bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of the tomato intake amount recommended in MyPlate to cardiovascular disease risk reduction (630.1)
Authors: Reimers Kristin , Andon Mark , Jacobson Mary , Nguyen Von , Rippe James
Published: June 2021

Tomatoes comprise 82% of the USDA MyPlate red and orange vegetable subgroup modeled by the 2010 DGAC, translating to a daily recommendation of 0.8 cups tomatoes in a 2000 kcal diet. Tomatoes are the primary dietary lycopene source and intakes of tomatoes and/or lycopene are inversely correlated with chronic disease risk. The purpose of this study was to quantify the change in serum lycopene caused by consuming approximately the MyPlate‐recommended tomato quantity, and to estimate the disease risk reduction potentiated by this upward shift. Participants (n = 58, ages 35 ‐ 70, BMI 27 ‐ 37) were asked to consume two ½ cup equivalents/d of canned tomatoes, sauce, or paste as part of their usual diet for six weeks. The result was an upward shift of approximately one quartile of the lycopene distribution curve. In population studies assessing the relationship between lycopene and cardiovascular and/or stroke risk, interquartile risk reductions were 22% ‐ 42% between Q1 and Q2, 1% ‐ 22% between Q2 and Q3 and 6% ‐ 12% between Q3 and Q4. This comparison shows that a lycopene concentration shift of one quartile, which is observed when moving from usual tomato intake to the MyPlate recommended amount, is associated with decreased risk of cardiovascular disease and stroke, especially in those with lowest initial serum lycopene concentrations.
Enhanced iron‐folic acid supplementation program reduces risk of under 5 mortality in Nepal (636.2)
Authors: Dibley Michael , Nisar Yasir , Mebrahtu Saba , Paudyal Naveen , Devkota Madhu , Maharjan Macha
Published: June 2021

Objective To investigate the impact of a program to improve coverage of antenatal IFA supplementation on child survival in Nepal using pooled data from 3 Nepal DHS (2001, 2006 and 2011).

Methods Survival information from 13,009 singleton most recent live‐born infants within the 5 years prior to each interview was used. The primary outcomes were mortality indicators for under‐5 children and the main exposure variable was implementation of enhanced IFA program. Multivariate Cox proportional hazards regression analyses was conducted and adjusted for X potential confounders and the sampling design.

Results After the implementation of enhanced IFA program, early neonatal mortality was significantly reduced by 53% (aHR: 0.47, 95% CI 0.26, 0.84, p=0.012) compared to before the program started. The risk of infant mortality was significantly reduced by 49% (aHR: 0.51, 95% CI 0.31, 0.82, p=0.006), and by 38% (aHR: 0.62, 95% CI 0.39, 0.99, p=0.043) for under‐5 mortality after implementation of the enhanced program.

Conclusion A program to improve IFA coverage significantly reduced the risk of under‐5 deaths in Nepal by nearly 40%. The greatest magnitude of risk reduction was for early neonatal deaths.
Effects of green tea on the cecal metagenome of mice fed either the AIN‐93 or Total Western Diet (637.16)
Authors: Ward Robert , Hintze Korry , Lefevre Michael , Benninghoff Abby , Li Minghao , Rompato Giovanni
Published: June 2021

The objective of this study was to determine the effect of green tea supplementation on the cecal microbiome and production of short chain fatty acids (SCFA) when provided with different background diets. Mice (n=7 per group) were fed either an AIN‐93G or a Western (TWD) background diet with or without green tea extract. The TWD is a rodent diet formulated to match the macronutrient and micronutrient intakes of Americans. Mice were provided the diets ad libitum and green tea extract was supplied in the drinking water for 16 weeks. Cecal contents were collected at sacrifice, and the cecal microbiomes were determined by shotgun metagenomic analysis of DNA extracts using a Roche 454 FLX. Results of these analyses were processed through MG‐RAST to obtain both taxonomic and functional annotations. Results of these analyses indicate that mice provided the green tea had significantly lower body mass (p<0.05). Both the diets and the green tea extract affected numerous functional (KEGG) pathway and bacterial lineages. The relative number of sequences assigned to the genus Bifidobacterium was significantly higher in mice provided the green tea extract compared to water. Conversely, the relative number of sequences assigned to butanoate metabolism was significantly lower in mice provided the green tea. Cecal levels of acetate, butyrate and total SCFA were significantly lower in mice fed green tea. These results suggest green tea supplementation at least partially attenuated weight gain via effects on cecal SCFA generation.

Grant Funding Source: College of Agriculture, Utah State Univeristy
Exposure of mice to high fat diet shifts gut microbiota community structure and alters microbial function in a diurnal manner (637.17)
Authors: Leone Vanessa , Hubert Nathaniel , Gibbons Sean , Zale Elizabeth , Musch Mark , Gilbert Jack , Chang Eugene
Published: June 2021

Many organisms exhibit circadian rhythms (CC) based on a 24‐hour light/dark cycle. Evidence in mammalian systems highlights the dominant role of CC in maintaining health, in that development of diet‐induced obesity is associated with CC disruption. Studies also show that high fat (HF) diet‐induced gut microbiota contributes to the development of obesity. Whether the gut microbiota exhibits its own diurnal patterns under healthy states that becomes perturbed under conditions of HF feeding has yet to be described. We hypothesized that HF diet‐induced gut microbiota exhibit altered structural and functional diurnal patterns that ultimately influence host metabolism. Thirty‐six individually‐housed adult C57/Bl6J male mice maintained on a 12/12 light:dark cycle were fed regular chow (RC) or HF diet for 5 weeks. Three mice per treatment were harvested over 24hrs at six time points. Assessment of cecal bacterial 16s rRNA V4‐V5 region via Illumina MiSeq showed MF diet resulted in significantly different α and β‐diversity community structure compared to RC. Diurnal variations in 16s structure were evident in both RC and HF communities, although significant differences over time were not achieved in either treatment. However, comparison of RC and HF cecal microbial community functional profiles via inoculation into Biolog GenIII plates (a spectrophotometric assessment of carbon‐based cellular respiration) showed that while RC and HF exhibited significantly different metabolic potential, only HF exhibited significant diurnal patterns. Together, the data suggest that HF diet alters community membership and only differences in diurnal community functional properties are exhibited. The role of the HF diet‐induced microbial functional changes on the development of obesity in the host remains to be elucidated.

