bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dairy, Dairy, Quite Contrary: Associations of Reported Dairy Consumption with Indices of Cardiovascular Health
Authors: Que Excel S , Krishnan Sridevi , Waller Justin , Lee Fanny , Horn William F , Vedula Aneeta , Hall Joanne , Welch Lucas C , Kishimura Katie , Keim Nancy L 
Published: November 2023

ObjectiveTo determine the associations between reported dairy consumption and indices of cardiovascular health.Methods33 women fitting pre‐metabolic syndrome criteria, mean age 46.9 y, mean BMI 32.5 kg/m2, were included in a 9‐week, free‐living, controlled‐feeding study. At baseline, the validated Block 2014 Food Frequency questionnaire (FFQ) was administered to determine habitual diet. Fasting blood was drawn to determine triglycerides (TG) and non‐HDL cholesterol (nHDL). The EndoPAT 2000, a non‐invasive finger plethysmography system, was used to measure cardiovascular functional parameters such as the reactive hyperemia index (RHI‐a measure of endothelial function), and augmentation index (AI – a measure of arterial stiffness). The AI was normalized to a 75 beats per minute heart rate across the volunteers to control for variation induced by differing heart rates (AI@75). Habitual intake of yogurt, milk, cheese, and total dairy (a summation of the aforementioned plus whey) in cup equivalents was obtained from the FFQ and used for this study. Spearman's non‐parametric correlation analysis was performed to evaluate associations between dairy intake and measured cardiovascular risk factors.ResultsFasting TG was inversely associated with habitual consumption of yogurt (r = −0.561, p = 0.0007), milk (r = −0.438, p = 0.011), combined milk, yogurt and cheese (r = −0.37, p = 0.0342), and total dairy (r = −0.35, p = 0.046). Yogurt consumption was also inversely associated with nHDL (r = −0.376, p = 0.03). EndoPAT indices were also correlated with dairy consumption. Contrastingly, AI@75 was associated with yogurt consumption (r = 0.378, p = 0.03), and RHI was inversely associated with cheese consumption (r = −0.34, p = 0.053).ConclusionsElevated TG and nHDL are associated with cardiovascular disease, and their inverse association with dairy consumption suggests a likely beneficial effect of consuming dairy products, such as milk and yogurt. However, physiological measurements of cardiovascular function give contrasting results in terms of dairy's influence on cardiovascular health. Yogurt was also positively associated with AI@75, and cheese was inversely associated with RHI. Further dairy intervention studies are needed to confirm these relationships.Support or Funding InformationNational Dairy Council Project 23370; USDA‐ARS‐CRIS Project 2032‐51530‐022‐00D
Increase in Serum Insulin, Urinary C‐Peptide Immunoreactivity (CPR) Excretion Levels by Skimmed Milk Intakes Is Attenuated by Endurance Physical Exercise
Authors: Yamada Tetsuo , Okada Masaki , Matsuzaki Masami , Tanaka Akira 
Published: November 2023

It is well known that insulin brings protein anabolism effects and hyperinsulinemia is improved by exercise. We investigated the effects of skimmed milk intakes and endurance physical exercise on serum insulin and urinary C‐peptide immunoreactivity (CPR) excretion levels.MethodsEight adult female volunteers participated in crossover trial, i.e., two experiments over five days. The first two days were an adjustment period consuming control diets (energy, 2,010 kcal; protein, 51.9 g). During the following three days as an experiment period, the participants consumed experimental diets (energy, 2,010 kcal; protein 82.3 g) which contained skimmed milk of 402 kcal, and either performed only normal daily activities (non‐Ex period) or exercised on a bicycle ergometer at a target intensity of about 50% of maximal oxygen intake expending additional energy of 402 kcal (Ex period). Total urine samples for 24 hours were collected during day (8am to 8pm) and night (8pm to 8am). Fasting blood samples were collected early in the morning before and after the experiment period.ResultsPlasma leucine, valine levels were elevated after both the non‐Ex and the Ex period, and serum insulin level was significantly elevated only after the non‐Ex period. Urinary CPR excretion level was significantly increased during the non‐Ex period, on the other hand, was significantly lower during the Ex‐period than during the non‐Ex period. Serum triglyceride, remnant lipoprotein cholesterol levels were decreased after the Ex period, and serum insulin level was significantly lower after the Ex‐period than after the non‐Ex period.ConclusionsIncrease in serum insulin and urinary CPR excretion levels is brought about by skimmed milk intakes, and is attenuated accompanying improvement of lipid metabolism by endurance physical exercise.Support or Funding InformationThis work was supported by JSPS KAKENHI Grant Number JP15K00852.
Differential Uptake of RRR α‐Tocopherol, All‐racemic α‐Tocopherol, and RRR γ‐Tocopherol into Primary Human Aortic Smooth Muscle Cells
Authors: Ranard Katherine M , Kuchan Matthew J , Lai Chron‐Si , Erdman John W 
Published: November 2023

