bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary Patterns are Associated with Obesity in Young Women
Authors: Lindgren Jessica A. , Hartman Terryl J. , Mitchell Diane C. , Coffman Donna L. , Van Horn Linda , Dorgan Joanne F. 
Published: June 2021

Dietary pattern (DP) analyses have been successfully used to study the effects of total diet on health outcomes. This cross‐sectional study used latent class analysis to derive DPs in a cohort of 250 young adult women (25–29y) originally enrolled between 8–10y into the Dietary Intervention Study in Children. Using repeated 24‐ hour dietary recall data, 15 food group variables were used to derive five DPs designated as “Western”, “Healthy”, “Low Energy”, “Alcohol”, and “Non‐drinking” patterns. Preliminary multivariable analyses suggest that body fatness (p= 0.002), waist circumference (p=0.004), and dietary energy density from food only (ED; p<0.001) were significantly different across DPs. Women in the “Western” pattern, which was characterized by high intakes of red meat, refined grains, and starchy vegetables, had the highest mean body fatness (40.3 ± 9.6%), waist circumference (91.1 ± 11.1 cm), and ED (2.15 ± 0.36 kcals/g). Women in the “Healthy” DP, which was characterized by high intakes of fruit, whole grains, and dark green and yellow vegetables, had a significantly lower mean ED (1.46 ± 0.39 kcals/g) than each other DP (all p<0.05). These results suggest that DPs may be associated with obesity.Grant Funding Source: R01CA104670
The effect of beta‐carotene on migration and invasion in SK‐N‐BE( 2)C neuroblastoma cells
Authors: Kim Yoo‐Sun , Lee Hyun‐Ah , Kim Yuri 
Published: June 2021

Neuroblastoma (NB) is the extracranial tumor of children. The invasive or metastatic NBs have poor clinical outcome, therefore, to understand the mechanism(s) that modulate cancer cell invasion is important to develop more effective chemotherapeutic agents. While Beta‐carotene (BC), the most active vitamin A precursor, has been previously shown to exert various antioxidant and anticancer effects, the anti‐metastatic effects of BC on NB cells remains poorly understood. The aim of this study is to investigate the anti‐metastatic effects of BC on highly malignant SK‐N‐BE( 2)C NB cells. We found that BC attenuated the migratory and invasive capabilities of the cells. The protein expression and enzymatic activity of matrix metalloproteinase‐2 (MMP2) was also suppressed by BC under normoxia or hypoxia determined by western blotting and gelatin zymography assay respectively. BC down‐regulated the expression of hypoxia‐inducible factor 1α (HIF‐1α), a well‐known tumor metastasis regulator and further down‐regulated its down‐stream genes, vascular endothelial growth factor (VEGF) and glucose transporter‐1 (GLUT‐1). In conclusion, the present study provided the first evidence that BC may be utilized as an effective chemotherapeutic agent by regulating invasion potential, thereby controlling the metastasis of neuroblastomas.[This research was financially supported by the National Research Foundation of Korea (Project Number is 2012–0008169)]Grant Funding Source: National Research Foundation of Korea
Effects of γ‐glutamyl hydrolase modulation on CpG promoter DNA methylation and gene expression in human colon cancer cells
Authors: Kim Sung‐Eun , Hinoue Toshinori , Kim Michael , Sohn Kyoung‐Jin , Cho Robert , Weisenberger Daniel , Laird Peter W. , Kim Young‐In 
Published: June 2021

γ‐Glutamyl hydrolase (GGH) plays an important role in folate homeostasis by catalyzing hydrolysis of polyglutamylated folate into monoglutamates, thereby facilitating export of folate from cell. We investigated whether GGH modulation would affect CpG promoter methylation and gene expression profiles in human HCT116 colon cancer cells. Illumina HT‐12 and Infinium Methylation assay were performed in the GGH‐modulated HCT116 cells, and Ingenuity Pathway Analysis was used for functional analysis. The mRNA expression of selected genes, expression of which was epigenetically regulated was confirmed by qRT‐PCR. We identified 153 differentially expressed genes (most involved pathways: cellular movement and cell death) associated with GGH overexpression, and 321 differentially expressed genes (most involved pathways: cell death and cell cycle) associated with GGH inhibition. 905 and 1869 genes showed altered CpG promoter methylation associated with GGH overexpression and inhibition, respectively. An integrated analysis revealed 5 and 16 genes, expression of which was regulated by CpG promoter methylation changes associated with GGH overexpression and inhibition, respectively. Thus, GGH modulation can affect differential gene expression and CpG promoter DNA methylation involved in important biological pathways and some of the observed altered gene expression appear to be epigenetically regulated.Grant Funding Source: CIHR Fund 14126
Lower natural killer cell cytotoxicity in smokers may be mediated by epithelial cells
Authors: Muller Loretta , Brighton Luisa E. , Jaspers Ilona 
Published: June 2021