Grant Funding Source: Supported By NIDDK P30DK42086
Dietary fish oil increases neutrophil development and recruitment to the colon in colitis‐prone mice (638.1)
Authors: Duriancik David , Langohr Ingeborg , Gardner Elizabeth , Fenton Jenifer
Published: June 2021

Fish oil, containing n‐3 polyunsaturated fatty acids, is generally considered to have anti‐inflammatory and immune suppressing properties. We have previously shown that dietary fish oil rich in docosahexaenoic acid (DHA) resulted in exacerbated colon inflammation and progression to adenocarcinomas in Helicobacter hepacticus infected colitis‐prone mice. The objective of this study was to characterize the effect of dietary fish oil on colon inflammation and immune cell changes in the absence of infection in genetically colitis‐prone mice. We employed immunohistochemistry and flow cytometric analysis to characterized inflammatory cell development and infiltration in the colon of mice fed either 6% menhaden oil (MO) or a soy‐based control diet (CON). We observed increased neutrophil development in the bone marrow and spleen in MO compared to CON fed mice. Neutrophil percent in the colon increased from 1.6% in CON fed mice to 4.2% in MO fed mice. In addition, MO consumption altered the activation state and function of neutrophils. No differences in intestinal permeability as assessed by absorption of FITC‐dextran were observed, however fecal IgA increased with MO feeding. Interestingly, we observed differential responses to dietary fish oil depending on the gender of mice. Pre‐illness diet fatty acid content may have profound effects on IBD development in susceptible populations.

Grant Funding Source: Supported by NIH RO3CA162427 to JIF
Adzuki beans (Vigna angularis var. nipponensis) ethanol extract inhibits the adipogenesis by downregulating adipogenic transcriptional factors on the 3T3‐L1 adipocytes (642.6)
Authors: Kim Min‐Ah , Park Jeong‐Eun , Bae Cho‐Rong , Cha Youn‐Soo
Published: June 2021

The primary objective of this study was to investigate the potential of Adzuki Bean Extract (ABE) in inhibiting the adipogenesis process in 3T3‐L1 pre‐adipocytes and to identify the underlying molecular mechanisms involved with their anti‐adipogenic effects. ABE did not cause any cytotoxic effect on 3T3‐L1 cell at 0.78 to 3.13 mg ml‐1. The pre‐adipocyte proliferation was inhibited in a dose‐ and time‐dependent manner. Treatment with ABE resulted in a dose‐dependent reduction in TG accumulation with treatment of 1 and 2mg ml‐1, compared to the control. The mRNA levels of the adipogenesis‐associated genes (PPARγ, C/EBPα, Glut4, FABP4, LPL) were significantly suppressed, while higher expression of lipolytic genes (ATGL, HSL) were observed in the treated group than the control. Overall, the anti‐obesity effects of adzuki bean extract demonstrated a potential dietary supplement capable of attenuating obesity. (This work was carried out with the support of “Cooperative Research Program for Agriculture Science & Technology Development Project No. PJ009218” Rural Development Administration, Republic of Korea)

Grant Funding Source: supported by Rural Development Administration(PJ009218), Republic of Korea
The effect of Ecklonia cava supplement on blood lipid profiles in hyperlipidemic Koreans: a 12‐week, randomized, double‐blind, placebo‐controlled clinical trial (642.7)
Authors: Park Eun‐Ock , Choi Eun‐Kyung , Kim Sun‐Young , Park Soo‐Hyun , Oh Mi‐Ra , Jung Eun‐Soo , Jang Yoon‐Jin , Chae Soo‐Wan , Kim Seong Ho , Shin Hyeon‐Cheol , Park Tae‐Sun
Published: June 2021

This study examined effect and safety of Ecklonia cava supplement on blood lipid metabolism in hyperlipidemic subjects. This study was a 12‐weeks, randomized, double‐blind, placebo‐controlled clinical trial. Inclusion criteria were age of 19 to 80 years and total cholesterol level蠅200mg/dL or LDL‐cholesterol level蠅110mg/dL. Eighty subjects were randomly assigned to two treatment groups: Ecklonia cava(SEPOLYNOL 400mg/day) and placebo group. The primary endpoint was total and LDL‐cholesterol level. Secondary endpoint was triglyceride and HDL‐cholesterol level. After 12 weeks of treatment, total cholesterol and LDL‐cholesterol of test group was significantly improved compared with those of placebo group (p=0.039, p=0.030). HDL‐cholesterol in test group showed a significant decrease compared with those of placebo group statistically (p=0.021), but not clinically. There were no significant adverse events relating to this trial. In conclusion, these results demonstrate that Ecklonia cava supplementation is considered to be safe and beneficial for improving blood lipid profiles by lowering total and LDL‐cholesterol with safety in hyperlipidemic subjects.
CLA intake from dairy fat in healthy young adults: beneficial effects on serum metabolome (643.6)
Authors: El Bacha Tatiana , Nunes Juliana , Torres Alexandre
Published: June 2021

