bluuebunny/crossref_metadata_2025 huggingface dataset:
Sources of Folate Intake in Women at Risk for Cervical Cancer (CC) in an Era of Folic Acid Fortification
Authors: Badiga Suguna , Piyathilake Chandrika J
Published: June 2021

A comprehensive evaluation of folate intake from different sources has not been documented among women at risk for CC in the US Post Folic Acid Fortification Era. The study objectives were to identify different sources of folate intake and document determinants of folate intake from these sources in 273 women of child bearing age tested positive for high‐risk human papillomaviruses (HR‐HPVs). Folate intake was assessed using the Block 98.2 semi‐quantitative food frequency questionnaire (FFQ). Daily folate equivalents (DFE) were calculated by multiplying synthetic folic acid (SFA) intake from fortified food and supplements with the correction factor of 1.7. The median intakes of natural folate (NF), SFA and total folate DFE were 175, 224 and 442 µg/d respectively. Higher DFE was associated with higher folate intake from SFA. Forty three percent of the women had folate intakes below the RDA (< 400 µg/d of DFE) and 8% of the women had intakes > 1000 µg/d of DFE, beyond the maximum safe amount. Women with lower education were less likely to have intakes > 175 µg/d of NF and > 224 µg/d of SFA (P=0.02 & P=0.04 respectively) while AA women and women in the highest tertile of HEI were more likely to have intakes > 175 µg/d of NF (P=0.003 & P=0.05 respectively). Current smokers were more likely to consume > 224 µg/d of SFA (P=0.003). Women with higher calories from alcohol were less likely to have an intake > 224 µg/d of SFA and > 400 µg/d of DFE (P=0.004 & P=0.02 respectively). These results demonstrated that race, level of education, HEI, smoking and alcohol consumption influences folate intake from different sources. Overall, however, below RDA consumption rather than exceeding intakes over 1000 µg/d is of concern in women at risk for developing CC. The study is supported by RO1 CA105448.
Quantitative assessment of red and processed meat intake and kidney cancer
Authors: Alexander Dominik D , Cushing Colleen A , Roberts Mark A
Published: June 2021

We conducted a quantitative assessment of red or processed meat intake and kidney cancer. Twelve case‐control and 3 cohort studies published through 2007 were included. Random effects meta‐analysis models were used to calculate summary relative risk estimates (SRRE). Sensitivity and influence analyses were conducted, including assessments of heterogeneity. The SRRE for studies that reported results for red meat (i.e., variable labeled as 'red meat') and single red meat items (i.e., beef, pork, liver) was 1.16 (95% CI: 0.99‐1.36), while the SRRE for studies that reported results specifically for a variable labeled red meat was 1.15 (95% CI: 0.94‐1.42). Significant variability was observed across studies in these models (p for heterogeneity < 0.02). In a meta‐analysis of the four studies that simultaneously adjusted for smoking, BMI, and total energy intake, the SRRE for red meat was 1.03 (95% CI: 0.87‐1.22) and the estimates were less variable (p for heterogeneity = 0.11). No significant association was observed in the meta‐analysis of 9 studies that reported data for processed meat intake (SRRE = 1.05; 95% CI: 0.90‐1.22). Although summary findings are based predominantly on data from case‐control studies, the currently available epidemiologic evidence does not support a causal relation between consumption of red meat or processed meat and kidney cancer. Partially funded by the Cattlemen's Beef Board and NPB.
Quantitative assessment and systematic literature review of red and processed meat intake and breast cancer
Authors: Morimoto Libby , Alexander Dominik D , Cushing Colleen A
Published: June 2021

To update the state of the science of red and processed meat consumption and breast cancer risk, we conducted a quantitative assessment and systematic review of the prospective cohort and nested case‐control studies published through 2007 that examined this relationship. Fixed and random effects meta‐analysis models were utilized to generate summary relative risk estimates (SRRE), and sensitivity analyses were conducted to examine potential sources of heterogeneity. No associations between the highest vs. lowest intake categories of red meat and breast cancer were observed in the meta‐analysis utilizing data from the 2002 Pooling Project publication (data from 8 cohorts), from five studies published between 2003‐2007 (5 additional cohorts), and from one study published in 1996 (1 additional cohort) (SRRE = 1.01, 95% CI: 0.95‐1.06). Associations for red meat were slightly stronger among premenopausal women (SRRE = 1.13) than postmenopausal women (SRRE = 1.05). No association between processed meat intake and breast cancer was found after meta‐analysis of data from seven studies (SRRE = 1.02, 95% CI: 0.97‐1.09). The results of this quantitative assessment do not support a causal association between red or processed meat intake and breast cancer. This work was partially funded by the Cattlemen's Beef Board and the NPB.
Estimation of cancer risks of Korean diet.
Authors: Park Min Kyung , Jung Hyun Ju , Paik Hee Young
Published: June 2021

Cancer is the number one cause of death in Korea. High intakes of red meat and low intake of fruits and vegetable are known risk factors of cancer. The second report of World Cancer Research Funds (WCRF) recommendations for cancer prevention include consuming less than 43g/day of red meat, and more than 600g/day of fruits and vegetables. Korean diet is considered to be low in meat and high in plant foods. However, there has been no report on the cancer risk of diet in Korea population. The present study was conducted to evaluate the prevalence of risks of consuming high red meat or low fruits and vegetable intakes among Korean adults based on WCRF recommendation. Diet survey data of 6381 adults over 21yrs from 2005 Korean National Health and Nutrition Survey were analyzed for intakes of red meat and fruits and vegetables. One day diet survey was conducted by 24‐hour recall method. The average intake of red meat was 56.3g and 36% of adults (42.4% in men, 30.8% in women) consumed more than 43g/d. Average intake of fruit and vegetable was 438.4g/day and 78.9% of subjects (87.4% in men, 82.2% in women) consumed less than 600g/day. The average meat intake was over 43g/d in males of 21~64 years of age and in women of 21~49 years of age. The average intakes of fruits and vegetables of all age and sex groups were below 600g/day. These results indicate that cancer risk of Korean diet is relatively high in all adult groups over 21 years of age.
The Legume Inflammation Feeding Experiment (LIFE): Weight Loss Effects
Authors: Fitzgerald Kathryn , Zhang Zhiying , Bagshaw Deborah , Colburn Nancy , Kris‐Etherton Penny , Lanza Elaine , Hartman Terry
Published: June 2021

