduced superoxide production and inflammation. Aortic SIRT1 activity (inverse of acetyl‐p53 protein expression) was markedly reduced in old (29–31 mo, n=11) vs. young (4–7 mo, n=11) control B6D2F1 mice (5.4±1.4 vs. 1.0±0.2 AU, p<0.005), and 4 weeks of treatment with SRT1720 (100 mg/kg body weight, Sirtris, a GSK Co.) in old mice (29–32 mo, n=19) restored SIRT1 activity (1.1±0.2 AU). In vivo aPWV was 14% greater in old (OC, 29 mo, n=8) vs. young control mice (442±16 vs. 387±9 cm/s, p<0.05), but was reduced by 13% after vs. before SRT1720 treatment in old mice (411±12 vs. 354±12 cm/s, p<0.005). Aortic superoxide production (3149±493 vs. 5038±899 AU, p<0.05) and expression of inflammatory cytokines IL‐6 (4.03±0.79 vs. 6.23±1.05 pg/mL, p=0.05) and TNF‐α (1.81±0.26 vs. 2.91±0.50 pg/mL, p<0.05) were lower in treated vs. control old mice. SIRT1 activation with SRT1720 may be an effective treatment for reducing aPWV and destiffening large elastic arteries in older adults, possibly by decreasing arterial superoxide production and inflammation.
Ellagic acid stimulates glucose transport in 3T3‐L1 adipocytes and C2C12 myotubes by AMP activated protein kinase mediated pathway
Authors: Poulose Ninu , Prasad Vishnu , Nidhina Haridas P. A , Gopalakrishnapillai Anilkumar
Published: June 2021

Glucose Transporter 4 (GLUT4) is an insulin sensitive glucose transporter isoform predominantly expressed in adipocytes and skeletal muscle. It is largely confined to intracellular compartments in an unstimulated state and undergoes translocation to the cell surface in insulin dependent and independent manner to facilitate the bulk uptake of glucose. The present work aims at finding novel modulators of GLUT4 translocation and glucose transport from natural products. Our results show that ellagic acid, a plant polyphenol, can stimulate glucose uptake in 3T3‐L1 adipocytes and C2C12 myotubes in a dose dependent manner. GLUT4 translocation assay in 3T3‐L1 cells stably transfected with myc‐GLUT4‐GFP chimera has shown a corresponding increase in GLUT4 translocation upon ellagic acid treatment. Unlike insulin, ellagic acid did not stimulate the Ser‐473 phosphorylation and activation of Akt. However, the compound was found to significantly activate AMP activated protein kinase (AMPK) which is another major pathway involved in GLUT4 translocation. Ellagic acid stimulated glucose transport was inhibited by pretreatment with Compound C, an AMPK inhibitor. These findings suggest that ellagic acid mediated GLUT4 translocation occurs though a mechanism distinct from that of insulin and involves AMPK activation. This work was supported by a grant from Council of Scientific and Industrial Research, Govt. of India.
Pre‐pregnancy micronutrient intake assessed by food frequency questionnaire in the Alberta Pregnancy Outcomes and Nutrition (APrON) Study
Authors: Ramage Stephanie M , Berglund Casey , McCargar Linda J , Bell Rhonda C
Published: June 2021

Nutrient intake prior to pregnancy may impact maternal health and fetal development. A food frequency questionnaire (FFQ) was used to retrospectively assess diet and supplement intake over the year prior to pregnancy in the first cohort of the APrON study. Fifteen participants were excluded based on extremes in average caloric intake (<600kcal/day, n=3; >3500kcal/day, n=12). The FFQ was successfully completed by 491 women with a mean age of 31 ± 4 years and a mean body mass index of 24.0 ± 4.6 kg/m2. Key micronutrients chosen for assessment were iron, calcium and vitamin D. Mean (± Standard Deviation) intakes from food and supplements were 21.5 ± 9.8 mg of iron, 1225.8 ± 565.2mg of calcium, and 11.7 ± 6.4 μg of vitamin D. The proportion of women meeting the recommended dietary allowance (RDA) from food and supplements during this potentially critical period was low for vitamin D (38%) and moderate for iron (64%) and calcium (62%). These data illustrate a low to moderate intake of key micronutrients in Alberta women prior to pregnancy. Assessment and counseling to improve key micronutrient intakes of women in their child‐bearing years may be warranted. Research supported by Alberta Innovates ‐ Health Solutions.
Adherence to Mediterranean diet assessed using various a priori scores is associated with reduced 6‐y risk of metabolic syndrome (MetS) in French adults
Authors: Ahluwalia Namanjeet , Lassale Camille , Hercberg Serge , Fezeu Leopold , Lairon Denis , Kesse-Guyot Emmanuelle
Published: June 2021

