bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin B12 Status and Infant Outcome in a Community‐Based Folic Acid Intervention Study
Authors: Hausman Dorothy B , Holder Angela , Park Hea Jin , Rosa Gisselle , Andersen Victoria , Fleming Jennifer , Kauwell Gail , Caudill Marie , Malysheva Olga , Fisher Susan , Bailey Lynn B 
Published: November 2023

Adequate vitamin B12 intake and stores during pregnancy are necessary to maintain maternal status and for adequate nerve myelination and hepatic stores in the developing fetus. Additionally, since the vitamin B12 and folate metabolic pathways are interrelated, a vitamin B12 deficiency can cause a functional folate deficiency that increases risk for neural tube defects during development. The objective of this study was to assess vitamin B12 status of women participating in a double blind randomized‐controlled folic acid supplementation study performed in collaboration with the Athens Regional Nurse‐Midwifery Practice, Athens, GA. Participants (n=49), recruited through this community‐based practice, were randomly assigned to take daily prenatal supplements containing 400 μg or 800 μg folic acid and all vitamins (including 6 mcg vitamin B12), minerals and DHA required for a healthy pregnancy beginning at the first prenatal visit (<12 wk gestation). Maternal blood samples collected at baseline, 28 weeks, and delivery, and cord blood samples at delivery were analyzed for plasma vitamin B12 and serum and RBC folate concentrations. At baseline, vitamin B12 concentrations < 200 pg/ml were detected in 3/49 women (6%). In those completing the intervention (n=28), vitamin B12 concentration decreased throughout the pregnancy and the concentration at baseline was highly correlated with those at 28 wk (r=0.739, p<0.001) and at delivery (r=0.0645, p<0.001). Vitamin B12 concentration in cord blood was higher than (p<0.0001) and highly correlated (r=0.755, p<0.0001) with maternal B12 concentrations at delivery. No differences were detected in maternal or cord blood vitamin B12 concentrations related to the dose of supplemental folic acid. In unadjusted analysis, gestational age at delivery was related to maternal vitamin B12 concentration (r=0.421, p<0.05) and baseline vitamin B12 correlated with serum folate concentration (r=0.542, p < 0.005). Vitamin B12 concentration in cord blood was not related to gestational age, infant height, weight, head circumference or Apgar score, or maternal or cord blood serum or RBC folate status. In this study, women retained their relative vitamin B12 status despite being supplemented with the same level of the vitamin, suggesting that optimal vitamin B12 status prior to pregnancy is essential for maintaining adequate vitamin B12 nutrition for the pregnant woman and her developing fetus. Accordingly, vitamin B12 interventions should be initiated pre‐conceptionally to optimize status during pregnancy particularly among those at greatest risk for low vitamin B12 status.Support or Funding InformationSupport provided by Georgia Experimental Agricultural Station, HATCH #GEO00706 and #GEO00707, Obesity Initiative at the University of Georgia (UGA) and UGA Office of Vice President for Research.
Glycation of transferrin affects chromium binding and transport
Authors: Vincent John B. , Deng Ge , Dyroff Samantha L. 
Published: November 2023

Chromium, as the trivalent ion, can act as a pharmaceutical agent, increasing the sensitivity of the body to insulin and improving the symptoms of conditions, such as type 2 diabetes, that result from insulin‐insensitivity. For chromium to act, it must enter insulin‐sensitive tissues including the skeletal muscle where most glucose metabolism occurs. Chromium is transported from the bloodstream (where it is stored) to the tissues by the protein transferrin. However, under conditions of high blood sugar concentrations (as would be experienced by a diabetic subject), transferrin is chemically modified by the blood glucose. This modification alters the ability of transferrin to bind chromium and to take the shape required for the transferrin to be bound and uptaken by cells to deliver the chromium. The rate at which chromium binds to transferrin is also altered. This should lead to a decreased ability of the chemically modified (glycated) transferrin to deliver chromium to tissues. The transport of chromium by transferrin and glycated transferrin in rats has also been examined as well as the effects of insulin stimulation of transferrin movement on glycated transferrin compared to unglycated transferrin. The results suggest the dose of chromium anticipated to be beneficial in increasing insulin sensitivity in diabetic subjects could be larger than that for healthy subjects.Support or Funding InformationThis work was funded in part by a University of Alabama College of Arts and Sciences Undergraduate Creativity and Research Activity award to S.D.
Flaxseed Lignan Metabolite, Enterolactone, Down‐regulated DNA Methyltransferase, Histone Deacetylase, and Methyl‐CpG‐binding Domain Protein Expression in Murine Adipocytes
Authors: Rhee Yeong 
Published: November 2023

