bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autooxidation Properties of Mycobacterium tuberculosis DevS and Impact of the Y171F Mutation on Gas Binding Kinetics
Authors: Ioanoviciu Alexandra Smaranda , Meharenna Yergalem , Poulos Thomas , Ortiz de Montellano Paul 
Published: June 2021

In Mycobacterium tuberculosis, DevS is responsible for DevR activation in conjunction with DosT. Exposure to unfavorable stimuli is translated via the DevS/DevR two‐component system into the expression of genes of the "dormancy regulon." The DevS kinase activity is modulated by the binding of nitric oxide, carbon monoxide, and oxygen to the heme iron. We have cloned and characterized both wild‐type DevS and the Y171F mutant. Mutation of tyrosine 171 to a phenyl alanine was previously shown to impact kinase activity.In the present study we examine diatomic gas binding kinetics to wild‐type DevS and Y171F DevS using stopped‐flow combined with UV‐visible spectroscopy and laser flash photolysis. The Y171F mutation increases the on‐rates of carbon monoxide and oxygen, probably due to the requirement for displacement of a hydrogen bonded water molecule located in the distal heme cavity of the reduced wild‐type protein.In addition, we examine the stability of the wild‐type DevS oxy‐complex in the presence of ubiquitous metal cations. Oxy‐DevS is stable to autooxidation, suggesting that it functions as a gas and not redox sensor in vivo.This work was supported by the National Institutes of Health through grant AI074824.
PAC‐1: A novel therapeutic approach to procaspase activation
Authors: Peterson Quinn Patrick , Hsu Danny , Goode David R , West Diana C , Ramsey Kara N , Hergenrother Paul J 
Published: June 2021

The recent emergence of proapoptotic small molecules as powerful anti‐cancer agents allows for the direct induction of apoptotic pathways. Central to these pathways is the activation of executioner caspases responsible for the proteolysis of a host of cellular substrates. This vital role presents caspases as a promising new target in the search for new chemotherapeutic agents.In a screen for small molecule activators of procaspase‐3, a novel compound, PAC‐1, was identified [Nature Chem. Biol. 2006, 2, 543]. The compound was shown to activate procaspase‐3 to caspase‐3 in vitro, kill cancer cells in culture and inhibit tumor growth in mouse xenograft models. Current work has elucidated the in vitro mechanism of action of PAC‐1 mediated activation of procaspase‐3, and has explored the effect of metal ions on procaspase activation. In addition, to further investigate the PAC‐1 mechanism of action we synthesized several derivatives to probe the structure‐activity relationship of this family of compounds. The ability of these derivatives to activate PAC‐1 sheds further light on the PAC‐1 mechanism of action and suggests means for the chemical optimization of this anti‐cancer agent.
Use of Artificial Nipple (Pacifier or Bottle) and Duration of Breastfeeding in Term Infants
Authors: Chung Mei , DellaValle Diane M , Yu Winifred W 
Published: June 2021

BackgroundBreast milk is the natural nutrition for all infants. Evidence suggests that breastfeeding (BF) decreases various disease risks for infants and mothers.MethodsSystematic review (SR) of all English‐language randomized controlled trials (RCTs), prospective cohorts (PCs), and SRs examining the use of artificial nipples and outcomes of BF duration in term infants (=35 weeks of gestation) published from 1985 to March 2008.Data SynthesisA total of 12 primary studies and 1 positive‐quality SR (with 9 PCs) were analyzed. Seven PCs consistently showed that use of pacifier was associated with shorter BF duration after controlling for potential confounders (adjusted rate ratio/hazard ratio of shorter BF duration ranged from 1.4 to 2.9 across studies), although the definitions of pacifier use varied across these studies. This is consistent with the findings from the prior SR. Additionally, the results from 2 RCTs and 3 cohort studies suggested that supplementary feedings (formula, water/tea, or expressed breast milk) using bottles or cups shorten BF duration compared to no supplementary feeding.ConclusionsEvidence suggests a negative impact of artificial nipple on the duration of all types of BF (from partial to exclusive). Observational evidence consistently showed an association between use of pacifier before 3 months of age and shorter BF duration in healthy term infants after controlling for potential confounding. Whether increasing frequencies or introduction of artificial nipple use beyond 3 months of age has differential impacts on BF duration is still unclear. Well‐designed RCTs with blinded assessments of BF outcomes and specifying the amount and frequency of artificial nipple use are needed to further support the validity of these findings.Grant Funding SourceADA Evidence Analysis Library
Resting energy expenditure of female adolescents with phenylketonuria: agreement of predictive equations
Authors: Quirk Meghan Elise , Schmotzer Brian , Singh Rani H. 
Published: June 2021