Few prospective studies in Spain and US have linked a Mediterranean (Med) dietary pattern with reduced MetS risk. We evaluated the prospective association of Med diet pattern, based on various diet scores, with 6‐y incident risk of MetS in 3,232 middleaged adults, free from diabetes and CVD at baseline, who participated in the French SU.VI.MAX study. Three different Med diet scores were computed from repeated (>=3) 24‐hr records over two years: the original Med diet score (MDS) and its recent revisions namely rev‐MDS (incorporating cereal/grain quality and sugared‐beverage consumption) and Med‐style diet pattern score (MSDPS) relating adherence to Med diet pyramid. MetS was defined by the 2009 Joint Interim Societies definition. In logistic regression models adjusted for confounders including traditional CVD risk factors, a lower risk of MetS was observed with increasing rev‐MDS score and MDS (P for trend: 0.001 and 0.03, respectively) but not with MSDPS. Relative risk (95% CI) for MetS risk comparing the 3rd to the 1st tertile were 0.47 (0.32–0.69) and 0.50 (0.32–0.77) for rev‐MDS score and MDS, respectively. These findings highlight the importance of following Med diet in MetS prevention.
Effect of nutrition knowledge on dietary attitude and self‐efficacy of senior elementary school students
Authors: Chung Hyun-Jung , Park Hee-Jung
Published: June 2021

This study was carried out to investigate the effect of nutritional knowledge on dietary attitude, eating behavior, and dietary self‐efficacy in elementary school children in Incheon, Korea to improve nutrition education in a practical class. To the question of nutritional knowledge, most students answered ‘little knowledge’. Their information resources on nutrition knowledge were from ‘TV, radio, books (except text books)’, ‘internet’, and ‘class of school’ in order. In terms of the nutritional knowledge, the mean awareness was 82.6%, and the mean accuracy was 84.6%. There was a significant difference among the level of nutritional knowledge, the sources of nutritional knowledge, and the awareness of knowledge (p<0.001, p<0.05). Regarding the questions on ‘reduced‐fat or fat‐free food and body weight’, ‘obesity and adult disease’, and ‘taking vitamins’, girls showed significantly higher scores than boys (p<0.001). The average score of eating behavior was 40.98 out of 55. The question about ‘brushing teeth’ showed a significant gender difference (p<0.001). Boys were more punctual than girls in having a dinner (p<0.001). The reason for skipping breakfast was because they were too busy in the morning. The dietary self‐efficacy scored 71.11 out of 90. Girls’ scores were significantly higher than boys’ (p<0.05). Nutritional knowledge affected the elementary school students on their dietary attitude (p<0.01), eating behavior (p<0.01), and self‐efficacy (p<0.001). In conclusion, accessible and continuous dietary education help improve dietary attitude, eating behavior, dietary self‐efficacy as well as nutritional knowledge of students. Dietary education at an elementary school should consist of various well‐organized programs to improve appropriate dietary attitude, eating behavior, and dietary self‐efficacy.

Grant Funding Source: Inha University
Dietary protein, skeletal muscle mass, and obesity risk in adolescent girls
Authors: Hasnain Syed Ridda , Buendia Justin G , Bradlee M. Loring , Moore Lynn L
Published: June 2021

Adolescence is a critical period for acquisition of skeletal muscle mass (SMM) as well as the development of obesity. Prospective data on the effect of dietary protein on these outcomes are sparse. The goal of the study is to estimate the effects of dietary protein on adolescent body composition, using data from the National Growth and Health Study, a prospective study of 2379 9–10 year old girls followed for 10 years. 3‐day records were used to assess diet during 8 years of follow up. Bioelectrical impedance data from annual clinic visits were combined with age and height to estimate percent of total body weight from SMM. Analysis of covariance and logistic models were used to control for potential confounding by age, race, SES, height, activity, TV/video viewing time, and age at menarche. Percent body fat in late adolescence declined linearly with increasing quintiles of protein intake (in g/kg/day) in early adolescence (37.2, 32.4, 29.9, 28.7, 27.4 % body fat, respectively, for quintiles 1–5; p‐trend<0.0001). Percent SMM increased from 28.9% to 36.6% with increasing quintile of intake. Compared with the lowest quintile of intake, there was a striking 96% reduced risk (95% CI: 0.02–0.05) of being overweight (BMI ≥ 25 kg/m2) at end of follow up. These results suggest that higher dietary protein intakes may benefit acquisition of SMM and reduce the risk of acquiring excess body fat during adolescence.

