bluuebunny/crossref_metadata_2025_split huggingface dataset:
SCD1 Inhibition Modifies Fatty Acid Regulation of Adipocyte Inflammation and Lipid Content
Authors: Ralston Jessica , Metherel Adam , Stark Ken , Mutch David 
Published: June 2021

During adipogenesis, adipocytes accumulate triacylglycerols concomitant with increases in the expression and activity of lipogenic genes such as stearoyl‐CoA desaturase 1 (SCD1). SCD1 is the rate‐limiting enzyme for the conversion of dietary and endogenous saturated fatty acids (SFAs) into monounsaturated fatty acids (MUFAs), specifically, palmitate (PA) to palmitoleate (PMA) and stearate (SA) to oleate (OA). Changes in SCD1 activity alter adipocyte SFA/MUFA ratios, which affects cellular function and the development of obesity‐related complications. We examined the bioactivity of 250µM PA, SA, PMA or OA on SCD1‐inhibited adipocytes. SCD1‐inhibited and differentiated 3T3‐L1 adipocytes were treated with fatty acids (FAs) for 48 hrs. FA composition, gene expression, and cytokine secretion were examined by gas chromatography (GC), qRT‐PCR, and multiplex immunoassays, respectively. Treating SCD1‐inhibited adipocytes with PA caused a substantial increase in SA levels that stemmed from an up‐regulation of elongase 6 activity, which was subsequently confirmed using a PA stable isotope tracer and GC coupled mass spectrometry. Adipocytes treated with SFAs showed larger increases in the expression and secretion of markers of inflammation (MCP1, IL6, and CCL5) compared to MUFAs, and these effects were accentuated with SCD1 inhibition. Taken together, reduced SCD1 activity in adipocytes up‐regulates the conversion of PA into SA, and enhances the pro‐inflammatory nature of SFAs.Grant Funding Source: Supported by NSERC
Characterization and Comparison of Beta‐Lactoglobulin Orthologs
Authors: Crowther Jennifer , Jameson Geoffrey , Hodgkinson Alison , Dobson Renwick 
Published: June 2021

Beta‐lactoglobulin (Blg) is the most abundant whey protein in the milk of ruminant animals, yet its physiological function is yet to be confirmed. It is not present in human milk and has been identified as one of the main immunogenic proteins in cow milk. Goat milk appears to be less allergenic and more easily digested than cow milk. As Blg is the most abundant whey protein differences in its structural, physicochemical and dynamic properties may be responsible for some of the differences seen between these milks.An ultra‐high resolution crystal structure of caprine Blg, along with sedimentation velocity and small‐angle X‐ray scattering data, suggest the presence of subtle differences between bovine and caprine orthologs. While both are dimeric in solution and crystalline states, our data suggest a flexible arrangement of subunits within the dimer. These structural findings have directed further studies into the stability and dynamics of the protein and their binding behaviors with other components in milk, which may provide insight into the differences between these species' milks and potentially the physiological role of this enigmatic protein.
Rumex crispus Phytochemicals: Chemopreventative Potential for Human Colon Carcinoma
Authors: Lee Dallas , Clack Beatrice 
Published: June 2021

The study and isolation of naturally occurring phytochemicals has produced several chemotherapeutic drugs and derivatives still in use today including: paclitaxel (taxol), etoposides (podophyllotoxin), and irinotecan. The objective of this study was to isolate novel chemotherapeutic compounds of Rumex crispus (R. crispus) using high performance liquid chromatography (HPLC), characterize with mass spectrometry (MS), and test with in vitro assays.Human colon adenocarcinoma cells (DLD‐1ATCC® CCL‐221™) were used to test the effectiveness of R. crispus phytochemicals as chemotherapeutics. Accelerated solvent extraction (ASE) was utilized to extract 0.1% TritonX‐100 soluble phytochemicals from R. crispus obtained in East Texas. Extracts from both rhizomes and leaves were screened for chemotherapeutic activity using CellTiter 96® Non‐Radioactive Cell Proliferation Assay (Promega, Corp.) and the Apo‐ONE® Homogeneous Caspase‐3/7 Assay (Promega, Corp.). To further explore the relative types of phytochemicals responsible for cytotoxicity and apoptosis in the cells, reverse phase HPLC and MS was utilized. Phytochemical fractions collected from HPLC were titrated with NaOH, to neutralize the H3PO4 present from HPLC. Each HPLC fraction was tested for levels of cytoxicity using the CellTiter 96® Non‐Radioactive Cell Proliferation Assay (Promega, Corp.). Those fractions with positive killing were then subjected to MS to identify specific phytochemicals present.Cytotoxic effects were observed in both rhizome and leaf extracts of R. cripsus, as well as the induction of apoptosis with increasing dosage of R. crispus extracts. Large amounts of benzylphytosterol or benzylisoquinalone type molecules were present in the MS data of ASE R.crispus root extracts.
Breakfast Eating and Incident Coronary Heart Disease in a Large Prospective Cohort of American women
Authors: Cahill Leah , Chiuve Stephanie , Mekary Rania , Jensen Majken , Flint Alan , Hu Frank , Mukamal Kenneth , Rexrode Kathryn , Rimm Eric 
Published: June 2021

