bluuebunny/crossref_metadata_2025_split huggingface dataset:
Who's Eating Spinach Again?
Authors: Dellava Jocilyn E. , Cuite Cara L. , Hallman William H. 
Published: June 2021

In September of 2006, the Food and Drug Administration issued an advisory warning against the consumption of fresh spinach due to contamination with E. coli 0157:H7. Subsequently, spinach was largely recalled by manufacturers. Spinach is a healthful, nutrient dense food. Generally, low income and African American groups have low quality diets lacking in healthful items. Therefore, the objective of this report is to determine if persons in these groups who ate spinach prior to the recall were less likely to consume spinach in the weeks following the recall.A national telephone survey of 1200 Americans was conducted in November, 2006. Within two weeks of the recall's end 55% of participants that ate spinach before the recall and heard about the recall had not returned to eating spinach. Using Student's t‐tests, factors associated with a lower likeliness of eating spinach immediately following the recall include African American ethnicity (p ≤ 0.001) and having an income less than 35,000/yr p ≤ 0.000.Overall, groups with traditionally poor quality diets were less likely to return to eating spinach in the weeks following the recall. Since this study only assessed spinach consumption following the recall in participants that consumed spinach before the recall, it is likely the recall had more adverse effects on these groups that are all ready at risk for unhealthy diets.Funding Source: Cooperative State Research, Education, and Extension Service of the United States Department of Agriculture under the National Integrated FoodSafety Initiative: Grant # 2005‐51110‐02335.
Compliance to an Exchange‐list Mediterranean Diet
Authors: Djuric Zora , Ren Jianwei , Radakovich Katherine , VanLoon Glee , DiLaura Nora Mary , Sen Ananda 
Published: June 2021

A Greek‐Mediterranean dietary pattern has great potential for cancer prevention. We developed an exchange list diet that would target key nutrient intakes of the Mediterranean eating pattern. The goals were to replace half of usual polyunsaturated fat intake with monounsaturated fats (MUFA) and to increase intakes of a wide variety of fruits and vegetables, including dark green vegetables, allium vegetables and herbs. A total of 69 women, ages 25–59, were enrolled in the study and randomized to the Mediterranean diet or not for 6 months. Subjects in the Mediterranean diet arm received individualized telephone counseling. Menus were provided as examples, but the diets were self‐selected. Compliance to the dietary goals was assessed by 7‐day food records and by levels of plasma fatty acids, lipids and carotenoids. The women were able to make large changes. Intake of MUFA increased by 48% without a change in overall fat intake. Fatty acids levels in plasma changed in the same direction as dietary fatty acids, but were smaller in magnitude. Intakes of carotenoids more than doubled in the Mediterranean diet arm, and plasma total carotenoids increased by 65%. A statistical model was developed to identify clustered outcome variables. This modified Mediterranean diet will be tested for its effects on markers of cancer risk in future studies.Supported by AICR grant #03B043.
Activation of the liver x receptor (LXR) in utero does not affect lipid metabolism in mouse offspring upon high fat dietary challenge
Authors: Plosch Torsten , van Straten Esther M.E. , Huijkman Nicolette C.A. , Baller Juul F.W. , Kuipers Folkert 
Published: June 2021

