bluuebunny/crossref_metadata_2025_split huggingface dataset:
hNAG‐1 increases survival by regulating metabolism and insulin/IGF‐1/mTOR signaling (LB432)
Authors: Wang Xingya , Kali Chrysovergis , Justin Kosak , Kissling Grace , Li ruifang , Eling Thomas 
Published: June 2021

Metabolic dysfunction is a hallmark of aging. High fat diet (HFD) promotes mortality and decreases lifespan in laboratory animals. Nonsteroidal anti‐inflammatory drug‐activated gene‐1 (NAG‐1) has been shown to play a role in adiposity homeostasis and metabolism. However, it has not been determined if hNAG‐1 increases survival and longevity upon high fat diet. Here we show that hNAG‐1 mice have both significantly increased mean and median life spans than wild‐type (Wt) littermates on a high fat diet. Over the course of the study, hNAG‐1 mice displayed reduced body and adipose tissue weight, lower serum IGF‐1, insulin and glucose levels, improved insulin sensitivity, and increased metabolism. Gene expression analysis revealed significant differences in conserved genes that are important regulators of longevity. Phosphorylation of major components of IGF‐1/mTOR signaling was significantly lower in hNAG‐1mice. Our study shows that hNAG‐1 improves mammalian survival by increasing oxidative metabolism and reducing IGF‐1/mTOR signaling. Our study suggest that hNAG‐1 is an important regulator of mammalian longevity and may act as a survival factor with potential therapeutic uses in obesity‐related diseases where life span is frequently shorter.Grant Funding Source: NIEHS Intramural Research Program (Eling) Z01‐ ES010016‐14
Effects of a high‐protein low‐calorie intermittent‐fast diet on plasma toxins and oxidative stress following weight loss (LB435)
Authors: Gumpricht Eric , Ward Emery , He Feng , Schuler Bradley , Cho Suk , Arciero Paul 
Published: June 2021

In obese subjects, the decrease in fat mass with weight loss is generally regarded as beneficial and may favorably alter oxidative stress. However, it also increases the release of polychlorinated biphenyls (PCBs) from fat depots. Thus, the purpose of this study was to examine the effects of a 10 week higher protein‐low calorie diet incorporating intermittent fasting (HPLC‐IF) on fat mass, plasma toxins (PCBs) and oxidative stress biomarkers, thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) in 43 obese men (n=22) and women (n=21). Fat mass, plasma PCBs and oxidative stress biomarkers were assessed at the beginning (pre) and end (post) of the intervention. Following the 10 week HPLC‐IF diet, fat mass decreased significantly (P<0.01) in both groups (males, n=21: 47.5 ± 14.8 vs 37.4 ± 13.3; females, n=19: 49.4 ± 9.6 vs 40.8 ± 9, kg) with males losing more fat mass (‐21.8 ± 5.5% vs ‐17.7± 5.3%, P<0.05; respectively). Eight of 11 individual PCB congeners and total PCB concentration increased significantly overall (Pre: 86.7 ± 45.6 vs Post: 115.6 ± 65.9 ng/g lipid; P<0.01). There were no gender‐specific differences in either individual PCB congeners (with the exception of one) or total PCBs. In addition, TAC increased (Pre: 19.0 ± 2.6 vs. Post: 19.9±2.6 nmol/mL; P<0.05), and TBARS decreased (Pre: 0.24 ± 0.16 vs. Post: 0.18±0.11 μM; P=0.01) overall, with no gender‐specific differences. Interestingly, the percent increase in TAC and total PCB concentration were significantly correlated with the decrease in total fat mass (r=‐0.35, P<0.05; r=‐0.42, P<0.01, respectively). These results suggest that an HPLC‐IF diet induces significant reductions in fat mass resulting in elevated PCB concentrations. Nonetheless, this fat loss‐induced increase in circulating toxins occurred in the presence of enhanced antioxidant status. Although additional study is required to determine the relevance of PCB release during weight/fat loss, our results suggest that an HPLC‐IF diet results in significant improvements in both body composition and antioxidant status.Grant Funding Source: Isagenix International, LLC
Assessing diet and physical activity related to obesity risk among Ugandan school children (LB462)
Authors: Christoph Mary , Grigsby‐Toussaint Diana , Baingana Rhona , Ntambi James 
Published: June 2021