Dairy fat is a rich source of the naturally occurring bioactive conjugated linoleic acids (CLA). We aimed to investigate the effects of dairy fat intake on serum metabolome in healthy young adults, in a CLA depletion‐repletion pilot study. Samples (n= 6) were analyzed in three sequential phases: (a) baseline; (b) at the end of an 8‐week period following a dairy fat restriction diet; and (c) at the end of an 8‐week period following a CLA‐repletion diet with regular dairy products and additional daily intake of 1.0 g of CLA from a naturally‐enriched butter. Serum metabolomic analyzes were carried out by 1H Nuclear Magnetic Resonance. Serum citrate increased in the CLA‐depletion period and returned to baseline values after CLA‐repletion (P= 0.0072; repeated measures ANOVA). Inversely, serum creatine and creatinine increased after CLA‐repletion (P< 0.05). We also observed alterations in branched‐chain aminoacids, with a tendency to decrease serum valine after CLA‐repletion. The observed changes in serum metabolites suggest a beneficial effect of dairy fat and CLA on insulin sensitivity and, possibly, on glucose homeostasis. Taken together, our results indicate that intake of natural food sources of CLA promoted beneficial changes on serum metabolic profile of healthy young adults and also demonstrated that metabolomics is an useful tool for assessing concerted metabolic effects of dairy fat intake on human health.

Grant Funding Source: Supported by FAPERJ, CNPq, CAPES (Brazil)
Effects of the menstrual cycle on the metabolic and vascular phenotype of healthy women (643.7)
Authors: Faustmann Gernot , Maimari Theopisti , Meinitzer Andreas , Tiran Beate , Öttl Karl , Gruber Hans‐Jürgen , Roob Johannes , Winklhofer‐Roob Brigitte
Published: June 2021

Goals: In the EU‐funded FP7 project BIOCLAIMS extensive metabolic phenotyping of healthy subjects is performed to identify and characterize biomarkers of metabolic robustness. This study aims at elucidating changes in these biomarkers during the menstrual cycle.

Subjects & methods: Healthy women (n=26) not taking hormonal contraceptives, aged 34±6.1 y, were investigated after an overnight fast at early (day 5.9±0.97, t1) and late follicular phase (day 12.0±1.82, t2), and mid (day 19.6±2.52, t3) and late luteal phase (day 25.2±2.12, t4). Time points of investigation were scheduled based on basal body temperature records prior to the study. Phenotyping included body composition (bioelectrical impedance), endothelial function (flow‐mediated dilatation, FMD), activation of p65, p50 and cRel subunits of transcription factor nuclear factor κB (NF‐κB) in peripheral blood mononuclear cells (TransAM®), vitamin A, C, E, carotenoids, symmetrical (SDMA), asymmetrical dimethyl (ADMA) and homo‐arginine (HA) and human mercaptalbumin (HMA), all by HPLC, leptin, adiponectin by ELISA; lipid status; vitamin B12 and folic acid by clinical chemistry.

Results: Significant differences between time points were observed for NF‐κB p65 activation (P=0.017), plasma ascorbate (P<0.001), B12 (P=0.002), folic acid (P=0.032), ADMA (P<0.001), SDMA (P=0.037), and HA (P=0.012), and LDL cholesterol concentrations (P<0.001), all significant for t1>t3, while FMD (P=0.011), leptin (P=0.024) and adiponectin (P=0.027) were significant for t3>t1. There were no significant changes in HMA, body composition and other variables.

Conclusions: Follicular and luteal phase differentially affect the metabolic phenotype of healthy women. Changes between t1 and t3 can be explained by previously shown estrogen effects, including reduction of NF‐κB activation in primary human macrophages, enhanced leptin synthesis and improvement of FMD due to decreases in ADMA, a nitric oxide synthase inhibitor.

Grant Funding Source: Supported by European Commission, FP7, contract 244995, and Austrian Government (bmwf)
Epoxy metabolites of docosahexaenoic acid inhibit angiogenesis and tumorigenesis (644.13)
Authors: Zhang Guodong
Published: June 2021

Lipid mediators, which are signaling molecules produced from fatty acids by the actions of cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) enzymes, regulate numerous biological processes including angiogenesis and tumorigenesis. Unlike the signaling lipids derived from COX and LOX enzymes, the effects of the CYP‐derived lipid mediators on cancer are largely unknown. Here we show that epoxydocosapentaenoic acids (EDPs), which are the CYP epoxygenase metabolites of omega‐3 docosahexaenoic acid (DHA), inhibit angiogenesis, tumor growth and metastasis; while the corresponding metabolites from omega‐6 arachidonic acid (ARA), epoxyeicosatrienoic acids (EETs), increase tumor progression. EDPs inhibit vascular endothelial growth factor (VEGF)‐ and fibroblast growth factor‐2 (FGF‐2)‐induced angiogenesis in vivo, and suppress endothelial cell migration and protease production in vitro via a VEGF receptor 2 (VEGFR2)‐dependent mechanism. When EDPs are co‐administered with a low‐dose soluble epoxide hydrolase (sEH) inhibitor, EDPs are stabilized in circulation and primary tumor growth and metastasis are reduced by ~70%. Contrary to the effects of EDPs, EETs increase tumor progression. Together, these results demonstrate EETs and EDPs as novel endogenous regulators of angiogenesis and tumorigenesis, and suggest the CYP/sEH pathway as a novel therapeutic target for angiogenesis and cancer.

Grant Funding Source: Supported by NIEHS R01 ES02710 and P42 ES04699
Capsaicin sensitizes small cell lung cancer cells to the apoptotic effects of camptothecin (644.16)
Authors: Perry Haley , Brown Kathleen , Stevenson Cathryn , Rollyson William , Stover Cody , Dasgupta Piyali
Published: June 2021

The administration of cisplatin is the cornerstone of SCLC therapy. Topotecan (a derivative of camptothecin) has been used as a second‐line therapy against SCLC. One of the major problems of SCLC therapy is that all the tumor cells do not undergo apoptosis upon treatment with chemotherapy and the residual cells contribute to the development of resistant disease. Therefore, agents that can potentiate the apoptotic activity of chemotherapeutic agents like cisplatin could be valuable for SCLC therapy. The present study tests the hypothesis that capsaicin can sensitize human SCLC cells to the apoptotic effects of cisplatin or camptothecin. Caspase‐3 activity assays reveal that the combination of camptothecin and capsaicin displayed greater apoptotic activity than any of the compounds used alone. We verified these results using a second apoptosis assay and obtained similar results. Currently, we are testing the anti‐cancer activity of capsaicin and camptothecin in human SCLC cells xenografted in athymic mice. Our data foster the hope of novel combination therapies for SCLCs.