ObjectiveTo determine the agreement of clinically‐used, predictive equations with measured resting energy expenditure (MREE) in a group of female adolescents with phenylketonuria (PKU).MethodsMREE was measured by indirect calorimetry in 36 female adolescents (11.5‐18.7 y) with PKU. Eight predicted resting energy expenditure values were calculated from published equations for each subject and compared to MREE. The level of agreement was determined using Bland‐Altman and regression‐based methods.ResultsMREE was greater than predicted values, on average, for each equation (each p<0.005). The Schofield equation based on weight had the lowest mean underestimation of MREE (144 kcal), the largest concordance coefficient (0.626), and the most observations within +/‐10% of MREE (38.9%).ConclusionsPredictive equations underestimate MREE in female adolescents with PKU. Of the eight equations evaluated, the Schofield equation based on weight had the highest level of agreement with MREE. Accuracy at the individual level was affected by systematic bias and interpersonal variability.Funded by private donations and Emory University Hospital General Clinical Research Center.
Association between dietary patterns and overweight/obesity in Mexican school children
Authors: Rodriguez Sonia , Mundo‐Rosas Verónica , García‐Guerra Armando , Shamah‐Levy Teresa 
Published: June 2021

ObjectiveTo identify dietary patterns and to evaluate their association with overweight/obesity (OW/OB) in Mexican school children.MethodsDietary patterns were defined by k‐means cluster analysis based on a 7 day semi‐quantitative FFQ from 8252 children (5 to 11 y old) from the Mexican National Health and Nutrition Survey (2006). Weight and height were measured and OW/OB prevalence was estimated with BMI. A logistic regression analysis was used to evaluate the association of dietary pattern with OW/OB adjusting by age, dwelling (rural or urban) and survey design. After logistic regression analysis, the estimation of prevalence ratio was estimated.ResultsFive dietary patterns were identified: pattern 1 (high consumption of sweet cereals), pattern 2 (high consumption of tortillas), pattern 3 (high consumption of sweet beverages, meat and candies) pattern 4 (high consumption of sweet beverage, snacks, fat), and pattern 5 (high consumption of milk and candies). The global prevalence of OW/OB in children was 25.5%. Pattern 4 was associated with more risk of OW/OB (PR=1.35, p<0.01). Patterns 1, 3, and 5 showed trend to increase the risk of OW/OB, but no significant differences were showed.ConclusionsA dietary pattern with high consumption of sweet beverages, snacks and fat was associated with increased risk of overweight and obesity in Mexican school children.
Sociodemographic disparities in adiposity distribution shifts in American children and adolescents
Authors: Wang Youfa , Beydoun May A. 
Published: June 2021

