bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthropometric Measurements Differ among Overweight and Obese Adults of Varying Socioeconomic Status but no Differences in Fruit and Vegetable Intake
Authors: Rhee Yeong , Honrath Kerrie , Wagner Meredith G.
Published: November 2023

Individuals of lower socioeconomic status (SES) tend to have higher rates of obesity and eat poorer quality diets than their counterparts of higher SES. The study was conducted to determine if fruit and vegetable (F/V) intake and anthropometric measurements differ among overweight and obese adults of varying SES. The study was a cross‐sectional design that included 38 adults from the Midwestern United States with a body mass index (BMI) of >25 kg/m2. The study looked at education level, personal income, and household income separately to assess SES. Weight, height, body fat percentage, and waist circumference were measured and BMI was calculated. Intake of F/V was measured by averaging daily intakes from three‐day food records. The results showed that F/V intake did not vary significantly among those of varying SES but BMI and body fat percentage did. Individuals with higher education levels as well as higher personal incomes had a significantly lower BMI and body fat percentage. Also, those with higher household incomes had a significantly lower body fat percentage. Overweight and obesity appear to be more prevalent among those of lower SES, which is why nutrition intervention is important for this population; however, focus should be on barriers to eating higher quality diets other than affordability such as taste, availability, and motivation to make changes.

Support or Funding Information

The research was funded by grants from the Department of Health, Nutrition, and Exercise Science and College of Human Development and Education at North Dakota State University.
Changes in Body Composition Despite Changes in Dietary Intake or Eating Behaviors During the Fall Semester in First Year College Students
Authors: Jones Kassandra , Vera Desiree , Dunn Sarah L.
Published: November 2023

Dietary intake and the attainment of nutrient recommendations may play a critical role in the maintenance of overall health by preventing disease. Disturbances in eating often result in negative changes in body composition from maladaptive lifestyle choices. Longitudinal studies observing the emerging college student found that the types of eating behaviors and body composition developed were maintained into adulthood. The aim of this study was to assess changes in the body composition, dietary intake and eating behaviors of first year college students in the fall semester of their first year. First year college students (N=23, age 18.3 ± 0.6 years, male n=10, female n=13) from the University of La Verne were asked to provide data for their eating behaviors and visit the laboratory for body composition assessments (Tanita 310, Tanita, Japan) which included; body weight (BW), percent body fat (BF%), fat mass (FM), fat free mass (FFM), and a calculated body mass index (BMI) pre and post first semester. Students completed the Eating Behavior Patterns Questionnaire adapted from the Situational Obstacles to Dietary Adherence Questionnaire in order to analyze certain classifications of behavioral eating. The subcategory factors used were: low‐fat eating (conscious of food composition), emotional eating (eating or not eating for comfort), lifestyle behaviors (location and social aspects surrounding meals), meal skipping (overeating or other meal skipping reasons), haphazard planning (the inability to meal prep or cook) and snacking on sweets (specifically eating or obtaining high sugar content foods such as cookies). A record of daily dietary intake for a total of 3 days, 2 days during the week and 1 day during the weekend was assessed using Dietary Analysis Plus software (Cengage, USA). A paired sample t‐test (SPSS v.21, P‐value of < 0.05 used to determine significance) assessing the changes over the semester for eating behavioral factors, dietary intake and body composition. Significant changes in BW [1.5 ± 2.1 kg, t (21) = −3.345, p < 0.05], BF% [2.1 ± 3.7 %, t (21) = −2.714, p < 0.05], BMI [0.5 ± 0.8 kg/m2, t (21) = −2.817, p < 0.05], and FM [2.6 ± 4.2 kg, t (21) = −2.970, p < 0.05], were found across the semester despite a lack of significant change in dietary intake and eating behaviors. Interestingly, while the change in FFM (−0.5 ± 2.8 kg) was not significant, a reduction despite no change in dietary intake or eating behaviors may represent a lack of physical activity throughout the first semester leading to the changes found in body composition. Future studies assessing body composition, dietary intake, and eating behaviors in college freshman should consider physical activity or barriers to physical activity when assessing body composition change across the first semester in first year college students.
Allicin Inhibits Lymphangiogenesis in vitro and in vivo
Authors: Wang Weicang
Published: November 2023

Allicin, the most abundant organosulfur compound in freshly crushed garlic, has been shown to inhibit tumor metastasis, however, the detailed mechanisms are largely unknown. Here we studied the effects of allicin on lymphangiogenesis, which is a critical step involved in tumor metastasis via generating new lymphatic vessels. Our results showed that allicin inhibited lymphangiogenesis in vitro and in vivo. In a Matrigel plug assay in mice, allicin inhibited the infiltration of podoplanin‐positive lymphatic endothelial cells induced by vascular endothelial growth factor C (VEGF‐C), suggesting its anti‐lymphangiogenic effects in vivo. In human microvascular lymphatic endothelial cells (HMVEC‐dLy), allicin showed its anti‐lymphangiogenic effects through inhibiting cell migration and tube formation. Allicin inhibited phosphorylation of VEGF receptor 2 (VEGFR2) and focal adhesion kinase (FAK) in a dose‐dependent manner, suggesting its regulatory effect on VEGF receptor pathway. Finally, S‐allylmercaptoglutathione (GSSA), a major metabolite of allicin, had no effect on lymphangiogenesis in HMVEC‐dLy cells. Together, our results demonstrate that allicin inhibited the lymphangiogenesis in vitro and in vivo, suggesting a novel mechanism for the health benefits of allicin.
DHA Supplementation Alters Cofilin1/pVASP‐S239 Expression, Sub‐cellular, Localization, and Suppresses Migration and Proliferation in Lung Cancer Cells
Authors: Ali Mehboob , Heyob Kathryn M , Rogers Lynette K
Published: November 2023

Cancer cells exhibit higher migration rates and greater cell viability facilitated by actin binding protein (ABP)‐mediated cytoskeletal remodeling and secondary messengers. APB like vasodilator stimulated phosphoprotein (VASP) and cofilin1 regulate actin remodeling. cGMP mediated VASP phosphorylation at serine 239 (pVASP‐S239) via PKG and cofilin1 are associated with actin stabilization. Docosahexaenoic acid (DHA) has been shown inhibit cancer cell metastatic phenotype. We hypothesize that DHA enhances pVASP‐S239 and its association with cofilin1 to attenuate actin dynamics‐mediated cancer cell migration and survival.