BackgroundThe 2010 Dietary Guidelines for Americans recommend breakfast for children but found insufficient evidence to make recommendations for adult eating habits (the timing and frequency of meals, snacks, and caloric beverages).ObjectiveTo conduct the first long‐term prospective study of eating habits and risk of incident coronary heart disease (CHD) in women.MethodsEating habits including breakfast eating and eating frequency were assessed in 2002 in 56,593 women from the Nurses' Health Study who were free of cardiovascular disease and cancer. During 8 years of follow‐up, 770 incident CHD cases were diagnosed. Cox proportional hazards models were used to estimate relative risks (RR) and 95% confidence intervals (CI) for CHD, adjusted for demographics, diet, lifestyle, and other CHD risk factors.ResultsAmong women less than 60 years old, those who skipped breakfast regularly had a higher risk of CHD (RR=3.82, 95% CI:1.07‐13.67) as compared to women who ate breakfast at least 5 times/week. However, this association was not present among women 60 years or over (RR=0.98, 95% CI:0.74‐1.30) (p, interaction = 0.05). No associations were observed between eating frequency (times/day) and risk of CHD.ConclusionEating breakfast was associated with a lower CHD risk in women under 60 years of age, but not in older women. SupportNIH Grants CA176726, HL034594
Xylooligosaccharide Induced Changes in Gut Microbiota in Healthy and Prediabetic Adults
Authors: Li Zhaoping , Yang Jieping , Carslon Paula , Henning Susanne , Hsu Mark , Tseng Chi‐Hong , Thames Gail , Finegold Sydney , Heber David 
Published: June 2021

BackgroundIt has been shown that the abundance and diversity of the gut microbiota is altered in individuals with metabolic disorders.ObjectiveThis study was conducted to evaluate the effect of prebiotics xylooligosaccharide (XOS) on gut microbiota and glucose metabolism in healthy and prediabetic subjects.DesignPrediabetic (n=18) or healthy (n=16) adult subjects were randomized to receive 2.8 g/day XOS or placebo in an 8‐week study. In prediabetic subjects, blood and stool were collected, and body composition and oral glucose tolerance test (OGTT) was done at baseline and after 8 weeks of intervention. Stool from prediabetic (n=13) and healthy (n=16) subjects at baseline and week 8 was processed for gut microbiota characterization using Illumina MiSeq sequencing.ResultsXOS induced notable similar changes in microbial diversity in both healthy and prediabetic subjects, as well as changes varied by the subject health status. The baseline increase of genera Enterorhabdus was seen in prediabetes compared to healthy subjects. XOS significantly reverse this transformation in prediabetes. The abundance of the class Coriobacteria was reduced by XOS in both healthy and prediabetic adults. Genera Dialister was only increased by XOS in prediabetic subjects. The increased of Dialister was reported in people receiving dietary whole grain intervention. XOS lowered 0‐2h OGTT insulin response (P=0.11), but had no effect on body composition, serum glucose, triglyceride, satiety hormone and inflammation markers in prediabetic subjects.ConclusionsFurther studies are needed to determine the role of Enterorhabdus, Coriobacteria and Dialister in the use of prebiotics in prediabetes.
Raisins (Vitis vinifera L.) as a Source of Prebiotic Functional Food
Authors: Mandalari Giuseppina , Ianson Kerry , Chan Luisa , Carughi Arianna 
Published: June 2021