In Uganda, 10.4% and 3.2% of adolescent girls and boys are considered overweight, even in the midst of malnutrition. However, few studies have explored risk factors associated with obesity among adolescents. We conducted a cross‐sectional survey of 151 randomly selected children aged 11‐ 16 years in two central Ugandan rural and urban schools in November 2013. Sociodemographic characteristics, diet, and physical activity were surveyed; height, weight, and waist circumference were measured (kg/m2, cm). Mean age of participants was 12.1 years (±1), with a mean BMI percentile of 43% (49% male). Sixty‐two percent of the children owned TVs, primarily driven by the urban sample, 73% of whom owned TVs. Soda consumption (64% having consumed within the past week) did not differ by school. Underweight was more common than overweight, with 10% of children being below the 10th percentile, and only 5.3% above the 80th percentile. Meat and fruit (but not vegetable) consumption and physical activity differed by rural‐urban residence (P<0.01), with rural children reporting lower physical activity and meat consumption, but higher fruit intake. This study is one of the first to assess the impact of diet and activity among rural and urban school children in Uganda. It provides a basis for understanding the risk factors associated with overweight and obesity in adolescents in Uganda.Grant Funding Source: This was was supported by the Agriculture and Food Research Initiative of the USDA National Institute of Food and Agriculture as part of the AFRI Childhood Obesity Prevention Challenge (2011‐67001‐30101) to the UIUC Division of Nutritional Sciences.
Macrophage migration inhibitory factor has a role controlling colorectal cancer (LB491)
Authors: Rodriguez‐Sosa Miriam , Pacheco‐Fernández Thalia , Juárez‐Avelar Imelda , Rodríguez‐Monroy Marco , Nieto‐Yañez Oscar , Chirino Yolanda , León‐Cabrera Sonia , Pérez‐Plasencia Carlos , Avila‐Moreno Federico , Terrazas Luis 
Published: June 2021

Chronic inflammation has been related with cancer development by counteracting and unbalancing the immune response. The inflammatory cytokine macrophage migration inhibitory factor (MIF) is overexpressed in many carcinogenic tumors, stimulates angiogenesis and metastasis promoting proliferation and survival in malignant cells. In the inflammatory disease ulcerative colitis MIF is early expressed and favors the inflammatory cytokine production like TNF‐α, and IL‐1β. As intestinal chronic inflammation may proceed to colorectal cancer, we are interested in determining the role of MIF on development and pathology on colorectal cancer. To elucidate this point we used MIF‐KO and WT mice, both with BALB/c genetic background, to develop a colorectal cancer model of Dextran Sodium Sulfate and Azoxymethane. As expected, MIF‐KO mice showed low levels of serum inflammatory cytokines TNF‐α, IL‐1β and IFN‐γ compared to WT mice. Strikingly, we found significantly more tumor and in a higher development stage on MIF‐KO mice (24.4+/‐2) compared to WT mice (12.6+/‐2). Higher number of activated macrophages and NK cells were detected in intestinal epithelium on WT mice compared to MIF‐KO mice. Therefore, although MIF has been recognized as a promoter of inflammation, which could favor the development of cancer; our results suggest that MIF is involved in controlling the development of colorectal cancer, possibly by its chemokine properties.Grant Funding Source: Supported by CONACyT (152224) and PAPCA‐2013. The student TPF holds a scholarship from CONACyt, #20465.
Systemic platelet‐activating factor‐receptor activation augments experimental lung cancer growth and metastasis (LB496)
Authors: Sahu Ravi , Hackler Patrick , Konger Raymond , Travers Jeffrey 
Published: June 2021