Non‐cancer (MLE12) and cancer (A549) cells were treated with DHA for 6h and 24h. pVASP‐S239 and cofilin1 expression were analyzed by western blot and total F‐actin content and VASP/cofilin expression and localization were assessed by immunofluoresence. Cell migration was estimated by wound assay and transwell apparatus. Ki67 and caspase 3 expressions measured by flow cytometry. Protein expression of pVASP‐S239 and cofilin1 increased with DHA supplementation compared to control. F‐actin content, cell migration, and proliferation were decreased with DHA supplementation in cancer cells but not in non‐cancer cells. With stimulation, cellular distribution of cofilin1 and pVASP‐S239 were observed in the perinuclear region while DHA supplementation caused the expression to moved towards cellular edges.

In conclusion, DHA specifically inhibits cancer cell migration and proliferation and this effect correlates with ABP expression and subcellular distribution patterns. DHA supplementation suppresses cellular changes related to metastatic potential in cancer cells and could provide therapeutic potential against cancer cell metastasis.

Support or Funding Information

This work was supported by the National Institutes of Health, NCCIH/ODS (LKR R01AT006880).
Antioxidative activity of (3R,3R’) and (3S,3S’) astaxanthin in Caenorhabditis elegans
Authors: Liu Xiaojuan , Luo Qingxin , Cao Yong , Liu Xin , Xiao Hang
Published: November 2023

As a potent antioxidant in human diet, astaxanthin (AST) may play important roles in alleviating oxidative stress‐driven adverse physiological effects. In this study, we determined the anti‐oxidative and anti‐aging effects of different stereoisomers of AST in Caenorhabditis elegans (C. elegans). Three stereoisomers of AST investigated herein included 3S,3′S (S) AST, 3R,3′R (R) AST and a mixture (S: meso: R=1:2:1) (M) AST. Under normal culture environment, treatment with S, R and M AST extended median lifespan of C. elegans by 27.61%, 25.25% and 22.69%, respectively. Under the peroxidation conditions, all three types of AST significantly enhanced survival rate of C. elegans. The accumulation levels of ROS were reduced by 40.12%, 30.05% and 22.04% by S, R and M AST, respectively (P<0.05). Compared with R and M AST, S significantly enhanced the expression levels of SOD‐3. The results of RNA‐Seq demonstrated that AST protected C. elegans from oxidative damage potentially by modulating the insulin/insulin‐(IIS) pathway and the oxidordeuctase system. It is noteworthy that the different stereoisomers of AST showed different effects on the expression levels of various genes related with oxidative stress. This study provided important information on the in vivo antioxidative effects of AST stereoisomers.

Support or Funding Information

National Natural Science Foundation of China (31401481)
Lutein‐supplemented formula enhances lutein accumulation in brain and other tissues in infant rhesus macaques
Authors: Jeon Sookyoung , Ranard Katherine M. , Neuringer Martha , Johnson Emily E. , Kuchan Matthew , Johnson Elizabeth J. , Erdman John W.
Published: November 2023

Lutein, a yellow xanthophyll, is well known for its critical role in eye health, and several recent studies also showed associations of lutein intake with improved cognitive function in adults. In addition, it has been suggested that lutein's presence as the most abundant carotenoid in brain may contribute to neural development. However, there is limited data on the effect of lutein bioaccumulation in early life. The purpose of this pilot study was to investigate if a lutein‐supplemented infant formula can increase lutein deposition in brain regions and other tissues using a nonhuman primate model. Infant rhesus macaques (1–3 months old) were fed either a control formula containing a basal level of lutein (10 nmol/L) (n=2) or a formula with a higher level of lutein (100 nmol/L) (n=2) to mimic the breast milk composition from mothers consuming a healthy vegetable‐rich diet. Serum carotenoids were measured monthly, and retina, brain, and other tissues were collected after 4 months of feeding. The levels of carotenoids in serum and tissues were analyzed by high‐performance liquid chromatography. Final serum lutein level in the supplemented group was 5 times higher than in the unsupplemented group (104 nmol/L and 21 nmol/L, respectively). Lutein accumulated differentially across brain areas. Occipital cortex exhibited the highest lutein level among brain areas regardless of the formula type, and was 3‐fold higher in the supplemented group (64 pmol/g versus 21 pmol/g). The other brain areas, including prefrontal and superior temporal cortex, striatum, hippocampus and cerebellum, all showed increased lutein concentrations in supplemented group; indeed, in the unsupplemented group, lutein was undetectable in prefrontal and superior temporal cortex and cerebellum. Lutein was two times higher in mesenteric and thigh subcutaneous adipose tissues, three times higher in abdominal adipose tissue and six times higher in brown adipose tissue in the supplemented group compared with the unsupplemented group. In addition, higher lutein deposition was found in liver, lung, kidney, heart, and other tissues. In conclusion, infant rhesus macaques showed enhanced lutein levels in serum, brain and other tissues in response to formula lutein supplementation, and lutein was preferentially deposited in the occipital cortex. This pilot study demonstrates that increased early exposure to dietary lutein substantially enhances lutein tissue deposition.