In the present work we report the potential prebiotic effect of sun‐dried raisins, known to be a source of fructo‐oligosaccharides (FOS). A full model of gastrointestinal tract digestion, including gastric and small intestinal environments and a colonic model of in vitro fermentation with representative human gut bacteria was used. Bacterial identification was performed by plate counting on selective media and 16S V4 rDNA analysis.Results from plate counting showed an increase in the numbers of beneficial bacteria, such as bifidobacteria and lactobacilli, after fermentation with raisins. Higher prebiotic index (PI) scores were recorded after 8 and 24 h fermentation with raisins compared with negative control (no carbon source added). Microbial profiling showed a bacterial abundance shift in the whole microbiome, with an increase of Bifidobacteria after fermentation with raisins and FOS, used as positive control. This trend was stronger with Bifidobacterium sp. than Lactobacillus sp. The concentration of lactic and acetic acids increased after fermentation with raisins (11.6 and 36.5 mmol/l after 24h, respectively), demonstrating a beneficial effect correlated to the increase in the number of beneficial bacteria.In conclusion, we have shown that bioactive components in raisins were able to modulate the growth of gut bacteria. Sun‐dried raisins exhibited the potential to be used as a novel source of prebiotics.
CYP2A6 Genetic Variation and Variable Nicotine Metabolism Among Two Distinct American Indian Tribal Groups With Different Levels of Smoking and Risk For Tobacco‐Related Cancer
Authors: Tanner Julie‐Anne , Henderson Jeffrey , Howard Barbara , Buchwald Dedra , Tyndale Rachel 
Published: June 2021

CYP2A6 variability, resulting in altered rates of nicotine metabolic inactivation, is associated with variation in smoking behaviors. Distinct patterns of smoking and disease prevalence of two American Indian (AI) tribes (Northern Plains, NP; Southwestern, SW) prompted our investigation of CYP2A6 genetic variability and nicotine metabolism in NP and SW AIs. Both tribes (NP n=426; SW n=210) were genotyped for multiple CYP2A6 variants representative of prevalent loss of function alleles from different ethnicities. Using 3'‐hydroxycotinine to cotinine (3HC/COT) ratio as a phenotype of nicotine metabolism, association between CYP2A6 genotype and rate of nicotine metabolism was examined. CYP2A6 genotype was associated with the rate of nicotine metabolism in both tribes (P<0.02), confirming that CYP2A6 genotype predicts rate of nicotine metabolism for these populations. The rate of nicotine metabolism was higher in NP compared to SW AIs when controlling for genotype (P<0.01). The frequency of reduced metabolizers, those with loss of function alleles, was higher in the SW compared to the NP tribe (P<0.01). Faster nicotine metabolism, and fewer reduced function variants, which was observed in the NP tribe, has been associated with higher levels of smoking and dependence, more difficulty quitting, and reduced response to some cessation pharmacotherapies in other populations.Funding: CIHR and the Collaborative to Improve Native Cancer Outcomes (NCI grant P50CA148110)
UM206, a Peptide Fragment of Wnt5a, Attenuates Adverse Remodeling after Myocardial Infarction in Swine
Authors: Hermans Kevin , Uitterdijk André , de Wijs‐Meijler Daphne , Daskalopoulos Evangelos , Verzijl Annemarie , Sneep Stefan , Blonden Lau , Reiss Irwin , Duncker Dirk , Blankesteijn W Matthijs , Merkus Daphne 
Published: June 2021

IntroductionFollowing myocardial infarction (MI), left ventricular (LV) remodeling aims to maintain cardiac function. Nevertheless, adverse remodeling results in thinning of the infarct and LV dilation which may subsequently lead to the development of heart failure (HF) with poor prognosis. Wnt/Frizzled signaling plays a key role in cardiac remodeling following MI. We have shown previously that blockade of Wnt/Frizzled signaling with UM206 suppresses adverse remodeling and prevents HF development in mice post‐MI. Here we investigated the effects of UM206 therapy in a clinically relevant large animal model.MethodsTwelve Yorkshire x Landrace swine were subjected to 2h of myocardial ischemia by ligation of the proximal left circumflex artery, followed by reperfusion. Starting 24h post‐MI, 6 animals were treated with UM206 (0.6 μg/kg/day i.v.) for 5 weeks. The 6 control swine were treated with vehicle. Cardiac dimensions and infarct mass (IM) were determined by echocardiography and dedicated markers, respectively.ResultsTreatment with UM206 for 5 weeks resulted in a significant decrease in IM compared to baseline, whereas IM remained unaffected in the control group. This was accompanied by progressive dilation of the LV in the control group between 3 and 5 weeks after MI while adverse remodeling was halted in the UM206 treated group.ConclusionUM206 treatment in a clinically relevant swine model of reperfused myocardial infarction attenuates adverse remodeling.Supported by the Dutch Heart Foundation (2010B196)
Genes involved in the development of cardiovascular disease: A genomic study of human arteries
Authors: Lu Tzongshi , Ho Li‐Lun , Liu Qinghua , Molostvov Guerman , Dong Ling‐Shen , Hiemstra Thomas , Zehnder Daniel , Hsiao Li‐Li 
Published: June 2021