The Liver X Receptors LXRα/ß are vitally important in regulating cholesterol and fatty acid metabolism in the adult. Earlier studies by us have shown that prenatal exposure to a synthetic LXR agonist induces hyperlipidemia and hepatic steatosis in fetal mice. Aim of this study was to investigate effects of LXR activation in utero on lipid metabolism at a later age. Methods: Pregnant C57BL/6 mice were fed a diet containing the synthetic LXR agonist T0901317 from E10.5 until delivery. Pups were weaned onto chow. Pups received a high‐fat/high cholesterol (HFHC) diet or chow (C) from 6 till 8 weeks of age, after which hepatic gene expression and lipid levels were measured. Results: The HFHC diet led to 2‐ to 3‐fold increased hepatic triglyceride concentrations in male offspring. Plasma cholesterol concentrations were increased 1.6 times, while plasma triglyceride concentrations were unchanged. However, no differences between groups having received T0901317 or chow during gestation were observed. The HFHC diet led to induction of LXR target genes, but no effect of gestational T0901317 exposure was seen: expression of the cholesterol transporter Abcg8 was increased 2 times in both HFHC groups (with or without T0901317) whereas the expression of lipogenic genes Srebp1c and Scd1 were increased 2.5‐fold and 3‐fold, respectively in both HFHC groups. Conclusions: Fetal activation of LXR does not influence short‐term coping with a high‐fat/high cholesterol diet in young mice. Long‐term studies should elucidate whether fetal LXR activation exerts long‐lasting effects on the health of the offspring.Supported by the Dutch Heart Foundation (2004T048).
Ethanol lowers blood pressure in conscious female rats via enhancing the phosphorylation of myocardial neuronal nitric oxide synthase
Authors: El‐Mas Mahmoud M , Fan Ming , Abdel‐Rahman Abdel A 
Published: June 2021

Intragastric (i.g.) ethanol lowers blood pressure (BP) in female rats via a reduction in cardiac output (CO) and stroke volume (SV). We tested the hypothesis that enhancement of myocardial nNOS and/or eNOS activity constitutes a cellular mechanism for ethanol‐evoked reductions in CO and BP. We investigated the effect of inhibition of nNOS (Nω‐propyl‐L‐arginine, NPLA) or eNOS [N5‐(1‐iminoethyl)‐L‐ornithine, L‐NIO] on hemodynamic, biochemical (nitrate/nitrite levels, NOx), and myocardial nNOS/eNOS phosphorylation elicited by ethanol (1 g/kg i.g.) in proestrus female rats. In saline‐pretreated rats, the hemodynamic effects of ethanol (reductions in BP, CO, and SV) were coupled with increases in plasma NOx and myocardial p‐nNOS, but not p‐eNOS, expression. nNOS inhibition by NPLA attenuated the hemodynamic effects of ethanol and associated increases in plasma NOx and cardiac p‐nNOS. eNOS inhibition by L‐NIO attenuated ethanol hypotension, but not concomitant CO/SV reductions. L‐NIO uncovered a dramatic increase in total peripheral resistance (TPR) in response to ethanol, which appeared to have offset the reduction in CO. These findings highlight: (i) myocardial nNOS as the cellular mechanism that underlies, in part, reductions in BP and CO caused by ethanol in female rats, and (ii) vascular eNOS‐NO signaling counterbalances ethanol‐induced increases in TPR.Supported by Grant R01 AA014441 from NIAAA.
Prevention of free fatty acids/high fat diet‐induced hepatic lipotoxicity by 18β glycyrrhetinic acid
Authors: Wu Xudong , Zhang Luyong , Shang Jiang , Gurley Emily , Studer Elaine , Hylemon Phillip B , Pandak William M , Sanyal Arun J , Zhou Huiping 
Published: June 2021

Free fatty acids (FFAs) are key players in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Inhibition of FFAs‐induced hepatic toxicity represents a potential therapeutic strategy. Glycyrrhizin (GL), the major bioactive component of licorice root extract, has been used to treat hepatitis to reduce liver inflammation and hepatic injury; however, the mechanism underlying the protective effect of GL remains unknown. GL exhibits its pharmacological functions through its biologically active metabolite, 18β glycyrrhetinic acid (GA), which is formed by presystemic hydrolysis. The aim of the present study was to examine if GA is able to prevent FFAs‐induced lipotoxicity and identify the potential cellular mechanisms. Both in vitro FFAs‐induced HepG2 NAFLD model and in vivo high fat diet (HFD)‐induced rat NAFLD model were used in the current studies.Results: GA not only prevented FFAs‐induced lipoapoptosis in HepG2 cells, but also prevented HFD‐induced liver injury in in vivo rat models. Furthermore, stabilization of lysosomal membrane, inhibition of cathepsin B expression and enzyme activity, inhibition of mitochondrial cytochrome c release, and reduction of oxidative stress represent the major cellular mechanisms underlying its protective effects on FFAs/HFD‐induced hepatic lipotoxicity.Conclusion: GA may be beneficial for preventing FFAs/HFD‐induced lipotoxicity or treating NAFLD.
Low Oxygen Affinity Hemoglobin HBOC‐201 enables increased Oxygen Uptake (VO2) In Bovine Pulmonary Artery Endothelial Cells (BPAEC)
Authors: Karaian John Edward , Mongan Paul D. , MacDonald Victor W. , Bunger Rolf 
Published: June 2021

