bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive list of sociodemographic, dietary and lifestyle factors has limited predictive power in determining RBC folate concentrations maximally protective against neural tube defects
Authors: Hartman Brenda , Hanley Anthony J , Aufreiter Susanne , Colapinto Cynthia K , Tremblay Mark S , O'Connor Deborah L 
Published: June 2021

Optimal maternal folate status is associated with a reduction in the occurrence of neural tube defects (NTD). Socio‐demographic and lifestyle factors collected as part of the Canadian Health Measures and the National Health and Examination Surveys account for less than 30% of the variation in RBC folate concentration, a measure of tissue stores. Using a comprehensive literature‐derived list of potential predictors of folate status, our aim was to re‐evaluate maternal socio‐demographic, dietary and lifestyle factors associated with a RBC folate maximally protective against NTD (≥906 nmol/L) to determine the feasibility of developing a tool that could be used by health clinicians to predict RBC folate ≥906 nmol/L. A Block food frequency questionnaire, and detailed additional questions on: dietary sources of folate; folic acid and B12 supplement intake; education; ethnicity; income; birth status; age, smoking; and alcohol use were collected from 101 women of reproductive age. Mean RBC folate was 849.9±264.6 nmol/L as determined by microbial assay; 39% had RBC folate concentrations ≥906 nmol/L. Only higher folic acid supplement intake had a positive association (OR=2.6; 95% CI 1.38, 4.9) with RBC folate ≥906 nmol/L while low alcohol intake was negatively associated (OR=0.3; 95% CI 0.09, 1.0). We conclude that use of a comprehensive list of factors did not improve the prediction of RBC folate protective against NTD.Grant Funding Source: CIHR (218776), NSERC (46513), and Hospital for Sick Children RTC Matching Funds Program (BH)
Effect of a flavonoid‐rich cacao extract on vascular reactivity in a mouse model
Authors: Castillo‐Hernández Karen Geneve , del Carmen Castillo‐Hernández María , Guevara‐Balcázar Gustavo , Coral‐Vázquez Ramón Mauricio 
Published: June 2021

BackgroundCardiovascular disease (CVD) is the second leading cause of death in Mexico in both women and men. Evidence based on epidemiological studies suggests that consumption of flavanolrich foods is inversely related to the development of CVD. It has been suggested that cacao flavonoids has positive effects on vascular system, and more specifically at the endothelial level.ObjectivesTo determine whether a treatment based on a flavonoid‐rich extract from Theobroma cacao beans could contribute to decrease the number of vasoconstrictions and improve vasodilator response in old mice.Materials and MethodsWe conducted an experimental, comparative, cross‐sectional study. Firstly ethanolic extraction was performed from Mexican Theobroma cacao beans, which was used for the experiments. We made two groups of mice (treated, untreated). Vascular reactivity was assessed with two experimental strategies: 1) Quantifying the presence of coronary artery vasoconstriction in both groups and 2) Evaluating the relaxant response to acetylcholine in an organ‐isolated system.ResultsThere were more vasoconstriction in the placebo group (no extract), and although there was no statistically significant difference (p = 0.4596), there was almost 50% less vasoconstrictions in mice treated with the extract. In evaluating the relaxant response to acetylcholine, the mice receiving the extract showed a relaxant concentration‐response that was significant at higher concentrations (p<0.01), unlike control mice.ConclusionsThrough the ethanolic extraction from Theobroma cacao beans we could obtain an extract rich in flavonoids. The administration of this extract improves endothelium‐dependent relaxant response in this animal model.Source of research support:CONACYT
Manganese supplementation reduces monocyte adhesion to endothelial cells by reducing ROS and downregulating ICAM‐1 independently of MnSOD
Authors: Burlet Elodie , Jain Sushil K 
Published: June 2021