Cardiovascular disease (CVD) is the leading pandemic health problem globally. In particular arteriosclerosis results in increased cardiac work and reduced coronary flow with the consequence of heart failure. In this study, we explore differential gene expressions and molecular mechanisms in arteries of patients with CVD and healthy control using RNA sequencing technology.Our data showed that among the 14 up‐regulated genes, hemoglobin‐β (HBB), hemoglobin‐α 2 (HBA2) and hemoglobin‐α 1 (HBA1) that involve in oxygen transport have the highest changes of expression (7.4, 5.0 and 4.6 folds changes, respectively). In addition, two up‐regulated genes, CD36 (3.56 folds) and fatty acid binding protein 4 (FABP4, 3.13 folds), are involved in fat and adipocyte metabolism and PPAR signaling pathway. Conversely, three highest changes genes among the 8 down‐regulated genes are: pentraxin 3 (PTX3, 3.9 folds) is associated with the regulation of inflammatory reactions; sodium channel, voltage‐gated, type VII, alpha subunit (SCN7A, 3.57 folds) is involved in the Adrenergic signaling in cardiomyocytes and heat shock protein A6 (HSPA6, 3.39 folds) plays important protective roles in maintaining normal protein folding under stress.In conclusion, we identified genes that are unique in patients with CVD when compared with healthy individuals, which may serve as genomic markers in the development of CVD.
Effects of Iron Deficiency in the Production of Oxidative Stress Biomarkers in the Central Nervous System and Spleen of BALB / c Mice
Authors: Martinez Anabella , Contreras Irazú , Pliego Bernardo , Estrada José Antonio 
Published: June 2021

ObjectiveTo determine the production of oxidative stress biomarkers in nervous system and spleen cells of iron deficient mice.Methods: 2 groups of BALB / c mice 60 days old were established (control and iron deficient). Iron deficiency was established in utero and sustained until its sacrifice. CNS and spleen samples from both groups were obtained to freeze and also to purify leukocytes. Frozen tissue samples were used for analysis with the kit for spectrophotometricall detection of thiobarbituric acid reactive substances (TBARS). Purified cells were cultured in duplicate under standard conditions at a density of 5x10 6 cells / cm 3 for the spleen and 0.5 x 10 6 cells / cm 3 for the CNS. A simultaneous test was performed with stimulated cells (LPS 1 µg / µL) and non stimulated cells to determine the production of nitric oxide by the method of GriessResults: No significant differences were found in the spleen and CNS lipid peroxidation; however, it can be seen a lower production of malondialdehyde (MDA) in the CNS of iron deficient mice. The nitric oxide production was not significantly different.Conclusion As There is no statistically significant difference but mathematical in the expression of oxidative stress biomarkers between groups it is suggested increasing the sample size for more relevant results. It is possible that some compensatory mechanisms against oxidative stress, such as increased levels of antioxidant enzymes and antioxidants are overexpressed in the iron‐ deficient group
Prolonged use of Chloramphenicol Induces Aplastic Anemia and Oxidative Stress in Broiler Chicken
Authors: Azeez Odunayo , Iji Oluwafikemi , Akinrinde Adeleye 
Published: June 2021