Hemoglobin‐based oxygen carriers (HBOCs) with various oxygen affinities are currently being evaluated for clinical use. We tested whether HBOCs with high vs. low oxygen affinities can affect cellular oxygen uptake (VO2), using a BPAEC model.Methods:Confluent BPAECs, passages 3–6, were maintained in RPMI media, supplemented with 10% FBS, L‐glutamine, and antibiotics. 5 ×107 cells, were placed in a respirometer, containing 100μl of room air saturated buffer in the absence or presence of 1.35 g/dl HBOC‐201® (p50=26 torr @ 21.5ºC) or 1.35 g/dl HbA0 (p50= 6.9 @ 21.5ºC). Uncoupling 0.3μM carbonyl cyanide 4(tri‐fluoromethoxy) phenylhyrdrazone (FCCP) was used to trigger maximal mitochondrial VO2. The HBOC‘s oxygen dissociation curves were corrected for pH and temperature (J Appl Physiol. 94(2):561–6.2003). VO2 was defined as use of (free + bound) O2 divided by the time to full O2 depletion.Results:Untreated BPAECs had a VO2 of 3.09 ± 3.9 nmoles O2/min, which increased to 7.34 ± 5.1 with FCCP. The VO2 of BPAECs treated with HBOC‐201 was 6.69 ± 2.5 nmoles O2/min, which increased to 10.43 ± 9.1 with uncoupler. When 2,3‐DPG‐free human HbA0 was combined with FCCP the VO2 was 4.41 ± 2.3 nmoles O2/min, higher than basal control VO2 but lower than that in presence of HBOC‐201 + FCCP.Conclusion:Low oxygen affinity HBOC‐201 facilitates VO2 by BPAECS relative to high oxygen affinity HBOC preparations such as human HbA0.
Downregulation of mechanosensitive βENaC and γENaC in VSMCs in ASIC2 +/− mice
Authors: Gannon Kim P , VanLandingham Lauren G , Drummond Heather A 
Published: June 2021

Previously, we evaluated the importance of the mechanosensitive protein ASIC2 in pressure‐induced constriction (PIC) in middle cerebral arteries in the ASIC2 mouse model. ASIC2 +/+ and −/− mice developed similar PIC (16 ± 2 and 10 ± 3%, respectively at 90 mm Hg). However, surprisingly, ASIC2 +/− mice developed less PIC (4 ± 2%). Since previous reports indicate 1) β and γENaC also mediate PIC and 2) ENaC can interact with ASIC2, the goal of our study was to determine if reductions in mechanosensitive γ and γENaC protein might contribute to loss of PIC in ASIC2 +/− mice. To address this, we used quantitative immunolabeling for ASIC2, βENaC and γENaC in VSMCs from ASIC2 +/+, +/− and −/− mice. Fluorescence intensity (FI) was normalized for α‐actin and background subtracted (Fig. 1).We found β and γENaC were suppressed in +/−, and γENaC upregulated in −/− mice VSMCs, suggesting an interaction between βENaC, γENaC and ASIC2. Next, we used co‐immunoprecipitation and confirmed a biochemical interaction among βENaC, γENaC and ASIC2 in isolated vessels. These findings suggest the loss of PIC in ASIC2 +/− mice may also be dependent on inhibition of VSMC β and γENaC expression and recovery of PIC in ASIC2 −/− mice may be due to compensatory upregulation of γENaC. Our findings support the hypothesis that mechanosensitive ion channels initiating pressure‐induced constriction in VSMCs include βENaC, γENaC and ASIC2. Supported by AHA and NHLBI.
Galectin 3‐binding protein and clinical outcomes in patients with angiographically significant coronary artery disease
Authors: Gleissner Christian Albert , Smalley David M. , Keeley Ellen Catherine , Ley Klaus 
Published: June 2021