Manganese (Mn2+ ) levels have been found to be lower in the plasma and lymphocytes of diabetic patients and in the heart and aortic tissue of patients with atherosclerosis. Studies in our laboratory have shown that Zucker diabetic fatty rats (ZDF) supplemented with Mn2+ had lower cholesterol (25%, p<0.05), ICAM‐1 (17%, p<0.04), and higher adiponectin (38%, p<0.01) levels in blood. Cell culture studies with Human Umbilical Vein Endothelial Cells (HUVECs) showed that Mn2+ supplementation reduces adhesion of monocytes to endothelial cells (ECs). This study examines the mechanisms by which Mn2+ supplementation decreases monocyte adhesion to ECs, a key event in the development of atherosclerosis. HUVECs were treated with Mn2+ (0, 5, 10 μM) for 24 hours, then exposed to high glucose (HG, 25 mM) for another 24 hrs. Results demonstrate that Mn2+ supplementation decreases ICAM‐1 surface (20%, p<0.05) and total expression (65%, p<0.005), MCP‐1 secretion (16%, p<0.05), and ROS levels (21%, p<0.02) in HG‐treated HUVECs. Silencing studies using siRNA against MnSOD showed that similar effects of Mn2+ on ICAM‐1 expression and ROS were observed in MnSOD knockdown HUVECs. This study suggests that Mn2+ supplementation can decrease monocyte adhesion to ECs, and thereby delay progression of atherosclerosis in diabetes, by decreasing ROS, MCP‐1 secretion, and ICAM‐1 expression, independently of MnSOD.Grant Funding Source: NIDDK and Office of Dietary Supplements
Physiological Responses to Caffeine are Moderated by Sex and Pubertal Phase
Authors: Ziegler Amanda M. , Graczyk Adam , Bendlin Ashley , Vattana Karina , Sion Teresa , O'Leary Shannon , Temple Jennifer L. 
Published: June 2021

ObjectivesThe purpose of the study was to determine whether sex differences in response to caffeine are related to puberty and menstrual cycle phase.MethodsMale and female participants (n=101), ages 8–9 and 15–17, had heart rate (HR) and blood pressure measured every 10min for 1hr after drinking a beverage containing placebo, or caffeine (1 mg/kg and 2 mg/kg). Participants received each treatment once during the first three visits and again two weeks later. Post‐pubertal girls began the first three visits 5–9 days after menstruation and the final three visits 5–9 days after ovulation.ResultsCaffeine treatment increased systolic blood pressure (SBP) and decreased heart rate based on dose. Pre pubertal children had greater decreases in HR than post pubertal children at the 2 mg/kg dose. In post pubertal participants only, sex differences in HR occurred while females were in the luteal phase, but not during the follicular phase. There was also an interaction of sex, pubertal phase, and caffeine treatment on SBP. Specifically, SBP increased for post pubertal males at 1mg/kg and 2mg/kg caffeine doses, but SBP increased for post‐pubertal females only after 2mg/kg caffeine treatment and only during the luteal phase.ConclusionsOur findings confirm previous studies that show that caffeine increases blood pressure and decrease heart rate. These effects are moderated by pubertal phase, sex, and menstrual cycle phase.
Identification of resveratrol‐3‐β‐glucoside in California almond varieties
Authors: Xie Liyang , Bolling Bradley 
Published: June 2021

Stilbenes have been identified in grapes, blueberries, peanuts and pistachios, but little is known about its abundance in other polyphenol‐rich foods, such as almonds. Therefore, the objective of this study was to screen Nonpareil, Butte and Carmel almond varieties from California for the presence of stilbenes (n = 3 samples/variety). Stilbenes were determined in ethanolic almond extracts by UPLC‐MS. Instrument conditions were optimized for quantitation of polydatin, piceatannol, resveratrol, pterostilbene, and oxyresveratrol. Polydatin, resveratrol‐3‐β‐glucoside, was identified in almond extracts, with mean contents of 7.19, 8.52 and 7.44 μg/100 g almond in Nonpareil, Butte and Carmel, varieties respectively. Among all varieties, polydatin was concentrated in almond skins, which accounted for 95.6–97.5% of total almond polydatin content. Other stilbenes were not detected in almond extracts. Therefore, almonds contain stilbenes in addition to the previously identified polyphenol classes of proanthocyanidins, hydrolyzable tannins, flavonols, and phenolic acids. This work was supported by the Almond Board of California.Grant Funding Source: Almond Board of California
Reactive Oxygen Species and Electron Flow Are Needed to Oxidize Cytochrome c at the Methionine Residues
Authors: Aluri Hema S. , Chen Qun , Hu Ying , Lesnefsky Edward J. 
Published: June 2021