In an attempt to combat bacterial infections in domestic poultry production in developing countries, poultry producers use antibiotics without recourse to its side effects. We investigated the effects of prolonged use of Chloramphenicol in the broilers and the antioxidant potential of four commercially available antioxidants and ascorbic acid. Two hundred and ten day old broilers were randomly divided into seven groups of thirty birds per group. Group A, (control) received Chloramphenicol for the first six days while all the other groups received it for six weeks. Group B did not receive any antioxidant. Group C received Vitamin C, Group D Selcon Forte, Group E Stressroak, Group F Superliv and Group G, Livestovit in drinking water. Blood samples were collected after six weeks in three replicates for haematological parameters and erythrocyte osmotic fragility, plasma ALT, AST and GGT. Five birds were culled from each group for the determination of the total GSH, H2O2 and lipid peroxidation in the liver, kidney and the cerebrum. Those birds that received Chloramphenicol alone presented with aplastic anemia, elevated erythrocyte osmotic fragility and increased AST, ALT and GGT values. The levels of GSH, H2O2 and lipid peroxidation also increased significantly. The anemia and oxidative stress was however corrected in the antioxidants groups. This study demonstrated that prolonged use of chloramphenicol induced non‐regenerative anaemia and oxidative stress, even at normal recommended dosage.
Brown Adipocyte Dysfunction in UCP1 Knockout Mice leads to Age‐Dependent Development of Type 2 Diabetes
Authors: Thoonen Robrecht , Hindle Allyson , Bezerra Miranda Alexandre , Yao Vincent , Tainsh Robert , Buys Emmanuel , Bloch Kenneth , Scherrer‐Crosbie Marielle 
Published: June 2021

Since the discovery of functional brown adipose tissue (BAT) in adult humans, an inverse correlation between aging, type 2 diabetes and the amount and activity of the BAT‐depots have been reported. Upon activation, BAT converts the energy of free fatty acids and glucose oxidation into heat through the mitochondrial carrier protein,uncoupling protein 1 (UCP1). BAT has recently been demonstrated to increase triglyceride uptake and insulin sensitivity. Although the thermogenic responses of UCP1 KO mice have been well studied, little is known about the short and long term effects of UCP1 deficiency and how it affects BAT function and metabolism in general.We used RNAseq to analyze and compare the BAT transcriptome of WT and UCP1 KO mice, under thermoneutral conditions at baseline and after catecholamine induced activation. The effects of aging on glucose and insulin tolerance and molecular markers of type 2 diabetes were investigated in WT and UCP1 KO mice in thermoneutrality for up to 1 year.Whole transcriptome analysis, followed by qPCR and immunoblotting, revealed marked dysfunction of key metabolic pathways in activated BAT from UCP1KO mice compared to WT mice, while at baseline thermoneutral conditions the BAT transcriptome from UCP1KO and WT mice were similar. Further, UCP1KO mice age‐dependently develop hallmarks of type 2 diabetes, such as impaired glucose tolerance and increased insulin resistance, without developing an obesity phenotype.We conclude that UCP1 KO mice are a model of severe BAT dysfunction. Long‐term BAT dysfunction is associated with age‐dependent development of hallmarks of type 2 diabetes.
Clathrin and TOM1L1 regulate Epidermal Growth Factor Receptor Signaling at the Plasma Membrane
Authors: Judge Gurjeet , Garay Camilo , Lucarelli Stefanie , Bautista Stephen , Pandey Rohan , Antonescu Costin 
Published: June 2021

Epidermal growth factor (EGF) receptor (EGFR) controls many aspects of cell physiology via the activation of intracellular signaling pathways. Ligand‐bound EGFR elicits phosphorylation of Gab1, which activates phosphatidylinositol‐3‐kinase (PI3K), which in turn leads to Akt phosphorylation and activation, controlling cell survival and metabolism. Rapidly upon binding EGF, the receptor is recruited to clathrin‐coated pits (CCPs), eventually leading to EGFR endocytosis. As such, receptor‐proximal EGFR signaling occurs while the receptor is enriched with clathrin‐coated plasma membrane microdomains. Whether and how clathrin microdomains may control EGFR signaling at the plasma membrane leading to Gab1 and Akt phosphorylation remains poorly understood. Using several specific molecular perturbations, we found that clathrin is required for EGF‐stimulated phosphorylation of Akt. Similar perturbations of dynamin were without effect on EGF‐stimulated Akt phosphorylation. This indicates that clathrin microdomains regulate EGFR signaling at the plasma membrane.Clathrin interacts with and recruits numerous proteins to the plasma membrane including TOM1L1. We have examined the role of TOM1L1, which interacts with clathrin, EGFR and Src‐family kinases (SFKs). SiRNA gene silencing of TOM1L1 impairs EGF‐stimulated Akt phosphorylation. Using fluorescent labeling of clathrin, TOM1L1 and other signaling intermediates coupled to total internal reflection fluorescence microscopy, we have examined the hierarchy of the recruitment of EGFR signals to clathrin‐coated plasma membrane microdomains. Our findings suggest that TOM1L1 has a clathrin‐localized regulatory role in EGF‐stimulated Akt phosphorylation.