Pro‐oxidative stressors including cigarette smoke (CS) generate novel lipids with Platelet‐activated Factor‐receptor (PAF‐R) agonistic activity and mediate systemic immunosuppression, one of the most recognized events in promoting carcinogenesis. Our previous studies have demonstrated that PAF‐R agonists mediated systemic immunosuppression augments the growth of experimental murine B16F10 melanoma tumors in a PAF‐R dependent manner. As CS generates PAF‐R agonists, the current studies sought to determine the impact of PAF‐R‐agonists on lung cancer growth and metastasis using an established experimental murine lewis lung carcinoma (LLC) model. We show that systemic PAF‐R agonist, CPAF augments the growth of subcutaneously implanted LLC tumors in a PAF‐R dependent manner as this effect was not observed in PAF‐R deficient (PAFR‐KO) mice. We next determined the ability of CPAF‐mediated PAF‐R dependent enhanced LLC tumor growth on lung metastasis. We observed increase number of lung mets only in CPAF‐treated WT and not in PAF‐R‐KO mice. In order to investigate the role of tumor or host cell PAF‐R in these effect, we first determined the expression of the PAF‐R in LLC tumor cells. Our results demonstrate that LLC tumor cells lack functional PAF‐R expression as measured by qRT‐PCR and functional Ca2+ mobilization assay and compared with arrays of PAF‐R sufficient and deficient cells. In addition, CPAF treatment failed to induce increase proliferation of LLC cells, indicating the role of host rather tumor cell PAF‐R in these events. This finding has clinical implications as it provides insight into a mechanism through which lung cancer cells evade immune surveillance.Grant Funding Source: NIH R01 HL062996, AICR 09A062, ACSIRG 4185607, Showlater Research Trust Fund 4485602
Investigating the effect of antibiotics on gut microbiota components and subsequent Clostridium difficile infection (LB516)
Authors: Schenck Louis Patrick , Hirota Simon , Armstrong Glen , MacDonald Justin , Beck Paul 
Published: June 2021

C. difficile (Cdif) infections (CDI) are a world‐wide epidemic. Recent small clinical trials have generated excitement for the use of fecal microbial transplants as a therapeutic option; however, the exact components of the microbiota needed for protection against CDI have remained elusive. This study assessed the specific intestinal microbiota components associated with prevention or exacerbation of CDI in a mouse model of disease. C57/Bl6 mice from two different vendors (A or B) were exposed to broad‐spectrum antibiotics before oral gavage with Cdif spores. Mice from A and B were co‐housed for 14 days, followed by exposure to antibiotics and development of CDI. Microbiota diversity and composition were analyzed using Illumina MiSeq Next‐Gen Sequencing of 16S rDNA in fecal samples. Mice from different vendors had distinct microbiota profiles both before and after antibiotic exposure. Mice from A developed severe CDI as evidenced by weight loss, histological damage, increased MPO levels and inflammatory cytokines, including KC and IL‐1β. Mice from B were resistant to CDI with minimal histological and cytokine changes from baseline. While similar at naïve levels, vendor B retained a high abundance of Bacteroidetes phyla after antibiotics. Following cohousing, mice from vendor A had less severe CDI and mice from vendor B had more severe CDI. Our data are the first to identify specific patterns in the intestinal microbiota that confer susceptibility to CDI. Furthermore, the bacterial populations that may be critical for preventing or reducing the severity of CDI were revealed. This study may lead to more targeted bacteriotherapy for the treatment and prevention of CDI.Grant Funding Source: Supported by Canadian Institute of Health Research and Alberta Innovates ‐ Health Solutions
Impaired microvascular function and increased vascular endothelial cell angiopoeitin‐2 and tie‐2 mRNA expression in human sepsis (LB527)
Authors: Wegman‐Points Lauren , Lane Abbi , Doerschug Kevin , Delsing Angela , Pierce Gary 
Published: June 2021

Sepsis is a systemic inflammatory syndrome resulting in acute organ failure attributable to heterogeneous tissue perfusion and microvascular endothelial vasodilatory and barrier dysfunction. Angiopoeitin‐2 (Ang2), a growth factor released into circulation that binds to the Tie‐2 receptor during sepsis, is a robust predictor of clinical disease severity. However, there is currently no direct evidence in humans that Ang2 and Tie2 mRNA/protein expression are elevated in the endothelium of critically ill patients with sepsis. Microvascular function (finger peripheral artery tonometry) was reduced 44% in septic patients (n=4) vs. age‐matched (n=8) controls (1.480.14 vs. 2.630.17%, P<0.01). Interestingly, Ang2 (+1.7 fold P<0.03) and Tie2 (+2.7 fold, P<0.04) mRNA (qRT‐PCR) were higher (vs. controls), in human aortic endothelial cells incubated 24 hrs in vitro with media + 10% plasma from sepsis (n=6) vs. control (n=6) humans. In a subset, there was no difference in Tie‐2 (n=3, 6.4e5 ± 1.5e5 vs. n=4, 4.4e5 ± 7.4e4, P=0.23) protein expression (corrected fluorescence) in isolated endothelial cells (J wire sampling/immunofluorescence), but Ang2 tended to be lower (n=2, 1.6e5 ± 7.8e3 vs. n=4, 2.1e5 ± 1.6e4, P=0.10) in sepsis vs controls. These data suggest that Ang2 and Tie‐2 gene expression are upregulated in the septic endothelium and lower protein Ang2 expression may indicate extracellular Ang2 protein release.Grant Funding Source: Supported by NIH 5R01HL092056‐05
Molecular and cellular mechanism of systemic vaso‐occlusion in Sickle Cell Disease (LB544)
Authors: Jimenez Maritza , Sundd Prithu 
Published: June 2021

