bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of resistance training combined with daily consumption of an egg‐based or bagel‐based breakfast on lipid concentrations and blood pressure
Authors: Hobb Kylee , Clayton Zachary , Shelechi Mahshid , Hernandez Lisa M. , Barber Anjee , Petrisko Yumi , Hooshmand Shirin , Kern Mark
Published: June 2021

Eggs have been negatively perceived by consumers for many years due to cholesterol content; however, recent studies have not demonstrated a clear adverse influence of eggs on blood lipids. Furthermore, exercise training promotes improved lipids and blood pressure. Our purpose was to examine the effect of eating isoenergetic (400 kcal) egg‐based (including two eggs per day) versus bagel‐based breakfasts daily combined with resistance training 3 times per week prior to breakfast on plasma lipids and blood pressure. Twenty healthy adult men and women (18–35 years of age) participated in the 12‐week study following random assignment to study groups. Lipids and blood pressure were examined at baseline and after 6 and 12 weeks. Diastolic blood pressure decreased (p<.05) in both groups; however, systolic blood pressure was only statistically reduced (p<.05) in those eating egg‐based breakfasts. No significant effects on TC, TG, HDL‐C or LDL‐C were detected; however, following a non‐significant transient increase (8%) after 6 weeks, the ratio of HDL‐C:LDL‐C was significantly (p<.05) reduced by 14% from week 6 to 12 in the egg group. Overall, daily breakfasts including two eggs for 12 weeks did not adversely affect lipids during a resistance training program and promoted improvements in blood pressure that appear to be better than those occurring with daily bagel‐based breakfast intake. Supported the Egg Nutrition Center.
Effect of Chlorella vulgaris on serum cholesterol‐regulation in healthy subjects and hypercholesterolemia
Authors: Ryu Na Hee , Kim Sang Mi , Park Ji Eun , Lee Yoon Jung , Kim Ji Yeon , Kwon Oran
Published: June 2021

Recently, patients with hyperlipidemia including hypercholesterolemia have increased steadily as dietary habit has been changed to western style based on high‐fat diet. Since hypercholesterolemia can develop serious cardiovascular diseases such as myocardial infarction, stroke and atherosclerosis, studies to prevent and treat this have been consistently reported. Chlorella contains a variety of nutrients such as chlorophyll, vegetable protein, essential amino acids, vitamins and dietary fiber. And its function has been approved in the aspects of its antioxidant capacity and enhancement of immune function. In the previous study, cholesterol level reducing effect has been confirmed in animal.

Therefore, this study aimed to confirm that ingestion of chlorella for normal subjects interferes with the absorption of cholesterol coming from high cholesterol diet and lowers the blood cholesterol level. Additionally, it aimed to confirm the reduction of blood cholesterol level before and after ingestion of chlorella for patients with hypercholesterolemia. This study is a randomized, parallel‐group, double‐blind, placebo‐controlled trial.

Besides cholesterol level, in order to confirm the extent of systemic absorption of carotenoids, the major active component of chlorella, we analyzed the level of lutein, zeaxanthin, alpha‐carotene, beta‐carotene, lycopene by HPLC in the serum before and after ingestion of chlorella.
Palm olein increases plasma cholesterol moderately compared with olive oil in healthy individuals
Authors: Tholstrup Tine , Hjerpsted Julie , Raff Marianne
Published: June 2021

Background

Despite the high content of palmitic acid, palm olein was demonstrated to have a neutral effect on plasma cholesterol concentration when compared with olive oil, suggested to be due to palmitic acid in the sn‐1 and sn‐3 position.

Objective

to investigate the effects of a diet rich in palm olein (fractionated palm oil), olive oil and lard on plasma blood lipids, inflammatory markers, glucose and insulin.

in a controlled double‐blinded, randomized 3 × 3 weeks crossover dietary intervention study, including 32 healthy men, who daily replaced part of their habitual dietary fat intake with approximately 17 energy percent (E%) from palm olein, olive oil or lard, respectively.

Results

Compared with intake of olive oil, palm olein and lard increased total cholesterol and LDL cholesterol (P < 0.0001). Palm olein resulted in a lower plasma triacylglycerol (TAG) concentration than olive oil (P < 0.01). No difference in effects was observed in plasma HDL cholesterol, high sensitive C‐reactive protein (hsCRP), plasminogen activator 1 (PAI‐1), insulin and glucose concentrations.

Conclusion

The present study did not support findings of palm olein being neutral compared to olive oil in regard to total plasma cholesterol and LDL cholesterol in healthy individuals with normal plasma cholesterol concentrations. Thus, the sn‐positioning was not confirmed to be important in regard to effect on plasma cholesterol.
Effects of high‐fat high‐fructose diet and EPA supplementation on adipose tissue gene expression in adult rats
Authors: Leray Véronique , Jonchère Camille , Zaman Muhammad-Quaid , Nguyen Patrick
Published: June 2021

The study of expression of genes involved in obesity‐related disorders provides a tool to elucidate the links between obesity, loss of insulin sensitivity (IS), and dyslipidemia. Our aim was to measure the effects of a high‐fructose diet and EPA supplementation on metabolic status and mRNA expression of genes involved in insulin‐signaling pathway, and glucido‐lipid metabolism in rats.

Rats were given for 10 wk either control diet or high‐fat high‐fructose diet (40% fructose, 40% lipid cal), supplemented or not with EPA (120 mg/d). At the end of the 10‐wk period, body composition and IS were assessed, lipid plasma were assayed, and mRNA expression of insulin receptor, IRS1, perilipin, leptin, ACC, FAS, HSL, LPL, GLUT, TNFα, SREBP‐1c, PPARγ was semi‐quantified from adipose tissue biopsies.