The LIFE study was a randomized controlled crossover feeding experiment intended to assess the effects of a low‐glycemic legume‐rich diet on biomarkers of inflammation and insulin resistance (IR). Sixty‐four male participants (35‐75 yrs) were recruited from Central Pennsylvania and divided into 4 possible groups: IR (Y or N) and history of adenomatous polyps (Y or N). All participants consumed a legume diet (LG; 1 1/2 cup cooked dry beans) and an average American diet (AA), each for four weeks split by a 3‐week washout interlude. A total of 44 of the subjects completed the required two dietary periods and then completed an optional 4‐week weight‐loss period. During the weight loss period we tested whether the legume rich diet would facilitate weight loss. Subjects were asked to consume the bean‐containing foods but were able to eliminate other foods. For the weight loss period, incipient mean BMI (±S.D.) was 29.04 (3.39). Initial results indicate a mean change in BMI of 1.36 (1.01) accounting for a 5.09% decrease in BMI with a significant difference over the dietary period (P=0.0001). Mean change in BMI was calculated for each of the classifications and proved to be significantly different from across strata (P= 0.0033). Those participants experiencing the most weight loss (> 5.2kg) also experienced a significant decrease in serum total cholesterol (TC) and LDL cholesterol (LDL‐C) (P=0.0345 and 0.001, respectively). Results indicate that the legume‐rich diet may have favorable effects on weight‐loss among individuals at high risk for colon cancer. Supported by the National Cancer Institute; partial support provided by the GCRC, PSU.
Modulation of Inflammatory Responses by Green and Black Tea Extracts in LPS‐Induced RAW 264.7 Cells
Authors: Summers Caroline , Cohen Sara , Watkins Ruth , Huang Zhengyue , Harris Gabriel
Published: June 2021

Tea is produced from the leaves of the Camellia sinensis plant and is one of the most popular beverages in the world. Tea polyphenols are thought to have chemopreventive and cardioprotective effects due to their ability to suppress inflammation. The goal of this study is to measure markers of inflammation in lipopolysaccharide (LPS) ‐ stimulated RAW 264.7 mouse macrophage cells in the presence or absence of varying concentrations of green tea (GT) and black tea (BT) to determine their effects on the inflammatory response. Tea phenolic contents were measured using the Folin‐Ciocalteu reagent (GT had a higher total phenol content than BT). Cell viability was assessed using the Trypan Blue and MTT assays. Prostaglandin E2 (PGE2) concentration was determined by ELISA (GT and BT increased PGE2 formation relative to controls.). The BCA assay was done to determine total protein concentration for Western blotting. The presence of cyclooxygenase‐2 (COX‐2) will be detected with Western Blotting. Based on preliminary data, we predict that the teas will modify the inflammatory response, and that GT will have a greater effect than BT due to differences in tea composition. This project was supported by the State of North Carolina.
CCR2+ and CX3CR1+ Bone Marrow‐Derived Cells Differentially Regulate Microvascular Remodeling in an Inflammation/Injury Model Without Transdifferentiating into Smooth Muscle
Authors: Meisner Joshua K , Nickerson Meghan M , Burke Caitlin W , Price Richard J
Published: June 2021

Monocytes are generally known to regulate vascular remodeling. However, monocyte subpopulations with distinct functional roles exist, and their relative contributions to remodeling are poorly understood. Here, the relative expression of CX3CR1 and CCR2, which mark inflammatory (CCR2high/CX3CR1low) and resident (CCR2low/CX3CR1high) monocytes, was used to study the roles of these cells in regulating microvascular remodeling during injury/inflammation. Dorsal skin‐fold window chambers were implanted into wild‐type (WT) c57bl/6 mice engrafted with bone marrow‐derived cells (BMCs) from WT (control), CCR2−/−, CX3CR1−/−, or EGFP+ mice. WT control chimeras exhibited significant increases in maximum arteriolar (68%) and venular (40%) diameters from day 7 to 14. In contrast, arteriolar remodeling (‐0.8%) was completely blocked in CCR2−/− chimeras, but no change in venular remodeling was observed compared to control (37%). Interestingly, CX3CR1−/− chimeras exhibited only a partial attenuation of arteriolar (32%) and venular (14%) remodeling. EGFP+ chimeras revealed no evidence that recruited EGFP+ BMCs transdifferentiate into smooth muscle, based on examination of >800 arterioles and venules. We conclude that CCR2+ and CX3CR1+ BMCs differentially regulate microvascular remodeling during the injury/inflammation response. Because these cells do not transdifferentiate into vascular cells, it is likely that both subpopulations serve as paracrine growth factor sources. Supported by NIH HL74082.
Regulating the activity of microRNPs in vertebrate cells
Authors: Steitz Joan A. , Vasudevan Shobha , Cazalla Demian
Published: June 2021