Grant Funding Source: Supported by an NIH R15‐Area Grant, and a FAMRI YCSA Grant
Extraction and normal‐phase separation of brain carotenoids and tocols (645.10)
Authors: Craft Neal
Published: June 2021

Tocopherols and carotenoids have been implicated in reduced risk of Alzheimer’s Disease and improved cognition. Aim: To develop an improved extraction of brain and normal‐phase separation to measure 4 tocopherols, 4 tocotrienols (T3) and xanthophylls and to avoid saponification. Methods: Brain tissue was extracted with several solvent combinations including SDS, MTBE, hexane, and THF. The extracts were separated using a Diol column with a gradient of hexane and dioxane and included two internal standards (Tocol and B‐apo8’ carotenoate). Carotenoids were measured at 450nm and tocols by fluorescence (296nm ex/340nm em). Results: No single solvent provided the best extraction of all the antioxidants. An initial MTBE extraction was followed by hexane/THF. Tocopherol recoveries ranged from 96‐103% with CVs of 6‐25% at sub‐ppm and xanthophylls at ppb levels. Four tocopherols, 4 T3s, a‐ and B‐cryptoxanthin, lutein and zeaxanthin were measured in 0.1g of human brain. Conclusions: A selective and sensitive method was developed to measure 8 tocols and several xanthophylls in 0.1g of brain without saponification.
Impact of vitamin A supplementation in low birth weight piglets similar to healthy weight piglets (645.17)
Authors: Heying Emily , Hovel Elizabeth , Tanumihardjo Sherry
Published: June 2021

Current vitamin A supplementation methods for infants in vitamin A‐deficient populations have no specific dosing recommendations regarding birth weight. A proposed intervention is to administer 50,000 IU retinyl palmitate to newborn infants to reduce mortality risk. To investigate birth weight effects, low birth weight (LBW) piglets (1.5 kg) from vitamin A‐depleted sows were dosed with either 25,000 or 50,000 IU retinyl palmitate at birth to compare liver vitamin A reserves and overall vitamin A status. Blood collection occurred at varying time points after dose and piglets were killed at 12 and 24 h for organ and serum collection. Serum, liver, kidneys, spleen, lungs, adrenals, and intestinal contents were collected and analyzed for vitamin A using HPLC methods. Both healthy weight and LBW piglets had significantly higher liver and kidney vitamin A concentrations than control piglets that received no dose (P = 0.0061 and <0.0001, respectively), but no significant differences between dose, weight, or time groups existed. However, total liver and kidney retinol was higher in healthy weight piglets (P < 0.0001). Vitamin A concentration in lung, spleen, and adrenal glands did not differ between any treated and control piglets. Serum retinol significantly increased with time for all treated piglets, regardless of birth weight (P = 0.005), but dose and weight had no effect on serum retinol concentration. In conclusion, healthy weight piglets stored more of the supplemental doses than LBW piglets.

Grant Funding Source: Supported by the Nutrition Unit at the World Health Organization.
Oral doses of α‐retinol track chylomicron delivery to crucial organs in a piglet model for newborn infants (645.18)
Authors: Riabroy Napaporn , Tanumihardjo Sherry
Published: June 2021

α‐Retinol (αR) has utility in determining chylomicra trafficking of vitamin A to tissues given that it will not be recirculated in blood on retinol‐binding protein (RBP). In this study, αR was used as a chylomicron tag for short‐term uptake to investigate supplementation practices to newborn infants using a piglet model. The distribution of orally administered αR doses in extrahepatic tissues was assessed at varying stages of vitamin A depletion. Male piglets were taken from sows that were on a vitamin A‐depleted diet for two gestation and lactation cycles to deplete liver reserves of vitamin A over time. Piglets (n = 24/group) were orally given 26.2 or 52.4 µmol α‐retinyl acetate, the molar equivalent of 25,000 and 50,000 IU vitamin A, respectively. Tissues were collected and analyzed by HPLC. Lung, spleen, and adrenal αR concentrations peaked at 7 h post dose and by 7 d, αR was cleared from these tissues. This suggests that lung, spleen, and adrenal require chylomicron vitamin A to maintain concentrations. On the other hand, storage of αR in the liver peaked at 24 h and was mostly retained through 7 d. This indicates that αR was not utilized or transported via RBP. In serum, the majority of αR was in the ester form, which confirms that αR does not bind to RBP. Collectively, these data suggest that crucial organs need constant dietary intake to maintain vitamin A concentrations.