In rats fed with high‐fat high‐fructose diet, plasma cholesterol level was higher than in control rats, as well as ACC and FAS mRNA levels. In rats fed with the same diet plus EPA, plasma cholesterol level was lower and PPARγ mRNA level higher compared with the rats fed with high‐fat high‐fructose diet.

Our results show changes in expression of lipogenic genes in rats fed high‐fat high‐fructose diet, that could reflect the obesogenic effect of such a diet. They also show that EPA could stimulate the transcription of PPARγ that could account for its beneficial effect on lipidemia.
Antioxidant capacity of tomato paste is stable during growing season and shelf‐life
Authors: Meckna Brian , Reimers Kristin , Mark Andon
Published: June 2021

Few data exist regarding the effect of growing season and shelf life on the stability of the antioxidant capacity of foods. To assess these factors in commercially available tomato paste, the sum of lipophilic and hydrophilic antioxidant capacity [oxygen radical absorbance capacity (ORAC), Brunswick Laboratories, Norton, MA] was measured in composite samples comprised of production lots prepared from tomatoes harvested during early, middle, and late growing season periods early in their shelf life (± 6 months) and at 12 and 18 months post‐production. All composites comprised 12 individual consumer units from the same production lot and where measured in duplicate. ORAC for tomato paste produced from early growing season tomatoes was 1341 (μmole Trolox equivalents/100 g). Values for composites made from tomatoes from middle and late growing season harvest were 109% and 118% greater, respectively. Compared to composites measured within 6 months post‐production, ORAC values were 105% and 109% greater at 12 and 18 months post‐production, respectively. These data demonstrate neither within season growing period, nor storage time, adversely affects the antioxidant capacity of tomato paste.

Supported by ConAgra Foods
Changes in lipid soluble antioxidants after computer tomography in children
Authors: Franke Adrian A. , Halm Brunhild M , Lai Jennifer F , Morrison Cynthia M , Custer Laurie J , Cooney Robert V
Published: June 2021

Objective

Computer tomography (CT) involves ionizing Xray‐radiation which can form free radicals. CT use has risen dramatically due to its high speed and diagnostic value but it leads to an estimated lifetime cancer risk of up to 4% with highest risk for children. We tested whether free radical scavenging antioxidant levels in children change after CT.

Methods

17 children aged 0.25–6 years and scheduled for medically indicated CT donated blood immediately before and 1 hour after a CT exam (93–526 mGy cm). Blood was immediately processed after the second blood draw and heparin plasma was frozen until analysis. HPLC with photodiode‐array (carotenoids, tocopherols, retinols) or electrochemical (coenzyme Q10) detection was applied. Significance was determined by paired t‐tests.

Results

In post versus pre CT plasma levels of carotenoids increased: lutein/zeaxanthin (−4%), cryptoxanthins (−8%), lycopenes (−8%), and total carotenes (−8%), as did those for tocopherols (a, −6%; B+y, −6%). Reduced (+24%), oxidized (+8%), and total (+22%) Q10 levels were higher (p>0.1) and retinol level was unchanged. After data were logged only cryptoxanthins and lycopenes lost significance.

Conclusions

The decrease of main lipid soluble antioxidants after CT in children may be due to free radical scavenging, thereby preventing damage. The increase in plasma Q10 levels after CT could be due to greater cell death.
Zinc transporter gene expression in type 2 diabetes mellitus is coordinated
Authors: Foster Meika , Chu Anna , Petocz Peter , Samman Samir
Published: June 2021

This study investigates the expression levels of zinc transporter and metallothionein (MT) genes in the mononuclear cells of 41 women with type 2 diabetes mellitus (DM) using Taqman real‐time PCR. It also explores the relationships between zinc transporter expression, plasma zinc concentrations, and dietary zinc intake. The mRNA level of Zip1 was correlated with the mRNA of intracellular zinc transporters ZnT5, ZnT7, and Zip7 (P<0.001). ZnT8 mRNA expression was detected in 21 participants. In the absence of constitutive ZnT8 gene expression, a higher (P<0.05) ZnT5 mRNA level was observed. In a stepwise regression analysis, MT‐2A mRNA (P=0.002) and dietary zinc intake (P=0.02) were identified as predictors of the plasma zinc concentration. The coordinated expression of Zip1 (cellular zinc import) and zinc transporters that sequester zinc within intracellular organelles is an important mechanism for the maintenance of cellular zinc homeostasis in DM. ZnT8, which is highly expressed in the pancreas, is not constitutively present in mononuclear cells; modulation of intracellular ZnT5 may compensate for its absence. Research support was provided by The Sydnovate Fund (University of Sydney) and The MAWA Trust.
Multi‐nutrient fortified juices improve vitamin D and vitamin E status in children
Authors: Moore Carolyn Elizabeth , Economous Christina D , Holick Michael F.
Published: June 2021

