bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parenteral lipid minimization versus composition for intestinal failure associated liver disease
Authors: Josephson Jessica K , Wales Paul W , Nation Patrick N , Wizzard Pamela , Mager Diana , Field Catherine J , Ball Ronald O , Pencharz Paul B , Turner Justine M 
Published: June 2021

IntroductionStrategies to treat intestinal failure associated liver disease (IFALD) manipulate dose or composition of parenteral lipids. We compared low dose omega‐6 (soybean oil), low dose omega‐3 (fish oil) and standard dose therapies using soybean or a combination of soybean, medium chain triglycerides, olive and fish oil, on liver and nutritional outcomes in neonates.Materials and MethodsNeonatal pigletswere allocated to: Group 1 (n=6) Omegaven® at 5 g/kg/d, Group 2 (n=8) Intralipid® at 5 g/kg/d, Group 3 (n=9) Intralipid® at 10 g/kg/d, Group 4 piglets (n=10) SMOFlipid ® at 10g/kg/d and Group 5 sow‐reared controls (n=8). After 14 days of total parenteral nutrition we compared bilirubin, bile flow, weight and brain weight.Results by Group (mean/SD)

1
2
3
4
5

Total Bilirubin (microM/L)
7.0a (5.3)
10.8a (3.2)
21.1b (10.7)
4.0c (1.2)
8.2a (3.9)

Bile flow (mcg/g liver)
12.3a (6.8)
7.9a (3.8)
5.4b (4.0)
13.5a (6.6)
9.0a (1.9)

Total weight gain (kg)
2.7a (0.2)
2.4a (0.3)
2.2a (0.5)
3.0c (0.3)
3.9b (0.9)

Brain weight (g)
35.3a (1.8)
36.3a (3.3)
41.6ab (4.6)
44.2b (3.4)
45.9b (3.4)

Superscripts refer to differences by ANOVA p<0.05
DiscussionGroups 1, 2 and 4 were equally effective in preventing IFALD. Based on weight gain and final brain weight SMOFlipid ® provides beneficial nutritional support to vulnerable neonates, while protecting from cholestasis.The source of research support is CIHR with Fresenius KabiGrant Funding Source:CIHR
In vitro inhibition of dipeptidyl peptidase IV by amaranth peptides
Authors: Velarde‐Salcedo Aida J. , Lara‐González Samuel , Monero‐Morán Gabriela M. , de Mejia Elvira Gonzalez , Barba de la Rosa Ana P. 
Published: June 2021

Dipeptidyl peptidase IV (DPPIV) is an enzyme that acts deactivating incretins, the hormones involved in insulin secretion and is being considered as target against diabetes. The objective was to investigate the inhibitory activity against DPPIV of amaranth peptides released after tryptic digestion and after in vitro simulated gastrointestinal digestion. Amaranth glutelins fraction showed the highest inhibitory activity against DPPIV in a dose‐dependent manner with an IC50 =1.6 mg/mL. Proteins from other seeds such as wheat, common beans and soybean were tested. The ligand‐enzyme docking simulations using peptides from amaranth globulins released by tryptic digestion showed that peptides larger than 13 amino acids are able to interact with DPPIV enzyme at the dimerization domain. Shorter peptides were located inside the large cavity of DPPIV where natural substrates are digested. The predicted interaction energy of the peptides ranged from −5.98 to 9.48 kcal/mol. In conclusion, our results indicate that amaranth peptides released after digestion are able to inhibit DPPIV by binding the active and dimerization domains. This function has the potential for amaranth peptides to act as antidiabetic compounds.Grant Funding Source: Ministry of Health, Mexico, Fondo Sectorial Salud No. 150873
Infant intake patterns vary by feeding method: results from a randomized controlled trial
Authors: Maalouf‐Manasseh Zeina , Chantry Caroline , Dewey Kathryn G 
Published: June 2021