Support or Funding Information

Funding provided by Abbott Nutrition through the Center for Nutrition, Learning and Memory, University of Illinois, Urbana‐Champaign, and NIH grant P51OD011092.
Retinoic Acid Pretreatment Promotes Vitamin A Accumulation in the Lung of Neonatal Rats
Authors: Li Yaqi , Urbanek Joanna K , Green Michael H , Tan Libo , Ross A. Catharine
Published: November 2023

Previous studies conducted in our laboratory have shown that a combination of vitamin A (VA) and retinoic acid (RA), known as VARA, increased total retinoid concentration in plasma, liver and lung in neonatal rats. Later studies have further shown that supplementation with VA alone may stimulate the uptake of VA into the liver, resulting in a significantly higher liver total retinol concentration. Here, in order to distinguish the effects of VA and RA, we examined the effect of RA pretreatment, preceding a single‐dose supplementation with VA, on the metabolism and kinetics of total retinoid in plasma and lung tissue of neonatal rats. Sprague‐Dawley female and male rats were mated, and the females were housed with continuous access to food and water and were fed a VA‐marginal diet (0.35 mg retinol equivalents/kg diet). On postnatal day 2 and 3, each pup received an oral dose of either RA (0.625μg /g body weight) or canola oil as the control treatment. Then, on postnatal day 4, all pups received an oral dose of VA (6 μg retinyl palmitate/g body weight) containing 2 μCi of [3H]‐retinol as tracer. Pups (n = 4–6/treatment/time point) were euthanized at 12 time points from 25 min to 30 h after dose administration and the following tissues were collected: plasma, liver, lung, spleen, kidney, heart, stomach, intestine, brain, skin, brown adipose tissue and carcass. Tissue retinoid concentration was determined by ultra‐performance liquid chromatography (UPLC), and the tissue tracer level was determined by liquid scintillation counting. Results showed that, in plasma, retinyl ester was first detected at the 30 min time point, then rapidly increased and peaked at approximately 2 h after dosing and gradually declined afterwards, whereas the retinol level increased slowly and peaked between 4.5–6 h and remained nearly steady until 30 h after dosing. Nevertheless, no significant difference was observed in the plasma 3H tracer response between the two treatment groups. Total retinol in the lungs of the RA‐pretreated group, integrated over the 30‐h study, was ~3 times higher compared to the oil‐pretreated group. In addition, our tracer data showed that a greater proportion of the newly ingested VA was present in the lung of the RA‐pretreated group compared to the oil‐pretreated group. In conclusion, our findings indicate that RA supplementation may modify lung uptake of VA even though RA was given prior to the VA dose.

Support or Funding Information

NIH grant HD‐066982
Selective Delivery of Xanthophylls to Human Retinal Pigment Epithelial Cells (ARPE‐19) via Human Lipoproteins
Authors: Thomas Sara , Harrison Earl H
Published: November 2023

Age‐related macular degeneration (AMD) is an incurable disease affecting older adults in the United States that leads to blindness. Xanthophylls are dietary carotenoids of interest because they selectively accumulate in the macula of the eye and are thought to provide protection against AMD. To reach the macula, xanthophylls and other nutrients such as β‐carotene must cross the retinal pigment epithelium (RPE) through the choroid from the human blood. Xanthophylls associate mostly with HDL (high density lipoprotein) in human serum while β‐carotene associates mostly with LDL (low density lipoprotein). HDL binds to cells via a scavenger receptor class B1 (SRB1)‐dependent mechanism while LDL binds via the LDL receptor (LDLR). Using an in‐vitro, human cell model (ARPE‐19), we studied the mechanisms of xanthophyll (lutein and zeaxanthin) uptake into the RPE cell by evaluating kinetics of cell uptake when carotenoids were delivered in LDL or HDL. For lutein and β‐carotene, LDL delivery resulted in the highest rate and extent of uptake. In contrast, HDL was more effective in delivering zeaxanthin resulting in the highest rate and extent of uptake of the 3 compounds. The preferential uptake of zeaxanthin from HDL and lutein from LDL may be facilitated by SRB1 and LDLR, respectively. Adding increasing amounts of unenriched LDL to lutein‐enriched LDL and unenriched HDL to zeaxanthin‐enriched HDL, decreased xanthophyll uptake in both instances. Competition for access to SRB1 or LDLR between the xanthophyll‐enriched lipoprotein and the unenriched lipoprotein may occur as the unenriched lipoprotein concentration increases. Because carotenoid uptake is lipoprotein‐dependent, we evaluated whether competition may occur between β‐carotene, lutein, or zeaxanthin for cell uptake. Using whole serum to deliver lutein or zeaxanthin in the presence of increasing amounts of β‐carotene, lutein, or zeaxanthin, we found that β‐carotene decreased lutein uptake. Zeaxanthin uptake was unaffected by either lutein or β‐carotene. Using serum amyloid albumin (SAA), an acute phase inflammatory protein known to block HDL binding to SRB1, and BLT‐1, a chemical inhibitor of HDL uptake by SRB1, we evaluated zeaxanthin uptake by HDL in ARPE‐19 cells. Compared to the control treatment, zeaxanthin delivery via HDL was reduced by 49% and 52% by SAA and BLT, respectively. Our results suggest a selective HDL‐mediated uptake of zeaxanthin via SRB1 and potentially a LDL‐mediated uptake mechanism for lutein via LDLR. Overall, our results may partly explain selective uptake of xanthophylls into the RPE.

Support or Funding Information

NIH Grant R01HL48679 and R01DK44498
Lutein HPLC Method Comparison and Validation
Authors: Craft Neal E , Springs Donna G , Chavan Jayanthi
Published: November 2023

Lutein is one of two pigments that accumulate in the macula of the human eye. It is yellow in color and a member of the carotenoid family. Lutein (and zeaxanthin) filter blue‐light and thereby protect the eye from damage. Lutein is very ubiquitous in plants but often masked by chlorophylls. Major dietary sources include spinach, kale, broccoli, eggs, peppers, corn and peas; however people seldom consume adequate amounts. As such, lutein has been incorporated into many dietary supplements generating a need for accurate measurement of this antioxidant pigment.