Nutrition influences gene expression via epigenetic control mechanisms such DNA methylation and histone modification by DNA methyltransferase (DNMT) and histone deacetylase (HDAC), respectively. Oxidative stress caused by reactive oxygen species (ROS) damages DNA or cells which can be regulated by antioxidants. Flaxseed is the richest source of secoisolariciresinol diglucoside, which is metabolized into enterolactone by bacteria in the gut. Enterolactone has antioxidant activities which lower ROS induced oxidative damages. Thus, this study was conducted to determine the effects of enterolactone on DNMTs, HDACs, and methyl‐CpG‐binding domain protein (MBD) expression in ROS treated murine adipocytes. Enterolactone (0, 10, 50, or 100 μM) or control antioxidant, such as superoxide dismutase (100 U/mL) or catalase (100 U/mL), treated adipocytes (1×107) were treated with hydroxyl or superoxide radical, and then total RNA was extracted and purified using an RNeasy Mini kit. DNMTs, HDACs, and MBD2 expression was measured by real‐time quantitative PCR. The fold change in DNMTs, HDACs, and MBD2 expression was calculated using 2−ΔΔCT method. The results showed that enterolactone down‐regulates DNMTs, HDACs, and MBD2 expression of hydroxyl radical treated adipocytes. However, no significant effects of enterolactone on DNMTs, HDACs, and MBD2 gene expression were seen in superoxide radical treated adipocytes. How DNMTs, HDACs, and MBD2 expression of hydroxyl radical treated adipocytes was down‐regulated by enterolactone is unknown and needs further study.Support or Funding InformationThe research was funded by grants from the Department of Health, Nutrition, and Exercise Sciences and College of Human Development and Education at North Dakota State University.
The effect of cranberry consumption on lipid and lipoprotein metabolism in human apolipoprotein A‐I transgenic mice fed a high fat and high cholesterol diet
Authors: Park Young‐Ki , Caceres Christian , O'Neill Edward N. , Bae Minkyung , Pham Tho X. , Lee Yoojin , Kim Bohkyung , Lee Ji‐Young 
Published: November 2023

Cranberries contain high levels of health‐promoting anthocyanins, which have been implicated in their potential role in the prevention of cardiovascular disease. The objective of this study was to determine the effects of cranberries on lipid and lipoprotein metabolism in mice expressing human apolipoprotein A‐I transgene (hApoAITg), which have similar HDL metabolism to that of humans. Male hApoAITg mice were fed a modified AIN‐93M high fat/high cholesterol control diet (HF/HC; 15% fat, 0.25% cholesterol, w/w; n = 15) or a HF/HC experimental diet supplemented with 5% (w/w) dried, whole cranberry powder (n = 16) for 8 weeks. Subsequently, the mice were sacrificed to obtain tissue and blood samples. There were no significant differences in terminal body weights, body weight gain, liver weights and epididymal fat weights between control and cranberry‐fed mice. Serum total cholesterol (TC) and apolipoprotein B cholesterol (ApoB‐C) levels were significantly lower in controls than cranberry group (238 ± 9.4 vs. 294 ± 20.3 mg/dL for TC; 43.9 ± 6.7 vs. 88.3 ± 15.0 mg/dL for ApoB‐C) with no significant difference in serum high‐density lipoprotein cholesterol (HDL‐C) concentrations. Serum triglyceride (TG) levels of cranberry group (55.5 ± 4.6 mg/dL) were also significantly higher than controls (37.7 ± 2.9 mg/dL). Hepatic expression of sterol‐regulatory element binding protein 2 and low‐density lipoprotein receptor was significantly lower in cranberry group, which may be responsible for the increased serum TC and apoB‐C, while HMG‐CoA reductase and proprotein convertase subtilisin/kexin type 9 mRNA levels were not different between two groups. Despite the significant increase in serum TG in mice‐fed cranberries, their mRNA abundance of genes responsible for lipogenesis (e.g., fatty acid synthase and stearoyl CoA desaturase) and fatty acid oxidation (e.g., carnitine palmitoyl transferase 1α and acyl‐CoA oxidase 1) was not significantly altered in the liver. In addition, the hepatic expression of genes involved in HDL metabolism, including human apoA‐I, lecithin:cholesterol acyltransferase, and scavenger receptor class B, type I, was significantly lower in cranberry‐fed mice compared with controls although serum HDL‐C levels were not different between two groups. Further study should be warranted to have better mechanistic insight into the changes in lipid and lipoprotein metabolism by cranberries.Support or Funding InformationNutricia Research Foundation
Lipotoxicity‐Evoked Reductions in Nitric Oxide Bioavailability and Exaggerated Oxidant Stress Are Blunted By Blueberry Metabolites in Human Vascular Endothelial Cells
Authors: Bharat Divya , Begaye Nathan , Ramos Renata , Ferreira Marina , Li Youyou , Cutler Brett , Bharath Leena P , Symons J David , Jalili Thunder , Pon Velayutham Anandh Babu 
Published: November 2023

The vascular benefits of blueberry (BB) anthocyanins reported in humans might be mediated by their circulating metabolites. To test this, we synthesized the BB‐metabolites vanillic acid‐4‐sulfate (V4S), isovanillic acid‐3‐sulfate (IV3S), and benzoic acid‐4‐sulfate (B4S), because these compounds are not commercially available. As hypothesized, a combination of V4S, IV3S, B4S, hydroxyhippuric acid (HHA), and hippuric acid (HA) at concentrations known to peak in human plasma following the consumption of 240 g of blueberries, suppressed chemokines (IL8 and MCP1) and adhesion molecules (ICAM1, VCAM1 and E‐selectin) unleashed by human aortic endothelial cells (HAECs) upon treatment with palmitate (500 μM for 5 h) vs. vehicle. Next, we determined whether vasculoprotection afforded by BB‐metabolites was secondary to preserved endothelial cell nitric oxide (NO) bioavailability. HAECs were treated ± a BB‐metabolite cocktail for 6 h ± 500 μM palmitate for the last 5 h. To determine agonist‐stimulated NO production, HAECs were treated with 100 nM insulin (or vehicle) for 30 min at the end of the experimental treatment. Human studies reported that blueberry intake increases the endothelium dependent vasodilation that was accompanied by the increases in the plasma concentrations of metabolites such as V4S, IV3S, B4S, HA, and HHA. Hence, BB‐metabolite cocktail contained these metabolites at physiological relevant concentrations. Palmitate increased reactive oxygen species (ROS) generation (assessed by H2DCFDA) and blunted insulin‐stimulated NO production (assessed by DAF‐FM) in HAECs (both p<0.05), but both responses were normalized in BB‐metabolite‐treated HAECs. This is consistent with our results on the beneficial effects of BB‐metabolites on endothelial inflammation. Ongoing studies are determining the extent to which these findings from HAECs can be translated to intact arteries. In this regard, preliminary results from murine femoral arteries indicate that palmitate‐induced endothelial dysfunction can be attenuated by concurrent treatment with BB‐metabolites. Blueberry supplement might provide a valuable adjunct therapy to traditional treatments for vascular complications known to exist in patients with metabolic syndrome.Support or Funding InformationUniversity of Utah Research Start‐up fund (to Anandh Babu Pon Velayutham), Native American Summer Research Internship (to Nathan Bagaye), Undergraduate Research Opportunities Program assistantship (to Brett Cutler), and Brazilian Scientific Mobility Program sponsorship (to Marina Ferreira and Renata Ramos).
Improving Wound Healing through the Use of Tetrazine‐Modified Alginate
Authors: De Leon‐Peralta Esmarline Jacely , Brudno Yevgeny , Kwee Brian J. , Mooney David J. 
Published: November 2023

Ischemic diseases, such as myocardial infarction and peripheral arterial disease, are a leading cause of death globally. There has been increasing interest in treating these diseases with factors that induce angiogenesis, the growth of new blood vessels from pre‐existing blood vessels. We have recently shown that alginate linked to tetrazine helps induce a greater recovery in blood perfusion compared to unmodified alginate in a murine model of hindlimb ischemia. The objective of this project is to understand how this biomaterial induces recovery in blood perfusion. Our hypothesis is that tetrazine acts directly on endothelial cells to induce angiogenesis and also activates immune cells that are proangiogenic. To validate our hypothesis, we have performed in vitro angiogenesis assays to study if tetrazine‐modified alginate induces endothelial cell sprouting. Additionally, we have performed histology and immunohistochemistry on ischemic muscles from our in vivo experiments to see if this biomaterial increases blood vessel density, blood vessel remodeling, and the presence of proangiogenic immune cells. Our findings may lead to a novel method for treating people with ischemic diseases.Support or Funding InformationWyss Institute for Biologically Inspired Engineering, Harvard John A. Paulson School of Engineering and Applied Sciences Research Experiences for Undergraduates (SEAS REU)
PERK Branch of the ER Stress Regulates FoxO to Mediate Homocysteine‐induced BKCa Channel Dysfunction
Authors: Sun Wen‐Tao , Wang Xiang‐Chong , Mak Shiu‐Kwong , Yu Cheuk‐Man , Yang Qin 
Published: November 2023

Large‐conductance Ca2+‐activated K+ (BKCa) channels play an important role in vascular tone regulation. The atherosclerotic risk factor homocysteine inhibits vascular smooth muscle BKCa channels whereas the mechanisms remain poorly understood. We studied the role of endoplasmic reticulum (ER) stress in homocysteine‐induced BKCa channel inhibition with further understanding of the molecular determinants. Vasorelaxant response to the BKCa channel opener NS1619 was studied in endothelium‐denuded porcine small coronary arteries in a myograph. Primary cultured porcine coronary arterial smooth muscle cells (PCASMCs) were used for mRNA and protein analysis of BKCa channels, as well as patch‐clamp recording of the BKCa channel current. NS1619‐induced vasorelaxation was significantly inhibited by homocysteine, which was restored by ER stress inhibitors either TUDCA or 4‐PBA. GSK2606414, a selective inhibitor of PKR‐like endoplasmic reticulum kinase (PERK) showed potent protective effect against homocysteine on the NS1619‐induced relaxation and the whole‐cell BKCa channel current. Homocysteine lowered the protein level of β1 but not α subunit of the BKCa channel. Exposure to homocysteine did not alter the mRNA expression of both subunits. Downregulation of BKCa β1 was attenuated by TUDCA, 4‐PBA, and GSK2606414. Pharmacological inhibition of PERK suppressed the nucleic translocation of forkhead box O transcription factor 3a (FoxO3a) in homocysteine‐exposed PCASMCs, associated with a decrease of atrogin‐1 protein and an increase of BKCa β1 protein. In PCASMCs transfected with FoxO3a siRNA, downregulation of atrogin‐1 protein expression and restoration of BKCa β1 protein level was observed after homocysteine exposure. This study suggests that ER stress mediates homocysteine‐induced BKCa channel inhibition in coronary arteries and activation of FoxO3a by PERK underlies ER stress‐mediated BKCa channel inhibition through a mechanism involving ubiquitin ligase‐enhanced degradation of the channel β1 subunit.Support or Funding InformationSupported by RGC/GRF CUHK4774/12M & CUHK14118414; Lui Che Woo Institute of Innovative Medicine ‐ CARE theme 8303303, and CUHK Direct Grant 4054182.
Enhanced generation of platelet‐activating factor‐receptor ligands via ethanol synergizes ultraviolet B mediated acute and systemic effects
Authors: Sahu Ravi P , Weyerbacher Jonathan , Ocana Jesus , Konger Raymond , Travers Jeffrey 
Published: November 2023

Alcohol (ethanol) intoxication remains one of the most abused substance in the United States and other part of the world. In addition, an association between alcoholism and trauma has long been recognized. Moreover, thermal injury after alcohol exposure have been shown to exhibit higher morbidity and mortality in humans. However, the mechanism of alcohol‐related toxicity with or without thermal injury is not entirely clear. Several studies including ours have shown that exposure to pro‐oxidative stressors including ultraviolet B (UVB) generate the potent lipid mediator with platelet‐activating factor‐receptor (PAF‐R) ligand activity. Notably, these PAF‐R ligands mediate UVB‐induced acute pro‐inflammatory effects and also augment photosensitivity associated with the deficiency of xeroderma pigmentosum complementation group A. Given that several agents can modulate PAF‐R ligands production and systemic ethanol exposure enhances UVB‐induced effects, we hypothesize that ethanol can synergistically potentiate UVB‐mediated PAF‐R ligands production as well as acute pro‐inflammatory and systemic effects. Using the human keratinocyte‐derived cell line, HaCaT, we demonstrate that preincubation with ethanol resulted in an augmentation of PAF‐R ligands production in response to low (sub‐erythematic) doses of UVB. Pre‐treatment of C57BL/6 mice with systemic ethanol resulted in an augmented skin production of PAF‐R ligands in response to UVB. We demonstrate that pre‐treatment with systemic ethanol followed by UVB irradiation of PAF‐R positive wild‐type versus PAF‐R‐deficient mice resulted in enhanced skin erythema response compared to UVB alone treated group in a PAF‐R dependent fashion. Moreover, the combination of ethanol + UVB resulted in increased systemic toxicity, including lung inflammation only in wild‐type mice and not in the PAF‐R‐deficient mice. These studies demonstrate the involvement of the PAF‐R pathway in ethanol‐induced acute toxic effects and that ethanol can synergistically potentiate PAF‐R‐mediated systemic effects when combined with agents (such as UVB) exhibiting pro‐oxidative stressors property. These studies indicate that blocking PAF‐R‐mediated pathway could be used as a promising approach to prevent ethanol ± UVB‐mediated acute and systemic toxicities.Support or Funding InformationNIH grant R01 HL062996 and K22 ES023850
Brain Damage Following Smoke Inhalation and Skin Burn
Authors: Randolph Anita , Ihara Koji , Escobar Kenneth , Fukuda Satoshi , Salsbury John Randall , Prough Donald , Herndon David , Enkhbaatar Perenlei 
Published: November 2023