While obesity prevalence in USA has been increasing, shifts in various adiposity measures may vary across socio‐demographic groups. We assessed over time distributional shifts in BMI, waist circumference (WC) and triceps skinfold thickness (TST); tested age, sex, ethnic‐differences and changes in associations between adiposity measures and family income; used nationally representative NHANES data (1988‐94; 1999‐04); estimated overall‐ and percentile group‐specific means and mean yearly shifts. Linear models assessed secular changes in associations. Mean 10‐y increases in these adiposity measures were statistically significant, varied by sex, age, ethnicity and population adiposity distributions. Mean BMI increased by 0.8‐0.9 kg/m2; WC increased by 3.3‐3.6 cm; TST, by 0.9‐1.3 mm. Ethnic, age, sex disparities in mean BMI became wider over time (eg, girls, 0.8 in blacks vs. 1.3 in whites). Major increases in these adiposity measures were mostly noted in upper percentiles in adolescents. BMI's association with WC became significantly stronger only in whites. Association between family income and TST/BMI ratio weakened in blacks. The rise in adiposity in US young people was unequally distributed across groups and the shifts varied across the spectrum of various adiposity measures. Solely examining changes in obesity/overweight rates based on BMI could not capture the complex patterns.This study is supported by the NIH (NIDDK R01 DK63383).
Prolonged red wine consumption changes hepatic redox status and inflammation
Authors: Pestana Diogo , Monteiro Rosário , Faria Ana , Calhau Conceição , Azevedo Isabel 
Published: June 2021

To understand the utility of red wine (RW) in the prevention of oxidative stress‐related diseases we investigated its effect on hepatic redox status and inflammation and determined the involvement of procyanidins in the effects. Groups of 5 male Wistar rats were treated with: water (control, C); aqueous procyanidin solution (PW, 200 mg/L); 13% ethanol (E); alcoholic procyanidin solution (PE, 200 mg/L of 13% ethanol); or RW (with 13% ethanol). Lipid, protein and DNA oxidation, glutathione status and the activity of enzymatic antioxidant defenses were determined in liver homogenates. Enzyme expression was assessed by RT‐PCR and NFκB activation by ELISA. RW prevented protein oxidation and changed glutathione (GSH) status and enzymatic antioxidant defenses. PE and RW treatments increased GSH synthetase expression (when compared to E). GSH reductase expression was decreased in all groups, while GSH peroxidase was decreased by PE and increased by RW. RW increased NFκB although TNFα was unchanged in RW group and reduced by PE. In conclusion, chronic consumption of RW altered hepatic redox status, its effects being partially justified by procyanidins in an alcoholic matrix. Ethanol seems critical for the effects of procyanidins, highlighting the importance of food matrix for the effects of these compounds.Supported by FCT (PTDC/QUI/65501/2006, SFRH/BPD/40110/2007) and Instituto de Bebidas e Saúde (iBeSa).
Resistant Starch reduces postprandial glycemic and insulinemic response and increases satiety in humans
Authors: Kendall Cyril , Esfahani Amin , Sanders Lisa , Potter Susan , Jenkins David 
Published: June 2021

ObjectiveTo assess the dose‐response effect of adding resistant starch to drinks on postprandial glycemia, insulinemia, satiety and post‐load ad libitum food intake.Methods22 healthy "unrestrained eaters" (13 male, 9 female, age 26±4y; BMI 23.7±2.4kg/m²) consumed meals containing 0g, 5g, 15g and 25g of PROMITOR(tm) RS in a randomized, double blind, crossover study. Using a visual analogue scale (VAS), subjects rated their satiety level and symptoms at 0, 15, 30, 45, 60, 90 and 120 min after eating. Blood samples were taken simultaneously. Using the satiety ratings, the satiety quotient and appetite score were calculated. Two hours after eating, subjects were given an ad libitum meal and total energy intake was recorded.ResultsAll meals were well tolerated and no significant adverse symptoms were reported. Compared to the control, the 25g dose of RS resulted in significantly lower blood glucose (P≤0.002) and serum insulin levels at 90min and 120 min. In addition the satiety quotient for mean appetite score for the 25g RS dose was significantly higher (P≤0.05) compared to the control at 15min and 45 min. However second meal ad libitum meal total energy intake was not different between treatments.ConclusionsThe inclusion of RS may effectively reduce the postprandial glycemic and insulinemic response of meals and increase satiety without adverse symptoms.
Mutual Interaction of Prostate Carcinoma And Benign Prostate Hyperplasia Cells With Human Lymphocyte Mononuclear Cells – Modulation of Parameters of Innate Immunity by PPAR‐gamma ligands
Authors: Koenig Wolfgang , Allhoff Ernst Peter , Ghebremedhin Beniam , Koenig Brigitte , Tammer Ina , Koenig Jens Ekkehard 
Published: June 2021