Tumor necrosis factor alpha (TNFalpha) mRNA bears in its 3' UTR a conserved AU‐rich sequence (ARE), a signal that exerts tight post‐transcriptional control over the expression of TNFalpha and other cytokines. We have discovered that the TNFalpha ARE increases translational efficiency when cell growth is arrested, a physiologically relevant state occurring during inflammation, angiogenesis and monocyte differentiation. Surprisingly, under these conditions, called quiescence, the microRNP‐associated proteins FXR1 and AGO2, which are usually considered negative regulators, are transformed into effector molecules that bind the ARE to activate translation. We then identified a specific microRNA that directs the association of AGO2 and FXR1 with the ARE during translation upregulation. Two other well‐characterized microRNAs likewise promote translation activation in quiescent or in contact‐inhibited cells; yet, they repress translation in proliferating cells late in S phase. We suggest that translation regulation by microRNPs oscillates between repression and activation as a function of the cell cycle. We are currently confirming the activating role of microRNAs in a naturally quiescent cell, the Xenopus oocyte. We are also investigating the mechanism by which H. saimiri, a primate gamma herpesvirus, regulates microRNA function in latently transformed T cells.
Effect of Aloe vera Supplements in Patients with Pre‐Diabetes
Authors: Devaraj Sridevi , Jialal Rohan , Jialal Ishwarlal , Rockwood Jason
Published: June 2021

Metabolic syndrome confers an increased propensity to diabetes and cardiovascular disease. Aloe vera, a plant used for dermatological applications, exhibits effects on blood glucose in diabetic mice. However, there is a paucity of data with regards to Aloe in improving glycemia. The aim was to examine the safety and antidiabetic effects of 2 aloe products, UP780, a chromone‐enriched Aloe gel fillet powder and AC952, Aloe gel fillet powder standardized to 10% polysaccharide without chromone, in a double‐blind, placebo‐controlled trial in patients with pre‐diabetes. 45 patients were randomized to 2 tablets/day of Placebo, UP780 and AC952(500 mg bid) for 8 weeks. Fasting blood and urine were obtained at baseline and 8 weeks. There were no significant changes in weight and routine chemistries, indicating safety of both Aloe supplements. In the UP780 group, there were significant reductions in HbA1C, fructosamine and insulin (p<0.05). Urinary f2‐isoprostanes were significantly decreased compared to baseline. In the AC 952 group, in addition to a decrease in fructosamine, there were significant reductions in total and LDL cholesterol levels and glucose and fructosamine values after supplementation. Thus, we report for the first time that 2 Aloe products significantly improved glycemic control in patients with pre‐diabetes.
Inhibition of nitric oxide production by feverfew supercritical extract as part of a migraine model in vitro
Authors: Aviram Anat , Tsoukias Nikolaos M. , Melnick Steven , Ramachandran Cheppail
Published: June 2021

Migraine is a chronic neurovascular condition characterized by a unilateral headache which affects approximately 12% of the population in the United States. Although the exact mechanism by which migraine headaches are initiated remains unknown, nitric oxide (NO) is suggested to play a key role in the pathogenesis of migraine and other headache syndromes. The purpose of this study is to examine the NO inhibitory properties of supercritical extract of feverfew (FF) as an herbal drug against migraine. To achieve this, we used murine macrophage (Raw 264.7) and human brain microvascular endothelial cell line (HBMEC) as migraine models in vitro. Each cell line was treated with lipopolysaccharide (LPS) or nitroglycerin (NTG) followed by treatment with varying concentrations of FF‐CO2 extract (0‐200 µg/ml) for 24 h. Supernatants were analyzed by nitric oxide quantification assay. In Raw264.7, LPS‐induced NO production was gradually inhibited by feverfew extract in a dose‐dependent manner. The inhibition commenced at 3% for 0.5 µg/ml feverfew extract to a maximum inhibition of 89% at 100 µg/ml FF. Furthermore, 100 µg/ml FF inhibited over 50% of LPS‐induced NO production in Raw264.7 within a period of 2 h. FF (50 µg/ml) also significantly inhibited 58% NTG‐induced NO production in RAW 264.7. In HBMEC, 100 µg/ml FF inhibited 27% of NTG‐induced nitrite + nitrate levels. These results serve as a prelude for further in vivo studies on the pre‐clinical development of feverfew supercritical extract against migraine headaches.

[AA is supported by NIH/NIGMS R25 GM061347]
Effect of leucine feeding on body weight and carbohydrate metabolism in dietary fat‐induced obese rats
Authors: Park Ji Min , Park Hoon Jung , Kim Mi Kyung
Published: June 2021

The aim of this study was to examine the effect of leucine on body weight and carbohydrate metabolism in 6 month‐old Sprague‐Dawley (n=80) rats. One group of 10 rats was fed control diet (control group) and another group of 70 rats was fed a high‐fat diet for 14 wks (high‐fat group) to induce obesity. Ten rats of each group were killed at this stage and the remaining obese rats were fed with one of six experimental diets containing 4%, 20% (w/w), two dietary fat levels (C‐, H‐) and three different Leu levels ; 0g, 0.6g, 1.2g /kg BW (‐LO, ‐LL, ‐LH) for 5 wks. Food intake, body weight, adipose tissues and organ weights were measured. To examine carbohydrate metabolism, oral glucose tolerance test (OGTT) conducted and the area under the curve (AUC) of each group was calculated. Body weight were significantly reduced in 1.2g/kg Leu groups (CLH, HLH) than 0g/kg Leu groups (CLO, HLO). Perirenal fat pad weights of 0g/kg Leu groups (CLO, HLO) were significantly higher than those of 0.6g/kg Leu groups (CLL, HLL) and those of 1.2g/kg Leu groups (CLH, HLH). AUC of 1.2g/kg Leu groups (CLH, HLH) were significantly lower than 0g/kg Leu groups (CLO, HLO). In conclusion, Leu administration might have weight loss effect and improve carbohydrate metabolism in dietary fat‐induced obese rats. * This work was supported by Sungshin Cement Co., Ltd. of Seoul, Korea and the second stage of the Brain Korea 21 project in 2008.
Growth and body composition in low‐body weight rats: influence of dietary fat
Authors: Suarez Cristina , Ferreira Andrea , Macri Vanesa , Ramos Cecilia , Gonzales Chaves Macarena , Pellegrini Gretel , Rodriguez Patricia , Zeni Susana , Friedman Silvia
Published: June 2021