Objectives

To compare and validate two HPLC methods for lutein analysis which use different columns and mobile phases. To compare cold and heated alkaline hydrolysis (saponification).

Methods

Acceptance criteria were established as Accuracy: 90–110%; Reproducibility: within‐day <5% CV, day‐to‐day <6% CV. Both Silica and Diol HPLC columns were tested. Mobile phases were 75 hexanes/25 ethyl acetate and 96 hexanes/4 IPA, respectively. Both systems were monitored at 448 or 450nm. Saponification was necessary for samples containing lutein esters or high oil and low lutein content. Both cold and heated (56°C and 70°C) saponification methods were compared.

Results

For both methods, calibration curves from 0.15–35 ppm were linear with r2 > 0.998. Recovery of low, mid and high lutein concentrations from spiked blank oil samples was 96–103%. Within day precision was 0.57–2.74% for esterified lutein and 0.74–3.84% for free lutein. Day‐to‐day precision was ≤3.1% for esterified lutein and ≤2.8% for free lutein. Heated saponification led to 9% less trans‐lutein and 4% less total lutein concentration compared to cold saponification.

Conclusions

Both methods met all of the criteria set forth for validation. Within day precision was less than 5% and day‐to‐day precision was less than 6%. Accuracy, as measured by spike recovery, was within the specification of 90–110%. Results were more accurate using refrigerated or 56°C saponification compared to 70°C. Both methods are aligned and produce similar results for lutein in oil‐based products. Additionally, zeaxanthin can be measured in both methods.

Support or Funding Information

Funding supplied, in part, by OmniActive Health Technologies.
Low intake of fruit and vegetables, body fatness and pro‐inflammatory/pro‐oxidant status are the major determinants of plasma carotenoids reduction in free‐living adults
Authors: Manda Rodrigo Minoru , Kano Hugo Tadashi , Vilches Gabriel Nogueira , Selingardi Roberta , Abe Ligia Mayumi , Correa Camila Renata , Burini Roberto Carlos
Published: November 2023

Previous data had shown that subjects involved in our ongoing epidemiological study “Move For Health” have a monotonous ingested (low variety) food in a poor quality (low HEI score) diet characterized by high sugar and oil servings and inadequacy of whole grains, fruits and vegetables. Fruits and vegetables are considered the main natural sources of carotenoids, detected in the plasma.

The aim of the study was to investigate the relationship of food intake with major circulating carotenoids, and related components either plasma lipids and/or pro‐inflammatory, pro‐oxidative markers, in female adult subjects enrolled in a lifestyle modifications Program (LSMP).

The cross‐sectional analysis involved retrospective data of demographic, anthropometric, dietary (24h food intake recall), plasma general chemistry (lipids), oxidative inflammatory (hs‐CRP, γ‐GT, HOMA‐IR, MDA, uric acid) markers and lipo‐soluble vitamins (retinol, α‐tocopherol, β‐carotene and others carotenoids (β‐criptoxanthin, lutein and lycopene). Mean (±SD) were compared by Student t‐test for age, and continued values among variables were correlated by the Spearman test for p=0.05.

Overweight (29.6±5.74 kg/m2) high body fat (37.0±8.79%) and abdominal fat (WC=96.8±13.8cm) women, presenting high plasma total cholesterol (tchol=201±30.1mg/dL) and triglycerides (TG=154±49mg/dL) levels along with high HOMA‐IR (3.38±3.05), presented circulating vitamins inside their normal range. However, the ingested sources of these vitamins were considered below the recommended amounts. All but lycopene carotenoids plasma levels were negatively related to BMI, %fat and WC as well as plasma TG (including lycopene), tchol and LDL‐chol (only β‐carotene). The inflammatory/oxidative/insulin resistance‐related markers showed reverse relationship with plasma carotenoids, more complete with γ‐GT and MDA (for β‐carotene, β‐criptoxanthin and lutein). The best relationship (β‐carotene, β‐criptoxanthin and lutein) was found with the food intake of fibers and vegetables. Thus, free‐living adults presenting lower intake of carotenoids might affect their plasma levels, which is aggravated by their hyperadiposity pro‐inflammatory status. Nutritional intervention with fruits and vegetables adequacy would reverse or attenuate the situation.

Support or Funding Information

Supported by CAPES and CNPq
The physical stability comparison of two types of resveratrol nanocarriers
Authors: Zu Yujiao , Wang Shu
Published: November 2023

Objective

Resveratrol (R) has anti‐obesity bioactivities, but its low level of aqueous solubility and stability limits its application. We successfully synthesized biocompatible and biodegradable R encapsulated lipid nanoparticles (R‐nano) and R encapsulated liposomes (R‐lipo). The objectives of this study are to measure the characteristics of R‐nano and R‐lipo and to compare their physical and chemical stability at three different temperatures.

Method

The particle size and polydispersity index (PI) of R‐nano and R‐lipo were measured using a Brookhaven BI‐MAS particle size analyzer, and their zeta potential were measured using a Brookhaven ZetaPALS analyzer. The R‐nano and R‐lipo were stored in dark at 4°C, 22°C and 37°C for 7 days, and their physical and chemical stability was measured every 24 hours. The freshly made R‐nano and R‐lipo were aliquot into black tubes and stored at the above three temperatures. The mean particle size, PI and zeta potential were measured every 2 hours for the first 10 hours, and every 24 hours for 7 days. The chemical stability of R‐nano, R‐lipo and native R were measured by a high‐performance liquid chromatography system.