Grant Funding Source: Supported by the Nutrition Unit at the World Health Organization.
Consumption of 12 eggs per week for 1 year increases serum zeaxanthin concentrations but not other major carotenoids, tocopherols, and retinol in humans (645.25)
Authors: Aljohi Hasan , Dopler‐Nelson Mindy , Wilson Thomas
Published: June 2021

Previous work has shown that egg yolk consumption yields increase bioavailability of lutein and zeaxanthin compared to dietary supplements. However, little is known of the effects of an egg‐rich diet on serum levels of the other carotenoids, vitamin A and vitamin E. This study investigated how a diet of 12 eggs per week for 1 year influenced serum carotenoid, tocopherol, and retinol concentrations in adults. A group of 45 adults were placed into either the intervention group (n=27; consumed 12 eggs per week for 12 months) or control group (n=18; consumed no eggs or high egg products for 12 months) after 6 weeks of an egg‐free diet. Serum carotenoid and vitamin concentrations were measured by high performance liquid chromatography (HPLC) at baseline and 12 months. Seven day diet records were collected and analyzed on a monthly basis to help ensure the egg consumption protocol. Results showed that the intervention group demonstrated a statistically significant increase (83%) in serum zeaxanthin concentrations after 12 months. A notable, but not statistically significant, increase in serum lutein concentration was also observed in the intervention group (52%) after 12 months. Although serum alpha‐carotene concentration did not change in the intervention group, it significantly increased in the control group (18%) after 12 months. No other serum carotenoid, retinol, or alpha‐ or gamma‐tocopherol concentrations changed significantly during the 12 months. The findings of this study suggest that egg yolk consumption does not significantly alter the serum concentrations of tocopherols, retinol, and carotenoids other than alpha‐carotene and zeaxanthin.

Grant Funding Source: Supported by the Egg Nutrition Center
Milling method affects zinc content of maize and health status of Mongolian gerbils (646.5)
Authors: Gannon Bryan , Tanumihardjo Sherry
Published: June 2021

Micronutrient deficiencies, especially vitamin A (VA), zinc, and iron, are of global health concern. Biofortified (orange) maize has provitamin A carotenoids and can support vitamin A status. Different maize milling methods, e.g. whole grain (‘roller’) and degermed (‘breakfast’), are commonly used and affect mineral content. Zinc plays a role in vitamin A metabolism and therefore it is pertinent to evaluate their interaction. Orange and white maize was milled using two methods and analyzed for mineral content. Gerbil diets were formulated to have maize as the sole vitamin A and zinc source. A 3x2 factorial study was carried out with three VA levels (i.e., white maize ‐VA, orange maize ‐VA, and white maize +VA) and two milling methods (i.e., roller and breakfast). Gerbils were depleted on white maize for 4 wk, and then put on treatments for 4 wk. Gerbil weights and food consumption were measured. Gerbils were killed; serum, liver, and fur were collected for analysis. Diets varied significantly in zinc content between roller and breakfast (11.0 ± 0.6 vs 2.8 ± 0.8 µg Zn/g diet; P < 0.0001), which was reflected in liver zinc (28.6 ± 2.4 vs 26.9 ± 3.6 µg/g; P = 0.038). Gerbils on roller diet grew significantly more than those on breakfast (76.1 ± 7.0 vs 69.4 ± 9.0 g; P = 0.0025), while VA level had no effect (P = 0.70). Serum retinol had no significant treatment or interaction effects (P > 0.074), with dietary VA trending towards a significant effect and VA‐ gerbils having a higher serum retinol than VA+ gerbils. A simple choice of processing method showed a difference in growth and liver zinc content. Although breakfast meal is preferred for consistency, roller meal shows great potential as a nutritionally superior option for better population health.

Grant Funding Source: Supported by NIH‐5T32DK007665 (BG) and Hatch WIS01528
Neuroprotective effects of resveratrol against β‐amyloid induced oxidative damage and memory loss in rat hippocampal (H19‐7) cells (647.44)
Authors: Rege Shraddha , Bottcher Mary , Geetha Thangiah , Broderick Tom , Babu Jeganathan
Published: June 2021

Resveratrol is a polyphenolic phytoalexin known to exhibit neuroprotective effects in several experimental models. Accumulation of amyloid beta in the Alzheimer disease patient brain seems to be the cause of cognitive impairment and neuronal loss. The present study evaluates the neuroprotective action of resveratrol on β‐amyloid induced oxidative stress and memory loss in cultured rat hippocampal H19‐7 neuronal cell line pretreated with 75 μM of resveratrol for 2 hrs followed by 25 μM of Aβ (1‐40) for 24 hrs. The lipid peroxidase levels were significantly increased in amyloid β treated H19‐7 cells. The enzymic antioxidants like superoxide dismutase, catalase, glutathione reductase, and non‐enzymic antioxidants like tocopherol, ascorbic acid and glutathione were decreased. amyloid β treatment also increased tau phosphorylation and decreased expressions of certain proteins like Insulin Degrading Enzyme (IDE), glycogen synthase kinase 3beta and p62, which are involved in Amyloid beta degradation and PSD‐95, Arc proteins essential for synaptic maturity and plasticity. Resveratrol treatment attenuated the lipid peroxide levels, up‐regulated the antioxidant activities and increased the expression of proteins involved in neuroprotection in H19‐7 cells. These findings suggest the neuroprotective effect of resveratrol in improving the β‐ amyloid induced oxidative damage and memory loss in vitro.
High molecular weight barley β‐glucan supports bacterial populations beneficial for gut health (647.45)
Authors: Wang Yanan , Ames Nancy , Li Shucong , Jones Peter , Khafipour Ehsan
Published: June 2021

Effects of short‐term consumption of barley β‐glucan (BBG) on gut microbiota were investigated using a controlled, single‐blinded, randomized crossover study consisting of four phases of 35 d intervention, each separated by 28d washout intervals. Subjects (n=22) received wheat and rice based control diet (CD), barley diet (BD) with 5g/d low molecular weight (MW) BBG, BD with 3g/d high MW BBG, or BD with 3g low MW BBG. DNA was extracted from feces taken at the end of each phase and the V4 region of bacterial 16S rRNA genes amplified and subjected to illumina sequencing. Data were analyzed using MIXED and GLIMMIX procedures of SAS, PLS‐DA of SIMCA and PERMANOVA of PRIMER. β‐Diversity of microbiota was affected by treatments (P = 0.02) with the most significant difference observed between 3g/d high MW compared to CD. At the phylum level, 3g/d high MW decreased (P < 0.001) Firmicutes (77.7% vs. 88.8%) and increased Bacteroidetes (18.2% vs. 10.0%) compared to CD. Among the core genera, 3 g high MW increased Bactroides (11.3% vs. 6.7%; P = 0.01) compared to CD. Other taxa which were positively associated with 3g high MW BBG included Prevotella, Akkermansia, Rikenellaceae and Lachnospiraceae. Data suggest that consumption of 3g/d high MW BBG supports particular bacterial populations that are beneficial to gut health.
Protective effects of notoginsenoside R1 on rat intestinal reperfusion injury (650.10)
Authors: Han Jing‐Yan , Li Chong , Li Quan , Liu Yu‐Ying , Wang Ming‐Xia , Pan Chun‐Shui , Yan Li , Chen Yuan‐Yuan , Fan Jing‐Yu
Published: June 2021