Galectin‐3 binding protein (G3BP) serum levels have been associated with cancer, viral infection and autoimmune disease. We found elevated G3BP levels in monocyte‐derived foam cells (RNA) and plasma‐ but not platelet‐derived microparticles (protein). We hypothesized that G3BP may represent a biomarker of severity and outcome in coronary artery disease (CAD).G3BP serum levels were measured by ELISA in 96 patients undergoing coronary angiography (58 male, age 63.6 ± 11.2 years), 79 of which had significant CAD (≥70% stenosis of epicardial vessels). Clinical follow‐up (up to 5 months) included myocardial infarction (MI), the need for revascularization, congestive heart failure, and death. Statistical analyses comprised Kruskal‐Wallis test, Pearson correlation, and multivariate analyses.The mean G3BP serum level was 10.37±6.5 mg/l. In multivariate testing, low G3BP levels predicted the combined outcome of the need for percutaneous or surgical revascularization in patients taking lipid‐lowering agents (OR 0.38, CI 0.17–0.87, p = 0.022), and this relationship remained strong after adjusting for CRP level (OR 0.46, CI 0.21–1.01, p = 0.052). Similar trends were seen for the combined endpoint of death or MI in patients with hypertension (OR 0.52, CI 0.25–1.10, p = 0.089), diabetes (OR 0.42, CI 0.17–1.06, p = 0.067), and those taking lipid‐lowering agents (OR 0.42, CI 0.15–1.16, p = 0.093).In summary, we propose that G3BP is a promising biomarker that appears to have predictive value in addition to that of CRP in patients with significant CAD. Additional studies analyzing larger numbers of patients will be needed to assess it potential role as a biomarker.
Sexual dimorphism in hypovolemic thirst induced by Furosemide and low sodium diet treatment (F/LSD)
Authors: Vivas Laura , Macchione Ana Fabiola , Dalmasso Carolina 
Published: June 2021

In a two‐bottle free choice test we investigated the F/LSD‐induced water and 2% NaCl intake in female (F), ovariectomized (FOVX) and male rats (M). We also studied estrogen receptor α immunoreactivity (ER‐α ir)and Fos‐ir in the subfornical organ (SFO) and median preoptic nucleus (MnPO), key areas involved in body fluid homeostasis.Before F/DBS treatment we found that salt preference (NaCl intake/NaCl + water intake) in F and FOVX was higher compared to M (p≤0.001). F/LSD‐induced depletion increased water intake in F versus FOVX and M (p≤0.001). However induced‐sodium appetite was similar in all groups.In the SFO, F/LSD increased Fos expression in F and M, but decreased Fos‐ir neurons in FOVX compared to non‐depleted rats (p≤0.001).Within the MnPO, Fos‐ir of control animals was higher in M and FOVX compared to F (p≤0.001). After F/LSD, Fos‐ir did not change in F, however we observed a decreased activation in both M and FOVX (p≤0.01).Regarding ER‐α, F/LSD increased the expression along SFO and MnPO only in F (p≤0.001). Besides, we found no differences after the treatment in both M and FOVX.Our data support previous evidence suggesting the MnPO as an inhibitor of water intake in males. We also shown the participation of ER‐αalong the SFO and MnPO after F/LSD treatment in females. In conclusion, we may suggest that hypovolemic thirst induced by F/LSD is a sexual dimorphic phenomenon.Supported by ANPCyT and CONICET.
Hepatic Stearoyl‐CoA Desaturase‐1 expression is required for Carbohydrate‐Induced Adiposity and Hepatic Steatosis
Authors: Ntambi James Mukasa , Flowers Matthew T. , Sampath Harini , Chu Kiki , Liu Xueqing , Miyazaki Makoto 
Published: June 2021