Alpha‐tocopherol (α‐Toc), one of the eight compounds constituting vitamin E, may play a role in preventing atherosclerosis in humans. Previous studies have shown that severe α‐Toc deficiency promotes atherosclerosis in mice and that α‐Toc is anti‐inflammatory. In contrast, another vitamin E vitamer, γ‐tocopherol (γ‐Toc), may be pro‐inflammatory. A synthetic (all‐racemic) form of α‐Toc is also commonplace in our food supply; this is important because humans may have a biological preference for natural (RRR) α‐Toc. Consuming foods with differing forms of tocopherol could impact the vitamin E profile in human tissues. Our in vitro study aimed to compare these three human disease‐relevant tocopherol forms (RRR α‐Toc, all‐racemic α‐Toc, and RRR γ‐Toc), by first focusing on uptake of the vitamers into human vascular aortic smooth muscle cells (HVASMC). Primary HVASMC (pass <8) were grown to 70% confluency in 6‐well plates. RRR α‐Toc, all‐racemic α‐Toc, and RRR γ‐Toc were added to the media in DMSO (0.2% v/v) at 25uM to simulate physiological conditions of human serum. DMSO vehicle was also added to cells alone to serve as a control. After 24, 48, and 72 hours of incubation, cells from each treatment well (n=3 per group) were trypsinized and pelleted. Tocopherols were extracted from the HVASMC and analyzed via high‐performance liquid chromatography (HPLC). After 48 hours, there was an approximately 5‐fold higher cell uptake of γ‐Toc than all‐racemic α‐Toc and a 6‐fold higher γ‐Toc uptake compared to RRR α‐Toc. After 72 hours, there was an approximately 6.5‐fold higher and 7.5‐fold higher cell uptake of γ‐Toc than all‐racemic α‐Toc and RRR α‐Toc, respectively. We will also report the impact of these vitamers on the transcription of atherosclerosis‐related genes in this cell line, as well as how stimulation by a pro‐inflammatory cytokine (TNF‐α) following a dose of tocopherol impacts the gene expression profiles. Differential changes in gene expression between the three tocopherol forms could support the suggested non‐antioxidative functions of RRR α‐Toc, as well as distinguish the impact of the individual tocopherol isomers.Support or Funding InformationFunding provided by Abbott Nutrition through the Center for Nutrition, Learning and Memory, University of Illinois, Urbana‐Champaign, and NIH grant P51OD011092.
Effect of vitamin D intake levels on vitamin D metabolism in high fat diet‐induced obese mice compared to the control
Authors: Park Chan Yoon , Zhu Shuang , Jung Youngsun , Han Sung Nim 
Published: November 2023