Intestinal ischemia and reperfusion (I/R) is a clinical problem occurred for diverse causes with high mortality. The present study was to explore the role of Notoginsenoside R1 (R1), a major component form Panax. Notoginseng, in management of intestinal I/R injury. Intestinal I/R was induced in male Sprague‐Dawley rats by clamping the superior mesenteric artery for 90 min followed by reperfusion for 60 min or 3 days. R1 (10 mg/kg/h) was administered either 20 min before ischemia or 20 min after reperfusion. Intestinal microcirculation was evaluated by intravital microscopy over 60 min reperfusion. Sixty min or 3 days after reperfusion, rats were killed for histological examination of the jejunum tissue and immunohistochemical localization of myeloperoxidase and CD68. ATP, ADP and AMP content in jejunum tissue was assessed by ELISA. Activation of NF‐κB, expression of ATP5D and tight junction proteins were determined by Western blotting. The results demonstrated that R1 is capable of attenuating intestinal I/R‐induced microvascular hyperpermeability, inflammatory cytokine production, NF‐κB activation and loss of tight junction proteins, as well as improving energy metabolism during I/R. The results of the present study suggest R1 as an option in protecting against intestinal I/R injury.
Role of adaptive immune cells in the anti‐colitic effect of helminth antigen‐pulsed dendritic cells (650.17)
Authors: Matisz Chelsea , Wang Arthur , Sharkey Keith , McKay Derek
Published: June 2021

Role of adaptive immune cells in the anti‐colitic effect of helminth antigen‐pulsed dendritic cells
Chelsea E. Matisz1, Arthur Wang1, Keith A. Sharkey1, Derek M. McKay1. Department of Physiology & Pharmacology, University of Calgary, AB, Canada.

Helminth parasites have evolved as potent modulators of the host immune system. Epidemiological, experimental, and clinical trials report that infection with helminths can attenuate concomitant inflammatory disease. The role of dendritic cells (DC) in these protective immune responses has only recently been explored. The adoptive transfer of in vitro derived dendritic cells, when pulsed with antigens from the helminth Hymenolepis diminuta (HD), protect recipient mice against dinitrobenzene sulfonic acid (DNBS)‐induced colitis. The transfer of HD‐pulsed DCs (HD‐DC) is associated with reduced disease activity scores, colonic myeloperoxidase (MPO) activity, improved histology damage scores, and increased IL‐4 and IL‐10 in stimulated splenocytes compared to DNBS only controls. As these cytokines are indicative of Th2 responses, we assessed the role of adaptive immunity in the protective effect of HD‐DCs. DCs were generated in vitro, treated with HD antigen for 24 hours, and transferred (106, ip) to wild type and RAG deficient mice, which lack T and B cells. DNBS colitis was induced 48 hours after cell transfer, and necropsies performed 3 days later. Significantly less DNBS‐induced disease was observed in WT animals treated with HD‐DCs, compared to RAG deficient mice treated with HD‐DCs (n=6‐12, 2 experiments; F(2,39)=8.45, p=0.001). HD‐DCs significantly suppressed colonic MPO in both WT and RAG deficient mice. These results suggest that while T and/or B cells are essential to the anti‐colitic clinical response driven by HD‐DC, they are not required for reduced granulocyte infiltration. Overall these experiments highlight the therapeutic value of helminth antigens, and their potential to program DCs to attenuate inflammatory disease.
Tight junction integrity diminished by hypoxia, indomethacin, and hydrocortisone in Caco2 cell line (650.5)
Authors: Barnes Rachel , Carr Nick , King Jonathan
Published: June 2021

Background: Inflammation, hypoxia and loss of barrier function hallmark inflammatory bowel disease. Tight junctions play a vital role in the regulation of intestinal epithelial permeability. Indomethacin and hydrocortisone are used clinically as first line agents for inflammatory bowel disease.

Objective: To examine the effects of indomethacin and hydrocortisone, concurrent with hypoxia, pro‐inflammatory cytokines, on tight junctional integrity and cell viability.

Methods: A Caco‐2 cell line was utilized in the setting of normoxia (160 torr) and hypoxia (20 torr) under varying conditions of pro‐inflammatory agents TNF (10ng/mL), IFN‐gamma (10ng/mL)) and anti‐inflammatory agents of indomethacin (50uM) and hydrocortisone (50ng/mL). Epithelial barrier integrity assessed using solute flux assays, tight junction expression and localization analysis. Cell survivability evaluated by LDH quantification and cytotoxicity assays.

Results: Epithelial barrier integrity was impaired under exposure of hypoxia alone; these effects compounded with exposure to pro‐inflammatory agents leading to increased cytotoxicity. Addition of anti‐inflammatory agents demonstrated improved cell survivability without improvement in barrier function as demonstrated by solute flux, confocal imaging, and cytotoxicity assays.

Conclusions: Anti‐inflammatory agents may alter the regulation of intestinal epithelium cytotoxicity without improvement in barrier function. These findings indicate the possible role of indomethacin, hydrocortisone in altering cell survival mechanisms leading to cellular necrosis vs. apoptosis under hypoxic, pro‐inflammatory environments.