Previous studies demonstrated the relationship between dietary fat and body composition. However, we studied the hypothesis that body weight (BW) of the infant, would influence body composition. At weaning female Wistar rats (n=70) were grouped according to BW (aged=21 day) as follows: control (C, n=31) >33.5 g BW and experimental (E, n=35) <33.5 g BW. C received a diet containing 7% w/w of fat (AIN‐G) and E was fed one of 2 diets; E1 (n=20), fat=7% w/w (AIN‐G) and E2 (n=15), fat=15% w/w. At aged 28, 35 and 49 (t28, t35 and t49, respectively), 8 rats per group were sacrificed. BW and % body fat and total skeleton body mineral content (BMC) by DEXA (Lunar DPX‐L) were evaluated. Body gain velocities (BGV) within times were calculated. BMC was analyzed per BW−0.75. Results (mean±SD) assessed by ANOVA and Dunnett test. At t28 and t35, CBW was higher than E (p<0.001) despite BGV in E groups was increased as compared to C (p<0.001). From t35, only E1 showed higher BGV (p<0.01). Body fat % and BMC/ BW−0.75 did not show significant differences throughout experimental period. Conclusion: We speculate that in low‐body weight individuals, dietary fat equal to RDA may be insufficient to achieve body size proportions, leading to a delayed in growth rate; meanwhile % body fat and BMC related to BW−0.75 appears to be in proportion to BW. Awarded by UBACyT O 004 and O015.
Anti‐inflammatory Actions and Mechanisms of γ‐Tocotrienol in Lipopolysaccharide‐stimulated Macrophages
Authors: Wang Yun , Jiang Qing
Published: June 2021

We have shown that gamma‐tocopherol (γ‐T), the major form of vitamin E in US diet, possesses anti‐inflammatory activity by inhibition of cyclooxygenase‐2 (COX‐2) catalyzed prostaglandin E2 (PGE2) synthesis in lipopolysaccharide (LPS)‐stimulated RAW264.7 macrophages. Here in the same cellular system we investigated potential anti‐inflammatory activity of gamma‐tocotrienol (γ‐TE), another vitamin E form with unsaturated hydrophobic side chain. γ‐TE at as low as 5 µM inhibited LPS‐activated PGE2 and dose‐dependently reduced nitrite accumulation, but had no effect on cell viability or LPS‐induced expression of COX‐2 or inducible nitric oxide synthase. γTE inhibited LPS‐stimulated interleukin‐6 (IL‐6), an pro‐inflammatory cytokine, in a dose‐dependent manner, but had no effect on interlukine 10, an anti‐inflammatory cytokine. Mechanistic studies indicated that in this cellular system, COX‐2 expression is regulated by p38 MAPK signaling pathway, while IL‐6 is regulated by NFkB. Consistently, γTE treatment did not show any effect on phosphorylation of p38, but rather resulted in an inhibition of phosphorylation of IkBa, a key event during NFkB activation. Studies are undertaken to further understand the molecular target/mechanism and anti‐inflammatory actions of γTE. (Supported by R01AT001821, P01AT002620 and P50AT000477)

Grant Funding Source

By R01AT001821, P01AT002620 and P50AT000477
Effects of folate on the brain gene expression of Tg2576 transgenic mice treated with Alzheimer drug memantine: a pilot study using cDNA microarray profiling
Authors: Chen Ta‐Fu , Chiu Ming‐Jung , Lu Jyh‐Feng , Tang Ming‐Chi , Huang Rwei‐Fen
Published: June 2021

Using Tg2576 transgenic mice that produce endogenous beta‐amyloid (Aβ) protein in brain, we have previously reported that high dose of folic acid supplemented to Alzheimer drug memantine (MT)‐treated AD mice significantly improved the neuronal functional performance on Morris water maze test. To further study effects of folate on the brain gene expression profile of MT‐treated transgenic mice, a total of 6 Aβ mice brains (3 from MT mice and 3 from folate+MT mice) were analyzed by cDNA microarrays. Total RNA isolation, cDNA synthesis and cy3 and 5 dye labeling were performed using standard protocols. The labeled samples were hybridized to Agilent Whole Mouse Genome Oligo Microarray containing 41,000+ annotated genes and transcripts. Expression data were analyzed using GeneSpring GX 10. Only genes with net expression changes of > 2‐fold occurring among 20‐100th percentile of expression levels in each hybridized arrays were considered for further analysis. Compared to MT‐treated Aβ mice brains, folate+MT brains showed a generalized up‐regulation of 72 brain gene transcriptions involving in neurogenesis, memory, action potential production, neurotransmitter receptors, vasodilation, and immune modulation. Down regulations were only found in 9 transcripts. Validation of gene expressions by real‐time PCR and the significance of modulated expression profiles by folate will be further discussed.
Effect of homocysteine (Hcy) lowering vitamins on S‐adenosylmethionine (SAM) and S‐adenosylhomocysteine (SAH) in older people.
Authors: Green Tim , Skeaff C Murray , Venn Bernard , Innis Sheila
Published: June 2021

Background

Elevated plasma Hcy is a risk factor for vascular disease but lowering Hcy with B‐vitamins, including folate, has generally not reduced vascular events in clinical trials. Elevated plasma SAH concentration may be a more sensitive indicator of vascular disease than Hcy (AJCN 2007;86:1581). However, SAH was not correlated with folate concentrations in one study indicating that folate supplementation may not lower SAH (Eur J Clin Invest 2003;33:17). The effect of Hcy lowering vitamins on plasma SAH is not clear.