An inverse relationship between vitamin D levels and body mass index (BMI) has been observed and vitamin D deficiency has been often reported in obese human. Previously, we observed an alteration of vitamin D metabolism associated with obesity in mice. In this study, we investigated whether obesity affects vitamin D status when various levels of dietary vitamin D were provided. We compared serum 25‐hydroxyvitamin D (25(OH)D) levels and expression of genes involved in vitamin D absorption and transportation in obese and control mice fed different levels of vitamin D.Six week old C57BL/6 mice were fed control (10% kcal fat, CON) or high fat diets (45% kcal fat, HFD) containing three different levels of vitamin D (cholecalciferol); low vitamin D (50 IU/kg of diet, LVd), control vitamin D (1000 IU/kg of diet, CVd) or high vitamin D (25000 IU/kg of diet, HVd) for 13 weeks. Serum 25(OH)D levels were determined by radioimmunoassay. mRNA levels of Mtp which is involved in assembly of chylomicron and cholesterol membrane transporters (Cd36, Sr‐b1, Npc1l1, and Abca1) in jejunum, and chylomicron remnant receptor (Lrp1) and 25‐hydroxylases (Cyp2r1 and Cyp27a1) in liver were determined by real‐time PCR.Overall, dietary vitamin D levels affected serum 25(OH)D levels. Serum 25(OH)D levels were lower in LVd groups and higher in HVd groups compared with CVd groups (P < 0.001). However, when 25(OH)D levels were compared between HFD and CON group, differential pattern was observed depending on dietary vitamin D levels. In vitamin D deficiency diet groups, HFD‐LVd group showed higher serum 25(OH)D levels than CON‐LVd group (P = 0.001, 76.6% higher). On the other hand, when vitamin D intake was at a supplementation level, HFD‐HVd group had lower serum 25(OH)D levels than CON‐HVd group (P= 0.005, 19.7% lower). In jejunum, mRNA levels of Mtp and Abca1 were significantly higher and Cd36 mRNA levels tended to be higher (P= 0.083) in HFD group compared with CON group. However, jejunal mRNA levels of Sr‐b1 were significantly lower in HFD group than CON group, notably HFD‐HVd group showed lower Sr‐b1 expression compared with CON‐HVd group (P = 0.013, 82.7% lower). Hepatic Lrp1 mRNA levels were also lower in HFD‐HVd group than CON‐HVd group (P = 0.004, 52.5% lower). mRNA levels of hepatic 25‐hydroxylases (Cyp2r1 and Cyp27a1) were not significantly different among groups.In conclusion, expression of genes involved in dietary vitamin D absorption and metabolism was altered by HFD‐induced obesity. When vitamin D intake was at a supplementation level, expression of Sr‐b1 and chylomicron remnant receptor was reduced in HFD group and might have contributed to a lower 25(OH)D level comapred with the control.Support or Funding InformationSupported by the grant from the National Research Foundation (NRF) of Korea (NRF‐2015R1D1A1A01059679)
Slow Release of Iron into Blood from Aspergillus Oryzae Compared to Ferrous Sulfate in Humans
Authors: Reddy Manju B. , Armah Seth M. , Bian Yilin 
Published: November 2023

Iron fortification and supplementation are the usual strategies employed to prevent or treat anemia, the most common world‐wide nutritional problem. Although used extensively and effectively, the ferrous sulfate supplement is known to cause adverse side effects and have presented problems with compliance. Ferrous sulfate is rapidly absorbed and the bolus of iron enters blood rather quickly possibly leading to higher concentrations of non‐transferrin bound iron which induces oxidative stress. The objective of this study was to determine how quickly iron enters into blood stream from the iron‐enriched Asperigillus oryzae (AspironTM, ASP) in contrast to ferrous sulfate. Iron‐enriched ASP was produced by using a proprietary technology developed by Cura Global Health, Inc. by growing the fungi with ferrous sulfate, dried, and ground to a fine powder. Eighteen healthy, female subjects (18–35 y), non‐pregnant, non‐anemic, and with low iron status (ferritin ≤30 μg/L), completed the study. A randomized, double blind, cross‐over experimental design was used with three treatments. Subjects were randomized to consume a test meal with three iron supplements (10 mg iron as FeSO4 and ASP as well as 20 mg iron as ASP) in the form of capsules during three separate visits: Blood samples were collected after consuming iron supplement capsules with a meal (rice and vegetables with orange juice) at 0, 30, 60, 90, 120, 150, 180, 210 and 240 min. The area under the curve (AUC) was calculated for FeSO4 and the two ASP doses based on changes in serum iron concentrations from baseline. Ferritin and hemoglobin concentrations were measured at the beginging of study but C‐reactive protein was measured at the beginning of each treatment. The average ferritin and hemoglobin concentrations were 18.3 μg/L and 131 g/L, respectively. The mean AUC of FeSO4 (1674.5 ± 1548.4) was significantly higher (p<0.05) than the AUCs of 10 mg Aspiron (868.7 ± 480.7; p<0.05) and 20 mg Aspiron (899.9 ± 771.4). After reaching their maximum iron levels (~120 min), serum iron levels with FeSO4 declined while both Aspiron doses seemed to remained constant. CRP concentrations were low (1.6 mg/L) didn't vary among the treatments. Based on the slow iron release results in our study, we can speculate that the ASP iron might be absorbed by a different mechanisms similar to ferritin iron or it might be digested slowly requiring longer time for iron to be released in to blood. Our results suggest strong potential for ASP's use as a supplement in polulations where ferrous sulfate supplementaion is of concern.Support or Funding InformationCura Global Health, Inc.
Se and Zn nutritional status of collegiate female athletes by exercise type
Authors: Okhee Lee 
Published: November 2023