We examined whether children consuming orange juice (OJ) fortified with calcium (Ca) and combinations of vitamins D, E and A could increase serum 25‐hydroxyvitamin D [25(OH)D], alpha‐tocopherol, and retinol levels. Boys and girls (6 to 12 yr) were recruited (n=179) and randomized into 3 groups: CaD (700 mg Ca+ 200 IU vitamin D), CaDEA (700 mg Ca + 200 IU vitamin D + 12 IU vitamin E + 2000 IU vitamin A as beta‐carotene), or Ca (700 mg Ca). Children consumed two 240 mL glasses of CaD, CaDEA, or Ca OJ for 12 weeks. We hypothesized the mean increase of 25(OH)D would be 1 SD higher in children consuming vitamin D fortified juice. Multivariate models and repeated measures of ANOVA tested for group differences. Baseline 25(OH)D was 27.4 ± 11.1 ng/mL with 26.2% deficient (≤ 20 ng/mL). The 25(OH)D increase in the CaD group was greater than the Ca group (P = 0.029). The increase in alpha‐tocopherol in the CaDEA group was greater than the Ca or CaD groups (P < 0.001). Retinol levels were not increased. Daily consumption of OJ providing 700 mg Ca and 200 IU of vitamin D improved 25(OH)D levels and provision of 12 IU vitamin E increased alpha‐tocopherol levels in children without gaining undesirable weight greater than expected growth changes. Support: Beverage Institute for Health & Wellness.
Lower dietary n‐6 polyunsaturated fatty acids: eicosapentaenoic acid plus docosahexaenoic acid ratio decreases the expression of inflammatory factors in livers and visceral adipose tissue in LDL receptor null mice
Authors: Wang Shu , Wu Dayong , Matthan Nirupa R , Lichtenstein Alice H
Published: June 2021

The effect of an atherogenic diet with different ratios of n‐6 polyunsaturated fatty acids to eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) on the expression of inflammatory factors in livers and visceral adipose tissue was assessed in LDL receptor null (LDLr−/−) mice. Mice were fed a high saturated fat diet (20% fat, 0.2% cholesterol, w/w) without EPA and DHA (HF n‐6), or with n‐6:EPA+DHA at ratios of 20:1 (HF R = 20:1), 4:1 (HF R = 4:1), and 1:1 (HF R = 1:1) for 32 weeks. The fatty acid profile in livers and adipose tissue was measured using gas chromatography. The mRNA levels of interleukin‐6 (IL‐6), tumor necrosis factor alpha (TNFα), monocyte chemoattractant protein‐1 (MCP‐1), and macrophage biomarkers including CD68 and F4/80 were measured using real‐time PCR. Tissue fatty acid profile reflected that of the diets. Mice fed the lower n‐6:EPA+DHA ratio diets had significantly lower mRNA levels of the above inflammatory factors and biomarkers compared to mice fed the HF n‐6 diet in livers and adipose tissue in LDLr−/− mice. These data suggest that lower n‐6:EPA+DHA ratio diets lowered some measures of inflammation in LDLr−/− mice.
Aronia melanocarpa (chokeberry) polyphenol rich extract reduces plasma cholesterol and improves antioxidant function in Apolipoprotien E knockout mice
Authors: Kim Bohkyung , Ku Chai Siah , Pham Tho , Park Youngki , Martin Derek , Xie Liyang , Taheri Rod , Lee Jiyoung , Bolling Bradley
Published: June 2021

The objective of this work was to evaluate the effect of polyphenol‐rich chokeberry extract (CBE) on lipid metabolism and antioxidant function in a mouse model for atherosclerosis. Male apoE−/− mice were fed a high fat/high cholesterol diet (15% fat, 0.2% cholesterol by wt) supplemented with 0.005% or 0.05% of CBE by wt for 4 weeks (n = 10/group). The 0.05% CBE diet provided daily doses of 0.19 mg anthocyanins, 0.17 mg phenolic acids, 0.06 mg proanthocyanidins, and 0.02 mg flavonoids. Mice consuming 0.05% CBE had ~20% lower plasma total cholesterol concentrations compared with control, without altering triglyceride levels. Despite the hypercholesterolemic effect of CBE, mRNA levels of low‐density lipoprotein receptor and HMG‐CoA reductase in CBE‐fed mice were not significantly different from controls. Dietary CBE did not alter hepatic lipids or expression of genes involved in lipogenesis and fatty acid β‐oxidation. Dietary 0.05% CBE increased plasma paraoxonase‐1 (PON1) activity 39%, but did not affect glutathione peroxidase and superoxide dismutase activities. Thus, dietary CBE improves antioxidant function and its cholesterol‐lowering effect may be independent of hepatic cholesterol metabolism. Supported by College of Agriculture and Natural Resources and Research Foundation at the University of Connecticut.
The Effect of Dietary Zinc Level over the IgG response in a Murine Model of Giardiasis
Authors: Iñigo-Figueroa Gemma , Maldonado-Fonllem Gabriela , Quihui-Cota Luis , Mendez-Estrada Rosa Olivia , Velasquez-Contreras Carlos , Canett-Romero Rafael , Rascon-Duran Lucila , Garibay-Escobar Adriana , Robles-Zepeda Ramon , Astiazaran-Garcia Humberto
Published: June 2021

Zinc is an essential micronutrient influencing growth and affecting the development and integrity of the immune system. It was of interest to evaluate the effect of varying dietary zinc level on host resistance to infection. The parasite Giardia lamblia, which infects millions of people around the world was chosen as a model for the study. CD1 mice (80 male 6–8wk old) were fed ad libitum on either low‐zinc, adequate, supplemented 1 or supplemented 2 diet (12.8, 24.6, 57.9 and 309.3 mg Zn/kg diet respectively). After 10 days on the experimental diets, part of the mice from each group were infected with 5×106 G. lamblia trophozoites. Body weight gain was recorded throughout the study. Serum zinc and IgG levels were measured. In all infected dietary groups, seric zinc levels and body weight gain were reduced in comparison to their uninfected counterparts (P=0.03). However, the effects were more pronounced in the low diet group irrespective of the infection. Within 2 weeks following immunization, the mice in all four dietary groups responded by producing significant levels of specific IgG antibodies. Greater IgG antibody response was observed in the zinc supplemented groups when comapred to the low or adequate ones (P<0.05). It appears that zinc supplementation triggers a higher production of IgG and so suggests that zinc was effective in up‐regulating the host's immune response against this parasite.