Aim

To determine in healthy older people with mildly elevated Hcy (Mean = 17.1 µmol/L) whether lowering Hcy with B vitamins effects plasma SAM and SAH concentrations.

Methods

This was part of a larger trial to determine the effect of B vitamins on cognition in which 276 healthy participants (= 65 y) were randomized to receive a supplement containing folate (1 mg), vitamin B12 (500 µg) and B6 (10 mg), or placebo, for two years. Of these participants, we selected the first 50 from each treatment group and determined SAM and SAH at baseline and two years by HPLC MS/MS.

Results

Plasma Hcy was 4.4 (95% CI 3.2, 5.6; P<0.001) µmol/L lower at 2 years in the Vitamins group compared with the Placebo group. At 2 years, there were no significant differences in plasma SAM [+4% (95% CI ‐2, 10); P=0.18], SAH [+2 (95% CI ‐10, 10); P=0.61], or the SAM:SAH ratio [+10% (95% CI 0, 20); P=0.10] between the Vitamins and Placebo groups.

Conclusion

Supplementation lowered plasma Hcy but had no effect on SAM or SAH concentration.
Hypoxia factors and cytokines mRNA expression in visceral and subcutaneous adipose tissues (VAT and SCAT) in obese insulin resistant dogs. Effects of weight loss and fenofibrate treatment.
Authors: Leray Veronique , Le Bloc'h Jerome , Serisier Samuel , Nguyen Patrick
Published: June 2021

Expansion of VAT and SCAT has been described to be associated with adipocyte hypoxia. That could lead to inflammation and insulin resistance (IR), but the link with obesity remains unclear. Our aim was to assess the expression of hypoxia and inflammation markers in VAT and SCAT, in obese IR dogs, and the effect of BW loss or fenofibrate treatment, which both improve insulin sensitivity.

VAT and SCAT biopsies were taken from dogs in 3 different times: (a) when dogs were obese (group 1), (b) after they had been given fenofibrate (10 mg/kg BW) for 15 d (group 2) and (c) after they had been given a hypoenergetic diet and had recovered their ideal BW (group 3). mRNA expression of HIF‐variants 1, 4, 7, 8, HIF‐1A, IL‐1B, TNF‐A, IL‐1A, ubiquitine ligase and very long chain fatty acid (VLCFA) ligase‐5 was quantified using real time RT‐PCR.

Fenofibrate did not affect BW (‐3%). Hypoenergetic diet resulted in a 25% BW lost. In VAT, mRNA expression was lower in groups 2 and 3, except IL‐1A and VLCFA‐ligase‐5. In SCAT, mRNA expression of only HIF‐1variant1 and VLCFA‐ligase‐5 was lower in the group 3 compared to group 1.

These results confirm different metabolic responses in SCAT and VAT. They show a dramatic decrease in hypoxia factors expression in VAT in dogs after weight loss as well as at the end of the 15‐d fenofibrate treatment. This was concomitant to a decrease in cytokine expression, that could explain the improvement in insulin sensitivity.
Supplementation with the probiotic Lactobacillus casei Shirota has no immunomodulatory effect in healthy men with a low baseline NK cell activity
Authors: Watzl Bernhard , Bub Achim , Franz Charles M.A.P. , Seifert Stephanie
Published: June 2021

Probiotics have been shown to modulate the immune system. In healthy humans, however, contradictory results were observed. Thus, in a randomized double‐blind, placebo‐controlled trial the effect of the probiotic Lactobacillus casei Shirota (LcS; 1,95x1010 cfu/day) on immune functions of healthy men with low baseline NK cell activity (n=34/group) was investigated (study period 8 wk, i.e. a 2‐wk run‐in period, 4 wk supplementation and a‐2 wk follow‐up). Individuals of the control group (n=34) consumed the same drink manufactured without LcS. LcS had no effect on NK cell activity and immune cell phenotypes in peripheral blood mononuclear cells. Further, phagocytic activity and intensity of monocytes and neutrophils, oxidative burst, cytokine secretion pattern and saliva SIgA concentrations did not differ between groups. The incidence of potentially pathogenic microorganisms including S. aureus and hemolytic streptococci in the nasopharyngeal microflora was also not changed. In summary, under the present conditions supplementation with LcS caused no immunomodulation. However, other dosages of LcS might be effective as indicated by trials using higher LcS dosages. Dietary habits of study subjects may also be relevant for the outcome of the trial and may impede a demonstration of immunomodulatory activities of probiotics in open studies.

The study was supported in part by a grant from Yakult Honsha CO., Ltd.
High fat diets increase TCR nano‐scale clustering
Authors: Shaikh Saame Raza , Boyle Sarah , Edidin Michael
Published: June 2021

High fat diets have immunomodulatory effects on CD4+ T cell frequency, activation, and signaling. However, the mechanisms by which high fat diets modify T cell function remains to be elucidated. One emerging viewpoint is that dietary fatty acids change the plasma membrane's biophysical organization on a nano‐scale, which in turn disrupts T cell receptor (TCR)/co‐receptor distribution and function. In the present study, we tested if high fat diets enriched in either saturated or monounsaturated fatty acids could modify TCR nano‐scale clustering of naïve CD4+ T cells using a new method of quantum dot imaging and k‐space analysis. CD4 transgenic B10.BR mice were fed for 2 weeks a normal diet (5% fat by weight) or high fat diets (20% fat by weight) enriched in saturated (SFA) or monounsaturated (MUFA) fatty acids. Although both high fat diets increased TCR clustering, the SFA‐rich diet had the greatest effect. Splenic CD4+ T cells increased TCR nano‐scale clustering by ~50% suggesting that a SFA‐rich diet can alter the threshold for T cell activation. Our findings are consistent with our recent in vitro studies with SFAs on antigen presenting cells to show that changes in plasma membrane structure can significantly modify lymphocyte function. We suggest that high fat diets can modify the biophysical organization of the TCR, which may explain changes in T cell function of obese individuals.
Academic stress in an undergraduate population is associated with increased likelihood of getting a cold
Authors: Herrlinger‐Garcia Kelli A , Voehl Amanda K , Padgett Emily M , Christman Mary C , Langkamp‐Henken Bobbi
Published: June 2021

The academic stress model (i.e., psychological stress associated with dysregulated immune function) typically uses medical students who are taking the same exams. This study determined whether an undergraduate population, which would provide a larger pool of subjects, could be used in this model. Healthy full‐time students (n=176, aged 18 to 29 yr) were recruited from a large undergraduate population (n=32,470). Students recorded their level of stress (0=no stress to 10=extremely stressed) and any cold symptoms daily for 8 wk (i.e., 4 wk before and 4 wk after fall 2007 final exams). Students completed the Perceived Stress Scale (PSS) at wk 0, ~wk 4 (post‐exams) and wk 8. The PSS was similar at baseline (22.6+0.5) and post‐exams (23.0+0.5) but decreased (P<0.001) at wk 8 after a 4‐wk break from classes (20.8+0.5). This suggests that perceived stress was elevated in the month before and during exams then reduced in the month following exams. The probability of getting a cold increased as average daily stress score increased (P<0.05). There were a total of 94 colds, defined as >2 cold symptoms for >2 days, and 71 students had at least one cold. Thus, fall‐term final exams in undergraduate students provide a model of psychological stress that is associated with the increased likelihood of getting a cold. This model could be used to investigate the effect of nutritional interventions on maintenance of health. Sponsor: Biothera
Absence of toll‐like receptor‐2 (Tlr2) attenuates diet induced obesity and adipose tissue inflammation and insulin resistance
Authors: Davis Jeremy E , Walker‐Daniels Jennifer , Spurlock Michael E
Published: June 2021

Toll‐like receptor‐4 (Tlr4) is involved in fatty acid (FA) induced inflammation and insulin resistance. However, less is known about toll‐like receptor‐2 (Tlr2), which is also activated by FA. To investigate the involvement of this receptor in diet‐induced obesity (DIO) in mice, we utilized male Tlr2‐/‐ and 6J controls. Mice were fed either low fat (low‐fat control, LFC), high unsaturated fat (high‐fat control, HFC), or high saturated fat + palmitate (HFP) diets ad libitum for 16 weeks. Means were considered significant at P<0.05. These data showed that Tlr2‐/‐ mice were protected from DIO, but without significant changes in body weight, energy intake, or lipid profile. Serum monocyte chemotactic protein‐1 (MCP‐1) was lower in Tlr2‐/‐ mice fed the high fat diet. Transcript abundance of inflammation and oxidative stress markers in adipose tissue (AT), including tumor necrosis factor‐á, interleukin‐6, MCP‐1, F4/80, and nitric oxide synthase‐2 were attenuated in Tlr2‐/‐ mice. Furthermore, these effects were more pronounced in mice fed the HFP diet. Blood glucose and insulin were unchanged in Tlr2‐/‐ mice. However, stromal vascular cells isolated from AT of Tlr2‐/‐ mice had a marked increase in insulin sensitivity. These data indicate that Tlr2, as well as Tlr4, are involved in obesity‐induced inflammation and insulin resistance, specifically when fed a high saturated fat diet.
Classic activation of 3D4/31 porcine alveolar macrophages using phorbol 12‐myristate 13‐acetate and ionomycin
Authors: Myers Jay L , Tagliaferro Anthony R
Published: June 2021

We hypothesize that dietary n‐6 fatty acids can convert alveolar macrophages to an alternative phenotype that promotes a Th2 immune response and respiratory allergy in humans. Our purpose was to establish an in vitro model using a transformed line of porcine alveolar macrophages (3D4/31). Cell populations of 3D4/31 cells were cultured in RPMI growth media (GM) supplemented with 10% fetal bovine serum (FBS) and incubated at physiological conditions (5% CO2 and 37 C). Three 24‐well plates were seeded at 100,000 cells/well and divided by serum conditions; 10% FBS or 10% porcine serum (PorS). After a 24‐hour incubation, wells were inoculated with phorbol 12‐myristate 13‐acetate (PMA; 0.01 mg/ml) and ionomycin (0.05 mg/ml). At various time points up to 12 hours, conditioned media was removed, centrifuged and stored at ‐80 C until ELISA analysis for TNF‐a and IL‐10. Total mean TNF‐a secretion was 22% higher when using PorS supplemented GM compared to FBS (n=18; p<0.05). Between 3 and 6 hours post‐activation, mean TNF‐a concentrations increased linearly and PorS supplemented GM was 29% greater than FBS (p<0.05) at 6 hours. The media was not found to contain measurable levels of IL‐10. 3D4/31 cells secrete TNF‐a and not IL‐10 when activated by PMA/ionomycin and are capable of providing a classically activated macrophage model to investigate potential influences of n‐6 fatty acids.