Grant Funding Source: NIDDK and a small grant
Glutamine prevents body weight loss in lactating gilts
Authors: Manso Helena Emilia Cavalcanti C.C. , Manso-Filho Hélio Cordeiro , Dutra-Júnior Wilson Moreira , de Aquino Rafael Santos , de Gouveia Ribeiro Carlos Roberto , Nogueira Eduardo Terra , Kutschenko Marianne , de Oliveira Deyvson Ferreira , D'Paula Joyci Torres , Watford Malcolm
Published: June 2021

Transition period represents a mild catabolic state accompanied by loss of lean body mass in many mammals. Effects of L‐Glutamine and L‐Glutamic acid (AminoGut) supplementation was evaluated on body composition and markers of nitrogen metabolism in gilts through the transition period. Thirty pregnant gilts were divided into two treatments: Control receiving a commercial feed, and AminoGut group receiving similar feed to the controls but with 1.5% AminoGut mixed into each kilogram of feed. The supplementation began one week before parturition and continued until weaning (day 21 post‐parturition). Blood samples were drawn prior to the beginning of supplementation, within 6 hours of parturition, at 7 and 21 days post‐parturition. In the control group at the end of weaning body weight had decreased 14% from that one week prior to parturition but no weight loss was seen in the group receiving AminoGut. Backfat thickness also showed a decrease by the end of weaning. Plasma creatinine and urea concentrations rose after birth and then stayed constant until weaning. Plasma uric acid was relatively high one week prior to parturition but then fell dramatically on the day of parturition. Results indicate that supplementation of AminoGut throughout the transition period prevented body weight loss, possibly through sparing of lean body mass, and thus may be beneficial in decreasing protein catabolism in gilts during lactation.
The impact of voluntary micronutrient fortification of breakfast cereals on nutrient intakes (NHANES 2003–2006)
Authors: Miller Kevin B , Liska DeAnn , Almeida Nelson , Fulgoni Victor
Published: June 2021

Much of the US population fails to achieve the dietary reference intakes (DRI) for key nutrients, including vitamins A, D & calcium. This study evaluated the contribution of micronutrient fortified ready‐to‐eat cereal (RTEC) toward meeting the DRI by modeling the NHANES (2003–2006) data. The NCI method was used to create usual intakes, percentiles, and probabilities of intakes below the DRI for consumers of fortified RTEC and hypothetical unfortified RTEC including only required nutrients. The percentage of children (4–18 years) predicted to fall below the DRI for vitamins A, B6, folate, C, D and E would increase by 27, 11, 15, 7, 19 & 5%, respectively. The percentage of children who would fail to achieve the DRI for calcium, iron, magnesium, phosphorus and zinc would increase by 7, 6, 7, 5 & 13%, respectively. The youngest children consuming fortified RTEC were most likely to meet their DRI compared to adolescents and teenagers as a result of their lower recommendations. Extrapolation of these data to the population indicates that voluntary fortification of RTEC helps millions of American children achieve the DRIs for many nutrients that are key to healthy growth. These data predict that consumption of RTEC without fortification would exacerbate already low nutrient intakes. These findings demonstrate that voluntary nutrient fortification of cereal grain products helps more Americans achieve recommended intakes.
Cholesterol‐lowering effects of Northern wild rice in LDL receptor knockout mice
Authors: Moghadasian Mohammed , Le Khuong , Zhao Zhaohui , Nicholson Tiffany , Goh Chunyan , Moghadasian Paymahn , Askarian Fatemeh , Beta Trust
Published: June 2021

We have recently reported that Northern wild rice produced in Manitoba, Canada possesses higher antioxidant properties as compared to conventional white rice. This observation plus other data from available literature suggest that Northern wild rice may have anti‐atherogenic properties. The objective of the current study was to investigate potential lipid‐modifying and anti‐atherogenic properties of Northern wild rice in LDL receptor knockout mice. Sixteen 4‐week male LDL receptor knockout mice were divided into two groups of 8 each. These experimental groups received a semi‐synthetic diet containing 0.06% (w/w) cholesterol; carbohydrates in this diet were replaced with Northern wild rice and used for the “treated group.” The experiment will be carried out for 24 weeks. Plasma total cholesterol and triglyceride levels were estimated at baseline and every four weeks using standard enzymatic kits. Body weight and estimated 24‐hour food consumption were recorded. These data are summarized in the following Table.

Data suggest strong cholesterol‐lowering activities for Northern wild rice in this animal model. It is most likely that such reductions in total cholesterol levels will lead to significant reductions in atherogenesis by the end of the study.

This study was supported by Agriculture Research and Development Initiative (ARDI), Winnipeg, Manitoba, Canada.
Effect of tomato and Tocopherols intake on IgE level
Authors: Godoy María Fernanda , Slobodianik Nora , Carrari Fernando , Insani Marina
Published: June 2021

The aim of this research was to evaluate the effect of tomato and tocopherols intake on IgE level in Lamina Propria of intestinal villi.

An experimental rat model of protein malnutrition at weaning was used. Rats of Wistar strain were fed a protein‐free diet until they lost 25% of their initial body weight. This feeding procedure develops an allergic state. Re‐feeding was performed by the administration of an experimental diet containing 20% casein as the only source of protein (Re‐nourished group=R). Other experimental groups received this diet plus tomato (R+T) – equivalent to 200g/day for an adult man of 70kg‐ or plus a tocopherols mix (á, â, ã, ä) equivalent to those present in tomato fruit (R+Tph), added to drinking water during 35 days.