Most collegiate athletes usually carry out hard training in order to promote exercise performance, hence the production of free radicals and ROS will increase through the higher energy metabolism and oxygen ingestion. Therefore, the requirements of antioxidant nutrients might be increased compared to sedentary people and be different by exercise type. However, the nutritional status of Se and Zn, antioxidant micro‐minerals, have been rarely reported among Korean collegiate players, possibly because of their analysis difficulties. In this study, we evaluated the nutritional status of Se and Zn level, and their relationship between their dietary intake and serum levels by exercise type. The collegiate athletic females of judo, aerobics, and basketball and sedentary females were recruited. And Se and Zn levels in serum were measured using NAA method and their dietary intake were calculated by using 24‐hour recall method and food mineral database of Korean Nutrition Society, respectively. Average serum level of Se was in range of 9.7~12.2ug/dL and lowest in judo players and tends to be higher in basketball player compared to sedentary. Average Zn level in serum was in range of 81.8~105.0 ug/dL and lower in judo, aerobic players compared to sedentary and basketball players. The dietary intake of Se was higher than the recommend amount of KDRI Se in all groups, and the highest among basketball players who ingested double amount of RNI Se of KDRI. The dietary Zn intake was higher in three exercise group compared to sedentary collegiate female. The rank of dietary Se and Zn levels by exercise type didn't correspond to those of serum levels, respectively. Despite of higher dietary intake of Se, it's nutritional status was lower in female judo player than sedentary female. It is suggested that higher Se intake may be necessary in judo female players, which should be confirmed with a wide and deep evaluation studies.Support or Funding Information2015 grant of Yongin university
Zinc Up‐regulates Nox1 Function by Increasing Mitochondrial ROS to Induce Senescence of Vascular Smooth Muscle Cells
Authors: Huang Jingwen , Feresin Rafaela G. , Salazar Gloria 
Published: November 2023

IntroductionZinc, an essential trace element, plays a significant role in the regulation of multiple cellular processes. We previously demonstrated that zinc overload up‐regulated reactive oxygen species (ROS) levels causing senescence. However, the source of ROS that mediates zinc effects was not determined.ObjectivesThus, the purpose of this study was to investigate whether increased ROS levels and senescence induced by zinc is attributed to increased mitochondrial ROS (mtROS), ROS produced by NADPH oxidases (Nox) or both.MethodsVascular smooth muscle cells (VSMCs) treated with 50 μM zinc were incubated with 2′,7′‐dichlorodihydrofluorescein diacetate (H2DCFDA) and MitoSox to measure hydrogen peroxide and mtROS, respectively. Western blots were used to determine the expression of Nox1, Nox4, antioxidant enzymes and the senescence markers, p21 and p53. After three days of the treatment, senescence was determined by measuring senescence associated β‐galactosidase (SA‐β‐gal) activity.ResultsWe found that zinc overload increased the expression of Nox1, but not Nox4, and promoted the accumulation of zinc in the mitochondria causing increased mtROS generation. Blocking mtROS with MitoTEMPO reduced Nox1 expression and senescence induced by zinc.ConclusionsIncreased zinc levels promote mtROS generation, which up‐regulates Nox1 expression increasing cytosolic ROS levels and inducing senescence of VSMCs.Support or Funding InformationThis study was supported in part by the American Heart Association (14GRNT20180028), the American Federation for Aging Research (AFAR) and the Florida State University Council on Research and Creativity (COFRS).
The MTHFR 677TT Variant is Associated with Impaired Acute Blood Pressure Response to Sodium Ingestion
Authors: Murphy Melissa A , Breslin Paul A S , Miller Joshua W 
Published: November 2023