Formula feeding is associated with greater intake and more rapid weight gain than breastfeeding. It is unclear if this is due to differences in composition of formula vs. human milk or the practice of feeding by bottle. We conducted a randomized controlled trial in which 231 infants whose mothers planned to provide at least some of the feeds (formula or human milk) by bottle were assigned to a novel bottle with a nipple allowing the infant more control over the flow of milk, or a conventional bottle. We also compared intake of human milk when consumed by bottle vs. at the breast. In infants who were fed only formula, intake per feed was lower with the novel vs. conventional bottle at both 3 mo (112 vs. 135 g, p=0.076) and 4 mo (129 vs. 152 g, p=0.039). However, the number of feeds/d was higher in the novel bottle group (15.2 vs 13.5, p=0.12 at 3 mo; 16.0 vs. 13.4, p=0.055 at 4 mo) and thus there was no significant difference between groups in 24‐h intake. In infants fed only human milk, intake per feed was greater when fed directly at the breast (87 g) than when fed by bottle (75 g, p=0.048) at 3 mo, but there were no differences in intake/feed or 24‐h intake between intervention groups at 3 or 4 mo. These results suggest that a novel bottle nipple that allows greater infant control over the rate of intake results in lower intake per feed, but that infants compensate over 24 hours by increasing feeding frequency.Research support provided by the National Institute of Child Health & Human Development, Grant Number: 1RC1DK087234.
Caffeine intake and the plasma proteome
Authors: Tian Ouxi , Josse Andrea R , El‐Sohemy Ahmed 
Published: June 2021

Caffeine intake has been associated with both an increased and decreased risk of various health conditions. However, the physiological pathways affected remain unclear. CYP1A2 is the major enzyme that metabolizes caffeine and a single nucleotide polymorphism (rs762551) affects the rate of caffeine metabolism. The objective of this study was to determine whether caffeine intake is associated with proteins in the plasma proteome, and whether CYP1A2 genotype modifies any of the associations observed. Subjects (n=1095) aged 20–29 years completed a 196‐ item semi‐quantitative food frequency questionnaire and provided a fasting blood sample from which DNA and plasma were obtained for genotyping and proteomic analysis with 54 plasma proteins. Subjects were categorized into three groups according to habitual caffeine intake (<100mg/d, 100–200mg/d, and >;200mg/d) and later stratified by CYP1A2 genotype. Among individuals with A/C or C/C genotypes (slow metabolizers), plasma concentration of complement component 3 (p=0.03) and gelsolin isoform 1 (p=0.005), were significantly lower in the highest category of caffeine intake. No differences in protein concentration were observed for A/A individuals (fast metabolizers). These results suggest certain plasma proteins are affected by caffeine intake, but only among slow metabolizers.Grant Funding Source: Canadian Institutes of Health Research
Hyperglycemia mediates a shift from cap‐dependent to capindependent mRNA translation through a 4E‐BP1 dependent mechanism
Authors: Dennis Michael D , Kimball Scot R , Jefferson Leonard S 
Published: June 2021

In both liver of diabetic mice and cells in culture exposed to hyperglycemic conditions 4E‐BP1 is modified by OGlcNAcylation concomitant with enhanced expression and interaction with the mRNA cap‐binding protein eIF4E. Interaction of 4E‐BP1 with eIF4E plays a major role in the regulation of gene expression by controlling the selection of mRNAs for translation. In the present study, we evaluated the hypothesis that hyperglycemia alters the profile of mRNAs selected for translation. Using pulsed stable isotope labeling by amino acids in cell culture (pSILAC) we identified proteins with altered rates of synthesis upon exposure to medium containing 25 compared to 5 mM glucose. The mRNAs encoding proteins whose synthesis was most enhanced contained longer, more complex 5′‐UTRs, suggesting hyperglycemia favors the translation of mRNAs with more structured 5′‐UTRs, including those containing internal ribosome entry sites. Using a bicistronic luciferase reporter assay, the high glucose condition also caused a repression of cap‐dependent and enhancement of cap‐independent mRNA translation. Notably, the glucose‐induced shift from cap‐dependent to cap‐independent mRNA translation did not occur in cells lacking 4E‐BP1. (Supported by NIH grant 13499 (LSJ) and an NIH Postdoctoral Fellowship (MDD))Grant Funding Source: NIH 13499
Rapamycin‐Regulated Ubiquitin Specific Peptidases Expression in Cardiocytes
Authors: Zanetti Arthus Vilar Deolindo , Santos Lucas Carvalho , Schoeps Vinicius Andreoli , Sanzovo Paula Sajovic , Carniello Jose Victor Scarpa , Manso Andre Augusto Simoes , Sellke Frank William , Bianchi Cesario 
Published: June 2021