Results

The mean particle size of freshly made R‐nano and R‐lipo were around 140 nm and 110 nm, respectively. The PI values of both R‐nano and R‐lipo were less than 0.3. Moreover, the zeta potential of R‐nano and R‐lipo were around −19 and −28mV. As compared to native R, R‐nano and R‐lipo dramatically increased the aqueous solubility of R by more than 30 times. Nanoencapsulation also significantly enhanced the chemical stability of R. The diameter and zeta potential of R‐lipo did not changed significantly at all temperatures (4°C, 22°C and 37°C) for 7 days, and the PI of R‐lipo remained under 0.3. R‐nano had lower physical stability than R‐lipo at 22°C and 37°C. After incubating at 22°C for 24 hours and at 37°C for 8 hours, the particle size was dramatically increased, and their PI and zeta potential values were also increased. The particle size, PI and zeta potential of R‐nano were stable at 4°C for 24 hours.

Conclusions

Both R‐lipo and R‐nano increased the aqueous solubility and stability of R. R‐lipo had higher physical stability than R‐nano. We are investigating the anti‐obesity bioactivities of nanoencapsulated R.

Support or Funding Information

Grant Funding Source: NIH 1R15AT008733‐01
Is Plasma Plant Sterols a Biomarker of Plant Sterols Intake Estimated from FFQ and Multiple Dietary Recalls?
Authors: Sirirat Rawiwan , Haddad Ella , Mashchak Andrew , Jaceldo‐Siegl Karen
Published: November 2023

Background

Plant sterols have many health benefits including reduce risk of heart diseases and prevent cancers. We have previously found that plasma plant sterols are higher in vegans than non vegetarians. It is not clear, howeer, if plant sterols in plasma reflect dietary intake.

Objective

We compared plasma plant sterol levels with plant sterol intake estimated from food frequency questionnaire (FFQ) and 24‐hours dietary recalls (24‐HR) of the Adventist Health Study ‐2 cohort.

Design

Plasma sitosterol and campesterol were measured by gas‐liquid chromatography. Intake of β‐sitosterol and campesterol was estimated from FFQ and six 24‐HR. The plant sterols content of foods were derived primarily from USDA SR 27 and also from available literature between years 1999–2011.

Results

Mean (SD) age of the analytic cohort was 60 (14) years, and included 34% men, and 54% non‐Blacks. Mean (SD) was 4.2 (2.3) μg/ML for plasma campesterol and 3.3 (1.6) μg/ML for plasma sitosterol. In FFQ, mean (SD) intake of campesterol and β‐sitosterol in mg/d was 38.03 (22.06) and 170.57 (95.72), respectively. Mean (SD) intake of campesterol and β‐sitosterol from 24‐HR were 22.80 (13.82) mg/d and 91.70 (50.09) mg/d, respectively. Correlations between plasma concentration and 24‐HR for campesterol and sitosterol were not significant. The correlation between 24‐HR and FFQ was 0.16 (p <.0001) for campesterol and 0.24 (p <.0001) for sitosterol.

Conclusion

Plasma concentration of plant sterols does not appear to be a biomarker of phytosterols intake. Although weak, correlations between plant sterols intake in FFQ and 24‐HR may be improved with adjustment for measurement errors or by food group assessment.

Support or Funding Information

This project was funded by Unilever. Collection of blood and dietary recalls was funded by the National Cancer Institute.
Nutritional Polyphenol Metabolites’ Kinetics in Plasma, Urine, and Saliva Following Consumption by Normal, Healthy, Subjects
Authors: Choy Ying Yng , Hester Shelly N. , Mastaloudis Angela , Wood Steve M. , Gray Russell , O'Donnell Robert P. , Barger Jamie L. , Quifer‐Rada Paola , Lamuela‐Raventós Rosa M. , Waterhouse Andrew L.
Published: November 2023

Several studies point to the health benefits of dietary polyphenols yet limited data can be found on the metabolites found in plasma and urine and negligible on saliva from supplemented polyphenol ingredients. Therefore this study was completed to obtain a better understanding of the kinetics of polyphenol ingredients in three fluids (plasma, urine, and saliva). A novel, dietary nutritional supplement containing several polyphenols including resveratrol, quercetin, anthocyanins, heperitin, naringin, d‐limonene combined with fish oil, vitamins, and carotenoids was studied. Healthy subjects (n=6 males and n=6 females) were fed three different acute doses in this cross‐over design, one treatment at a time, with at least a one week washout interval. Blood plasma, saliva and urine samples were collected for metabolite analysis at baseline, 0.5, 1, 2, 3 (only plasma and saliva), 8, and 24 hours post intake. Blood was also collected in PAXgene tubes at baseline, 8, and 24 hours post intake for gene expression analysis. Metabolites analyzed included 3‐hydroxyphenylacetic acid, 4‐hydroxyhippuric acid, hippuric acid, hesperetin, naringenin, naringenin 7‐O‐glucuronide, protocatechuic acid, quercetin, quercetin 3‐O‐glucuronide, resveratrol 3‐O‐glucuronide, resveratrol 4‐O‐glucuronide, trans‐resveratrol, and cis‐resveratrol. Most of the metabolites that were analyzed peaked at 2 and 8 hours and returned to baseline by 24 hours in plasma, urine, and saliva. A dose response was not observed for all metabolites in plasma, urine, and saliva. Female and male kinetics of many of the polyphenols and metabolites appears to be different. This data is important in further understanding the levels of these polyphenols and their metabolites, so that tissue exposure can begin to be assessed.