CONACyT 151287
Inhibitory effects of dietary resveratrol on allergic responses in mast cells and passive cutaneous anaphylaxis in mice
Authors: Han Seon-Young , Kang Young-Hee
Published: June 2021

Resveratrol is a polyphenol rich in the skin of red grapes and is effective in anti‐tumor and anti‐inflammation. We investigated the suppressive effects of resveratrol on IgE‐mediated allergic response in RBL‐2H3 mast cells and on passive cutaneous anaphylaxis (PCA) in mice. Mast cells sensitized with anti‐DNP‐IgE and subsequently stimulated by DNP‐HSA increased the release of β‐hexosaminidase enzyme and histamine, indicative of mast cell degranulation. This induction was diminished by nontoxic resveratrol at 1–25 μM. Western blot analysis showed that 1–25 μM resveratrol dose‐dependently mitigated the induction of FcεRI responsible for the IgE binding onto mast cells. Protein expression levels of Syk, PLCγ and PKC, all involved in allergic responses, were enhanced in activated mast cells and such levels were dampened by resveratrol. Furthermore, the Evans blue staining was evident in the ear of IgE‐mediated mice, which was diminished by oral administration of 10 mg/kg resveratrol. Edema, a usual component of most allergic reactions, apparent in the ear and dorsal skin was alleviated by resveratrol administration to IgE‐mediated mice. Taken together, the anti‐allergic responses of resveratrol suggest possible therapeutic strategies in preventing allergic diseases possibly through inhibiting mast cell degranulation and ameliorating passive cutaneous anaphylaxis.
Lessertia frutescens (Sutherlandia), an African herb, modulates reactive oxygen species (ROS) and nitric oxide (NO) generation by murine macrophages
Authors: Lei Wei , Browning Jimmy , Eichen Peggy , Lu Chi-Hua , Folk William , Fritsche Kevin
Published: June 2021

Lessertia frutescens (Sutherlandia) is a medicinal plant native to southern Africa and is currently in clinical trials as a co‐therapy for HIV/AIDS patients in South Africa. Our laboratory is investigating the immune‐modulatory activities of this herb. In these experiments we sought to better characterize the impact of Sutherlandia on ROS and NO generation by macrophages. Various concentrations of aqueous and ethanolic extracts of Sutherlandia were cultured with a murine macrophage cell line (i.e., RAW 264.7 cells). Surprisingly, we found that the aqueous extract significantly enhanced (i.e., more than doubling) basal and immune‐stimulated ROS generation by RAW cells. In contrast, the ethanolic extract consistently decreased ROS production by as much as 30%. Similar results were observed when primary peritoneal macrophages from BALB/c mice were used instead of the macrophage cell line. The impact of Sutherlandia on macrophage NO production was generally similar to our findings with ROS, however, the ability of the aqueous extract to stimulate NO production was much more modest than its impact on ROS. Our results suggest that Sutherlandia possesses immune‐modulating components that can both stimulate and inhibit critical functions of phagocytes. The net effect of this herb on the immune system may depend upon how it is prepared as well as which part of the immune response one investigates.
Nutritional risk factors for hookworm infection among school age children in the Kintampo North Municipality, Ghana
Authors: Humphries Debbie , Simms Benjamin , Davey Dylan , Otchere Joseph , Quagraine Josephine , Berg Elyssa , Newton Samuel , Harrison Lisa , Boakye Daniel , Wilson Michael , Cappello Michael
Published: June 2021

Hookworm is highly prevalent in the Kintampo North Municipality of Ghana, and a previous study identified a significant relationship between BMI and infection status in adults.

Objectives

To investigate the role of nutritional status and dietary risk factors on hookworm infection and response to deworming treatment in school‐age children.

Methods

Children (n=812) ages 6 to 11 years attending 16 schools were screened for participation on the basis of HAZ scores (low and high). Household level food security and socioeconomic variables, child‐level dietary diversity, hookworm and malaria infection status and response to albendazole were measured in a cross sectional sample (n=286).

Results

Prevalence of hookworm was 39%, and anemia was 62%. Significant risk factors for hookworm infection included lower consumption of protein‐rich food groups (p<0.05), malaria co‐infection (p<0.05), access to health care (p<0.01), and household geographic location (p<0.05) after controlling for age, gender, household wealth, and recent deworming. The degree of stunting and anemia did not correlate with hookworm infection status.

Conclusions

Dietary diversity may influence the risk of hookworm infection in Ghana. In areas of high prevalence but low intensity infection, hookworm may not cause traditionally recognized clinical sequelae such as anemia and stunting.
The impact of sociocultural influences on the eating attitudes of Lebanese and Cypriot students: a cross‐cultural study
Authors: Zeeni Nadine , Gharibeh Nathalie , Katsounari Ioanna
Published: June 2021

The aim of this comparative cross‐cultural study was to explore the relationship between eating behavior and sociocultural attitudes towards appearance and body image in female university students from two distinct cultural contexts, Cyprus and Lebanon. The Dutch Eating Behavior questionnaire (DEBQ) and the Perceived Sociocultural Influences on Body Image and Body Change Questionnaire were used to assess the different variables in 200 students from each culture. Results indicated that the Lebanese students engaged more in emotional and external eating and were impacted to a larger extent by sociocultural influences including media influences compared to the Cypriot students. In addition, a positive relationship was found between emotional and external eating in both cultures. Finally, significant correlations were found between sociocultural influences and eating scores only in the Cypriot sample. Culture specific factors such as the individualistic or collectivistic aspect of the culture, the societal values and norms specific to Lebanon and Cyprus as well as the westernization history of each are discussed as underpinnings for the dissimilarities found among the two samples. These findings are significant in understanding the high rise of eating pathology in these two cultures.
Perspectives of Nigerian policy actors concerning NCDs
Authors: Adeyemi Olutayo Adedayo , Pelletier David
Published: June 2021