We studied the mutual interaction of human lymphocyte mononuclear cells on co‐incubation with prostate carcinoma (PCA) and BPH cells in the presence of 15d‐PGJ2 and glitazones (troglitazone, ciglitazone). The cells were stimulated with growth factors (VEGF, EGF, HGF, IGF, FGF) at various concentrations (1‐100 ng). PPAR‐gamma ligands at various concentrations were either added prior to or after co‐incubation with PCA and BPH cells for 24 hours; the release of mediators (IL‐6, IL‐8, TNF‐alpha, VEGF, TGF‐beta, PGE2) was studied by Elisa; RT‐PCR and Taqman analysis were applied for the analysis of parameters of innate immunity, e. g. p22‐, 47‐, 67‐, gp91‐phox, cysteinylleukotriene receptors 1, 2, protease activated receptors (PAR1‐4), toll‐like receptors (TLR2, 4, 9), COX2, CD14, TRAF6, MD2, MYD88, CXCR2.Our results show: 1) Human lymphocyte mononuclear cells modulate various parameters of innate immunity on carcinoma as well as BPH cells after co‐incubation. 2) PPAR‐gamma‐ligands interact differently when given prior or after co‐incubation of tumor cells with human lymphocyte mononuclear cells. 3) Differences in pro‐ and antiinflammatory responses depend on the individual cell line as well as the stimulus via differences in cellular signal transduction. The results suggest a potential use of PPAR‐gamma‐ligands to dampen inflammation and potentially tumor development.
Na+/H+ exchanger isoform NHE3 and NHERF adaptor protein expression, localization and function in the small and large intestine of CD45RB high transfer colitis
Authors: Yeruva Sunil , Goldstein Julia , Lünnemann Maria , Chen Mingmin , Singh Anurag kumar , Riederer Brigitte , Gereke Marcus , Bruder Dunja , Manns Michael peter , Seidler Ursula 
Published: June 2021

BackroundThe molecular mechanisms for inflammatory diarrhea are multifactorial and incompletely understood.AimWe investigated the expression, localization and function of the major intestinal sodium absorptive transporter, the Na+/H+ exchanger NHE3, as well as its regulatory PDZ‐adapter proteins NHERF1 and PDZK1, in the small and large intestine of mice after induction of a CD45RBhigh transfer colitis.ResultsAfter colitis induction, TNF‐alpha levels were increased both in the inflamed colon and microscopically normal‐appearing small intestine. NHE3 mRNA expression was upregulated in the colon and unaltered in the small intestine, NHE3 protein expression and localization in the brush border membrane (BBM) was not altered, but acid‐activated NHE3 transport rates in small intestinal villous and colonic surface cells were severely decreased, and fluid absorption in vivo was decreased in the small intestine. PDZK1 mRNA expression was downregulated, whereas that of NHERF1 was not altered. Glucocorticoid treatment of colitic mice for 4 days decreased colonic mucosal cytokine expression and increased PDZK1 expression as well as fluid absorption.ConclusionWe suggest that during immune‐mediated intestinal inflammation, NHE3 BBM protein abundance is normal, but the regulation of its transport activity is disturbed. PDZK1 downregulation during inflammation may be one factor responsible for inflammation‐associated NHE3 dysfunction
MMP activation peptide detection in biological samples as a diagnostic marker of idiopathic pulmonary fibrosis
Authors: Voeghtly Laura M , Kaminski Naftali , Oury Tim D 
Published: June 2021