INTRODUCTIONThe mechanistic target of rapamycin (mTOR) regulates protein degradation through autophagic/lysosomal activity. However, the mTOR effects on protein degradation by the ubiquitin/proteasome pathway have not been established. Protein ubiquitination is regulated by a balance of polyubiquitin ligases and ubiquitin specific peptidases (USP).OBJECTIVETo determine whether mTOR inhibition could modify the ubiquitin/proteasome pathway.METHODSPigs were treated with placebo or 4mg/daily rapamycin (RAPA; mTOR inhibitor) for 1 week (n=5/group). H9C2 (cardiomyocytes) cells were cultured in DMEM and treated with 600 nM RAPA for up to 3 days. RNA and protein levels were quantified by q_PCR and western blotting and statistically analyzed (ANOVA / t‐Test).RESULTSRAPA treatments inhibited mTOR [lower p‐P70S6K(T389)] both in vivo and in vitro. In vivo RAPA decreased protein levels of USP11 and 28 and in vitro RAPA decreased mRNA levels of USP11, 24, 28 and 39 and proteins levels of USP28 and 39 that were associated with increased total protein ubiquitination.CONCLUSIONThese results document the regulation of the ubiquitin/proteasome pathway by mTOR and reveals that mTOR activity may regulate cellular protein levels through degradation by both lysosomal and proteasomal pathways. Further studies will address the importance of RAPA‐regulated USP11, USP28, and USP39 levels in cardiac cells.
TCP‐1 as a novel phage‐display peptide targeting colon cancer
Authors: Lan Lu , Hin Cho Chi 
Published: June 2021

TCP1 is a novel vasculature‐targeting peptide. It was discovered through the in vivo phage library selection. It was demonstrated that TCP1 peptide exhibited the homing ability to the tumor neovasculature and was capable of efficiently delivering imaging agents and chemotherapeutic drugs to this target site. The current study is to further investigate the targeting ability of TCP1 to deliver anti‐cancer drugs and imaging agents, and demonstrate the specificity of TCP1 on the putative target on tumor blood vessels and explore the potential mechanisms.In this study, we observed that TCP‐1 peptide delivered GFP only to tumor blood vessel other than normal organs after GFP or TCP‐1/GFP injection. Results in TNF‐α or TCP‐1/TNF‐α targeted delivery showed that TCP‐1/TNF displayed stronger effects than TNF‐α alone in the induction of apoptosis and reduction in number of microvessels in the tumors but without significant effect in systemic toxicity.To identify the cell surface targets for TCP1, we incubated the colon 26 cell with biotin‐TCP1 probe peptide and performed the pull‐down assay by neutravidin‐agarose beads. Preliminary western‐blot data showed that some membrane proteins on colon 26 cells could bind to TCP1 after incubation with biotin‐TCP1 probe.Taken together TCP1 peptide appears to be a promising agent in molecular imaging and drug delivery for gastrointestinal cancers.
Bifidobacteria confer protection against NSAID‐enteropathy independently of acetate production
Authors: Syer Stephanie D. , Martin Rebeca , McKnight G. Webb , Langella Philippe , Wallace John L. 
Published: June 2021