Support or Funding Information

Supported by Nu Skin Enterprises, Provo, Utah
The mediation of intracellular Ca2+ by resveratrol
Authors: Mecham Jeffrey C
Published: November 2023

Breast cancer constitutes a major problem among American Women. Current chemotherapeutic options for breast cancer are limited by their toxicity to normal tissue. The naturally occurring polyphenol resveratrol has been shown to induce tumor‐cell specific apoptosis in many cancer‐cell lines, including breast cancer cells. Treatment of MDA‐MB‐231 with resveratrol leads to an upregulation of tumor suppressor protein p53, a key protein in the apoptotic pathway. Using the intracellular‐calcium chelator BAPTA, we show inhibition of the upregulation of p53 upon treatment of resveratrol, indicating that Ca2+ regulation in the cytosol plays a crucial role in the mechanism of resveratrol in mediating cell death. Plasma Membrane Calcium ATP‐ase (PMCA) extrudes calcium from the cytosol into the extracellular space. Because of the characteristic upregulation of PMCA in MDA‐MB‐231 cells and other cancer cell lines as compared to normal cells, it is a novel target for chemotherapeutic treatment. Using the known PMCA inhibitor LaCl3, we show that resveratrol inhibits PMCA, leading to upregulation of p53. We further determine the role of the hydroxyl groups of resveratrol in p53 upregulation
Microbial‐derived metabolites of oat avenanthramides
Authors: Yerke Aaron , Wang Pei , Sang Shengmin
Published: November 2023

Oat is a multifunctional crop nutritionally superior to many other unfortified cereals. It is commonly consumed as whole grains and known to provide healthy nutrients to humans. Oats contain a unique type of compounds, avenanthramides (AVAs), which are a group of substituted N‐cinnamoylanthranilic acids. They are all composed of an anthranilic acid part and a cinnamic acid part, where the substitution pattern on the two parts is what distinguishes the different AVAs from each other. AVAs have been reported to have anti‐oxidative, anti‐inflammatory, anti‐itching, and anti‐cancer activities. However, the biotransformation of AVAs is still largely unknown. We recently studied the biotransformation of the three major AVAs in mice and by human gut microbiota. Our results indicated that reduction of the double bond in the cinnamic acid unit and the cleavage of the amide bond are the major metabolic pathways of AVAs in mice and by human gut microbiota. Further mechanistic studies demonstrated that the AVAs are mainly metabolized by gut microbiota instead of liver and intestinal microsome and S9. In addition, we also observed inter‐individual variations on the metabolism of AVAs by human gut microbiota.
Intake of 2 eggs for breakfast increases plasma lutein concentration in association with increased large HDL and zeta potential as compared to an oatmeal breakfast
Authors: Missimer Amanda C , Hu Siqi , Luo Yangchao , Blesso Christopher N , Fernandez Maria‐Luz
Published: November 2023

We investigated the effects of two different breakfasts on HDL antioxidant and size properties. This was a randomized crossover design in which 48 subjects (24 women and 26 men) aged 18 to 30 y had for breakfast either 2 eggs/d or 1 packet of oatmeal/d. Participants were randomly assigned to consume the egg or oatmeal breakfast for 4 weeks and after a 3 week washout period, they were allocated to the alternate breakfast. Blood was collected at the end of each period to assess plasma total and HDL lutein concentrations, HDL subfractions by use of nuclear magnetic resonance (NMR), HDL particle size by dynamic light scattering (DLS) with a scattering angle of 173 ° and zeta potential calculated from electrophoretic mobility (Malvern Zetasizer ZS). There was a significant increase in lutein concentration both in plasma and HDL following the egg period (p < 0.05). Additionally, following the egg period, there was a significant increase in HDL mean particle size as measured by DLS (p< 0.05) and the larger HDL (8.8–13 nm) as measured by NMR (p < 0.001). Futhermore, zeta potential, which measures the mobility of a particle in a liquid when an electrical field is applied to determine ability of particles to aggregate, was 5.5% more negative following egg consumption. There was a significant negative association between HDL particle size as measured by NMR and HDL zeta potential suggesting that possibly the composition of phospholipids in the HDL, due to egg consumption, contribute to more negative charges. These novel findings will help to further document the relationship between egg consumption and HDL particle composition.
Curcumin metabolites induce autophagic cell death through PI3K/AKT‐mTOR signaling in COLO205 human colon adenocarcinoma cells
Authors: Cheng An‐Chin , Lee Ming‐Fen , Chiou Bin‐Hao , Yen Yu‐Zhu , Pan Min‐Hsiung
Published: November 2023

Autophagy, type II programmed cell death, is crucial for maintaining cellular homeostasis and plays a role in many diseases including cancer. Tetrahydrocurcumin (THC), a major metabolite of curcumin, has been demonstrated an autophagy‐inducing effect in human HL‐60 promyelocytic leukemia cells. In the present study, we found that THC and two other curcumin metabolites, tetrahydrodemethoxycurcumin (THDC) and tetrahydrobisdemethoxycurcumin (THBC), decreased the survival ratio of COLO205 human colon adenocarcinoma cells, but did not increase the sub‐G1 cell population, one of the hallmarks of apoptosis. THC and its derivatives, THDC and THBC, induced autophagic cell death in COLO205 cells by increasing acidic vascular organelle (AVO) formation, an autophagy marker. The results also indicated that the numbers of the methoxy groups in the curcumim metabolites were negatively correlated with their autophagy‐inducing effects. The amounts of LC3‐I/II and beclin‐1 increased and the phosphorylation levels of PI3K, AKT, and mTOR decreased with the addition of THBC in a dose‐dependent manner. Taken together, these data demonstrated the anticancer efficacy of curcumin metabolites which suggest a potential translational application for the prevention of human colon cancer.