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown etiology. Historically, IPF has been seen as a gradually progressive disease. However some patients with IPF experience acute exacerbations of IPF characterized by a rapid deterioration of lung function and accelerated death. Matrix metalloproteases (MMPs) are a family of proteases that regulate extracellular matrix turnover. Some MMPs have been shown to be upregulated in IPF and these MMPs are thought to directly contribute to disease progression. MMPs are proteases that are subject to inhibition once activated. The inhibited complexes are rapidly cleared preventing accurate biological detection of MMP activation. In contrast, the mechanism of clearance of the activation peptides released from the MMPs is unknown.ELISA experiments show that the activation peptides of MMP2, MMP7, and MMP9 are elevated in the urine of mice with pulmonary fibrosis compared to WT mice and in the urine of human patients with IPF compared to healthy controls. These data suggest that urine detection of MMP activation peptides is feasible and correlates with disease. Because MMP activation contributes to disease initiation and progression, we hypothesize that the accurate detection of the activation of these proteases will be relevant clinically and may allow for earlier detection of disease as well as allow for prediction of acute exacerbations.
Pro‐inflammatory cytokines characterize vulnerable carotid atherosclerotic plaques
Authors: Bazan Hernan Antonio , Sam Albert D , Sheahan Malachi , Abbruscato Frank 
Published: June 2021

The mechanisms involved in the transition from a stable to an unstable or vulnerable carotid atherosclerotic plaque are not clearly understood. We sought to test the hypothesis that pro‐inflammatory cytokines are related to carotid plaque instability and thus their modulation might be related to the prevention of stroke. Patients with at least 50% internal carotid artery stenosis undergoing carotid endarterectomy were included in this study; plaque stability was determined on the basis of clinical criteria and confirmed histologically. Intra‐plaque protein were extracted and analyzed by ELISA. Statistical testing was performed using the two‐tailed unpaired t‐test.Carotid plaques were obtained from 53 patients; 33 were considered stable and 19 unstable. Unstable carotid atherosclerotic plaques had significantly higher levels of expression of the chemokine MCP‐1 (19.8 ± 0.61 pg/ml vs. 17.3 ± 0.56 pg/ml; p=.0051) compared to stable plaques. Intra‐plaque levels of C‐reactive protein (CRP) (20.7 ± 0.64 pg/ml vs. 18.3 ± 0.53 pg/ml; p=.0056) and tumor necrosis factor‐alpha (TNF‐alpha) (450.1 ± 6.23 pg/ml vs. 326 ± 12.7 pg/ml; p<.0001) were similarly elevated in unstable compared to stable plaques. Conversely, the anti‐inflammatory cytokine interleukin‐10 (IL‐10) was decreased in unstable plaques (27.4 ± 0.40 pg/ml vs. 30.3 ± 0.52 pg/ml; p=.0002). Unstable carotid plaques exhibit a pro‐inflammatory cytokine profile. MCP‐1, which aids in the chemotaxis of monocytes, is elevated in unstable carotid atherosclerotic plaques. Small molecule inhibition of MCP‐1 may help in vulnerable plaque stabilization.
Cardiac myocyte‐specific caveolin‐3 overexpression modulates ANP production and attenuates cardiac hypertrophy in vivo
Authors: Horikawa Yousuke T , Tsutsumi Yasuo M , Patel Hemal H , Roth David M 
Published: June 2021