RATIONALEIn the U.S., there is an estimated 300,000 to 500,000 patients hospitalized annually due to burn related injuries. Mortality and morbidity of burn patient's increase significantly when combined with smoke inhalation injury. Previous studies have shown combined burn and smoke inhalation results in systemic changes including hypermetabolic response, microvascular hyperpermeability and multiorgan dysfunctions. With the advanced technology and treatment, mortality of burn victims is remarkably reduced. However, there is no follow up study, among the survivors, on possible effects of burn and smoke on brain dysfunction. In this study, we tested the hypothesis that burn and smoke inhalation injury is sufficient to induce brain dysfunction by activating astrocytes and causing neuronal injury.METHODSTo test our hypothesis, we used our well‐characterized ovine model of skin flame burn (40% TBSA, 3rd degree) and smoke inhalation (48 breaths of cooled cotton smoke). After the injury we studied the animals 48 hours in a conscious state under mechanical ventilation, recording hemodynamics and ventilator variables as well as taking blood samples every 6 hours. Postmortem, brains were taken and placed into 10% formalin for 4–6 weeks. We compared 3 different groups: n=3 sham (no injury), n=3 smoke only, n=3 combined burn and smoke. Brain tissue slides were prepared from the hippocampus and basal ganglial area (ten slides for each sheep) and stained with Luxol Fast Blue (LFB) to assess myelinated axon damage and Hematoxylin & Eosin (H&E) to assess astrocyte activation and neuronal damage/death.RESULTSAverage carboxyhemoglobin levels were 2.1%, 67.3%, 60.4% in sham, smoke only and burn/smoke groups, respectively. No noticeable brain tissue changes were observed in sham, whereas there were clear evidences of astrocyte activation and neuron death in the smoke only group. The number of activated astrocytes per field and damaged neurons were significantly increased in the smoke only and burn/smoke groups. The percentage of damaged neurons in the smoke only and burn/smoke groups were 41.0% and 59.9% respectively compared to sham of 19.2%. Observed basophilic neuronal necrosis in smoke only vs. sham was increased as well. These changes were augmented by skin burn. In addition, vascular congestion and hemorrhage were observed in both smoke only and combined burn/smoke groups.CONCLUSIONSSmoke inhalation causes brain damage characterized by astrocyte activation, neuronal and myelinated axon damage and hemorrhage. Presence of skin burn exacerbates smoke‐induced brain injury.Support or Funding InformationShriners Hospital for Children SHC84050; SHC85220
microRNA profiling in rat model of neurofibrillary degeneration
Authors: Cente Martin , Kosikova Nina , Filipcik Peter , Novak Michal 
Published: November 2023

Neurofibrillary tangles composed of post‐translationally modified protein tau are major hallmarks of neurodegenerative diseases collectively known as tauopathies. Pathogenesis of these disorders is characterized by gene expression changes resulting to altered signalling pathways. Moreover, deregulation of microRNA levels has been also associated with many neurodegenerative diseases, suggesting possible employment of miRNAs as diagnostic biomarkers. In order to identify differentially expressed microRNA molecules during neurofibrillary degeneration we have performed complex miRNA profiling in rat model of tauopathy (expressing human truncated Tau151‐391,4R) that recapitulates major features of neurodegeneration of AD type.Transcriptomic analysis of brain tissue samples showed significantly increased expression of several particular miRNAs involved in the regulation of neuroinflammation (4,1‐fold), innate immune response (2,6‐fold), intracellular trafficking (2,4‐fold) and signal transduction (2,3‐fold). Interestingly, correlation analysis revealed strong positive relationship between dysregulated microRNA molecules.The data suggest that expression of truncated tau protein leads to deregulation of signalling pathways during the neurodegeneration process manifested by altered miRNA expression.Moreover, identified miRNA markers can be potentially applied for the monitoring of the neurodegenerative cascades in Alzheimer's disease and related tauopathies.This work was supported by Research grants: APVV‐0677‐12 and VEGA 2/0141/15 and research grant from Axon Neuroscience SE.