Grant Funding Source: Supported in part by NSF‐MRI #1229702
FGF and Notch signaling hierarchy in sensory neurogenesis (651.18)
Authors: Voelkel Jacob , Harvey Jamison , Adams Jason , Lassiter Rhonda , Stark Michael , Molteni Agostino
Published: June 2021

The purpose of this study was to determine the regulatory relationship of sensory neurogenesis in the trigeminal placode between the Fibroblast Growth Factor (FGF) and Notch signaling pathways. To do this, FGF signaling was blocked cell autonomously or globally while simultaneously downregulating Notch signaling in 10‐12 somite stage Gallus gallus chick embryos. Cell autonomous FGF inhibition with global Notch downregulation significantly reduced the number of proneural cells contributing the future trigeminal ganglion (p=0.0002). A similar reduction was found with concurrent global inhibition of FGF and Notch (p<0.0001). Remarkably, blocking FGF either cell autonomously or globally with simultaneous Notch downregulation reversed the effects of robust neurogenesis seen with Notch downregulation alone (p<0.0001). Further, Notch downregulation for 4 or 12 hours showed no difference in the level of FGF‐receptor 4 mRNA expression when compared to controls. It did however result in a highly fragmented basal lamina, which was reversed when blocking FGF signaling. From these data, we invalidate the FGF downregulates Notch in sensory neurogenesis model and propose a mechanism for parallel regulation of FGF and Notch leading to basement membrane fragmentation and subsequent delamination of differentiating opV placode cells.

Grant Funding Source: Supported by NIH/NICHD ‐ R01 HD046475
Psychosocial status of patients with acne (651.23)
Authors: Batpenova Gulnar , Tarkina Tatiyana , Kotlyarova Tatiyana , Sadykova Gulnaz
Published: June 2021

The goal: a comparative assessment of the psychological status of various group contingents, including patients with acne. The study included 60 people aged 18‐25 years. Of these patients with varying severity of acne ‐ 20 people; patients with severe infectious dermatoses ‐ 20 people; healthy ‐ 20 people. The psychosocial status of patients was assessed by the index for the psychological and social impact of acne on the personality APSEA (Assessment of Psychological and Social Effect of Acne), the maximum number of 144 points.

Results: the value of the index ARSEA in acne patients group was 47.9 points; the group of patients with acute infectious dermatoses ‐ 30.8 points; in a group of healthy ‐ 23.7 points. It is indicates to a possible negative impact on the scope of the patient's psychosocial disorders with significant cosmetic defect that is characteristic of acne.

The frequency of selecting an adverse additional colors on the test Lusher, all groups were as follows: patients with acne ‐ 70%; acute infectious dermatoses ‐ 50%; healthy‐45%. Within the group of patients with acne selected violet in 25%; gray‐30 %; black‐15%. Of the 70% of patients with acne in 10% for first position two depressive colors. 60% of the patients selected one color. Of the 50% of patients with acute infectious dermatoses in 10% of cases selected two depressed colors. In the healthy group, 45% selected to first position one depressivecolor.
Altered cerebrospinal fluid lipids in preclinical Alzheimer’s disease (651.6)
Authors: Fonteh Alfred , Chiang Jiarong , Cipolla Matthew , Harrington Michael
Published: June 2021

Background and Objective: Although lipids constitute a major portion of the brain, preclinical changes in lipid metabolism in cerebrospinal fluids (CSF) have not been determined in sporadic Alzheimer’s disease (AD). Our objective is to test the hypothesis that altered brain lipid metabolism precedes AD clinical symptoms.

Methods: We fractionated CSF into a 200,000 g supernatant fluid (SF) and nanoparticles (NP) fractions and used liquid chromatography tandem mass spectrometry to determine the glycerophospholipid (GP) and sphingolipid (SP) composition of these fractions from cognitively healthy (CH) subjects. We further analyzed lipids in subgroups of CH participants with normal beta amyloid to total Tau (Aβ/Tau) (CH_NAT) or with preclinical AD‐like Aβ/Tau pathology (CH_PAT), and in AD study participants.

Results: Levels of some GP classes and species are higher in the SF fraction from CH_PAT compared with CH_NAT. In contrast, levels of some SP classes and species are higher in the NP fractions from CH_PAT compared with CH_NAT. Activity of metabolic enzymes, PLA2 and acid SMase are significantly altered in AD compared with both CH subgroups.

Conclusions: Differences between CH_NAT and CH_PAT suggest increased turnover or remodeling of GP in brain interstitial fluid and SP in brain membrane‐derived lipids in preclinical AD. Means of regulating these lipid metabolic pathways may be beneficial in AD prevention.

Grant Funding Source: L.K. Whittier and the Helen Posthuma Foundations
Cerebrospinal fluid fatty acid composition changes in Alzheimer’s disease (651.7)
Authors: Cipolla Matthew , Harrington Michael , Fonteh Alfred
Published: June 2021

Objectives: To test the hypothesis that levels of saturated fatty acids (SAFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) that are structural components of neuronal membranes or are precursors of signaling molecules change in Alzheimer’s disease (AD).

Methods: We recruited and collected cerebrospinal fluid (CSF) from cognitively healthy (CH), mild cognitively impairment (MCI), and AD study participants. After fractionation of CSF into a 200,000 g supernatant fluid (SF) and nanoparticle (NP) fractions, we used gas chromatography‐ negative ion chemical ionization/mass spectrometry to determine the total fatty acid composition of these fractions.