Support or Funding Information

This study was supported by NSC102‐2320‐B‐309‐001‐MY3 to M‐F Lee and NSC100‐2313‐B‐309‐003 to A‐C Cheng.
Protective effect of betaine against liver steatosis involves depletion of homocysteine via upregulation of betaine‐homocysteine methyltransferase (BHMT)
Authors: Ahn Chul W , Jun Doo S , Na Jong D , Choi Yeo J , Kim Young C
Published: November 2023

Accumulation of lipids in hepatocytes plays an important role in the development of metabolic diseases. Adenosine monophosphate‐activated protein kinase (AMPK) has emerged as a potential target for intervention in hepatic fat accumulation. In this study we determined the effect of betaine, a substrate utilized in remethylation of homocysteine to methionine in the transsulfuration reactions, on the AMPK pathway and lipogenesis in liver. Male rats were fed methionine‐choline deficient diet (MCD) for 3 wk. Intake of MCD resulted in a marked accumulation of lipids in liver. Phosphorylation of AMPK, acetyl‐CoA carboxylase (ACC), sterol regulatory element binding protein (SREBP)‐1c, and liver kinase B1 (LKB1) was inhibited significantly. Betaine supplementation (1 %) prevented or reversed all the changes induced by MCD intake. The underlying mechanism of AMPK activation provided by betaine was investigated using different hepatoma cell lines. Betaine treatment enhanced phosphorylation of AMPK, SREBP‐1c, and ACC in H4IIE, but not in HepG2 cells. Betaine‐homocysteine methyltransferase (BHMT) was induced and homocysteine levels were reduced by betaine only in H4IIE cells. Homocysteine treatment decreased pAMPK, pACC, pSREBP‐1c, and pLKB1 in a dose‐dependent manner, which was all prevented by betaine. BHMT protein expression was inhibited by homocysteine and betaine reversed its inhibition in H4IIE cells. Treatment of hydroxylamine, a cystathionine β‐synthase inhibitor, resulted in a significant increment of homocysteine, while decreasing phosphorylation of AMPK, ACC, and SREBP‐1c. Metformin treatment to HepG2 cells increased phosphorylation of AMPK, ACC, and SREBP‐1c, which was suppressed by homocysteine. Taken together, the results show that the elevation of homocysteine in hepatocytes may be responsible for the inactivation of the AMPK pathway. It is strongly suggested that anti‐lipogenic activity of betaine is associated with depletion of homocysteine via upregulation of BHMT.

Support or Funding Information

Supported by National Research Foundation (NRF) grants (No. 2014‐R1A2A1A11052967 and No. 2009‐0083533) funded by the Ministry of Education, Science and Technology (MEST), Korea.
Role of acetyl‐CoA metabolizing enzyme ACSS2 and dietary acetyl‐CoA precursors in transcription and lipid disorder
Authors: Moreau Regis , Erickson Anjeza , Bruner Noel , Xia Mengna , He Bo
Published: November 2023

Dyslipidemia and fatty liver that occur secondarily to obesity result from extensive gene expression changes in tissues throughout the body. By converting acetate into acetyl‐CoA, acetyl‐CoA synthetase 2 (ACSS2, cytoplasmic) raises the levels of acetyl‐CoA with an expected impact on histone acetylation and lipid production. We created two stable AML12 liver cell lines that exhibit normal or high (mRNA, +1300%; protein, +1600%) levels of ACSS2 and in this model asked how dietary precursors of acetyl‐CoA modulate histone acetylation and lipid metabolism. ACSS2 raised global histone H3 acetylation (+53%), increased fatty acid synthase abundance (+67%), and induced albumin expression (cellular, +643%; secreted, +284%). Acetate further stimulated histone H3 acetylation (+96%) and albumin expression (+473%). In the present study, we further investigate the regulation of these genes by ACSS2 in the presence of acetate and ethanol. Our results provide new insights into how precursors of acetyl‐CoA found in our diet regulate transcription in an ACSS2 dependent manner. The long‐term goal of this study is to identify diet‐dependent epigenetic mechanisms that modulate lipid risk factors for cardiovascular diseases and hepatosteatosis.

Support or Funding Information

Supported by UNL Hatch Act, Tobacco Settlement Funds, UNL UCARE Program, and Allen Foundation.
Korean red ginseng extract inhibits p53‐dependent apoptosis in Helicobacter pylori‐infected gastric epithelial cells
Authors: Kang Hyun Ju , Lim Joo Weon , Kim Hyeyoung
Published: November 2023

Helicobacter pylori (H. pylori) infection is related to the development of gastritis and gastric cancer. H. pylori infection induces oxidative DNA damage, apoptosis and p53 expression in gastric mucosa, which may be involved in gastric carcinogenesis. Prolonged apoptosis may stimulate hyper‐proliferation of neighboring cells.

DNA damage responses coordinate DNA repair and apoptosis through the activation of ATM and their target proteins. ATM phosphorylates Ser15 of p53 directly and Ser20 through activation of CHK2, leading to stabilization of p53 and reduces its interaction with MDM2. The level of tumor suppressor protein p53 depends on the levels of MDM2 and ARF. MDM2 is a negative regulator of p53 by its binding to p53. ARF binds and inhibits the activity of MDM2, indicating that ARF disrupts the negative feedback inhibition of p53 by inactivating MDM2. Therefore, prevention of ATM activation, MDM2, and ARF may suppress p53‐mediated apoptosis.

Previously, we showed that Korean red ginseng extract (RGE) inhibits NADPH oxidase and reduces the production of reactive oxygen species. H. pylori infection induces oxidative DNA damage and activates DNA damage responses including ATM activation.

The present study was purposed to investigate 1) whether H. pylori‐induced apoptosis is mediated with changes in DNA damage response proteins such as ATM, MDM2, ARF, and p53, and 2) whether Korean red ginseng extract (RGE) inhibits H. pylori‐induced apoptosis by regulating DNA damage response proteins in human gastric epithelial AGS cells.

The cells were treated with RGE and infected with H. pylori. Cell viability was determined by Trypan blue exclusion assay. Nuclear level of p53 was observed by immunocytochemistry. Protein levels of ARF, MDM2, ATM, p53, Bax, Bcl‐2, and PARP were assessed by Western blot analysis.