UNH Experimental Station Project H495.
2‐Monopalmitin treatment induces a greater inflammatory response than palmitate in 3T3‐L1 adipocytes
Authors: Luchtel Rebecca Ann , Walker‐Daniels Jennifer , Wang Tong , Spurlock Michael E
Published: June 2021

Palmitate has been shown to induce a localized inflammatory response when applied to 3T3‐L1 adipocytes, thereby contributing to inflammation characteristic of obesity and insulin resistance. Furthermore, newly adapted inter‐esterification procedures in human foods markedly increase the abundance of triacylglycerol molecules with palmitate or stearate in the sn‐2 position. Saturated fatty acids are more readily absorbed as sn‐2 monoacylglycerol (MAG) than free fatty acid lipase cleavage products. Although these modified fats are known to perturb lipoprotein metabolism and glucose homeostasis in humans, the extent to which MAG structure influences inflammation is unknown. To investigate the response of 3T3‐L1 adipocytes to treatment with 2‐monopalmitin (MP), cells were administered one of the following treatments: control, vehicle, palmitate, MP, or lipopolysaccharide. MP, but not palmitate treatment resulted in a significant increase of both interleukin‐6 (IL‐6) expression and IL‐6 concentration in culture media (p<0.05). Moreover, monocyte chemoattractant protein‐1 (MCP‐1) expression was significantly higher in MP‐treated cells vs. palmitate (p<0.05). Taken together, these results demonstrate that MP induces expression of proinflammatory cytokines, IL‐6 and MCP‐1, to a greater degree than palmitate, suggesting signaling differences in activation of immune response mediators.
A beef meal elicits a decrease in post prandial vascular function whereas a bison meal does not
Authors: Bennett Danielle , Askew E.W. , McDaniel J. , Fjeldstad A.S. , Mihalopoulos Jason , Harris R. A. , Richardson R.S.
Published: June 2021

The flow mediated dilation (FMD) test is a noninvasive measurement that provides an index of vascular function. A high fat meal has been recognized to negatively impact endothelial‐mediated vasodilation and thus attenuate FMD. Bison meat typically contains 1/3 of the total fat compared to beef and has less saturated fat.

Purpose

This study sought to determine the impact of an acute meal consisting solely of beef or bison meat on post prandial vascular function.

Methods

Nine healthy males (30 ± 5 yrs) participated in two brachial artery FMD trials before (PRE) and 4 hours after (POST) ingestion of 12 ounces (cooked weight) of bison or beef. The meals were ingested in random order with several weeks of washout between FMD measurements. Brachial artery diameter, blood velocity, and shear rate (area under the curve) were determined by ultrasound Doppler following 5 minutes of supra‐systolic cuff occlusion of the forearm.

Results

There was no effect of either the beef or bison meal upon FMD when expressed traditionally as % dilation. However, FMD when corrected for shear rate revealed a significant decrease in FMD from PRE to POST for the beef meal (4.00 ± 1.24 x 10−4 vs. 2.66 ± 1.60 x 10−4) (P<0.01), but not the bison meal (4.96 ± 3.13 x 10−4 vs. 3.50 ± 1.49 x 10−4).

Conclusion

When variations in shear rate, the major stimulus for FMD, are taken into account, vascular function is significantly compromised by a beef meal, but not by an equivalent bison meal. The negative vascular impact of the beef meal, but not the bison meal was likely due to lower fat content of the bison or the differing fatty acid composition of the two meats.
Peer‐counseling and inflammatory markers in Latinos diagnosed with type 2 diabetes. Results from the DIALBEST trial
Authors: Calle Mariana C , Vega‐Lopez Sonia , Puglisi Michael J , Segura‐Pérez Sofia , Chhabra Jyoti , Pérez‐Escamilla Rafael , Volek Jeff S , Fernandez Maria Luz
Published: June 2021

Anthropometrics, cytokines [C reactive protein (CRP), interleukin‐6 (IL‐6), tumor necrosis alpha (TNF‐alpha)], leptin, adiponectin, plasma lipids and 24h dietary recalls were analyzed for Latino subjects diagnosed with type 2 diabetes recruited from the DIALBEST trial (n = 22 men and 60 women, 32‐76y). Parameters were measured at baseline (BL) and after 3 and 6 mo of intervention. Subjects were randomly assigned to a peer counseling (PC) or a control group (CG) receiving the standard of care from Hartford Hospital. There were no changes in macronutrient intake over time except for total and soluble fiber, which were increased between baseline and 6 mo by 7 and 12% in the PC group and decreased by 35 and 29%, respectively in the CG (P < 0.05). IL‐6 decreased by 20% in all subjects between baseline and 6 mo (P < 0.01). However, when the group was divided on the basis of statin use, only those subjects prescribed a reductase inhibitor decreased IL‐6 over time (p=0.01). No changes were observed in CRP, leptin, adiponectin or TNF‐alpha levels over time or between groups. There was a negative correlation between changes in HDL cholesterol and CRP between baseline and 6 months (r = ‐0.297, P < 0.05) and a positive correlation between adiponectin and HDL at 6 mo (r = 0.363, P < 0.01). The data suggest that both statins and HDL play an important role in improving inflammation in this population. In addition, PC did not affect inflammatory markers in this population. [Supported by NIH‐NCMHD EXPORT Center grant P20MD001765].
Effects of Zn and Fe supplementation on the iron status and immunity in female athletes
Authors: Lee Okhee , Kim Mijin , Kim Wokeung , Chung Yongsam , Moon Jongwha
Published: June 2021

Athletes are exposed to acute and chronic stress that may lead to suppression of the immune system and increased oxidative species generation. Normal Fe and Zn levels are essential for the development and maintenance of immune functions and antioxidative system for athletes. This study evaluated the effect of Fe and Zn combinative supplementation on the immune function in female athletes with oxidative stress. The experiment group was supplemented with Zn and Fe as Zn glyconate and Fe‐glycerite, respectively, for 2 month. Before and after supplementation, they exercised in treadmill until exertion according to Bruce protocol. The serum concentrations of Fe and Zn were measured by neutron activation analysis method. The hemoglobin levels were not changed in supplemented athletes in contrast to significant decline in placebo athletes. Declines of resting serum Zn and Fe level after 2‐mo. period in athletes were diminished by Zn and Fe supplementation. The reduction of serum Zn levels after exercise was diminished in athletes with Zn and Fe supplements compared to the placebo group. The decline of basophile proportion was significantly diminished by 2‐mo supplementation (p<0.05). However, the increase of PHA‐induced lymphocyte proliferation was lowered by Fe and Zn supplementation in resting state in contrast to increase of ConA‐induced lymphocyte proliferation after exercise.
Association between time of energy consumption and body weight in U.S. children
Authors: Marshall Ying Wen , Eng Stephanie , Wagstaff David , Kranz Sibylle
Published: June 2021