Results: Levels of some SAFA, MUFA, and PUFA differed between the SF and NP fractions. Docosahexaenoic acid [DHA, (C22:6, n‐6)] levels were lower in AD compared with CH while alpha linoleic acid [α‐LNA, (C18:3, n‐3)] levels were lower in MCI compared with CH in the SF fraction. In the NP fraction, levels of SAFAs (C15:0, C16:0) and a MUFA (C15:1) differentiated CH from MCI while levels of MUFAs (C15:1, C19:1) and PUFAs (C20:2, C20:3, C22:4, C22:5) were altered in AD compared with CH.

Conclusions: Fatty acid metabolism is compartmentalized in CSF fractions and differences between clinical groups suggest that energy metabolism or oxidative pathways are important in AD pathophysiology. Some fatty acids in CSF fractions may be biomarkers of AD. Thus, dietary or pharmacological approaches to regulate brain fatty acid levels and measurement of fatty acid in CSF fractions may be helpful in prevention or monitoring AD.

Grant Funding Source: L.K. Whittier and the Helen Posthuma Foundations
Blood‐brain barrier function and it’s relation to dementia development (651.8)
Authors: Andersson Mats , Skoog Ingmar
Published: June 2021

Our aim was to further investigate the relation to BBB and the developing of dementia.

We investigated blood‐brain barrier (BBB) function by measuring cerebrospinal fluid (CSF,) mg/l, in relation to serum albumin (g/L) ratio (CSF/S‐albumin x 10‐3) in a population‐based sample of 85‐year‐olds. Sixty‐five underwent a lumbar punctured (LP) at the age of 85‐year, measuring CSF‐albumin, ‐β ‐amyloid and ‐Tau. Fifty‐three of them also underwent a Computed Tomography CT. The participants were then followed up until death. Repeated studies (e.g. at age 88, 90, 95, 97, 100 and for survivors, in cases possible, every year until death) were conducted in search of dementia signs.

Several previous CSF studies (1,2, 3, 4), but not all (5, 6, 7), reported a BBB dysfunction in AD. Decreased mitochondrial content and increased pinocytotic vesicles in capillary endothelium of AD patients (8) support that BBB dysfunction may be involved in the pathogenesis of AD (9, 10, 11, 12, 13). BBB dysfunction may also be secondary to AD. β‐amyloid has been reported toxic to blood vessles, thus stimulation atherosclerosis (14). BBB dysfunction may thus be both involved in the pathogenesis and a consequence of AD.

LP was performed at baseline, 25 participants were demented and showed highest mean of CSF/S‐albumin ratio; 8.743. Out of the non‐demented 12 participants developed dementia before they died, mean ratio; 7.433 in CSF/S‐albumin ratio. The 30 participants that did not develop dementia had the lowest ratio of CSF/S‐albumin; 6.652. There were no significant difference between the three groups (p = 0.312), although the samples were small.

Further analyses are presently conducted in relation to BBB, different dementia subtypes, β‐amyloid and Tau. Also Computed Tomography findings (atrophy, White‐matter lesions and multiple cerebral infarcts) will also be analyzed in relation to BBB function.
Chronic β1‐blockade impairs ischemic tolerance and preconditioning in murine myocardium (652.2)
Authors: See Hoe Louise , Headrick John , Peart Jason
Published: June 2021

β‐adrenoceptor (β‐AR) antagonists are commonly applied in ischemic heart disease (IHD) patients, yet may impact negatively upon signaling and efficacies of experimental ‘cardioprotective’ interventions. We assessed the effects of chronic β1‐AR antagonism on myocardial resistance to ischemia‐reperfusion (IR), and on the ability of ischemic preconditioning (IPC) and sustained ligand‐activated preconditioning (SLP) to reduce IR injury in murine hearts.

Male C57/Bl6 mice were administered the β1‐AR‐blocker atenolol for 4 weeks (0.5 g/L in drinking water) before subcutaneous implantation of morphine (SLP) or placebo pellets 5 days prior to analysis of ischemic outcomes ex vivo.

Post‐ischemic contractile function was substantially impaired in control (placebo) hearts, with ~50% recovery of ventricular force, significant diastolic dysfunction and cellular lactate dehydrogenase (LDH) release. Chronic ß‐AR blockade with atenolol significantly worsened contractile dysfunction and LDH release. Contractile dysfunction and LDH loss were reduced 50% or more with IPC, however protection was negated by ß‐AR treatment. SLP significantly improved post‐ischemic outcomes irrespective of ß‐AR blockade.

Data indicate that chronic β1‐AR blockade impacts negatively on both intrinsic ischemic tolerance and preconditioning responses whereas novel SLAP retains protective efficacy.
δ Opioid receptor agonist, DPDPE, enhances neuronal excitability in mouse enteric nervous system (653.4)
Authors: Hashimoto Atsushi , Dewey William , Akbarali Hamid
Published: June 2021

μ‐opioid agonists are known to inhibit gastrointestinal motility and cause constipation. But a role for the δ opioid receptor activation in propulsive motility is controversial. Previously, it was shown that μ opioid receptor agonist, morphine, decreases enteric neuron excitability via inhibition of sodium channels. Here we examined electophysiological properties by patch clamp techniques and determined the mechanism for δ opioid receptor agonist DPDPE‐induced increase in neuronal excitability in mouse single isolated enteric neurons. DPDPE (5μM) evoked spontaneous action potentials and depolarized the resting membrane potentials from ‐61.3 ± 1.3 mV to ‐52.3 ± 2.8 mV (n=3). DPDPE‐induced action potentials were reversed by ICI 174864, a δ receptor antagonist. In the presence of DPDPE, sodium channels were activated at lower membrane potentials, indicated by a leftward shift of sodium channel voltage‐dependent steady‐state activation curve. The V0.5 significantly increased from ‐28.2 ± 1.4 mV in the absence of drug to ‐37.2 ± 2.3 mV in the presence of DPDPE (n=4). We hypothesize that δ opioid receptor agonist enhances neuronal excitability by increasing sodium channel activity in mouse enteric neurons.

Grant Funding Source: Supported by NIH DA024009