Stearoyl‐CoA desaturase is a delta‐9 desaturase that catalyzes the desaturation of saturated fatty acids into monounsaturated fatty acids, which serve as the preferred substrates for synthesis of numerous tissue lipids. It is also a critical regulator of energy metabolism and its expression is implicated in numerous human diseases that include obesity, non‐insulin‐dependent diabetes, hypertension, cardiovascular disease and immune disorders. We investigated the role of SCD1 in liver metabolism by generating mice with a liver‐specific knockout of Scd1 (LKO) using Cre‐lox technology. We found that unlike global SCD1 KO (GKO) mice, LKO mice fed high‐fat diet were not protected against obesity, hepatic steatosis, and whole‐body insulin resistance. On the other hand, LKO mice were protected from high‐carbohydrate diet‐induced adiposity and hepatic steatosis similar to GKO mice. The LKO mice displayed a marked decrease in the rate of lipogenesis with decreased expression of the nuclear contents of SREBP‐1 and ChREBP and their target genes. Oleate but not stearate supplementation to the high carbohydrate diet normalized adiposity, triglyceride secretion and hepatic lipogenesis of LKO mice. These results indicate that hepatic SCD1 expression, and thus oleate is required for carbohydrate‐induced adiposity and lipogenesis but loss of SCD1 activity in extra hepatic tissues is required to protect mice from high‐fat diet‐induced obesity and insulin resistance.Supported by NIH grant DK 62388.
Amygdala projecting solitary tract nucleus (NTS) neurons receive both direct and indirect cranial visceral afferent connections
Authors: McDougall Stuart J , Andresen Michael C 
Published: June 2021

The solitary tract nucleus (NTS) is the central site of cranial visceral afferent termination within the CNS. Information arrives in the NTS via the solitary tract (ST) and is broadcast to other brain regions including the amygdala. Little is known about the organization and processing of such information by forebrain projecting NTS neurons that likely contribute to complex behaviors. We aimed to determine how cranial visceral afferent information reaches amygdala projecting NTS neurons. In horizontal slices (250 μm) from rats previously stereotaxically injected with rhodamine beads into the central nucleus of the amygdala, retrogradely labeled cell bodies were found throughout caudal NTS. Shocks to the ST evoked postsynaptic currents (PSCs) in labeled neurons. Some amygdala projecting NTS neurons exhibited constant latency ST‐evoked excitatory PSCs with no failures, indicating monosynaptic ST contacts. The remaining neurons exhibited multiple glutamatergic and GABAergic PSCs with highly variable latencies and frequent failures – findings consistent with polysynaptic ST pathways. These preliminary data suggest that cranial visceral afferent nerves, including the vagus, connect differentially to amygdala projecting NTS neurons.Supported by: NHMRC of Australia (SJM ‐ C. J. Martin Fellow) and HL‐041119 (MCA).
Formation of signaling‐related oxidative base modifications in the hypoxic response element (HRE) of the VEGF gene in hypoxic pulmonary artery endothelial cells (PAECs) is associated with chromatin remodeling
Authors: Ruchko Mykhaylo V. , Gorodnya Olena , Pastukh Viktor M. , Gillespie Mark N. 
Published: June 2021