This study focused on the association between time of day when energy is consumed and body weight status in various subgroups of the pediatric population. A nationally representative sample of 2‐18 year olds (N=11,072; NHANES 1999‐2004) was examined to compare total and proportion of total energy intakes in one‐hour time increments and their association to children's body weight status. General estimation equation models were employed to quantify the effect of time trends on energy intake in the total sample by sex, body weight status, ethnic and age group. Complex sample survey Student t‐tests and chi‐square tests were used to obtain statistical significance at a p‐value of <0.05.The eating pattern of healthy weight, overweight and obese children were the similar in the morning but differed in the evening. Healthy weight children consumed higher proportions of energy in the morning but had lower energy intake the rest of the day. Obese children had less energy in the morning and larger proportions of total energy than overweight and healthy weight children between 7pm to midnight. Study results also showed a time‐trend effect in overweight school‐age children indicating higher energy intake in the evening. Further research is needed to examine in detail the long‐term effect of higher proportions of total energy consumed later in the day on childhood obesity in the American children.
Food consumption patterns among peri‐urban Guatemalan children
Authors: Marcinkevage Jessica Ann , Ramirez‐Zea Manuel , Zuleta Clara , Stein Aryeh D
Published: June 2021

As part of an ongoing study of diet among school‐age children, we administered a qualitative FFQ ‐ measuring the frequency of 75 foods consumed in the past week, but without measuring portion size ‐ to mothers of 50 7‐10 year‐olds attending public schools in peri‐urban Guatemala. Each mother also completed 24‐hour recalls of her child's food intake on three different days in the preceding week. As derived from the FFQ, mean (SD) caloric intake was 1747 (710) kcal; 61% of calories consumed came from carbohydrates and 27% from fat. Based on the 24 hour recalls, mean (SD) caloric intake was 1751 (513) kcal; 59% of energy came from carbohydrates and 26% from fat. These data suggest that the two instruments provide consistent estimates of energy and macronutrient intake. Analysis of the FFQ showed that these children consumed, on average, ~28 different foods during the week, including 7.7 servings of complex carbohydrate‐rich foods, 1.0 serving of meat, 1.1 servings of dairy, 0.8 servings of vegetables, and 0.5 servings of fruits per day. The children also consumed, on average, 1.8 servings of snack foods daily, primarily corn chips and soda. The most commonly consumed foods were tortillas, sweet breads, corn chips and coffee. The FFQ data suggest that the diets of urban Guatemalan children are high in snack food items, but deficient in fruits and vegetables.
The relationship between meal frequency and BMI in school‐children
Authors: Goldsbury Savannah J , Leidy Heather J , Gibson Cheryl A , Sullivan Debra K
Published: June 2021

Purpose

To identify the relationship between meal frequency and BMI in children. Methods: This was a cross‐sectional, observational study involving 1070 children in grades 3‐5 (age 7‐12 y) from 12 elementary schools within the Kansas City, KS Public School District. Each child completed one testing day of height and weight measures to determine BMI for age and sex percentiles (BMI%); total energy intake and number of eating occasions per day (EO) were identified using a multiple pass 24‐h diet recall administered by trained nutritionists. Correlational analyses were performed to determine relationships between BMI%, EO, and total energy intake. BMI% was also examined according to EO categorized as <3, 3‐4, >5 EO.

Results

BMI% was 74 ± 27% (range: 0‐100); EO was 4 ± 1 (range: 1‐8); and total energy intake was 1677 ± 786 kcal/d (range: 104‐7273). Lower BMI% was associated with higher total energy intake (r: ‐0.116; p<0.001) and greater EO (r: ‐0.091 p<0.005). Main effects of categorized EO were observed for BMI% (p<0.05). Children consuming <3 EO had higher BMI% (80± 24%) vs. those consuming 3‐4 EO (73± 27%; p<0.05) and >5 EO (72 ± 28%; p<0.01).

Conclusion

Increased energy intake in combination with increased meal frequency positively impacts BMI% in school‐aged children. This data suggests that increasing the number of eating occasions may be a beneficial strategy to combat obesity. Support: NIH: R01 HL080967‐01A2

Grant Funding Source

NIH R01 HL080967‐01A2
Dietary Dehydroepiandrosterone Raises Serum Cytokine Levels in Zucker Rats
Authors: Svec Frank , Porter Johnny R.
Published: June 2021

The effect of dietary DHEA (dehydroepiandrosterone) on the levels of serum cytokine of male Zucker rats was studied. There were 8 groups of rats with 5 animals in each group; half of the 40 rats were obese while the others were lean. Half of each phenotype were made diabetic with streptozocin and half of each group were fed rat chow that was supplemented with 0.15% DHEA for 7 days before sacrifice. Body weights, corticosterone, DHEA, glucose and insulin levels were measured as well as TNF‐alpha, IL‐1 , IL‐1 alpha, IL‐1 beta, IL‐2, IL‐6, and IL‐10. The animals that were diabetic lost weight over the period of observation while the non‐diabetic controls gained weight. DHEA had no statistically significant effect on body weight. Diabetes did not affect cytokine levels. DHEA treatment, on the other hand, led to clear increases in the levels of IL‐1 alpha, IL‐2,IL‐6. Subgroup analysis showed that the effect of DHEA was seen in both lean and obese animals. These results point to the mechanism by which DHEA enhances the immune response.

(Supported by Millenium Trust Excellence Fund Grant HEF (2000‐05)‐04 and American Hear Association Grant Southern Consortium 9808326V)