Rats were orally treated with vehicle or Bifidobacterium longum subsp. Adolescentis (BA), a low acetate producer, or B. longum subsp. longum (BL), a high acetate producer (both at 109 CFU), for 9 days. In addition, two isogenic strains were also tested: a second BL strain (BN) and its derivative (BNKO) in which a gene deletion results in low acetate production. Naproxen (20 mg/kg) was co‐administered on the final 4 days, then small intestinal damage was blindly scored.Treatment with BA decreased naproxen‐induced intestinal damage by 82%; p<0.05, while BL exerted no effect. BN reduced damage by 75% (p<0.05), and a similar beneficial effect was observed with the low acetate‐producing knockout bacterium, BNKO (62% reduction; p<0.05).Small intestinal injury by NSAIDs is a serious clinical problem, with no available treatments. Acetate production by these Bifidobacterium strains does not appear to be important for prevention of NSAID‐enteropathy, given that a high acetate producing Bifidobacteria (BL) exhibited no protective effect, while a low acetate‐producing mutant (BNKO) was as effective in reducing damage as another high acetate‐producing bacterium (BN).
GPR124 coupling and function in astrocytomas
Authors: Cherry Allison , Lin Yi Hsing , Hague Chris , Ong Shao‐En , Stella Nephi 
Published: June 2021

GPR124 is an orphan receptor that belongs to the Adhesion GPCR family. Members of this family are characterized by long N‐terminal segments that contain many of the same functional domains found in cadherins, integrins, and tyrosine kinases, but are typically absent in GPCRs belonging to other families. While little is known about adhesion GPCRs, recent results show that GPR124 plays a role in endothelial cell migration and differentiation during angiogenesis. We found that GPR124 mRNA is highly expressed by various human astrocytoma cell lines. Due to the high expression of GPR124 in GBM cells and its known role in cellular migration and differentiation, we hypothesize that these orphan receptors control the migration of GBM cells through specific signal transduction pathways and thus represent promising new therapeutic targets to treat brain tumors.To test our hypothesis, we used a proteomics approach to determine the effector proteins that couple to this GPCR and measured the migration of human GBM cell lines expressing various levels of GPR124. Myc‐tagged GPR124 was heterologously expressed in the human GBM cell line U87MG and the proteins associated with these receptors were analyzed by Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) mass spectrometry. We found a concise list of effector proteins that are known to control cell migration. To determine if GPR124 levels affect cell migration, we used a modified Boyden chamber assay that was developed in our laboratory. We found that GPR124 over‐expression increases the migration of U87MG cells stimulated by lysophosphatidic acid (LPA). Together, our results suggest that GPR124 is expressed by astrocytomas and tightly regulates how these cells migrate toward select chemokines.
A behavioral assessment of the aversive properties of delta‐9‐ THC in Fischer‐Lewis rats.
Authors: Presley Alison , Riley Anthony 
Published: June 2021

Although Lewis (LEW) and Fischer (F344) rats differ in their sensitivity to the rewarding effects of THC, no data have been reported on differences in their sensitivity to the drug's aversive effects, a limiting factor in drug use and abuse. Examining the degree of differences (if any) in such effects in these strains may help further characterize the factors important to abuse vulnerability. Accordingly, the aversive effects of THC were examined in 32 F344 and 32 LEW subjects using the conditioned taste aversion procedure. Core body temperatures were also examined 2 weeks following the final conditioning cycle. Subjects in both strains displayed dose‐dependent THC‐induced taste aversions, with no significant strain difference. Core body temperatures of F344 subjects were significantly higher than LEW rats, although these differences were independent of THC (which itself induced hypothermia in both strains). These results suggest that the reported differences between the strains in THC self‐administration reflect differences in the drug's rewarding (and not aversive) effects and that such aversions are not due to druginduced hypothermia.This research was funded by a grant from the Mellon Foundation.
The Type of Production System Affects the Polyphenolic and Flavonoid Content of the Gourmet Mushroom, Hericium erinaceus
Authors: Sobel Bryan , Guo Huiyan , Mudge Kenneth , Liu Rui Hai 
Published: June 2021