ObjectiveWe hypothesize that during oxidative stress, an increase in intra‐mitochondrial reactive oxygen species (ROS) generation coupled with electron flow into the cytochrome c (cyt c) segment of the electron transport chain (ETC) is required to modify cyt c at key methionine residues, including methionine 81 (Met‐81) that forms a neo‐peroxidase activity catalyzing the oxidation of cardiolipin.MethodsMitochondria were isolated from C57BL6 mice (MITO). MITO were incubated with specific substrates and inhibitors to isolate segments of the ETC: (1) succinate + rotenone; (2) succinate + rotenone + Thenoyltrifluoroacetone (TTFA) (3) succinate + rotenone + antimycin A (4) succinate + rotenone + azide. Following incubations, cyt c was immunocaptured and methionine sulfoxide [Met (O)], a marker of methionine oxidation, including at Met‐81, was assessed using immunoblotting, normalized to cyt c content.Results

ETC Blockers incubated with MITO, succinate and rotenone
Conditions cyt c exposed to
fold increase compared to succinate + rotenone

Control: No blocker
none
1.0±0.0

Complex II: TTFA
ROS
1.03±0.38

Complex III: A.A
ROS
0.87±0.16

Complex IV: Azide
ROS, electron flow
3.5±1.1*

N=5–7; Mean ± SEM; one‐way ANOVA;
p<0.05 vs. no blocker

ConclusionsFrom the MITO incubations, it is clear that both ROS and electron flow into the cyt c segment are required for methionine oxidation and the likely formation of cyt c peroxidase. Supported by Research Service, Department of Veterans Affairs and the Pauley Heart Center of Virginia Commonwealth University.
Identification of PKM2 Interacting Proteins by Tandem Mass Spectrometry
Authors: Hwang Steven Ray , McDonnell Scott RP , Basrur Venkatesh , Conlon Kevin P , Fermin Damian , Murga‐Zamalloa Carlos , Elenitoba‐Johnson Kojo SJ , Lim Megan S 
Published: June 2021

Pyruvate Kinase M2 (PKM2) plays a key role in aerobic glycolysis and the metabolic phenotype that is critical for cancer cell growth and proliferation. Recent studies have demonstrated that PKM2 may have nonmetabolic functions like regulation of gene transcription and protein phosphorylation. We hypothesized that liquid chromatography tandem mass spectrometry (LC‐MS/MS) “interactome” analysis of PKM2 will identify additional functional roles of PKM2. We carried out immunoprecipitation (IP) of DEL cells stably expressing FLAG‐tagged wild type (WT) PKM2 and the Y105F mutated PKM2 (glycolytically active) and subjected the IP to LC‐MS/MS. A total of 274 proteins were detected in the WT PKM2 pull down. There were 57 proteins unique to WT PKM2 relative to the Y105F PKM2 mutant. We carried out validation via IP and western blot for three proteins involved in RNA metabolism and gene regulation (HMGA1, RNF20, and PTBP1). Interaction of these proteins was predominantly detected with the WT isoform and not the Y105F isoform. DAVID analysis showed that WT PKM2 interacted more with proteins involved in nuclear functions such as RNA metabolism and gene expression than its mutated counterpart. Our results indicate that PKM2 may have a role in RNA metabolism and gene regulation through its interaction with HMGA1, RNF20, and PTBP1.Funding support comes from the University of Michigan, Department of Pathology development funds.
mTOR inhibition leads to decrease of breast cancer progression in vitro via cytoskeleton remodeling
Authors: Cherednyk Olga , Khoruzhenko Antonina , Kosach Viktoria , Filonenko Valeriy 
Published: June 2021

Kinase mTOR is one of the main links in signal transduction from variety of growth factors/hormones into the cell. Earlier it was shown its overactivation in numerous of cancers. mTOR inhibitors are regarded as antitumor drugs.Immuunofluorescent analysis was applied to detect subcellular localization of mTOR in MCF‐7 cells and human breast tumor. The effect of rapamycin on cultured cells was tested by MTT‐test, migration, adhesion/spreading assay, zymography, actin detection with falloidin, confocal microscopy.Cell behavior under the condition of inhibited mTOR activity was analyzed in vitro. It was revealed decrease of MMP‐9 activity, cell adhesion (up to 40%), cell spreading, migration in “wound healing” model (up to 80%). It was shown the apparent change in actin cytoskeleton organization in paranuclear space.Detection of mTOR localization with anti N‐terminal antibodies revealed a stained network in cells. Confocal microscopy analysis shown a strong colocalization of mTOR and intermediated filaments in MCF‐7 and Hela as well at histological sections of normal and malignant breast tissue.The effect of mTOR activity inhibition on cell behavior can be explained by its relation with cytoskeleton.
Activation of the G(s) heterotrimer monitored in living cells with novel G(s) biosensors
Authors: Yano Hideaki , Provasi Davide , Filizola Marta , Ferre Sergi , Javitch Jonathan A 
Published: June 2021

Our understanding of conformational changes associated with receptor activation has been advanced profoundly by the crystal structure of agonist‐bound β2 adrenergic receptor (β2AR) coupled to G(s). However, there is uncertainty regarding the extent to which conformational changes in G protein are conserved in living cells as well as across different receptors.We set out to understand the movement of the G(s) heterotrimer after activation of β2AR in intact cells. Using bioluminescence resonance energy transfer, we made observations on movement within the G protein and between the receptor and the G protein. Using a library of novel G(s) biosensors with either luciferase or GFP inserted at various positions throughout the structure, we studied conformational changes in cells and compared the results to the crystal structures of the inactive and active conformations. We also studied conformational changes in G(s) protein induced by the D1 dopamine receptor and A2A adenosine receptor.Our analysis using these G(s) biosensors suggests that conformational changes within the G(s) heterotrimer are largely conserved among different G(s)‐coupling receptors. Using this set of G(s) biosensors, partiality of agonists can be studied in relation to structural changes and subsequent effector activation. Thus, these biosensors represent a novel pharmacological tool to study structure‐function relationships.
Induction of CXCR7 Switches SDF‐1 Signaling and Phagocytic Function in Macrophages: a Potential Role in Atherosclerosis
Authors: Ma Wanshu , Liu Yiwei , Ellison Nicholas , Shen Jianzhong 
Published: June 2021

ObjectiveThe discovery of CXCR7 as a new receptor for SDF‐1 places many previously described SDF‐1 functions attributed to CXCR4 in question, though whether CXCR7 acts as a signaling or “decoy” receptor has been in debate. It is known that CXCR7 is not expressed in normal blood leukocytes; however, the potential role of leukocyte CXCR7 in disease states has not been addressed.Methods and ResultsWe show that CXCR7 was detected in macrophage‐positive area of aortic atheroma of ApoE‐null mice, but not in healthy aorta. During monocyte‐to‐macrophage differentiation, CXCR7 was up‐regulated at mRNA and protein levels, with more expression in M1 than in M2 phenotype. In addition, CXCR7 induction was associated with a SDF‐1 signaling switch from pro‐survival ERK and AKT pathways in monocytes to pro‐inflammatory JNK and p38 pathways in macrophages. The latter effect was mimicked by a CXCR7‐selective agonist TC14012 and abolished by siRNA knockdown of CXCR7. Furthermore, CXCR7 activation increased macrophage phagocytic activity, which was suppressed by CXCR7 siRNA silencing or by inhibiting either the JNK or p38 pathways.ConclusionsCXCR7 is induced during monocyte‐to‐macrophage differentiation, which is required for SDF‐1 signaling to JNK and p38 pathways, leading to enhanced macrophage phagocytosis, thus possibly contributing to atherogenesis.
Bioenergetic immunostimulation, metabolism, and nutrition support in lung cancer: a case study
Authors: TULP ORIEN LEE , Einstein George P , Kowaleski Janusz , Dancewicz Maciej 
Published: June 2021

The most common type of cancer [Ca]in the USA is lung Ca, where it contributes to >; 150,000 deaths annually despite many advances in early diagnosis and treatment modalities. The patient was a 64 y.o. WM, no prior Hx of Ca or other major illness. Patient underwent lobectomy of a 5.4 cm mass R lung which confirmed Ca, followed by a vigorous bioenergetics regimen including Nutritional [macrobiotic: 65% mixed grains, 20% mixed veg, 15% fruits, exercise [<800 m swimming daily], and maintaining a positive attitude. Pt resumed full time work after 2 w, and remains Ca‐free and in excellent health at 7 y followup.ConclusionPatients require adequate nutritional, physical and emotional Rx following lobectomy for lung Ca. Bioenergic Rx may result in improved CD4, CD25, & T cell function and decrease mortality & improve survival in Lung Ca. Institutional Support.
Effects of popcorn butter flavorings, diacetyl and 2,3‐pentanedione, on isolated airway preparations
Authors: Zaccone Eric J , Thompson Janet A , Shimko Michael J , Fedan Jeffrey S 
Published: June 2021

RATIONALE“Popcorn workers’ lung” is a life‐threatening, fixed obstructive pulmonary disease caused by inhalation of butter flavoring vapor. Histological evidence from animals exposed by inhalation to the butter flavorings, diacetyl (2,3‐butanedione), and a diacetyl substitute, 2,3‐pentanedione (acetyl proprionyl), demonstrated vapor‐concentration‐dependent damage to epithelial cells. Because nothing is known about the effects of diacetyl and 2,3‐pentanedione on airway smooth muscle (ASM), we investigated the pharmacological activity of these two flavorings on isolated airways.METHODSIn rat isolated, perfused tracheas, the contractile and relaxant effects of diacetyl and 2,3‐pentanedione applied to the serosal and mucosal surfaces of intact and denuded contracted (MCh; 3×10−5 M) tracheas were evaluated.RESULTSConcentrations of both agents greater than 3 mM resulted in ASM relaxation. Relaxation of the trachea by diacetyl and 2,3‐pentanedione was not dependent upon the presence of the epithelium.CONCLUSIONSOur findings indicate that both flavorings are similar in their effects as ASM relaxants.
Protein Carbonylation Regulates Renal Proximal Tubular Na/K‐ATPase signaling and Sodium Transport
Authors: YAN YANLING , Xie Zi‐jian , Shapiro Joseph I. , Liu Jiang 
Published: June 2021