SCD is a genetic disease caused by a single point mutation in the β‐globin gene of hemoglobin, which leads to sickling of RBCs under deoxygenated condition. Sickle RBCs (sRBCs) are not only less deformable, but also express enhanced levels of major adhesion molecules compared to normal discoid shaped RBCs of healthy patients. In addition to RBC sickling, SCD is also associated with a hyper‐inflammatory state, which accounts for enhanced adherence of leukocytes to vascular endothelium. Leukocyte‐endothelium adhesion starts with leukocyte rolling mediated by P‐selectin‐glycoprotein‐ligand (PSGL)‐1 on leukocytes binding to P‐selectin on endothelium. Rolling is followed by firm arrest, which is medicated by activated β¬2‐integrins (LFA‐1 and Mac‐1) on the leukocytes binding to inter‐cellular‐adhesion‐molecule (ICAM)‐1 on endothelium. Although neutrophils have been shown to play a role in the onset of vaso‐occlusion by interacting with sRBCs in systemic venules of SCD mice, the cellular and molecular mechanism that enables systemic vaso‐occlusion in human patients is not completely understood. Heparinized blood from SCD patients and race matched control subjects is perfused through a microfluidic flow chamber with a glass bottom coated with either human microvascular endothelial cells or a cocktail of P‐selection, ICAM‐1 and CXCL‐8 at a physiological shear stress (2‐10 dyn cm‐2). Fluorescent Abs against CD16 and glycophorin‐A are added to the blood to stain neutrophils and sRBCs, respectively and cellular interactions recorded using multi‐color Quantitative Dynamic Footprinting or epifluorescence microscopy. Preliminary results reveal that neutrophil arrest is facilitated by the formation of a thick trunk like structure at the rear, which also enables capturing of free flowing sRBCs by arrested neutrophils. Understanding the molecular mechanism behind vaso‐occlusion will be useful in designing prophylactic interventions for SCD patients.Grant Funding Source: This study is supported by 11SDG7340005 from the American Heart Association (P.S.), VMI start‐up funds (P.S.) and CBTP‐T32 fellowship (M.J).
Hyperoxia and Regulatory T cell (Treg) development in neonatal mice Hardik Patel1, Angela Leon Hernandez1, Mark Pezzano2 and Mohamed Ahmed1 1Neonatology Research Lab, The Feinstein Institute for Medical Research, Manhasset, NY. 2Department of Biology, The City College of NY, New York, NY (LB546)
Authors: Patel Hardik , Leon Hernandez Angela , Pezzano Mark , Ahmed Mohamed 
Published: June 2021

Oxygen is the most common therapy used in Neonatal Intensive Care Unit (NICU). The potential effect of hyperoxic exposure has become a focus of concern. In our preliminary findings, we found decreased levels of CD4+ cells and Tregs (FOXP3+) in the thymus of hyperoxia exposed neonatal mice. Our aim is to find the mechanism by which hyperoxia decreases Treg cells in neonatal mice thymus. Chemokines such as CCL19 and CCL21 and their receptors CCR7, CCR9 and CxCR4 are crucial for development of Treg cell in the thymus. Therefore, we hypothesized that hyperoxia disrupt Treg cell development through an imbalance in chemokine expression or its target receptors.Neonatal mice were housed either at room air (FiO2 21%), or hyperoxia (FiO2 95%) for five days. After exposure, thymus immunostainined for FOXP3, CD4, CCL19 and K14. Chemokines CCL19 &amp; 21 expression was done using RT‐qPCR. CCR7, CCR9, CxCR4 and FOXp3 were assayed using for flow cytometery.Immunostaining showed arrest of FOXP3 positive cells at the cortico‐medullary junction and increased expression of CCL19 in cortical area of thymus of hyperoxia group. CCL19 and CCL21 mRNA levels were higher in hyperoxia group. CCR7, CCR9 and CxCR4 chemokine receptors were significant decrease on double negative (CD4‐CD8‐) cells. CCR7 expression was also significantly decreased on FOXP3 expressing double positive cells.Suppression effect of hyperoxia on Treg development and maturation is possibly due to down regulation of receptor (CCR7, CCR9 and CXCR4) expression in the early developmental stage. Treg cells arrest in the cortico‐medullary junction, even with higher expression of chemkines, is possibly related to low CCR7 expression on CD4+ CD8+ double positive cells.
Cardiac responses to selected cranial osteopathic manipulations in healthy young men (LB656)
Authors: Ioudina Marina , Toder Eric , Baldwin Cory , Lowe Rachel 
Published: June 2021