Cigarette smoking is a risk factor for viral infections, yet the mechanisms underlying this susceptibility remain unknown. Natural killer (NK) cells play an important role in fighting influenza and signals from epithelial cells (EC) likely regulate NK cell activity. We have previously shown that markers of cytotoxicity are reduced in nasal NK cells from smokers after influenza infection. This study investigated if human EC from smokers and nonsmokers differentially affect NK cell activity in the context of influenza infection.EC were infected with influenza and subsequently co‐cultured with NK cells. NK cells were also incubated with apical washes and basolateral supernatants of EC to identify the role of soluble mediators.At baseline, co‐culturing NK cells either directly with smoker EC or stimulating with basolateral supernatants from these cells reduced markers of cytotoxicity. Similarly, after influenza infection markers of cytotoxicity as well as levels of IFN‐γ, IL‐4 and granzyme B were decreased in NK cells incubated with basolateral supernatants of smoker EC.Co‐culturing NK cells with EC from smokers reduced markers of cytotoxicity in NK cells through a potential mechanism involving EC‐derived soluble mediators. Thus, EC‐mediated modification of NK cell activity may contribute to the higher susceptibility to influenza infections seen in smokers.The work was supported by NIH, EPA and FAMRI.
Knockdown of CCR1 suppresses expression of Intercellular Cell Adhesion Molecule‐1 induced by hypoxia/reoxygenation in endothelial cells and reduces infarct sizes after myocardinal ischemia/reperfusion
Authors: Kim Jiyoung , Park Keun Hyung , Lee Tae Hoon 
Published: June 2021

It has been reported that CCL15, a CCR1 ligand, induces proatherogenic factors and has been implicated in atherosclerosis. The present study showed that exposure of human endothelial cells (ECs) to hypoxia and reoxygenation (H/R) resulted in a rapid increase in expression of ICAM‐1 and CCR1 ligands. Our results revealed that knockdown of CCR1 attenuated expression of ICAM‐1 in ECs after H/R. Stimulation of ECs with CCL15 increased expression of ICAM‐1 compared with those in non‐stimulated cells predominantly via CCR1. Our data showed that CCL15 increased cell adhesion of monocytoid cells to endothelial cells. Pretreatment of these cells with CCR1 siRNA prevented the CCL15‐induced expression of ICAM‐1 and monocyte adhesion to ECs. We further investigated expression of CCR1 ligands and ICAM‐1 in vivo after myocardinal ischemia and reperfusion (MIR). Enhanced expression of ICAM‐1 and CCR1 ligands has been demonstrated in rat hearts in vivo after MI‐R. Direct injection of CCR1 siRNA onto the ventricular wall reduced expression of ICAM‐1 in rat hearts activated by MI‐R. Staining of hearts revealed that silencing of CCR1 markedly reduced the infarct sizes after MI‐R. Our results indicate that CCR1 and its ligands play important roles in inflammatory responses after MI/R via upregulating expression of cell adhesion molecules.This work was supported by a grant from National Research Foundation of Korea.
The Impact of Age on the Vasodilatory Capacity of Human Skeletal Muscle Feed Arteries
Authors: Park Songyoung , Ives Stephen J , Andtbacka Robert H.I , Gifford Jayson R , Richardson Russell S 
Published: June 2021

The effect of aging on the vasodilatory capacity of human skeletal muscle feed arteries (FAs), recognized to be important regulators of muscle blood flow, has not been elucidated.PurposeTo determine the impact of age on FA vasodilatory capacity. We hypothesized that vasodilation will be attenuated in FAs from old compared to young individuals and that this difference will be endothelium dependent.MethodsFAs (754.5±53.3 μm) were obtained from young (33±2 yr; n=10) and old (62±2 yr; n=7) human subjects and studied using pressure myography. Vasodilation (%) was assessed in response to three stimuli 1) flow induced shear stress (Δ29 mmHg), 2) acetylcholine (ACh, 10−3M), and 3) sodium nitropusside (SNP, 10−4M), with the latter two discerning endothelium dependent and independent vasodilation.ResultsBoth flow (old: 32±7 vs young: 68±11 %) and ACh (old: 73±4 vs young: 92±3 %) ‐induced vasodilation of the FAs were significantly blunted (p < 0.05) in the old compared to the young. In contrast, there was no impact of age on the vasodilation induced by SNP (old: 102±4 vs young: 112±11 %).ConclusionThis study has documented that the endothelium‐mediated vasodilatory capacity of FAs, but not smooth muscle function, is impacted by age. Given the potential role of FAs in the regulation of blood flow, these findings may help to explain the attenuated perfusion of skeletal muscle associated with aging.
Exercise prevents Western‐diet associated erectile and coronary artery endothelial dysfunction mediated by NADPH oxidase
Authors: La Favor Justin D , Anderson Ethan J , Dawkins Jillian T , Hickner Robert C , Wingard Christopher J 
Published: June 2021

The purpose of this study was to investigate NADPH oxidase as a common mechanism underlying both erectile dysfunction (ED) and coronary artery disease (CAD) in inactivity and diet‐induced obesity. Male Sprague‐Dawley rats were fed a Western diet (WD) or Control diet (CD) for 12 weeks. Subgroups within each diet remained sedentary (Sed) or engaged in treadmill exercise (Ex) throughout the dietary intervention. Erectile function was evaluated by measuring the mean arterial pressure and intracavernosal pressure in response to electrical field stimulation of the cavernosal nerve, prior to and following an intracavernosal injection of apocynin (Apo; an NADPH oxidase inhibitor). Coronary artery endothelial function (CAEF) was evaluated ex vivo with cumulative doses of acetylcholine (ACh) applied to coronary artery segments pre‐constricted with serotonin. CAEF was assessed in the presence and absence of Apo. Erectile function (p < 0.0001) and CAEF (p < 0.001) were attenuated in WD‐Sed rats. Erectile function (p < 0.01) and CAEF (p < 0.05) were augmented by Apo only in WD‐Sed rats. Ex preserved erectile function (p < 0.0001) and CAEF (p < 0.05) within the WD. This study suggests that erectile function and CAEF are impaired by NADPH oxidase in chronic WD‐fed rats, while Ex training may be a practical means of preventing WD‐induced ED and CAD.Supported by the Sexual Medicine Society of North America.
Effects of ASEA beverage intake on endurance performance in mice
Authors: Knab Amy M , Nieman David C , Shanely R. Andrew , Zwetsloot Jennifer J , Cialdella‐Kam Lynn , Meaney Mary Pat 
Published: June 2021

Previous research with ASEA (a saline beverage with stable superoxide complexes) found increased fatty acid mobilization in cyclists after 7 d ingestion. We hypothesized that run time to exhaustion would be favorably influenced by ASEA intake due to enhanced fatty acid oxidation and muscle glycogen sparing. Sixty mice were randomized to 1 of 4 treatment groups (n=15 each): placebo sedentary (PS), ASEA sedentary (AS), placebo run (PR), and ASEA run (AR). Mice were gavaged daily with ASEA or placebo (0.3 ml/d) for 7 d. PR and AR groups were run to exhaustion (24 m/min) at the end of the 7‐d gavage period, with AR running significantly longer than PR (68.0±9.2 vs. 52.8±7.4 min, respectively) (p<0.001). At the point of exhaustion, liver glycogen was undetectable for both AR and PR. When adjusted to run time, the estimated rate of muscle glycogen depletion was different between AR and PR (0.036±0.014 and 0.052±0.018 ug/mg protein per min, respectively, p=0.017). Skeletal muscle phosphorylated acetyl‐CoA carboxylase (p‐ACC) was significantly increased in AR compared to AS (p=0.020) and PR (p=0.045). Fatty acyl CoA transport (CPT1), and beta‐oxidation (beta‐HAD) were not different between AR and PR. ASEA increased run time to exhaustion by 29% in mice, potentially through less inhibition of fatty acid oxidation via increased P‐ACC, and muscle glycogen sparing percent (30%).Funded by Reoxcyn Discoveries Group.
Kinetic examination of femoral bone development in modern broiler chickens
Authors: Prisby Rhonda D , Campbell Jeremiah , Menezes Thomas , Benson Tyler , Samraj Enoch , Pevzner Igal Y. , Wideman Robert 
Published: June 2021

BACKGROUDLameness in broiler chickens often presents as femoral head separation, degeneration and necrosis. The etiologies of these disorders are unknown and may results from compromised blood flow to femora and/or imbalances in bone resorption and formation.METHODSWe examined developmental changes in femoral bone volume and metabolism, via histomorphometry, at 7, 15, 21, 28, and 42 days. Bone volume (BV/TV, %), osteoid surface (OS/BS, %), osteoblast activity (Ob.S/BS, %) and osteoclast activity (Oc.S/BS) were evaluated.RESULTSBody mass increased 23‐fold from 7 to 42 days. BV/TV remained stagnate (range: 5%–8%) and reached its highest value at day 28. Bone volume‐to‐body mass ratio (range: 0.057%–0.002%), Ob.S/BS (range: 1.3%–0.5%) and OS/BS (range: 22.9%–5.6%) declined significantly (p < 0.05) with age and Oc.S/BS was so excessive throughout development that analysis was not possible. In addition, vast areas of chondrocyte columns often expanded into the secondary spongiosa.CONCLUSIONSDevelopment of broiler femora failed to sufficiently match overall body growth. The lack of bone development corresponded to diminished osteoblast and augmented osteoclast activity. The large chondrocyte columns possibly coincide with a lack of blood vessel penetration that is necessary for calcification of the cartilage template and subsequent bone development. Supported by Cobb‐Vantress Inc.
INTRAUTERINE GROWTH RESTRICTION MODIFIES THE NORMAL GENE EXPRESSION IN KIDNEY FROM RABBIT FETUSES
Authors: Lozano Mauricio , Figueroa Horacio , Suazo Cristian , Illanes Sebastian , Eixarch Elisenda , Gratacós Eduard , Hernández‐Andrade Edgar , Irarrazabal Carlos E 
Published: June 2021

Intrauterine growth restriction (IUGR) is associated with increased risk of neonatal complications; birth hypoxia; impaired neuronal and kidney development; and stillbirth.New Zealand white pregnant rabbits were used to establish a model of IUGR. Rabbit fetuses with twenty‐five days of gestation (25D) were subjected to severe restriction by 40–50% ligature of uteroplacental vessels. At day 30 (120 hrs after surgery) newborns were obtained by caesarean. After delivery, living newborns were weighed. Kidneys were extracted from 39 fetal rabbits (19 controls and 20 IUGR) and gene expression of genes related with hypertonicity (NFAT5), hypoxia (HIF‐1α), and endothelial activity (Arg2, iNOS and eNOS) were evaluated by qRT‐PCR.Experimental IUGR fetuses were significant smaller than controls (39 vs. 48gr, p<0.05). The qRT‐PCR analysis showed a significant increasing in the NFAT5 (1.7 fold, p<0.05), iNOS (3.4 fold, p<0.05) and Arg2 (6.3 fold, p<0.05) mRNA. On the other hand, a significant reduction of eNOS mRNA level (0.34 fold, p<0.05) was observed. The HIF‐1α did not show changes in its mRNA expression.The selective ligature of uteroplacental vessels in the pregnant rabbit demonstrated an important mRNA dysregulation of essential proteins involved in fetal kidney development and adult kidney maintenance. Fondecyt 1100885 and Fondecyt 1110869.
Cerebral erythropoietin regulates the respiratory control system during early postnatal life
Authors: Caravagna Céline , Schneider Gasser Edith M. , Soliz Jorge 
Published: June 2021

Apart from its role in neuroprotection, erythropoietin (Epo) synthesized by neurons and astrocytes modulates the respiratory control system in adult mice. However, the impact of Epo in the regulation of the neural control of breathing during the postnatal development remains unknown. Here we use a transgenic mouse line (Tg21) constitutively overexpressing human Epo in brain to investigate whether Epo interacts with the brainstem centers associated with respiration during postnatal life. Our immunohistochemical analysis revealed that Epo and Epo receptor (EpoR) are expressed in the main central respiratory nuclei at 1, 4, 7, 10, 15 and 21 days of age. Furthermore, by using antibodies to choline acetyltranferase (ChAT), somatostatin (SST) and neurokinin receptor 1 (NK1), EpoR was localized to the pre‐Bötzinger complex nucleus at all studied postnatal days. Whole body phtethysmography technique was used to evaluate basal ventilation and ventilatory response to hypoxia at 10% and 6% O2. Compared to wild type animals, Tg21 mice showed improved hypoxic ventilation (both at 10% and 6% O2) at postnatal days 15 and 21, but not 7 and 10. These results are in line with data obtained by radioimmunoassay, showing that overexpression of Epo in transgenic mice brains dramatically increases after 10 days of postnatal life. These results imply that cerebral Epo plays a key‐regulating role in the neural control of breathing in a period in which the central respiratory network undergoes full development and maturation.Source of research support is Molly Towell Perinatal Research Foundation (MTPRF).
Prolonged intermittent hypoxia activates p38 MAP kinase in the phrenic motor nucleus
Authors: Peterson Timothy J , Huxtable Adrianne G , Mitchell Gordon S 
Published: June 2021