Results showed that Lamina Propria of intestinal villi of R+T group presented higher % of IgE+ B cells compared to R (99±8; 62±11) and intake of tocopherols mixture reverted that situation lowering the levels to 31±6. These results would suggest that tomato could be an allergenic food as tested in this model. Instead, tocopherols were effective to alleviate the basal allergic status.
Reported changes in feeding practices during and after illnesses in 6 to 23 month old children receiving continued breastfeeding in the Western Highlands of Guatemala
Authors: Vossenaar Marieke , Garcia Rosario , Doak Colleen M , Solomons Noel W
Published: June 2021

Background

The WHO recommends that fluid intake be increased during illness and that foods be offered more often after illness.

Objective

To describe feeding practices during and after illness in a sample of young Guatemalan children aged 6–23 mo.

Methods

Mothers of 300 young children attending two public health centers in the Western Highlands of Guatemala were interviewed regarding past feeding practices with a structured questionnaire.

Results

238 mothers (79%) reported offering the young child additional liquids when ill; the most commonly reported liquids were water (offered by 41% of mothers), ritual fluids (28%), oral rehydration solutions (17%) and breastmilk (7%). 85 mothers (28%) offered different foods during illness. 132 mothers (44%) reported withholding certain foods, whereas some foods were specifically offered during child illness by 88 mothers (29%). Most commonly avoided foods were beans, eggs, fatty‐foods and other items culturally believed to be “cooling” to the body (“cold foods”), as well as coffee. Most commonly promoted foods were soups, broths, ritual fluids, foods low in fat and breastmilk. Only 99 mothers (33%) reported offering the child more foods in convalescence.

Conclusion

A substantial proportion of mothers appropriately adapt feeding practices surrounding child illness in accordance with WHO guidance.

Funded by Sight and Life, Switzerland
Tackling poverty through private sector microcredit programs in Ghana: Does infant and young child nutrition improve?
Authors: Friesen Valerie , Marquis Grace S. , Fallon Kathleen , Colecraft Esi K.
Published: June 2021

Low income is a barrier to optimal feeding practices of infants and young children (IYC). Microcredit programs for rural Ghanaian women aim to improve incomes and may have the additional benefit of improving IYC nutrition. A cross‐sectional study was conducted in the Upper Manya Krobo District in Ghana to determine the association between a mother's participation in a rural bank microcredit program and IYC dietary quality and nutritional status. Participants included 102 active microcredit member mothers and 102 non‐microcredit member mothers and their youngest child (6–23 mo). Non‐members were matched to the microcredit group by community and child age. Information was collected on IYC feeding practices, length and weight and household socio‐demographic characteristics. IYC in the microcredit group (MC) consumed more dairy products (p < 0.01) and iron‐fortified foods (p < 0.05) while IYC in the non‐microcredit group (NMC) consumed more legumes and nuts (p < 0.05). Overall, more MC than NMC children (57 % vs. 43 %; p < 0.05) met minimum dietary diversity recommendations (≥ 4 food groups). Weight‐for‐age z‐scores tended to be higher among MC vs. NMC children (−0.43 ± 1.13 vs. −0.69 ± 1.03; p = 0.09). Microcredit programs may contribute to improving IYC nutrition in Ghana; longitudinal studies are needed to understand the role that this component of the private sector plays.

Funding: IDRC #1045519‐017 & McGill U.
Effects of lipid emulsions on markers of inflammation in human umbilical vein endothelial cells
Authors: Reyes Sarah , Williams Janet , Rezamand Pedram , McGuire Mark
Published: June 2021

Atherosclerosis is a vascular inflammatory disease. Cytokines and other markers of inflammation mediate the inflammatory response. Dietary lipids are known to alter serum concentrations of markers of inflammation in vivo and specific fatty acids can alter cytokine production in vitro. Our goal was to study the effects of common dietary lipids on markers of inflammation in vascular endothelial cells. To reflect postprandial conditions, human umbilical vein endothelial cells were treated with lipid emulsions of butter, margarine, corn oil, canola oil and olive oil at concentrations of 0, 75, 150, 300 and 600 mg/dl for up to 6 h. Total RNA was extracted and quantitative PCR measured the relative abundance of mRNA of interleukin (IL)‐6, IL‐8, vascular cell adhesion molecule (VCAM)‐1, tumor necrosis factor (TNF)‐α and IL‐1β. Lipid emulsions did not stimulate expression of TNF‐α or IL‐1β. For all other genes, olive oil up‐regulated up to 2‐fold (p < 0.05) expression of mRNA compared with the other oils. The subtle changes in inflammatory markers caused by emulsions of dietary lipids are less dramatic when compared with studies evaluating specific fatty acids. Funded by United Dairymen of Idaho.
Effect of inflammation on biochemical markers of nutritional assessment
Authors: Zago Liliana , Infantino Carlos González , Danguise Eduardo , Río María Esther
Published: June 2021