Previous studies have documented the increasing burden of non communicable diseases (NCDs) in developing countries, including Nigeria. The WHO and other bodies have emphasized the need for a “sound and explicit government policy” as fundamental for the prevention and control of NCDs. The formulation of such a policy, in turn, requires a certain level of awareness, understanding and concern among policy makers. This research assessed the perspectives of federal and state policy actors in Nigeria about NCDs, where preliminary research revealed some limited policy awareness of NCDs but no official policy document. Key policy actors were identified using the snowball sampling technique. The perspectives of participants were assessed using the Q‐methodology and interviews. Three dominant groups were identified. All groups believe that NCDs are a serious problem in Nigeria and that effective action, which has been slow till date, is possible within the system. However, there were differences in the emphasis of each of the groups. One group emphasized collective action, another focused on individual responsibility, and the third group stressed the effectiveness of local institutions. The study found that some type of policy attention on NCDs is likely in the immediate future, but it may not be the concerted multi‐sectoral efforts urged by global authorities.

Research support: Division of Nutritional Sciences, Cornell University; Mario Einaudi Center for International Studies, Cornell University; First Presbyterian Church in Ithaca International Hunger Student Grant
The Use of Mixed Methods Evaluation for Effective Program Scale up
Authors: Phillips Erica Lyn , Pelletier David , Gervais Suzanne , Stoltzfus Rebecca , Young Sera , Michaud Lesly
Published: June 2021

Many international nutrition programs struggle with achieving effectiveness at scale. Requisites for program success at scale include sound program theory, the ability to be adapted by varied implementing organizations in diverse contexts and timely monitoring and evaluation.

Our purpose was to identify and resolve bottlenecks for a large maternal and child health mobile clinic program in rural Haiti before national scale up. A participatory workshop based on the Program Assessment Guide was held with staff from all program levels to systematize contextual knowledge of the delivery systems for iron folic acid (IFA) supplements and related behavior change communication. Workshop participants produced an operations research agenda which was implemented in addition to a survey of program beneficiaries and an assessment of anemia prevalence.

This research uncovered important constraints that need to be remedied before effective scale up, such as irregularities in the IFA supply chain, inconsistent implementation of clinics and gaps in the monitoring and evaluation system. The operations research clarified the reasons for these problems and the survey characterized clinic access and attendance and IFA behavior. Mixed methods and triangulation of results were critical for insight and staff participation was instrumental for the utilization of findings.

Research support: USAID, NIH/NIDDK
Enhancing protein quality by lysine and soy protein prevents growth suppression under protein, energy and micronutrient restriction in young male rats
Authors: Furuta Chie , Murakami Hitoshi
Published: June 2021

Malnutrition is linked to suppression of linear growth which leads to stunting of children in developing countries. Some evidence indicates that micronutrient supplementation prevents growth suppression, but dependence on poor quality dietary protein such as maize, may also be a risk factor. To understand the effect of dietary protein quality on the prevention of growth suppression, linear growth was compared in young male rats (4 week‐old) fed a 70% calorically restricted cornmeal (C), C+micronutrient (CM), CM+soy protein (CMS) or CMS+0.3% lysine (CMSK) for 3 weeks (n=5–6 per group). The total calorie intake was equivalent between the groups. The body weight of CM slightly increased compared to the C group, but addition of soy protein (CMS and CMSK) significantly increased body weight (C:15.8±2.6, CM:20.9±2.1, CMS:48.2±2.3 and CMSK:52.3±3.5g). Change in body length had the same tendency as the body weight in each group but was significantly larger in CMSK compared to CMS (C:1.7±0.4, CM:2.0±0.2, CMS:2.8±0.4 and CMSK:3.4±0.3cm,). The addition of protein and lysine altered muscle weight gain and adipose tissue deposition resulting in a decrease of total lean body mass. From these results, improvement of dietary protein quality by using plant source protein and amino acid could potentially prevent growth suppression such as stunting in weaning children in developing countries.
Does High Blood Pressure Increase Perceived Healthiness of Foods with Sodium Claims on the Label?
Authors: Wong Christina L. , Mendoza Julio , L'Abbé Mary R.
Published: June 2021

This study measured Canadian consumers’ perceived clarity of the wording and the healthiness perception of food products carrying different types of claims related to sodium and examined the effect of having high blood pressure (BP) on these perceptions. Online panellists (n=803) were randomly assigned to one of four identical mock canned soup labels carrying the same Nutrition Facts table, differing only by the claim on the label: 1) nutrient content (NC), 2) function claim, 3) disease risk reduction (DRR) claim, or 4) ‘tastes great’ claim acting as a control. Overall, panellists, regardless of BP, rated the NC claim as the most clear, while the function claim was found to be the least clear (p<0.001). DRR and taste claims were intermediate. Despite the NC claim being the most clear, participants perceived the product with the DRR claim as the healthiest, and all 3 sodium claims were perceived healthier than the taste claim (p<0.001). Those with high BP (n=226) consistently rated all products with sodium related claims healthier compared to those with normal BP (p=0.02); furthermore products with sodium claims, irrespectively of the type, were perceived as healthier than the one with the taste claim. This study demonstrates that, although clarity was rated similarly irrespective of BP, having high BP increases the perceived healthiness of products carrying claims mentioning sodium. Supported by: AFMNet; CIHR STIHR