Plasticity is a fundamental property of the neural system controlling breathing. Although inflammation is prominent during most clinical disorders that challenge ventilatory control, little is known concerning the influence of inflammation on respiratory plasticity. One trigger to systemic (and neural) inflammation is prolonged (one day) intermittent hypoxia (IH‐1; 2 min hypoxia/2 min normoxia, 8 hrs), simulating intermittent hypoxia during sleep disordered breathing. IH‐1 abolishes an important model of respiratory plasticity, phrenic long‐term facilitation, but this effect is reversed by spinal application of a p38 MAP kinase inhibitor. p38 MAPK both initiates and is activated by inflammation. Here, we sought to determine which cells in the phrenic motor nucleus express increased phosphorylated (activated) p38 MAPK following IH‐1. Using immunofluorescence (n=5), increased phospho‐p38 MAPK was detected in identified phrenic motoneurons (Cholera Toxin B labeled) and adjacent microglia (cd11b positive cells). These results suggest that p38 MAPK activity may impair pLTF following IH‐1 by: 1) disrupting pLTF within phrenic motor neurons; and/or 2) initiating microglial inflammatory cascades that indirectly impair pLTF. p38 MAPK may be a viable therapeutic target to reduce the impact of inflammation on respiratory plasticity.Supported by HL111598, APS UGSRF Program
Functional glycomics of the pulmonary and systemic vasculature: Lectin histochemistry for probing differentiated glycoproteins
Authors: Cioffi Eugene A , Finnorn Brandon , Cioffi Donna L 
Published: June 2021

Endothelial cells line the inside of blood vessels and form a semi‐permeable barrier. Curiously, arteriosclerotic vascular disease (ASVD) is frequently exhibited within the systemic vasculature, whilst ASVD is rarely observed within the pulmonary vasculature. Since both vessel types transport the same components, this suggests some differences between the pulmonary and systemic endothelium that may underlie development of ASVD. We hypothesize that the surficial glycocalyx of the vessels plays a significant role in arteriosclerotic plaque formation.The glycan compositions of the pulmonary and systemic vasculatures have not been examined in detail. We compared rat pulmonary artery (PAECs) and rat pulmonary microvascular endothelial cells (PMVECs) with rat aortic endothelial cells (AOECs, systemic) and human coronary artery cells (HCACs, systemic) using a panel of fluorescently‐tagged lectins; key differences in the surficial carbohydrate expression on the glycocalyx in the pulmonary versus systemic vasculatures was observed. Most notably, systemic AOECs and HCACs showed a very high expression of 9‐acetylated sialic acid (9‐OAc‐Neu5Ac), whilst the pulmonary PAECs and PMVECs had little. In contrast, the pulmonary cells strongly expressed terminal á‐mannose, whereas the systemic cells showed a weak á‐mannose expression. Supported by 5R00HL089361.
MicroRNA‐29 expression in pancreatic islets correlates with the impairment of maternal glucose homeostasis induced by glucocorticoid excess in late pregnancy
Authors: Gomes Patricia Rodrigues Lourenço , Graciano Maria Fernanda Rodrigues , Pantaleão Lucas Carminati , Lellis‐Santos Camilo , Carpinelli Angelo Rafael , Latorraca Marcia Queiroz , Bordin Silvana 
Published: June 2021

We investigated the long‐term effects of dexamethasone (DEX) administration during late gestation in glucose homeostasis and in the expression of miRNAs in pancreatic islets. Pregnant Wistar rats received dexamethasone (DEX), 0.2 mg/kg daily in drinking water during the last five days of pregnancy (Preg‐DEX). Age‐matched virgin female rats either treated (CTL‐DEX) or not (CTL) with DEX, as well as untreated pregnant rats (Preg) were used as controls. All groups were subjected to glucose and insulin tolerance tests at weaning and at 3, 6, and 12 month after weaning. Pancreatic islets were isolated for glucose stimulated insulin secretion (GSIS) and miRNA expression. Compared to control groups, glucose intolerance was observed in Preg‐DEX rats from weaning to 12 months after weaning. In all periods insulin sensitivity was normal. An upregulation in miR‐29 family (miR‐29a/b/c) was observed in Preg‐DEX islets at the end of gestation and 12 months after weaning. In the later period, mir‐29 expression paralleled a decrease in GSIS. In conclusion, we show that the excess of glucocorticoid in late pregnancy permanently impairs pancreatic islets function, which is correlated with persistent upregulation of miR‐29 expression.Financial support: FAPESP 2011/01568–5, PRONEX‐FAPEMAT.