Biochemical markers are the most sensitive parameters to detect subclinical deficiencies. Inflammation constitutes a confusion factor because result in modifications attributable to nutritional deficiencies. In order to evaluate the influence of inflammation on biochemical indicators, data from 104 surgical patients from programmed surgeries were studied. Serum levels of vitamins A (VA) and C (VC), Zn and Se, albumin (Alb), transferrine (TSF), transthyretin (TTR) and retinol binding protein (RBP) were evaluated in fasting samples taken before surgical procedure. Patients were classified by C‐Reactive Protein (CRP <0.5, n=70; 0.5–4, n=28; and >4 mg/dl, n=6). Results for the 3 above ranges were as follows: VA (40.6(18.6, 43.1(18.7, 23.8(3.3 μg/dl); VC (0.57(0.34, 0.68(0.39, 0.48(0.13 mg/dl); Zn (90.1(16.9, 85.2(29.0, 55.0(23.2 μg/dl); Se (57.6(19.0, 43.4(15.0, 39.7(15.1 μg/L); Alb (3.7(0.8, 3.8(0.8, 3.5(0.6 g/dl); TSF (234(76, 220(55, 166(61 mg/dl); TTR (27.9(8.5, 24.3(8.2, 13.4(2.8 mg/dl); and RBP (4.2(1.6, 4.2(1.4, 2.7(0.6 mg/dl). We conclude that chronic inflammation, especially high levels, exposes the patient to a higher chance of deficient values, that even when considered no genuine deficiency, affect nutrient availability of the body, and then, nutritional state. VA, Zn, Se, TSF, TTR and RBP are the most affected. Supported by UBACyT CB03.
Acute alcohol exposure impairs macrophage function on clearance of apoptotic cells via inhibition of MFG‐E8 gene expression through a H2O2 dependent mechanism
Authors: Wang Xiao , Bu Heng-Fu , Asai Akihiro , Tan Xiao-Di
Published: June 2021

Alcohol is found to inhibit macrophage (MΦ) function on clearance of apoptotic cells. Milk fat globule‐EGF factor 8 (MFG‐E8) is an important molecule for MΦ to identify apoptotic cells. We hypothesized that alcohol impacts MΦ function on clearance of apoptotic cells through alteration of MFG‐E8 levels in MΦ. To this end, we treated mouse MΦ with alcohol (25 mM) for 18 h and processed the cells for determining MFG‐E8 expression, activity of MFG‐E8 gene promoter, and ability of the cells to clearance of apoptotic cells. We found that acute alcohol exposure resulted in repression of MΦ activity on clearance of apoptotic cells. This effect was associated with down‐regulation of MFG‐E8 gene expression as well as reduction of its promoter activity. Recombinant MFG‐E8 (10 nM) rescued alcohol‐treated MΦ from clearance of apoptotic cells, suggesting that down‐regulation of MFG‐E8 contributes to alcohol effect on impairment of MΦ functions on clearance of apoptotic cells. In addition, we revealed that H2O2 mimics alcohol effect on MFG‐E8 gene expression and phagocytosis of apoptotic cells. Antioxidant NAC (10mM) attenuated the alcohol action. Collectively, our data suggest that acute alcohol exposure impairs macrophage function on clearance of apoptotic cells via inhibition of MFG‐E8 gene expression through a H2O2 dependent mechanism. This effect may play an important role in pathogenesis of alcohol‐induced tissue injury. (Supported by NIH R21AA020494 & R01DK064240).
CIKS is critical mediator of isoproterenol/β‐AR induced cardiomyocyte hypertrophy in vitro and in vivo
Authors: Murray David R , Valente Anthony J. , Siebenlist Ulrich , Chandrasekar Bysani
Published: June 2021

Chronic inflammation and persistent activation of sympathetic nervous system play critical roles in the pathophysiology of the hypertrophied failing heart. CIKS (connection to IKK and JNK), also known as Act1, mediates agonist‐induced NF‐κB and AP‐1 activation. Since the β‐AR agonist isoproterenol (ISO) induces the prohypertrophic interleukin (IL)‐18 via NF‐κB and AP‐1, we investigated whether ISO‐induced, IL‐18‐mediated, cardiomyocyte growth is CIKS‐dependent.

Results

ISO‐induced hypertrophy of wild type (WT) mouse cardiomyocytes in vitro was significantly attenuated by CIKS knockdown. Importantly, ISO failed to induce hypertrophy in cardiomyocytes isolated from CIKS null mice. ISO‐induced IKK and JNK activation, NF‐κB and AP‐1 DNA binding and reporter gene activation, Il18 transcription, and IL‐18 mRNA expression and protein secretion were all markedly attenuated by CIKS knockdown. Pre‐treatment with IL‐18BP or IL‐18 neutralizing antibodies also blocked ISO‐induced cardiomyocyte hypertrophy. Infusion of ISO for 7 days induced myocardial hypertrophy in wild type but not CIKS null mice. Myocardial levels of phospho IKK, JNK, p65 and c‐Jun, NF‐κB and AP‐1 DNA binding activity and IL‐18 expression were all markedly attenuated in ISO‐infused CIKS null mice compared to WT mice in vivo.