The mushroom, Hericium erinaceus, has received attention for its functional properties. Some of those properties may be related to phenolic and flavonoid compounds, which are believed to promote positive health outcomes. The objective of this study was to determine the effect of production system on the phenolic and flavonoid content of the gourmet mushroom, Hericium erinaceus. Mushrooms were grown in an indoor commercial system, on a prepared substrate or in a forest farming system, outdoors, on a wooden log substrate. Concentrations of phenolic compounds were determined using a Folin‐Ciocalteu based assay. Flavonoid concentrations were determined through a sodium borohydride/chloronil based assay. Units are expressed, based on the standard, in gallic acid equivalents (GAE) for phenols, catechin equivalents (CE) for flavonoids, ascorbic acid equivalents for antioxidant capacity. All measurements are adjusted for moisture content and based on 100 g samples. Commercial mushrooms were (34.17 +/− 1.19 mg GAE & 108.95 +/− 6.98 mg CE) significantly less than forest farmed mushrooms that were harvested in the spring (240.61 +/− 12.80 mg GAE & 595.33 +/− 22.03 mg CE) and fall (313.2±16.8 mg GAE & 1162±108 mg CE) of 2011. Data indicates that mushrooms grown in a more ecologically based production system may contain greater concentrations of potentially health promoting compounds.Grant Funding Source: McIntire‐Stennis
Evaluation of Oral Dabigatran Etexilate Pharmacokinetics and Pharmacodynamics in Hemodialysis Patients
Authors: Goralski Kerry , Morrison Matthew , Mossop Paula , Soroka Steven , Anderson David , Wilson Jo‐Anne 
Published: June 2021

BackgroundDabigatran etexilate represents a possible improved alternative to warfarin for anticoagulation in hemodialysis patients with atrial fibrillation (AF). The object was to determine dabigatran plasma concentrations and anticoagulant effects following administration of a single 110 mg oral dose of dabigatran etexilate to hemodialysis patients.MethodsDabigatran etexilate (110 mg) was administered to 10 adult patients (25–69 yrs‐old) of the CDHA Renal Program immediately prior to starting hemodialysis. Plasma and dialysate samples were collected intermittently over 48 hours. A thrombin‐based hemoclot assay was used to determine sample‐clotting times, which were compared to dabigatran standards to estimate sample dabigatran concentrations.ResultsThe mean time (tmax) to reach maximum plasma concentration (Cmax) was 2.1 hours, and the Cmax was 72.8 ± 31.5 ng/mL. The mean elimination half‐life on hemodialysis (t1/2ON) was 1.1 hours and the half‐life off hemodialysis (t1/2OFF) was substantially longer (41.0 hours).ConclusionsA 110 mg oral dabigatran dose prior to hemodialysis was rapidly absorbed and achieved therapeutic concentrations. Hemodialysis effectively removed dabigatran from the plasma and is a possible mechanism for dabigatran detoxification.Funding was provided by the Faculty of Health Professions, Dalhousie University and the Division of Nephrology, CDHA
Rock Inhibition Reduces Senescent Cell Size
Authors: Simay yaprak dilber , Hosbas sanem , Ibisoglu burcin , Yildiz metin , Ozdemir aysun , Ark mustafa 
Published: June 2021