In PAECs, hypoxia causes oxidative DNA modifications in the HRE of the hypoxia‐inducible VEGF gene (FASEB J., 19:387–394, 2005). Because introduction of a base oxidation product mimicking the effect of hypoxia facilitated both transcription factor binding to the VEGF HRE and reporter gene expression, we proposed that hypoxia‐induced base modifications regulate VEGF expression. If this hypothesis is valid, then base oxidation products should be detected in the VEGF HRE upon transcriptional activation. Accordingly, DNA released from normoxic and hypoxic PAECs by micrococcal nuclease treatment was separated into transcriptionally‐active mono‐ and di‐nucleosomes and inactive multi‐nucleosomes. Southern blot analysis indicated that hypoxia‐induced VEGF mRNA expression was linked to redistribution of the HRE from multi‐nucleosomes to mono‐ and di‐nucleosome fractions. A simple PCR method showed that hypoxia‐induced base oxidation products in the VEGF HRE accumulated exclusively in the mono‐nucleosomal fraction. When redistribution of the VEGF HRE into mono‐nucleosomes was suppressed by a histone deacetylase inhibitor, formation of base oxidation products in the sequence was prevented. These findings suggest that hypoxia‐induced oxidative modifications targeted to specific nucleotides in the VEGF HRE are associated with chromatin remodeling and transcriptional activation.Supported by NIH.
TGF β‐1 mediated increase in Nox‐4 expression enhances hypoxic pulmonary vasoconstriction in bovine pulmonary arteries
Authors: Ahmad Mansoor , Zhao Xiangmin , Kelly Melissa R. , Kaminski Pawel M. , Wolin Michael S. 
Published: June 2021

Hypoxic pulmonary vasoconstriction (HPV) in de‐endothelialized bovine pulmonary arteries (BPA) is potentially mediated through lowering of superoxide derived peroxide and removal of its basal relaxing effect. Simultaneous force and peroxide measurements showed decreased peroxide levels preceding HPV. Peroxide scavenging with 0.1mM ebselen increased 25mM KCl force and attenuated HPV. BPA pretreated with copper chelator 10mM diethyldithiocarbamate (DETCA), for inactivating Cu Zn SOD, increased 5μM lucigenin‐detectable superoxide and decreased horseradish peroxidase‐luminol detectable peroxide. DETCA also increased 20mM KCl force and attenuated HPV. 48 hr culture of BPA with 10nM Transforming growth factor β‐1 (TGF β‐1) increased NAD(P)H oxidase‐4 (Nox‐4) expression along with superoxide and peroxide levels. 10μM plumbagin (Nox‐4 inhibitor) reversed the increase in superoxide and peroxide with TGF β‐1, however 100μM apocynin (Nox‐2 inhibitor) did not reverse the increased superoxide level. Also TGF β‐1 decreased 20mM KCl force and increased HPV in BPA. Thus, TGF β‐1 mediated increase in Nox‐4 resulted in higher levels of superoxide derived peroxide in BPA which increased HPV.NIH grants (HL31069/HL66331).
Effect of cardiovascular exercise on CRP levels in previously sedentary older men and women
Authors: Pence Brandt D. , Vieira Victoria J. , Baynard Tracy , Keylock K. Todd , Lowder Thomas W. , Woods Jeffrey A. 
Published: June 2021

Purpose:To assess changes in serum C‐reactive protein (CRP) with 10 mo of cardiovascular exercise training in sedentary 65–80 yr old subjects.Background:CRP is a clinical marker of systemic inflammation, and a chronic inflammatory state has been implicated in the pathogenesis of diseases including type 2 diabetes (T2D) and coronary heart disease (CHD), which are often found in aged persons.Methods:Sedentary male and female participants (n=120, 70 ± 1 years) were randomly assigned to 2 groups: a cardiovascular exercise group (EX; n = 61) and a flexibility/balance control group (CON; n = 59). EX subjects completed 10 mo of training (3x/wk walking, cycling, elliptical) at 65–70% VO2 max. CON subjects completed flexibility exercises 2x/wk to eliminate attention bias. Serum CRP was analyzed via an enzyme‐linked immunosorbant assay.Results:The EX group showed reduced CRP levels over the course of the intervention (3.66 ± 0.34 vs. 3.22 ± 0.36 mg·L−1; P < 0.01), with no reduction in CRP levels in the CON group (3.21 ± 0.28 vs. 3.31 ± 0.28 mg·L−1).Conclusion:Ten months of endurance exercise training reduced serum CRP in older subjects exhibiting elevated CRP levels. The reduction in CRP seen with cardiovascular exercise training suggests an overall decrease in systemic inflammation. This may contribute to the reduction in the risk of diseases such as T2D and CHD with exercise.Supported by R01 AG‐18861 to J.A. Woods