Conclusions

CIKS is a critical mediator of β‐AR‐induced, IL‐18‐mediated myocardial hypertrophy and failure.
MCC‐555 induces apoptosis through the combination of PPARγ‐dependent and ‐independent pathways in pancreatic cancer cells
Authors: Min Kyung-Won , Baek Seung Joon
Published: June 2021

MCC‐555 is a novel PPARα/γ dual ligand of the thiazolidinedione class that was recently developed as an anti‐diabetic drug with anti‐cancer activity. Nonsteroidal anti‐inflammatory drug (NSAID)‐activated gene (NAG‐1) is involved in pro‐apoptotic and anti‐tumorigenic properties in colorectal and lung cancer, as assessed by NAG‐1 transgenic mice; however, its roles in pancreatic cancer have not been studied. We found that MCC‐555 elicits changes of various genes such as NAG‐1, p21, and cyclin D1, which are involved in cell proliferation and apoptosis. NAG‐1 and p21 expression was not blocked by PPARγ‐specific antagonist GW9662, suggesting that MCC‐555‐induced NAG‐1 and p21 expression is independent on PPARγ activation. However, decreasing cyclin D1 by MCC‐555 seems to be affected by PPARγ activation. For NAG‐1 transcriptional regulation by MCC‐555, the GC box located in the ‐133/+41 NAG‐1 promoter plays an important for NAG‐1 transactivation by MCC‐555 and KLF4 binds to this region. Chip assay confirmed that KLF4 binds to the GC box region in the NAG‐1 promoter and regulates NAG‐1 expression in response to MCC‐555. Further, expression of KLF4 precedes NAG‐1 and p21 expression in the presence of MCC‐555. Therefore, MCC‐555′s actions on anti‐tumorigenesis involve in both PPARγ‐dependent and ‐independent pathways, thereby enhancing anti‐tumorigenesis in pancreatic cancer cells.
The Function of FIT Proteins in Triglyceride Storage
Authors: Silver David L
Published: June 2021

Fat storage‐Inducing Transmembrane proteins 1 & 2 (FITM1/FIT1 & FITM2/FIT2) are an evolutionarily conserved family of endoplasmic reticulum resident membrane proteins that play an important role in the formation of triglyceride lipid droplets (LDs). FIT1 and FIT2 have 6 transmembrane domains with their N‐ and C‐termini facing the cytosol. However, FIT proteins do not have similarities to known protein domains, making it difficult to infer mechanism based on primary sequence. We have utilized both novel in vitro biochemical assays and mouse transgenic and gene‐targeted knockouts of FIT genes to determine function. These studies aimed at understanding the biochemical mechanism and physiological function of FIT proteins will be presented.
Effects of methamphetamine self‐administration and withdrawal on sleep in rhesus monkeys
Authors: Diaz Maylen Perez , Andersen Monica , Murnane Kevin , Howell Leonard
Published: June 2021

Published studies indicate that methamphetamine (METH) abuse may lead to impaired sleep and a higher risk of developing sleep disorders which could contribute to continued drug use. To understand the effects of METH abuse on sleep, we determined how METH self‐administration (SA) in rhesus macaques alters sleep parameters. The subjects were trained to self‐administer METH under a fixed‐ratio schedule of reinforcement in 60‐minute sessions conducted 5 days per week. We measured sleep parameters such as the latency to fall asleep, the duration of sleep, and sleep fragmentation using actigraphy‐based monitors. We also determined the effects of METH SA on sleep by examining several weeks of baseline sleep measures prior to each bout of METH SA, sleep parameters during 5‐week bouts of METH SA, and several weeks of sleep parameters following each bout of METH SA. METH SA elicited modest sleep fragmentation, but did not alter sleep latency or duration when the unit dose available for SA was 0.01 mg/kg and the maximum dose available per day was 0.6 mg/kg. METH induced sleep fragmentation during the active bout of METH SA, but sleep returned to baseline levels within the first week after METH SA. Different effects were apparent when the unit dose available for SA was 0.03 mg/kg. We will further elucidate the effects of METH on sleep and we will determine whether sleep‐promoting drugs reverse these effects.
Effects of non‐contingent and contingent quipazine on heroin self‐administration in rhesus monkeys
Authors: Maguire David Richard , France Charles P.
Published: June 2021