IntroductionThe organization of signaling molecules in cardiac hypertrophy are incompletely understood. Caveolae, invaginations of the sarcolemmal membrane localize signaling molecules involved in cardiac hypertrophy. Atrial naturetic peptide (ANP) regulates endothelin‐1 release and cardiac hypertrophy. Furthermore, ANP is secreted via and stored within caveolae. We hypothesized that cardiac myocyte‐specific overexpression of Cav‐3 (Cav‐3 OE) modulates ANP production attenuating cardiac hypertrophy in vivo.MethodsCav‐3 OE and littermate controls (C) were subjected to transverse aortic constriction (TAC) for 4 weeks. Echocardiography, histology and molecular analysis were performed.ResultsCav‐3OE mice had reduced heart weights post TAC compared to C. Furthermore, Cav‐3 OE and C mice had similar fractional shortening (FS) pre TAC but had greater FS compared to C post TAC. mRNA levels of ANP were 7‐fold greater in Cav‐3 OE at baseline compared to C, resulting in increased protein expression of ANP in the cardiac myocyte and blood. Disruption of caveolae with colchicine in adult cardiac myocytes isolated from Cav‐3 OE resulted in a decrease in ANP.ConclusionWe show that Cav‐3 OE alters ANP production in cardiac myocytes blunting cardiac hypertrophy while preserving cardiac function post TAC. This suggests a therapeutic role for overexpression of Cav‐3 in pathological cardiac hypertrophy.
Protective effects of auricularia auriculajudae polysaccharide on vascular of streptozotocin induced diabetic rats
Authors: Wang Linlin , Situ Wangmin , Fei Jiaqian , Zhang Xiaoming , Ye Tingmei , Shen Yueliang , Chen Yingying 
Published: June 2021

AimTo investigate the direct vascular effects of auricularia auriculajudae polysaccharide (AAP) and the underlying mechanisms on the thoracic aorta of streptozotocin(STZ) induced diabetic SD rats.MethodsThe thoracic aortic rings with endothelium from STZ induced diabetic rats were mounted in an organ bath. Isometric contraction of aortic rings was measured. On the other hand, isolated aortic rings from normal control SD rats were conducted with immuno‐histochemical analysis for induced nitric oxide synthase (iNOS) expression after they were pre‐incubated with APP (10 μg/ml) for 0~50 minutes.Results(1) Cumulative administration of AAP (2‐20 μg/ml) did not affect the vasomotion of aortic rings of diabetic rats in basal tension. (2) After incubation with APP (10 μg/ml) for 30 minutes, aorta rings with endothelium were pre‐contracted with PE (10−6 M) and then acetylcholine (Ach) were added. The vascular relaxation response to Ach was significantly impaired in diabetic group, which was completely reversed by APP treatment. (2) The expression levelof iNOS in aortic rings was markedly increased after incubated with APP. iNOS expression had a peak level at time point of 10 minutes.ConclusionAPP could restore the vasorelexation dysfunction in diabetic rat aortic rings, in which the activation of NO pathway may probably be involved.
Bkca potassium channels and sympathetic transmission in the pulmonary artery from pulmonary hypertensive rats
Authors: Oriowo Mabayoje , El‐Hajj Hanadi 
Published: June 2021

Pulmonary hypertension (PH) is a chronic disabling disease that affects the pulmonary vasculature. In this study, we have examined the effect of blocking potassium channels on sympathetic neurotransmission in the pulmonary artery and how this is influenced by PH.The right ventricular pressure was 30.4±3.5 mmHg and 52.8±5.4 mmHg in control and hypertensive rats respectively. These values were significantly different from each other indicating pulmonary hypertension. Electrical stimulation of the pulmonary artery produced frequency‐dependent contractions with LogES50 values of 1.13±0.18 and 0.44±0.26 in control hypertensive rats, respectively. There was no significant difference in the maximum response between the groups. TEA (1 mM), a BKca channel blocker, produced a nonsignificant increase in maximum response in control rat but produced a significant shift of the frequency‐response curve to the left reducing the LogES50 value from 1.13±0.18 to 0.37±0.32 (n=5). In hypertensive rats TEA (1 mM) shifted the frequency‐response curve to the left and significantly increased the maximum response. It was concluded that BKCA channels modulated adrenergic transmission in the rat pulmonary artery and this was not affected by pulmonary hypertension.