Grant Funding Source : AFMNet; CIHR Strategic Training Program in Public Health Policy (CW); University of Toronto McHenry Chair (ML)
Evaluating the impact of the Nutrition Facts table and front‐of‐pack nutrition rating systems on consumersˈ product healthiness evaluations
Authors: Emrich Teri E. , Mendoza Julio E. , LˈAbbe Mary R.
Published: June 2021

Few studies have examined how consumers use the Nutrition Facts table (NFT) and front‐of‐pack nutrition rating systems (FOPS) when presented with one or both sets of nutrition information, and whether there is an interaction between the two systems. 337 online survey participants were randomized to rate the healthiness of a frozen meal under one of five FOPS conditions, with or without a NFT: 1) no‐FOPS, 2) a manufacturer or 3) a non‐profit style summary indicator system (SIS), or 4) a traffic light or 5) a percent daily value nutrient‐specific system (NSS). Mann‐Whitney U tests were used to evaluate rating differences. When consumers were shown the various FOPS without a NTF, the non‐profit SIS group gave higher healthiness ratings than the NSS groups; the no‐ FOPS and the manufacturer SIS groups gave higher ratings than the percent daily value group (P<0.05). Other group comparisons were not significant. When consumers were shown the various FOPS with a NFT, none of the FOPS groups ratings were significantly different. Between no‐NFT/NFT conditions, consumers in the no‐FOPS and SIS groups gave higher healthiness ratings without a NFT. These results suggest that when provided with additional nutrition information on a product, as in NSSs and NFTs, consumers incorporate this information into their healthiness evaluations. Supported by Dairy Farmers of Canada, AFMNet, & CCO/CIHR Training Grant(#53893)
Macrophages from patients affected by Lysinuric Protein Intolerance (LPI) exhibit an impaired phagocytosis
Authors: Rotoli Bianca Maria , Barilli Amelia , Visigalli Rossana , DallˈAsta Valeria
Published: June 2021

Lysinuric Protein Intolerance (LPI) is a recessive aminoaciduria caused by defective cationic amino acid transport in epithelial cells of intestine and kidney. SLC7A7, the gene mutated in LPI, codifies for the y+LAT1 subunit of system y+L amino acid transporter. LPI patients frequently display severe complications, such as pulmonary disease, haematological abnormalities and disorders of the immune response, that can not be explained by the transport defect.

Aim of the study is to investigate the consequences of SLC7A7 mutations on specific macrophage functions, so as to elucidate the role of macrophage dysfunction in the development of pulmonary and immunological complications of LPI.

Peripheral blood monocytes were isolated from 3 LPI patients and 5 normal healthy donors and cultured for 7 days in the presence of GM‐CSF so as to obtain monocyte‐derived macrophages (MDM). System y+L activity appears markedly compromised in LPI monocytes and macrophages, as measured both as an influx or efflux route of 3H‐arginine. Moreover, LPI macrophages display a significant impairment of the phagocytic activity, detected by the internalization of fluorescent latex beads. These results demonstrate that SLC7A7/y+LAT1 mutations lead to a defective phenotype of macrophages, supporting the pathogenetic role of these cells in the development of LPI‐associated complications.
Antitumor effect of metformin is mediated by AMPK and FOXO3a
Authors: Fonseca Eveline Aparecida Isquierdo , Oliveira Maria A. , Eichler Rosangela , Akamine Eliana H. , Carvalho Maria Helena C. , Tostes Rita C. , Barbosa Aneli M. , Dekker Robert F.H. , Khaper Neelam , Fortes Zuleica B.
Published: June 2021

The objective of this study was to analyze the antitumor effect of metformin in‐vitro and in‐vivo. Breast cancer MCF‐7 cells were treated with metformin for 24, 48 and 72h. Antiproliferative activity was analyzed by the MTT assay. Oxidative stress was measured by the CM‐H2DCFDA assay. Apoptosis and cell cycle were analyzed by flow cytometry. mRNA expression was determined by RT‐PCR and protein expression by Western Blot. Metformin demonstrated an time‐ and dose‐dependent antiproliferative effect. This effect was associated with an increase in oxidative stress, apoptosis and cell cycle arrest. And, an increase in AMPK and FOXO3a activity was observed. Control and obese rats of 16 weeks of age received Walker‐256 tumor cells(1×107 cells/mL, sc) and metformin(300mg/kg, by gavage, for 15d, CTM and OTM). Control rats received tap water (CT and OT). On the 18th week the tumor development was analyzed. Tumor development was higher in OT rats than compared with CT. Metformin reduced it and increased the pRb and p27 mRNA expression. In conclusion, we demonstrated that metformin has an antitumor effect which was mediated by pRb, p27, AMPK and FOXO3a. Financial support: FAPESP(Brazil), NSERC‐RCD and NOSM(Canada)
Dopamine Transporter Interacts With Sigma‐1R
Authors: North Ashley Monique , Khoshbouei Habibeh
Published: June 2021