Selective 5‐HT receptor agonists enhance the antinociceptive effects of morphine at doses that attenuate its discriminative stimulus effects, suggesting that these compounds might enhance the therapeutic effects of opioids without enhancing their abuse liability. This study examined the effects of the 5‐HT2A receptor agonist quipazine on heroin self‐administration under two conditions: in one experiment (n=4), quipazine (0.32–3.2 mg/kg) was administered i.v. 5 min prior to a heroin (0.0032–0.1 mg/kg/infusion, i.v., FR 30) self‐administration session; in a second experiment (n=3), quipazine (0.32 mg/kg/infusion) was self‐administered alone and in combination with heroin. Non‐contingent administration of quipazine enhanced responding for saline and for small doses of heroin in 3 monkeys and attenuated responding for heroin in a fourth monkey. Quipazine alone (contingent) did not maintain responding and in combination with heroin did not clearly enhance the reinforcing effects of heroin. Increased responding for some doses of heroin in the presence of quipazine in both studies could be due to a reinstatement‐like effect of quipazine. These results provide support for the view that 5‐HT receptor agonists might enhance therapeutic effects of opioids without enhancing abuse liability. Supported by USPHS Grants R01DA05018, K05DA017918, CPF, T32DA031115, DRM.
The Zebrafish Neurophenome Database (ZND): a dynamic open‐access resource for zebrafish neuroscience research
Authors: Kyzar Evan , Zapolsky Ivan , Gaikwad Siddharth , Green Jeremy , Roth Andrew , Stewart Adam , Collins Christopher , Monnig Louis , Davis Ari , El-Ounsi Mohamed , Freeman Andrew , Capezio Nicholas , Kalueff Allan
Published: June 2021

Zebrafish (Danio rerio) are widely used in neuroscience research, where their utility as a model organism is rapidly expanding. Low cost, ease of experimental manipulations and sufficient behavioral complexity make zebrafish a valuable tool for high‐throughput studies in biomedicine. To complement the available repositories for zebrafish genetic information, there is a growing need for the collection of zebrafish neurobehavioral and neurological phenotypes. For this, we are establishing the Zebrafish Neurophenome Database (ZND; www.tulane.edu/~znpindex/search) as a new dynamic online open‐access data repository for behavioral and related physiological data. ZND, currently focusing on adult zebrafish, combines zebrafish neurophenotypic data with a simple, easily searchable user interface, which allow scientists to view and compare results obtained by other laboratories, using various treatments in different testing paradigms. As a developing community effort, ZND is expected to foster innovative research using zebrafish by federating the strong body of zebrafish neurophenotypic data. This study was supported by the National Institute on Drug Abuse (NIDA) R03 grant to AVK.
PFOA‐mediated regulation of Bcrp transporter expression and function
Authors: Eldasher Lobna M , Yacovino Lindsay , Wen Xia , Aleksunes Lauren M
Published: June 2021

Due to prior industrial use and lack of biodegradability, perfluorooctanoic acid (PFOA) has accumulated in human serum, which may have negative health effects. However, transporter‐mediated excretion of PFOA has not yet been elucidated. The purpose of this study was to determine if interactions exist between PFOA and the breast cancer resistance protein (BCRP/ABCG2), an efflux transporter found in hepatocytes and renal proximal tubule cells. ATPase assay and membrane vesicle experiments were used to assess PFOA interactions with BCRP. Protein and mRNA were measured in kidneys and livers of male C57BL/6 mice treated with PFOA (1 or 3 mg/kg/d po for 7 days). In the ATPase assay, PFOA decreased transporter activity in sulfasalazine‐activated BCRP membranes. PFOA inhibited BCRP‐mediated transport in membrane vesicles between 47 and 69% at high concentrations (25 and 50 μM). As expected, PFOA treatment increased liver weights and hepatic and renal Cyp4a14 mRNA and protein in mice. Likewise, Bcrp mRNA and protein increased in livers by 136% and 128% from baseline, respectively. In kidneys, Bcrp protein levels were elevated 50% and a trend for increased mRNA was observed. In conclusion, PFOA induces Bcrp protein and mRNA transcript levels in mice and may inhibit Bcrp transporter function at high concentrations; whether inhibition is competitive or allosteric was not evident.
Subunit dependent modulation of ASIC currents by intracellular pH
Authors: Li Minghua , Ingram Susan L , Simon Roger P , Xiong Zhigang
Published: June 2021

Activation of acid‐sensing ion channels (ASICs) plays an important role in acidosis‐mediated, glutamate receptor‐independent ischemic brain injury. Although ASICs are activated by a decrease in extracellular pH, our recent studies have demonstrated that neuronal ASICs are closely regulated by changes of intracellular pH (pHi). Since ASICs in native neurons are composed of different subunits with distinct electrophysiological/pharmacological properties, we determined whether the modulation of the ASIC activity by pHi is subunit dependent and determined potential sites on the ASIC channel involved in the modulation by pHi. We show that the potentiation of ASICs by pHi alkalizing agent quinine depends on the presence of the ASIC1a or 2a subunits. Similar to its effect on the ASICs in native neurons, increasing intracellular pH shifted the activation curves of the ASIC1a and 2a channels to less acidic pH values while the steady state inactivation curve was shifted to more acid pH values. To identify the amino acids involved in the modulation of ASICs by pHi, the effects of quinine on point mutation mutants were determined. Quinine still potentiates ASIC currents in ASIC1a K4R, S17A, Q19A, Y36A and L39A mutants. Quinine also potentiates ASIC currents from ASIC1b (N‐1‐42aa)/1a(43aa‐C‐terminus) chimeras. However, quinine failed to potentiate the current from an ASIC1b(N‐1‐52aa)/1a(54aa‐C‐terminus) chimera.
Hydrogen Sulfide as an allosteric modulator of ATP sensitive potassium channels in experimental colitis
Authors: Gade Aravind R , Kang Minho , Akbarali Hamid I
Published: June 2021