Recently drug‐induced senescence has gained importance in cancer therapy. It has been demonstrated that cardiac glycosides induce senescence in several cancer cell lines. On the other hand, small G protein Rho is involved in the formation of morphological features of the senescent cells. However, there is no report whether Rho kinases, important effectors of Rho, contribute to the development of the senescent morphology in cancer cell lines. In the current work, we evaluated this possibility in the cardiac glycoside‐induced senescence in HeLa cells. The xCELLigence real time cell analyzer system, senescence associated β‐galactosidase staining and cell size measurements were used to determine ouabain‐induced senescence. Cells were treated with high (0.1–1 μM, 48h) and low concentration (10–30 nM, 48h) of ouabain. In contrast to the treatment of ouabain in high concentrations which resulted in cell death, low nanomolar concentrations of ouabain induced senescence in HeLa cells. Although preincubation of specific Rock inhibitor Y‐27632 (0.1–10 μM, 30 min) did not inhibit the occurrence of ouabain‐induced (30 nM) senescence in cells, it reduced the cell size. Our results indicate that instead of the induction of senescence, rho kinases involves in the development of drug‐induced senescence morphology.This study was supported by TUBITAK in 110S426 project.
The upregulation of skeletal muscle inflammatory genes links inflammation with impaired insulin resistance in women with the metabolic syndrome
Authors: Hopman Maria T.E. , Lammers Gerwen , Poelkens Fleur , Tack Cees J. 
Published: June 2021

The metabolic syndrome is a combination of interrelated metabolic risk factors that promote the development of cardiovascular diseases and type 2 diabetes mellitus. A close link with inflammation exists, but the underlying mechanisms remain elusive. Therefore, the aim of this study was to identify differentially expressed inflammatory genes in insulin resistant skeletal muscle tissue of women with the metabolic syndrome compared to healthy controls. Physical characteristics and blood plasma levels of 19 women with the metabolic syndrome and 20 healthy controls were determined. Insulin resistance was determined using a hyperinsulinaemic euglycaemic clamp and a muscle biopsy was obtained. Gene expression levels were determined for six women in each group using microarrays. As expected, there was a significant correlation between insulin resistance and percentage of total fat mass. The upregulated genes in skeletal muscle of these women were primarily enriched for inflammatory response‐associated genes. The three most significantly upregulated of this group, interleukin 6 receptor (IL6R), histone deacetylase 9 (HDAC9), and CD97 molecule (CD97) correlated with insulin resistance in all women. This suggests an important role for these inflammatory‐related genes in the development of skeletal muscle insulin resistance.Funding: GL by GO‐EFRO, FP by ZonMW
Connecting Tubule Glomerular Feedback (CTGF) in Dahl Salt‐Sensitive (Dahl S) and Spontaneously Hypertensive Rats (SHR)
Authors: D'Ambrosio Martin A. , Wang Hong , Garvin Jeffrey L. , Ren YiLin , Carretero Oscar A. 
Published: June 2021

Increasing Na delivery to the distal nephron causes connecting tubule glomerular feedback (CTGF) that dilates the Af‐Art. Augmented CTGF may allow increased transmission of systemic pressure to the glomerulus, leading to sustained elevations in glomerular capillary pressure (PGC). In hypertension, this would result in glomerular damage. Hypertensive Dahl S fed high salt have higher PGC and glomerular damage than SHR with similar blood pressure. We hypothesized that this is due to enhanced CTGF in Dahl S compared to SHR. We used in vivo micropuncture of single nephrons. Stop‐flow pressure (PSF) was measured as an index of PGC. CTGF was measured as the difference between two consecutive PSF curves generated by raising nephron perfusion from 0 to 40 nL/min before and during blockade of CTGF with benzamil. Dahl S displayed an enhanced CTGF response compared to Dahl R (P < 0.001), and this was exacerbated by high salt feeding (P < 0.001). The results in Dahl S are in stark contrast with those in SHR. SHR displayed little or no CTGF under normal salt diet. SHR had a reduced CTGF compared to WKY (P < 0.001) and to Dahl S (P < 0.001). In conclusion, under normal salt feeding Dahl S have significant CTGF, while SHR have little or no CTGF. High salt enhances CTGF in all rat strains, especially in Dahl S. Increased CTGF may cause an increase in PGC and enhance hypertensive renal damage.Supported by NIH Grants HL028982 and HL088036.