The dopamine transporter (DAT) is a plasma membrane transporter that is implicated in neuropsychiatric and neurodegenerative diseases. DAT is a target for psychostimulants such as methamphetamine. Interestingly, it has been shown that activation of sigma‐1R, an ER protein, can increase dopamine synthesis and release. The sigma‐1R is a novel non‐opioid protein discovered by Dr. Tsung Ping‐Su. Sigma‐1R antagonists have shown to prevent neurotoxicity and dopamine depletions while sigma‐1R agonists thought to increase the synthesis and release of dopamine. In this study we asked whether DAT and sigma‐1R interact. We used florescence recovery after photobleaching (FRAP) and florescence resonance energy transfer (FRET) in order to examine the potential interaction between CFP‐sigma‐1R and YFP‐DAT in CHO cells stably expressing YFP‐DAT, and transiently expressing CFP‐sigma‐1R. In cells co‐expressing CFP‐sigma‐ 1R and YFP‐DAT, there is a positive FRET signal between CFP‐sigma‐1R and YFP‐DAT. This positive FRET signal is detectable at the plasma membrane. Therefore, our preliminary data suggest a potential interaction between sigma‐1R and DAT. Furthermore, we found that the frequency of positive FRET signal between CFP‐sigma‐1R and YFP‐DAT increases when the cells are pre‐treated with methamphetamine a DAT substrate and a sigma‐1R ligand. Our FRAP data further confirms this potential interaction. We found that the mobility of globular CFP‐sigma‐1R increases in YFP‐DAT expressing cells. Importantly, methamphetamine exposure increases the mobility of sigma‐1R in the presence or absence of YFP‐DAT. Currently, we are examining the cell surface and intracellular dynamic of filament clusters of sigma‐1R in DAT expressing cells as well as when the cell are exposed to methamphetamine. Understanding the molecular mechanism of potential DAT/sigma‐1R interaction is critical in understanding of dopaminergic system in the brain under normal condition and when it is exposed to psychostimulants.
Protective Effect of Grape Powder On Anxiety‐Like Behavior, Blood Pressure and Learning and Memory
Authors: Salim Samina , Allam Farida , Chugh Gaurav C , Asghar Mohammad , Dao An T , Taneja Manish , Saha Kaustuv
Published: June 2021

About 40 million people in the United States have anxiety disorders, 10 million of which have hypertension. Anxiety is a known contributing factor to hypertension. However, mechanisms responsible for this association are unclear. A causal role of oxidative stress in anxiety‐like behavior and hypertension in rats is known. Oxidative stress also is known to contribute to learning and memory deficits. In this study, using L‐Buthionine‐(S,R)‐sulfoximine (BSO) (300mg/Kg i.p; 7 days), an oxidative stress inducer, we examined the effect of a 2 week treatment of grape powder extract on oxidative stress induced anxiety‐like behavior (open‐field and light dark tests), hypertension and learning and memory function (radial arm water maze test) in rats. BSO treatment increased anxiety‐like behavior of rats and treatment with the antioxidant grape powder prevented this behavior. BSO rats exhibited just as many errors in the short‐term memory test as the grape powder treated rats, but made slightly more errors in the long‐term memory test. Also, BSO rats displayed significantly higher systolic, diastolic, and mean arterial pressure as compared to controls while grape powder treatment prevented BSO‐induced increase in blood pressure. Our studies suggest a potentially protective role of grape powder extract on anxiety‐like behavior, learning and memory function and hypertension in rats.
When One Plus One Equals 10: Unique Rewards and Daunting Challenges of Being an MD‐PhD Clinician‐Scientist
Authors: Hsu Stephen I-Hong
Published: June 2021

Clinicians, scientists and clinician‐scientists each have unique and critical roles to play in advancing the successful completion of the clinical translational mission. In choosing a specific training and career development path, the goal is to make a truly informative and authentic decision based on a clear sense of personal calling, character and mission that will persist throughout a long, successful and productive career. For the intrepid prospective MD‐PhD student, it is critical that such a decision occur in the context of personal and concrete explorations posed by a series of important questions: “What is the lived daily experience of MD and MD‐PhD clinician‐scientists?” and “How do clinician‐scientists manage to navigate back and forth between patient care and their research efforts and the mounting pressures to write even more grants late into the night and over weekends—and still remain excited about starting anew each morning?” One approach towards understanding the unique rewards that are afforded clinician‐scientists and how well they face the daunting challenges they inevitably encounter, is to assess how successful they have been at developing creative and often non‐traditional career models that combine the skill sets and competencies of highly integrated MD and PhD training into something that is more than the sum of its parts—namely, MD‐PhD training.
POLY(ADP‐RIBOSE) POLYMERASE‐2 DEPLETION REDUCES DOXORUBICIN‐INDUCED DAMAGE THROUGH SIRT1 INDUCTION
Authors: RUTKAI IBOLYA , SZÁNTÓ MAGDOLNA , HEGEDÛS CSABA , CZIKORA ÁGNES , RÓZSAHEGYI MÁTÉ , KISS BORBÁLA , VIRÁG LÁSZLÓ , GERGELY PÁL , TÓTH ATTILA , BAI PÉTER
Published: June 2021

Doxorubicin (DOX) is used in cytostatic treatments, although it may cause cardiovascular dysfunction. DOX treatment leads to enhanced free radical production that in turn cause DNA strand breakage culminating in poly(ADP‐ribose) polymerase (PARP) activation, mitochondrial and cellular dysfunction. DNA nicks can activate the PARP‐2 enzyme. Depletion of PARP‐2 has been shown to result in a protective phenotype against free radical‐mediated diseases suggesting similar properties in the case of DOX‐induced vascular damage. PARP‐2(+/+) and (−/−) mice and aortic smooth muscle (MOVAS) cells were treated with DOX (25 mg/kg, or 3 μM, respectively). Aortae from PARP‐2(−/−) mice displayed partial protection against DOX toxicity. Depletion of PARP‐2 prevented DOX‐induced mitochondrial dysfunction through SIRT1 activation. Genetic deletion of PARP‐2 resulted in the induction of SIRT1 promoter and consequently increased SIRT1 expression both in aortae and in MOVAS cells. SIRT1 activation enhanced mitochondrial biogenesis. Our data identify PARP‐2 as a mediator of DOX toxicity by regulating vascular SIRT1 activity and mitochondrial biogenesis. Moreover, to our best knowledge this is the first report of SIRT1 as a protective factor in the vasculature upon oxidative stress. This work was supported by TÁMOP 4.2.1./B‐09/1/KONV‐2010‐0007 and 4.2.2‐08/1‐2008‐0019.
Relationship of neuronal NOS to HIF‐1alpha induction in acetaminophen toxicity in mice
Authors: Chaudhuri Shubhra , McCullough Sandra S , Brown Aliza T , Hinson Jack A , James Laura P
Published: June 2021