The ATP sensitive potassium channel (KATP) in mouse colonic smooth muscle cell is a complex containing a pore forming subunit (Kir6.1) and a sulfonyl urea receptor subunit (SUR2B). We used whole‐cell voltage‐clamp techniques to study the alterations in these channels in smooth muscle cells in experimental colitis. Colitis was induced in BALB/C mice following an intracolonic administration of trinitrobenzene sulfonic acid. KATP currents were measured at Vh −60 mV in high K+ external solution. The dose‐response to levcromakalim (LEV), a KATP channel opener, was significantly shifted to the left in the inflamed smooth muscle cells. Both the affinity and maximal currents induced by LEV were enhanced in inflammation. The EC50 in control was 6489 nM (n=10) and 423.4 nM (n=8) in inflamed colon while the maximal currents were 9.3 ± 1.1 pA/pF (60 μM) in control and 47.7 ± 16.8 pA/pF (3 μM) following inflammation. Similar to LEV, KATP currents activated by sodium hydrogen sulfide (NaHS) (10–1000 μM) were significantly greater in inflamed compared to controls. In control cells, pretreatment with 100 μM NaHS shifted the EC50 for LEV‐induced currents from 6489 nM (n=10) to 180.9 nM (n=8). These data suggest that NaHS can act as an allosteric modulator for LEV‐induced KATP currents. Decreased colonic motility may result from enhanced KATP activation by increased release of H2S in colitis. Supported by NIH DK046367.
Pharmacological characterization of the rhesus monkey TRPA1 channel
Authors: Bianchi Bruce R , Zhang Xu-Feng , Reilly Regina M , Kym Philip R , Yao Betty B , Chen Jun
Published: June 2021

The transient receptor potential ankyrin‐1 (TRPA1) channel is an attractive drug discovery target for pain and inflammation. Drug discovery has been hampered, however, by differences between human and rodent species. To further explore the scope of these species differences, we cloned and functionally characterized the rhesus monkey TRPA1 channel. The rhesus monkey TRPA1 channel showed a robust response to mustard oil (MO) in whole‐cell patch clamp recordings and Ca2+ influx assay, and furthermore, the response was completely blocked by the selective TRPA1 antagonist A‐967079. An in‐depth pharmacological characterization of rhesus monkey TRPA1 was carried out, and its profile was compared to human, rat and mouse TRPA1 channels. Menthol, caffeine and various ‘hits’ from real‐life drug screening displayed species‐specific differential pharmacology at TRPA1. The pharmacological profile of the rhesus monkey TRPA1 channel was found to be similar to the human TRPA1 channel. In contrast, the rat and mouse TRPA1 channels closely resembled each other, but were pharmacologically distinct from either human or rhesus monkey TRPA1 channels. Our findings demonstrate that TRPA1 function differs between primate and rodent species, and suggest that rhesus monkey could serve as a surrogate species for humans in preclinical studies. Supported by Abbott.
Modulation of AMPA and kainate receptors by galectins
Authors: Bhangoo Sonia , Copits Bryan , Nakamura Yuka , Frausto Shanti , Robbins John , Gill Martin B , Smith Caleb , Ogawa Tomohisa , Muramoto Koji , Sakai Ryuichi , Swanson Geoffrey T.
Published: June 2021

N‐glycans covalently attached to integral membrane proteins on neurons act as a reservoir for considerable structural diversity and represent potential sites of modulation by oligosaccharide‐binding proteins known as lectins. We found that galectins, a family of galactose‐binding lectins, act as allosteric modulators of ionotropic glutamate receptors (iGluRs) and engage signaling pathways that lead to alterations in dendritic structure. These proteins could potentially impact synaptic transmission and likely have diverse effects on neuronal signaling in the mammalian CNS.

Natural galectins isolated from a marine sponge and the Conger eel, as well as recombinant human galectin‐1, exhibited diverse activity on iGluRs. Several types of receptors, including GluA4 AMPA and GluK2 kainate receptors, responded with slowed desensitization kinetics and increased steady‐state currents. Peak current amplitudes from homomeric GluA1 AMPA and GluK1 kainate receptors were reduced. AMPA and kainate receptors assembled with their respective auxiliary proteins, stargazin and NETO, also were sensitive to allosteric modulation. Galectin modulation of GluK2 receptor function was eliminated by mutation of three extracellular asparagines near the ligand‐binding domain. Hippocampal neurons exposed to galectin‐1 exhibited rapid activation of the MAPK/Erk signaling pathway and longer‐term alterations in neuronal morphology. This spectrum of effects suggests that galectins could impact neuronal function through actions on a variety of signaling pathways. Because they are secreted at high levels in several pathological states, their activity on neurons could potentially exacerbate excitotoxicity.