The results show that H. pylori decreased cell viability, and increased levels of the apoptotic Bax/Bcl‐2 ratio and PARP cleavage. H. pylori increased phosphorylation of ATM and levels of ARF and p53, but decreased MDM2 level. The results suggest that H. pylori‐induced apoptosis is mediated with activation of ATM, decreased MDM2, and increased ARF and p53 in AGS cells. RGE decreased Bax/Bcl‐2 ratio and PARP cleavage, and increased cell viability in H. pylori‐infected cells. RGE inhibited H. pylori‐induced alterations (phosphorylation of ATM, increased ARF and p53, and decreased MDM2) in AGS cells. H. pylori‐induced nuclear translocation of p53 was inhibited by RGE. RGE inhibits p53‐dependent apoptosis by regulating DNA damage response molecules in H. pylori‐infected gastric epithelial cells.

In conclusion, Korean red ginseng extract may be beneficial for preventing gastric carcinogenesis associated with H. pylori infection.
Docosahexaenoic Acid Inhibits Cytokine Expression through Suppression of NF‐κB Activation in Rat Pancreatic Stellate Cells
Authors: Eum Hae Rin , Chung Sun Ah , Lim Joo Weon , Kim Hyeyoung
Published: November 2023

Pancreatic stellate cells (PSCs), when activated by cytokine such as tumor necrosis factor α (TNF‐α), plays an important role in the development of chronic pancreatitis. Induction of inflammatory cytokines and fibrotic proteins contribute to development of chronic pancreatitis. NF‐κB is known to induce pancreatic and systemic inflammatory response. Docosahexaenoic acid (DHA), omega 3‐polyunsaturated fatty acid, shows anti‐inflammatory and anti‐fibrotic effects.

In the present study, we investigated whether DHA decreases expression of inflammatory cytokines (MCP‐1, CX3CL1) and fibrotic proteins (alpha smooth muscle actin, α‐SMA; desmin, collagen such as COL1A1 and COL1A1; transforming growth factor beta 1,TGF‐β1) as well as and NF‐κB activity in PSCs exposed to PSCs activating factor TNF‐α.

The cells were isolated from pancreas of the rat and cultured in the presence or absence of DHA. mRNA and protein levels were determined by real time PCR and ELISA or western blot analysis.

The results show that expression of inflammatory cytokines (MCP‐1, CX3CL1) and fibrotic proteins (α‐SMA, desmin, COL1A1, COL1A1, TGF‐β1), and DNA binding activity of NF‐κB were increased by TNF‐α in PSCs. DHA suppressed TNF‐α‐induced expressions of cytokines and fibrotic proteins by inhibiting NF‐κB activity in PSCs.

In conclusion, DHA may inhibit inflammation and fibrosis in pancreatic stellate cells exposed to inflammatory stimulus such as TNF‐α. DHA may be beneficial for preventing development of chronic pancreatitis.

Support or Funding Information

This study was supported by a grant (NRF‐2015R1A2A2A01004855) from the NRF of Korea.
Effects of Pomegranate Extract on High Fat/High Sucrose Diet induced Obesity are Dependent on the Intestinal Formation of Urolithin A
Authors: Yang Jieping , Henning Susanne M , Lee Rupo , Hsu Mark , Grojean Emma M , Ly Austin , Heber David , Li Zhaoping
Published: November 2023

Recent studies strongly suggest the association of gut microbiota and obesity related diseases. Published data from a mouse study demonstrated that pomegranate extract (PomX) administration increased cecum Bifidobacteria, decreased inflammation and counteracted the HF‐induced expression of inflammatory markers both in colon and visceral adipose tissue. The major phytochemicals in PomX are ellagitannins (ETs), which are not absorbed in the small intestine. ETs are hydrolyzed to ellagic acid (EA) in the stomach and further metabolized to urolithin A (UA) by bacteria in the gastrointestinal tract. Inter‐individual differences in the production of UA from PomX were previously reported in humans. About 30% of individuals cannot produce UA when consuming POM.The aim of the present study was to investigateand link the potential effects of PomX on metabolic abnormalities of mice fed with HF/HS diet to intestinal UA formation.

C57BL/6 male mice were randomly assigned to two treatment groups: control high fat /high sucrose [HF/HS (32% kcal from butter fat and corn oil, 25% kcal from sucrose)], or a HF/HS diet supplemented with 0.25% PomX for 4 weeks. In the mice receiving 0.25% PomX diet, stool samples were collected and analyzed by high performance liquid chromatography for UA production. We observed two distinct groups: UA producer (Producer) and UA non‐producer (Non‐P). All observations are in comparison to the HF/HS fed control mice. About 40% of mice fed the 0.25% PomX diet did not produce UA during the 4 week feeding period. The Non‐Ps showed significantly higher concentration of EA in blood and feces compared to producers. PomX administration significantly decreased liver lipid content and serum endotoxin in both producers and Non‐Ps associated with increase of hepatic AMPK phosporylation. However epididymal and mesenteric fat depots were only significantly increased by PomX consumption in producers meanwhile the cecum Bifidobacterium and Lactobacillus abundance only increased in Non‐Ps. In both Non‐Ps and producers PomX consumption did not significantly modify body weight gain, subcutaneous fat, Bacteroidetes/Firmicutes ratio and Akkermansia abundance.

In summary, mice lacking UA production show higher EA concentrations in blood and feces while UA producers showed higher UA in blood and feces. Depending on their capacity to form UA we observed different effects of PomX diet on Bifidobacterium and Lactobacillus abundance and fat disposition using this HF/HS diet induced obesity mouse model.

Support or Funding Information

Supported by departmental funds from the Center for Human Nutrition, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles.