bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating The Impact of Two Functional Polymorphisms of Lipoprotein Lipase (LPL) Gene In the Occurrence of Hypertension
Authors: Khan Mariam , Al‐Lahham Yara , Salah Amna , Habibullah Samar , Esmail Najma 
Published: June 2021

BackgroundLipoprotein lipase (LPL) is a rate limiting enzyme responsible for the hydrolysis of triacylglycerol‐rich lipoproteins releasing monoglycerides and free fatty acids, which are taken up by skeletal muscles, adipose tissue.AimTo investigate the effect of genetic polymorphisms of LPL S447X and Hind III on blood pressure and its related phenotype.MethodsS447X variant genotype and Hind III (+) variant of LPL were determined by polymerase reaction restriction fragment length polymorphism (PCR‐RFLP) assay in 50 hypertensive patients and 50 normotensive as a control group. Anthropometric measurements and serum lipoproteins were also determined in both groups. Analysis of data was done by using SPSS program.ResultsThe frequency of (SS) and (H+/H+) genotype were 78% and 62% respectively in the hypertensive group compared to 66% and 38% in normotensive group. Carrier of either (SS) or (H+/H+) genotype were at higher risk of developing hypertension (OR=1.8, 95% CI=0.8–4.4) and (OR=2.4, 95% CI =1.1–5.5) respectively when compared with carrier of other genotypes. The risk for hypertension was increased when the individuals were carrier of (SS) and (H+/H+) haplotype (OR = 6 and 95% CI =2.5–14.2). Furthermore carrier of either (SS) or (H+/H+) genotype were at higher risk of developing atherogenic phenotype manifested by central obesity and/or abdominal obesity and dyslipdemia.ConclusionIt was found that carriers of (SS) genotype and/or (H+H+) genotype were at high risk of developing hypertension and its related atherogenic phenotypes.Source of research support: Dubai Medical College for Girls
Acrolein Inhalation Suppresses Recruitment and Mobilization of Endothelial Progenitor Cells
Authors: Wheat Laura Anne , Hellmann Jason , Habertzettl Petra , Conklin Daniel J. , O'Toole Timothy E. , Bhatnagar Aruni 
Published: June 2021

Exposure to cigarette smoke decreases the level of endothelial progenitor cells (EPCs) in peripheral blood (PB). We investigated the cardiovascular effects of inhaled acrolein, an unsaturated aldehyde present in high levels in tobacco smoke (up to 150 ppm). Adult male C57BL/6 mice were exposed to room air or acrolein (0.5, 1 or 5 ppm) for 2h, 6h, 1d, 2d or 4d (6h/d) and the EPC level in PB was measured by flow cytometry. To examine the proliferative capacity of EPCs, bone marrow cells (BMCs) were cultured on fibronectin‐coated slides. Brief exposure to acrolein (5 ppm, 6h) or 4 day (1 ppm) exposure led to a 42% decrease in PB Flk+/Sca+cells (air‐exposed: 8.9±1.7/μl, n=4; acrolein‐exposed: 4.9±0.5/μl, n=4, p<0.05). BMCs isolated from mice exposed to acrolein for 1d (5 ppm) or 4d (1 ppm) formed more colonies than BMCs of air‐exposed mice (air‐exposed: 7±1 colonies; acrolein 14±1 colonies at 1d in culture, p<0.001; air‐exposed 3±0.47 colonies; acrolein‐exposed 9±2 colonies after 4 days in culture, p<0.001). Combined VEGF‐A (100 μg/kg, ip, 4d) and AMD3100 (5 mg/kg; ip, last day only) treatment increased PB Flk+/Sca+ cells (air‐exposed: 5.7/μ1±1.8, n=4; acrolein‐exposed: 11.06/μl±2.2, n=4, p<0.05) in air‐exposed mice but not in acrolein‐exposed mice (1 ppm, 4d). These data indicate that PB EPCs are a sensitive target of airborne pollutants and that acrolein at concentrations encountered in tobacco smoke suppresses PB EPC level yet increases the proliferative capacity of BMCs. Acrolein‐induced depletion of circulating EPCs appears in part to be due to a defect in EPC mobilization and recruitment.COBRA: P20RR024489; PPG: P01ES011860
Maturation and Effects of In‐Utero Brain Ischemia on IL‐1 and IL‐6 Protein Expression in Ovine White Matter and Cerebral Cortex
Authors: Sadowska Grazyna Barbara , Threlkeld Steven W , Flangini Alexia , Surendra Sharma , Stonestreet Barbara S 
Published: June 2021

We examined the effects of maturation and ischemia‐reperfusion (IR) injury on changes in IL‐1β and IL‐6 protein expression in the ovine brain.Ovine fetuses were studied after 30 min of bilateral carotid artery occlusion and 72 h of reperfusion. Fetal and maternal control groups had no ischemia. IL‐1β and IL‐6 protein expression was compared between cerebral cortex (CC) and white mater (WM) in the same study groups using Western immunoblot.IR resulted in a 26% decrease in IL‐1β in CC and a 173% increase in WM as compared to the control fetuses. IL‐1β was 34% higher in WM than CC after IR. IL‐6 expression did not change in CC or WM after ischemia. IL‐1β was 31% higher in maternal than fetal control CC and 61% higher in maternal than fetal control WM. IL‐1β was 59% higher in fetal control CC than WM and 25% higher in maternal CC than WM. IL‐6 expression was significantly higher in maternal CC as compared to fetal control; there were no differences between fetal control and maternal WM. However, IL‐6 was 36% higher in control fetal WM compared to CC.IR results in down regulation of IL‐1β expression in fetal CC and up regulation in WM, and does not affect IL‐6 expression in either region. There is a differential response between IL‐1β and IL‐6 after ischemia in fetal CC and WM. There are also regional differences in IL‐1β and IL‐6 expression in normal fetal and maternal brain.
Regulation of cell adhesion and motility: a novel function of arrestin proteins
Authors: Cleghorn Whitney , Bulus Nada , Chen Dong , Zhang Xi , Zent Roy , Gurevich Vsevolod 
Published: June 2021

Arrestins bind G protein‐coupled receptors and more than 100 non‐receptor partners, regulating various signaling pathways and cellular functions. The interactions of many proteins (e.g., Src, JNK3, ERK½, Mdm2, etc.) with receptor‐bound arrestin localize these molecules to receptor‐rich membranes. Our recent finding that arrestins bind microtubules and recruit signaling proteins to the cytoskeleton prompted us to investigate whether arrestins affect cell adhesion, motility, and morphology. Here we show that arrestin double knock‐out (DKO) and arrestin2 knock‐out (A2 KO) cells stained with Rhodamine‐Phalloidin look drastically different than arrestin3 knock‐out (A3 KO) and wild type (WT) cells. DKO cells appear to spread in an integrin‐independent manner, in contrast to its single knock‐out and WT counterparts. Additionally, DKO cells show a significant deficit in cell adhesion to extracellular matrix protein fibronectin, whereas A2 KO cells show a dramatic increase. WT and A3 KO cells are similar. DKO cells have dramatically decreased active Rho compared to A3 KO and WT cells. Thus, arrestins differentially regulate cell adhesion and spreading.NIH Grants GM77561, GM081756 (VVG), VA Merit Award (RZ), training grant EY07135 (WMC).
Gene‐orientation‐dependent DNA methylation patterns in the mouse prolactin (Prl) family gene cluster locus
Authors: Hayakawa Koji , Hattori Naoko , Nakanishi Momo , Ohgane Jun , Tanaka Satoshi , Yagi Shintaro , Shiota Kunio 
Published: June 2021

DNA methylation is an epigenetic modification involved in gene silencing and genome stability. In mice, Prl family genes form gene cluster in about 1‐Mbp region. The Prl family genes other than Prl can be divided into two groups based on their expression patterns. One group is expressed only in placenta (group I), and the other group is expressed in placenta and a few other tissues (group II). This suggests that each group has gained specific regulation system for expression pattern. In our previous study, rat PL‐I, a member of Prl family, has been shown to have a tissue‐dependent and differentially methylated region (T‐DMR) hypomethylated in placenta. To explore epigenetic regulation of all the Prl family genes, we analyzed methylation status of them in placenta, liver and brain. We found that all the Prl family genes have T‐DMRs. Moreover, group I genes tended to have T‐DMRs hypomethylated specifically in placenta, and group II genes tended to be hypomethylated in placenta but showed variable methylation level in other tissues. Two groups of DNA methylation patterns were associated with the gene orientation in the cluster. The present study suggests that tissue‐specific expression patterns of Prl family genes are regulated by DNA methylation in association with the gene orientaion.This work was supported by KAKENHI (21248039) from MEXT, japan.
Zucker lean and fatty rat hepatocytes respond differently to insulin and retinoids in the expression of glucose and lipid metabolic genes
Authors: Li Rui , Chen Guoxun 
Published: June 2021

We found that retinoids synergized with insulin to induce glucokinase gene (Gck) expression in primary hepatocytes, indicating their roles in modulating insulin sensitivity. Whether any change of this synergy exists in insulin resistant animals is unknown. The expression levels of Gck, Srebf‐1c, Pck1 and Fas in hepatocytes isolated from Zucker lean (ZL, insulin sensitive) and fatty (ZF, insulin resistant) rats in response to increasing concentrations of all trans retinoic acid (RA) with or without 1 nM insulin were analyzed by real time PCR. For Gck, RA started to induce its expression at 0.1 uM and 3uM, and synergized with insulin in ZL and ZF hepatocytes, respectively. The Srebf‐1c mRNA was induced by RA at 0.1 uM and insulin in ZL, but not ZF hepatocytes. The Pck1 mRNA was induced by RA at 0.1uM or higher in both ZL and ZF hepatocytes. Insulin‐mediated suppression of Pck1 expression was attenuated by RA at 3uM in ZL, but not ZF cells. Fas mRNA was not affected by RA in both ZL and ZF hepatocytes after 6 hours of treatment. Our results showed that ZL and ZF hepatocytes respond differently to insulin and RA treatments, suggesting alterations of RA responses in liver of insulin resistant rats.Grant Funding Source: AHA
Effects of dietary conjugated linoleic acid (CLA) on intestinal absorption of vitamin A
Authors: Giordano Elena , Banni Sebastiano , Quadro Loredana 
Published: June 2021

Conjugated linoleic acid (CLA) is a polynsaturated fatty acid of ruminant origin. We previously showed that CLA t10, c12 and CLA c9, t11 isomers elevate vitamin A levels in rodent liver. To investigate whether this hepatic vitamin A accumulation results from increased intestinal vitamin A absorption, we performed gavage experiments with wild‐type male mice. 12 hr prior the experiment, mice were injected with P‐407, a lipase inhibitor that blocks chylomicrons clearance. Next morning, they were given an oral bolus of all‐trans‐[3H] retinol (2× 106 cpm) and unlabelled all‐trans‐ retinol (6μg) in 100 μl of olive oil or olive oil + either CLA isomer (70:30, v:v). 3 hr after the gavage, mice were sacrificed to collect serum and tissues.HPLC analysis of retinoids and [3H]‐counts/min revealed reduced retinoids levels in the intestine of mice gavaged with olive oil + either CLA isomer compared to those given olive oil. In serum, retinoids levels were not different among groups, but triglycerides were elevated in the olive oil group compared to mice given olive oil + either CLA isomer.These results suggest that a single dose of dietary CLA could affect intestinal chylomicron assembly and/or secretion, as well as vitamin A incorporation in these particles. Further experiments are ongoing to elucidate the molecular mechanisms of this effect and the consequences of chronic dietary CLA intake on intestinal vitamin A absorption.
Elucidating the mechanism of vitamin A uptake in tumor‐prone, vitamin A‐sensitive tissues
Authors: Schulte Christina Elaine 
Published: June 2021

Vitamin A (retinol) is not only essential for maintaining normal eye, brain, placenta, and skin function, but its active derivatives have powerful effects on cell proliferation and differentiation. The long‐term goal of this study is to understand how cancer incidence can be reduced through the optimization of vitamin A trafficking and signaling in tissues prone to tumor development. Retinol, the major circulating retinoid, travels to peripheral tissues in complex with retinol binding protein (RBP). Recently, a retinoic acid responsive protein with no known biological function, STRA6, has been identified as an essential transmembrane receptor that mediates retinol uptake in retinal epithelial cells. It conferred RBP binding to retinal cells transfected with a STRA6 expression vector, as well as increased cellular uptake of vitamin A. The goal of our current study is to examine the mechanism of RBP‐bound retinol uptake in mammary, prostate, and colon epithelial cells, which express abundant levels of STRA6. We will utilize siRNA to determine whether knockdown of STRA6 inhibits retinol‐RBP uptake as assessed by tracer assays and fluorescent microscopy, as well as the requirement of STRA6 for retinol‐mediated differentiation, apoptosis, and cell cycle arrest. These studies will lay the foundation for developing strategies for optimizing vitamin A status and retinol trafficking in tissues prone to tumors.Grant Funding Source: NIH SR03CA128091‐0
Gymnasterkoreayne B exerts chemopreventive effects through regulation of Nrf2 and p53 cooperatively
Authors: Lee Saet Byoul , Kang Kyungsu , Pan Cheol‐Ho , Lee Jae Kwon , Jung Sang Hoon , Lee En‐Ha , Nho Chu Won 
Published: June 2021

Phytochemicals prevent cancer either through blocking initiation by detoxification of carcinogens or through suppressing by apoptosis. In this study, we have identified a Gymnasterkoreayne B (GKB), a polyacetylene compound, isolated from Aster koraiensis as a major principle for a significant quinone reductase (QR) induction via Nrf2‐ Antioxidant response element (ARE) pathway. Furthermore, the induction of QR activity was increased by GKB in vivo. Interestingly, GKB induced apoptosis and p53 and p21 protein levels. In p53‐ or p21‐ knock out cells, Nrf2 activation and stabilization was decreased than wild type cells. However, apoptosis was induced by GKB in the knock out cells, and more induced in Nrf2 knock down cells. From the results, we can suggest that Nrf2 and p53 have a close relationship in cancer cell model induced by phytochemicals in terms of cancer chemoprevention. Taken together, we present here that GKB not only increases QR through Nrf2‐ARE pathway but also induces apoptosis through p53, and that it could be induced cancer chemoprevention effect by the cooperative regulation of both blocking and suppressing of cancer.Grant Funding Source: KIST‐Gangneung Institute intramural research grant (2Z03300)
Age‐dependent changes in the sphingolipid composition of CD4+ T cell membranes and immune synapses
Authors: Huang Zhaofeng , Marko Melissa G. , Bunnell Stephen C. , Wu Dayong , Merrill Alfred H , Meydani Simin Nikbin 
Published: June 2021

Optimal T cell activation requires the formation of an immunological synapse (IS) and is driven by signaling ‘microclusters’ that associate with ordered membrane microdomains. Aging is associated with impaired IS formation and T cell activation. We hypothesized that age‐dependent changes in T cell lipid profiles impair IS formation and T cell activation in the aged. Total cell membrane (TCM) and IS fractions were prepared from the CD4+ T cells of young and old mice and subjected to ‘sphingolipidomic’ analysis. Both TCM and IS of aged CD4+ T cells have significantly higher levels of sphingomyelins and ceramides than young T cells. A subset of the lipids containing C14, C18:1, C26, and C26:1 fatty acid (FA) species was preferentially enriched in the IS. Young IS were enriched in C14 ceramide, C18:1 ceramide, C26:1 ceramide, and C14 hexosylceramide. Since sphingolipids are implicated in T cell activation and function, age‐dependent changes in the FA chain lengths and sphingolipid species retained in IS could influence T cell activation and function and may contribute to functional T cell defects in the aged.Supported by NIA R21‐AG030931, R01‐AG009140‐14, Office of Dietary Supplement, USDA‐ARS contract number 58‐1950‐7‐707, and LIPID MAPS Consortium.
Curcuma or citrus extract supplementation does not improve body condition nor insulin sensitivity in obese cats
Authors: Leray Veronique , Jeusette Isabelle , Serisier Samuel , Freuchet Benjamin , Torre Celina , Nguyen Patrick 
Published: June 2021

The putative therapeutic properties of curcuma and citrus could be associated with their antioxidant and anti‐inflammatory properties. Our aim was therefore to examine the effects of citrus or curcuma extract supplementation on body condition and inflammatory state in obese cats.Eight obese cats participated in this study that was conducted as a cross‐over, with two 8‐week periods. The diets were supplemented with either curcuma or citrus extract. Body composition (D2O dilution method), insulin sensitivity (euglycemic hyperinsulinemic clamp technique), plasma leptin level (RIA), and TNFα, IL1β and IFNγ mRNA expression in leucocytes (real‐time PCR) was assessed prior to and at the end of the test period.Body weight was unchanged by either diet. Both diets lowered fat‐free mass whereas the percentage of fat mass increased. Basal glycemia, basal insulinemia, insulin sensitivity and plasma leptin level were not modified whatever the diet. TNFα, IL1β and IFNγ mRNA levels were not affected by either diet.Similar plasma leptin level in both groups is consistent with their body weight and body composition. Our results suggest that curcuma or citrus extract supplementation is not effective in improving body weight, body composition, insulin sensitivity, or inflammatory state in obese cats.
Effect of Methyl Nutrients on Feline Lymphoma Growth
Authors: Mabasa Lawrence , Cho Kyongshin , Fowler Andrea W. , Park Chung S. 
Published: June 2021

Feline lymphoma is one of the most frequently diagnosed tumors in cats. Lipotropes are dietary methyl donors and cofactors that are involved in one‐carbon metabolism and DNA methylation. However, little is known about their role in feline lymphoma. We hypothesized that supplementation of lipotropes would modulate the DNA methylation status and the expression of genes involved in cell growth and apoptosis of feline lymphoma cells. The objective of the study was to determine if lipotropes affect growth of feline lymphoma cells: entailing examining a correlation between lymphoma cell growth and caspase‐3 enzyme activity. Feline lymphoma cell lines, F1B and FeLV‐3281, were cultured and treated with 20 times the level of each lipotrope contained in the basal culture medium (control). Cell growth and caspase‐3 activity were measured. Lipotropes significantly reduced cell growth (45.4%) and increased caspase‐3 activity (4.9%, P = 0.01) of F1B cells after 72 hours. However, cell growth and caspase‐3 activity of FeLV‐3281 were not affected by lipotropes. These results suggest that methyl nutrients may play a role in reducing cell growth of F1B, but not FeLV‐3281. Further studies are warranted to determine the mechanism underlying the inhibitory effect of lipotropes on F1B lymphoma cell growth.Supported by Morris Animal Foundation (D08FE‐047).
Dietary fish oil decreases DNA adducts in the rat colon independent of estrogen status
Authors: Armstrong Cameron , Allred Clinton D. 
Published: June 2021

Colon cancer is the third leading cause of cancer related death in men and women in the United States. Data from multiple studies show that dietary fish oil is associated with a decrease in colon cancer incidence. Estradiol (E2) has also been demonstrated to be protective against colon tumor formation and we have shown that E2 induces colonocyte apoptosis in conjunction with reducing formation of premalignant lesions. To date, however, possible relationships between estrogen status and the benefits of fish oil have not been thoroughly examined. We hypothesized that E2 could enhance the effects of dietary fish oil by additively decreasing DNA damage and increasing apoptosis. Dietary fish oil significantly decreased immunohistochemical staining intensity of O6‐methyldeoxyguanosine DNA adducts independent of the presence of E2 at 9h and 12h post treatment with carcinogen. E2 resulted in a significant increase in apoptosis independent of diet group at 12h post carcinogen, most notably in the luminal third of the crypts. Fish oil was not associated with an increase in apoptosis. These data are important because they demonstrate that fish oil is protective against DNA damage in the colon regardless of E2 status. In addition, our data demonstrate that induction of apoptosis in colonocytes at the point of DNA damage may serve as a primary mechanism for how E2 suppresses colon tumor formation.Grant Funding Source: American Institute for Cancer Research
Water turnover assessment in overweight adolescents
Authors: Weinheimer Eileen , O'Connell Bláthnaid N , Martin Berdine R , Schoeller Dale A , Weaver Connie M , Campbell Wayne W 
Published: June 2021

Adequate intake (AI) standards for water (H2O) in adolescents range between 2.4 – 3.3 L/d for males and 2.1 – 2.3 L/d for females, independent of obesity status. Water intakes and excretions of this population are not well documented.PurposeTo assess H2O turnover, inputs and outputs in overweight adolescents.Methods18 girls (BMI 31.7 ± 1 kg/m2; mean ± SEM) and 9 boys (BMI 26.3 ± 1 kg/m2) aged 12–15 y completed two 3‐wk metabolic balance trials. Rate of H2O turnover (rH2O) was measured by tracking the decline of deuterated H2O from the body over 14 d. Water inputs (diet*, ad libitum#, metabolic#) and outputs (urine*, feces*, insensible#) were assessed (*=measured, #=estimated).ResultsUsing both trials (girls n = 36 trials; boys n = 18 trials), rH2O was higher (p<0.05) in boys vs. girls (4537 ± 202 vs. 3742 ± 122 g/d). Per kg body weight, rH2O was 28% lower in girls vs. boys (46 ± 7 vs. 64 ± 9 g kg−1 d−1). Water input from diet, ad libitum intake and metabolic production were 44, 19, and 28% lower, respectively, in girls vs. boys. Urine, fecal and insensible H2O losses were 29, 17, and 29% lower in girls v. boys. BMI did not influence rH2O. The intraclass correlation of rH2O between trials was 0.981 (p < 0.001).ConclusionThese overweight adolescents consumed H2O well in excess of sex specific AI standards. The higher rH2O in boys vs. girls is consistent with adult males vs. females.
Convenience Drives Choice in School Lunch Rooms: A Salad Bar Success Story
Authors: Smith Laura E. , Just David R. , Wansink Brian 
Published: June 2021

Efforts to improve food choice in high schools and middle schools often focus on either taxing or on eliminating less healthy alternatives ‐‐ both which could drive students away from the school lunch program. Building on the premise that two influences on school lunch decisions are salience and convenience, a field was conducted in a middle school where the objective was made to make the salad bar more salient and convenient to students. Instead of being placed parallel to a lunchroom wall, it was moved 4 feet and rotated 90 degrees perpendicular to the cash registers. Depending on the specific food items, the resulting salad sales increased 300 to 400 percent compared from year‐to‐date figures. Additionally, these sales occurred without a decrease to overall lunchroom sales or per/person expenditures. A variety of additional “healthy‐foods‐made‐more‐convenient” opportunities are suggested as next‐step interventions worth of investigation.Grant Funding Source: none