Observational and genome‐wide association studies indicate that a common polymorphism (677C‐‐>T) in the FAD‐dependent enzyme, methylenetetrahydrofolate reductase (MTHFR), is associated with elevated blood pressure (BP) and increased risk of hypertension. This association is modified by riboflavin status and riboflavin supplements reduce BP in individuals homozygous for the variant form of the enzyme (677TT). However, little is known about the effect of the 677TT variant on dynamic responses of BP to vaso reactive stimuli. Previously, we demonstrated that systolic BP (SBP) drops in healthy adults within one hour after ingestion of a sodium chloride (NaCl) solution. To determine if MTHFR genotype impacts this acute BP response to NaCl ingestion, we tested 20 normotensive individuals (age 18–35y), 9 with the 677TT variant and 11 wild‐type controls (677CC) in a repeated measures design. On 6 different days, BP was measured in the subjects in the sitting position with a mercury brachial sphygmomanometer every 10 minutes for 60 minutes post ingestion of 475 mL of either a 157 mM NaCl solution or water with no NaCl. Plasma riboflavin was determined by HPLC. In all subjects there was an average of 3.1 ± 2.7 mmHg greater drop in SBP after ingesting the NaCl solution compared with water alone (p = 0.018). Additionally, the decrease in SBP was greater for 677CC individuals compared with 677TT individuals in both conditions: 677CC‐NaCl = −8.18 ± 3.62 mmHg vs. 677TT‐NaCl = −6.59 ± 2.15 mmHg and 677CC‐Water = −6.94 ± 2.01 mmHg vs. 677TT‐Water = −5.37 ± 2.78 mmHg (p = 0.013). Plasma riboflavin was not different between the 677CC and 677TT groups (14.4 ± 8.8 vs. 17.2 ± 11.9 nmol/L, respectively). These data indicate a lesser SBP response to NaCl ingestion, independent of riboflavin status, in the 677TT group, suggesting that acute regulation of BP in response to a vasoreactive stimulus may be impaired as a result of this gene variant.Support or Funding InformationNIH DC02995
The Inhibitory Effects of HJC0416 on Liver Fibrogenesis in Activated Hepatic Stellate Cells
Authors: Nunez‐Lopez Omar , Wang Xiaofu , Graham Gabriel , Kandathiparampil Arline , Ye Na , Chen Haiying , Chen Haijun , Zhou Jia , Radhakrishnan Ravi S 
Published: November 2023

IntroductionThe STAT3 signaling pathway regulates activation of hepatic stellate cells (HSCs) and promotes its fibrogenic behavior. Using a fragment‐based drug design approach, our group has developed HJC0416, a novel orally bioavailable small‐molecule inhibitor of STAT3. HJC0416 was found to induce apoptosis and decreased tumor growth in breast cancer models. In the present study, we studied the antifibrogenic properties of HJC0416 in activated hepatic stellate cells (HSC), which are the major effector cells of liver fibrosis.MethodsHuman (LX‐2) and rat (HSC‐T6) hepatic stellate cell lines were used. Cell proliferation was measured by Alamar Blue assay. Cellular protein expression levels were determined by Western blotting and immunofluorescence. Cell cycle was assessed by flow cytometry. Yo‐pro‐1 staining was used to measure apoptosis.ResultsHJC0416 treatment significantly inhibited LX‐2 and HSC‐T6 cell proliferation in a dose‐dependent fashion, and induced apoptosis and S‐phase cell cycle arrest. HSC activation marker α‐smooth muscle actin was also attenuated. HJC0416 suppressed Tyr705‐phosphorylated STAT3 (pSTAT3) and impaired pSTAT3 nuclear translocation and transcriptional activity. STAT3 target genes cyclin D1 and c‐myc were down‐regulated by HJC0416. Static, a well‐known STAT3 inhibitor, confirmed that HSC proliferation was suppressed by STAT3 inhibition. Extracellular matrix (ECM) proteins collagen type I (Coll.I) and fibronectin (FN) are major components of hepatic scar, with TGFβ being the most potent stimulator for ECM production. Our data revealed that endogenous Coll.I and FN expression were suppressed by HJC0416 in a dose‐dependent manner; TGFβ‐stimulated Coll.I and FN production were prevented by pretreatment with HJC0416.ConclusionHJC0416 inhibits HSC activation via the STAT3 signaling pathway. HJC0416 represents a promising anti‐hepatic fibrogenic agent.Support or Funding InformationThis work was supported by grants P50 CA097007, P30 DA028821, R21 MH098344 (JZ) from the National Institutes of Health, Cancer Prevention Research Institute of Texas award, R. A. Welch Foundation Chemistry and Biology Collaborative Grant (JZ) from the Gulf Coast Consortia, and John Sealy Memorial Endowment Fund and the Center for Addiction Research (JZ) from the University of Texas Medical Branch.