We have shown that cardiotonic steroids signaling through the Na/K‐ATPase regulate sodium reabsorption in renal proximal tubule (RPT). Here we report that protein carbonylation is critical in modulation of Na/K‐ATPase signaling and RPT ion transport. In RPT LLC‐PK1 cells, both ouabain (100nM) and glucose oxidase (GO, 1 and 3mU/ml) stimulated protein carbonylation of Na/K‐ATPase α1 subunit and c‐Src, activated c‐Src, stimulated redistribution of Na/K‐ATPase α1 and NHE3, and inhibited active transepithelial 22Na+ flux. Pretreatment with the antioxidant, N‐Acetyl‐L‐Cysteine (NAC), can prevent these effects in a dose‐dependent manner. Furthermore, disruption of the Na/K‐ATPase/c‐ Src signaling complex and c‐Src inhibitor PP2 abolished ouabain‐induced ROS generation and protein carbonylation. Moreover, it appears that there is a self‐regulatory mechanism to reverse carbonylation after removal of ouabain from culture medium, evaluated in the presence of protein biosynthesis inhibitor cycloheximide, proteasome inhibitor MG132, and lysosomotropic weak base agent chloroquine.In summary, our data indicated that protein carbonylation is involved in a feed‐forward mechanism in regulation of Na/K‐ATPase/ c‐Src signaling and related sodium transport. The data also suggested that the Na/K‐ATPase/c‐Src signaling might be a functional receptor of ROS. (Supported by NIH HL‐109015 to Z.X. and J.I.S.).
What is the physiological relevance of the renal H,K‐ATPase type 2? Example of K+ reabsorption during K+ depletion, gestation and circadian rhythm.
Authors: Crambert Gilles , Lamouroux Christine , Salhi Amel 
Published: June 2021

The existence of a renal “nongastric” H,K‐ATPase (HKA2) has been puzzling for decades. Indeed, whereas its stimulation in response to K+ depletion is well established, HKA2 null‐mice do not display a clear renal phenotype under these conditions. This last result had raised doubts about its physiological relevance until now and we started to revisit this problematic. Recently, we identified progesterone as an adrenal mediator that is produced in response to K+ depletion and that activates the renal expression of HKA2. In this situation, acutely preventing progesterone from acting abolishes the stimulation of HKA2 and leads to a higher urinary K+ loss. This finding led us to investigate the role of renal HKA2 during pregnancy. We indeed found that the renal HKA2 is stimulated during gestation and that its absence, in the HKA2‐null mice, leads to gestational problems (decreased fertility, increased maternal mortality) that correlate with an impaired K+ balance. Finally, we identified the renal HKA2 as a component of the renal adaptation to the circadian rhythm, which allows the organism to maintain stable the plasma K+ levels during rest periods by mediating K+ reabsorption when K+ intake is low.These recent results indicate that the renal HKA2 is not an epiphenomenon and plays important physiological roles.
Water drinking enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in healthy humans
Authors: Vianna Lauro C , Fernandes Igor A , Martinez Daniel G , Silva Bruno M , Fadel Paul J , Nobrega Antonio C 
Published: June 2021

Water drinking increases efferent sympathetic outflow in young healthy subjects in the absence of a pressor response, whereas in autonomic failure patients and healthy older adults water‐induced sympatho‐excitation is accompanied by a large pressor response. The extent to which the arterial baroreflex (ABR) buffers the blood pressure (BP) response to water intake is unclear. We tested the hypothesis that water drinking increases ABR control of muscle sympathetic nerve activity (MSNA) in young healthy subjects. MSNA (microneurography) and arterial BP (Finometer) were measured in 8 men (24 ± 1 yrs) before, and for 60 min after drinking 500 mL of room‐temperature (22°C) tap water or saline. Weighted linear regression analysis between MSNA and diastolic BP was used to assess spontaneous ABR MSNA gain. As expected, MSNA was elevated after water intake (22 ± 4 baseline to 36 ± 5 bursts/100 heart beats at 30 min, P<0.05) and BP was unchanged. ABR MSNA gain for burst incidence (−2.4 ± 0.3 baseline vs. −4.4 ± 0.6 bursts/100 heart beats/mmHg at 30 min; P<0.05) and total MSNA (−3.6 ± 0.8 baseline vs. −5.6 ± 0.8 au/beat/mmHg at 30 min; P<0.05) were increased and tended to return to baseline at 60 min. ABR‐MSNA gain remained unchanged following saline intake. These data indicate that ABR MSNA gain is enhanced following water intake in healthy young subjects, which likely contributes to the maintenance of BP.Supported by CAPES, CNPq & FAPERJ