The contribution of neuronal nitric oxide synthase (nNOS) to oxidative stress in APAP toxicity was previously suggested by in vitro studies showing that treatment with the nNOS inhibitor 7‐nitroindazole reduced toxicity and protein nitration in hepatocytes exposed to APAP (Burke et al., 2010). In addition, nNOS KO mice were recently shown to be less sensitive to APAP in the early stages of toxicity (Agarwal, in press, 2011, JPET). We previously reported the induction of hypoxia inducible factor‐1 alpha (HIF‐1α) in APAP toxicity in mice. To examine the relationship of nNOS to HIF‐1α induction in APAP toxicity, male B6129SF2/J mice (WT) and 6129S4Nos1tm1Plh/J mice (nNOS KO) were treated with APAP (200 mg/kg IP) and sacrificed at 1, 4, 8, 12 and 24 h. Control mice received saline. Mean (± SE) values for ALT were 1113 (± 238) IU/L and 357 (±181) IU/L for WT and KO at 4 h (p≤0.05), suggesting early protection from toxicity. By 8 h, mean ALT in the KO mice was 2808 (± 672) IU/L compared to 803 (± 327) IU/L in WT mice (p≤0.05). ALT levels were comparable between the two groups of mice at 12 and 24 h. Reduced necrosis was present in the KO mice at 4 h, but greater levels of hemorrhage were observed at 4 and 8 h in the KO mice, compared to the WT mice. Hepatic glutathione and APAP protein adducts were comparable in the WT and KO mice at 1 and 4 h. HIF‐1α induction was absent in the nuclear extracts of KO mice at 1 and 4 h and reduced by 70% at 8, 12 and 24 h compared to WT mice (p≤0.05). Cumulatively the data suggest a role for nNOS in HIF‐1α induction in the early stages of APAP mediated hepatotoxicity.

This work is supported by NIDDK grant (075936).
Pathogenesis of renal fibrosis: Role of Proteinase‐activated Receptor‐2
Authors: Chung Hyunjae , Muruve Daniel , Hollenberg Morley
Published: June 2021

OBJECTIVES

To evaluate the role of proteinase‐activated receptor‐2 (PAR2) in renal fibrosis.

METHODS

We used both cultured acutely isolated human‐derived proximal tubular cells (HPTCs) and an in‐vivo murine unilateral ureteral obstruction (UUO) model of renal fibrosis, with wild‐type and PAR2 null mice (Jackson Labs). HPTCs at passage 3 were activated with a PAR2‐activating peptide (PAR2‐AP) and trypsin without or with co‐stimulation by transforming growth factor‐ β (TGF‐ β) and the expression level of connective tissue growth factor (CTGF) was measured by western blot analysis. Cells were activated with and without the signal pathway inhibitors for MAPKinase (PD98059) and Rho‐kinase (Y‐27632). Kidneys from wild‐type and PAR2‐null mice with or without (sham) UUO were obtained at 7, 14, 21 and 28 days after UUO. Renal tissue was fixed and evaluated histopathologically for morphology (H & E), collagen deposition (Masson's Trichrome) and biochemically (western blot) for α‐smooth muscle actin.

RESULTS

(1) PAR2‐AP activation of HPTCs alone significantly upregulated CTGF expression and did so synergistically to augment TGF‐β‐induced CTGF production. This synergy was reduced by MAPKinase but not Rho‐kinase inhibition. (2) PAR2 null UUO mice had less tubular injury and fibrosis and reduced alpha‐smooth muscle actin at day 7 but not at 28 days.

Our results support a role for PAR2 in acute renal fibrosis.
mAChR Dependent Contraction of Pulmonary Arteries with Functional Endothelium from Chronically Hypoxic Fetal and Adult Sheep
Authors: Kim Joon , Blood Quintin , Longo Lawrence D , Wilson Sean M
Published: June 2021

Muscarinic acetylcholine receptor (mAChR)‐dependent arterial relaxation is often used to test for a functional endothelium, where inability to relax is indicative of endothelial damage. The present studies test the hypothesis that mAChR activation can contract pulmonary arteries (PA) with intact endothelium from chronically hypoxic sheep. The hypothesis was tested in PA isolated from term‐fetal sheep, ~10 days old newborns, and in adult ewes that lived at 3,200 meters for <100 days, which provides a chronic hypoxic insult. Dose‐dependent vasoreactivity to carbachol, a mAChR agonist and bradykinin (BK) were examined in PA pre‐constricted with 10 μM phenylephrine (PE). Carbachol caused robust dose‐dependent contraction of PA from adult sheep, fetal PA contracted somewhat, and PA from newborns relaxed. Bradykinin (1 μM) relaxed carbachol treated PA, indicating the endothelium was functional. Bradykinin caused dose‐dependent relaxation of PE‐constricted newborn and adult arteries to a similar extent, while fetal arteries relaxed somewhat. Carbachol (100 μM) contracted BK‐relaxed arteries from fetal and adult, but not newborn sheep. mAChR‐dependent contraction may therefore provide a novel mechanism to match ventilation to perfusion in the lung. Targeted therapies could increase lung perfusion and improve oxygenation in patients with pulmonary vascular disease. NIH P01HD031226, R01HD003807 (LDL)