Background and Purpose: Cranial manipulations (CM) as a part of osteopathic manipulative treatment have been used to treat patients. However, physiological responses to CM are not well defined in literature. The purpose of this study was to measure changes in heart rate (HR), heart rate variability (HRV), stroke volume index (SI), and cardiac index (CI) in response to selected CM and sham manipulation.Method: Healthy 25‐35 year old men participated in this study. Non‐invasive impedance cardiography method was used to measure changes in cardiac parameters before and after manipulations. Data were recorded and analyzed using BIOPAC Systems, Inc. equipment and software. All manipulations were performed by the same osteopathic physician.Results: CM increased parasympathetic input (70%) to the heart resulting in decreased HR (5%) and CI (7%) without significant effect on SI. These changes were not seen in sham manipulation.Conclusion: Selected CM decreased CI by decreasing HR without significant effect on cardiac contractility in healthy young men. Future studies will compare gender and age differences in response to osteopathic techniques.Grant Funding Source: This project was funded by the TUN Research Grant Award
High‐intensity interval exercise protects against postprandial endothelial dysfunction in obese adolescent males (LB662)
Authors: Ryder Justin , Hultgren Neil , Barazza Estela , Gaesser Glenn , Shaibi Gabriel 
Published: June 2021

In adults, consuming a high‐fat meal can induce endothelial dysfunction while exercise may mitigate postprandial endothelial dysfunction. Whether exercise is protective against postprandial endothelial dysfunction in youth is unknown. The purpose of this study was to determine if high‐intensity interval exercise (HIIE) performed the evening prior to a high‐fat meal protects against postprandial endothelial dysfunction in obese adolescent males. Fourteen obese adolescent males (BMI%tile=98.5±0.6; 14.3±1.0yrs; VO2peak=2.6±0.5 L/min) completed a single HIIE session on a cycle ergometer (8 X 2min at 蠅90%HRmax, with 2min active recovery between bouts, 42min total) in the evening. Participants returned at 09:00 the following morning where brachial artery flow‐mediated dilation (FMD) was measured using duplex ultrasound after 20min of supine rest in the fasted state. Following baseline FMD (7.5±3.0%), a high‐fat milkshake (; 60% Fat, 35% CHO) consisting of 0.7g/kg of body weight was consumed (766±84 kcal). FMD was subsequently measured at 2hr and 4hr post‐consumption. Despite consuming a high‐fat meal, endothelial function was preserved at 2hr (8.4±3.4%) and 4hr (8.8±3.9%) post‐meal (p(time)=0.598). These data suggest that HIIE may protect against the deleterious vascular effects associated with a high‐fat diet in obese adolescent males.Grant Funding Source: American College of Sports Medicine
Dietary sodium loading increases systolic BP variability in salt resistant adults: a role for serum sodium (LB701)
Authors: Brian Michael , Wenner Megan , Evan Matthews , Ramick Meghan , Edwards David , Stocker Sean , Farquhar William 
Published: June 2021

Dietary sodium loading increases systolic BP variability in salt resistant adults: a role for serum sodium Michael S. Brian1, Megan M. Wenner1, Evan Matthews1, Meghan G. Ramick1, David G. Edwards1,2, Sean D. Stocker3, William B. Farquhar1,2 1Department of Kinesiology &amp; Applied Physiology and 2Department of Biological Sciences, University of Delaware, Newark, DE, 3Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA.Increased systolic blood pressure (SBP) variability has been linked to poor cardiovascular outcomes. We examined the effects of dietary sodium‐induced increases in serum sodium (s[Na+]) on SBP variability in salt resistant adults. Twenty‐nine subjects (38±14 yrs) were randomized to low (LS: 20 mmol/d) and high (HS: 300 mmol/d) sodium diets (1‐week each). All subjects were salt resistant (mean BP change < 5 mmHg between diets). Subjects were ranked based on the increase in s[Na+] going from LS to HS diet, and a median split was utilized such that two groups were compared (s[Na+] responders: 2.6±0.8 mEq/L vs. s[Na+] non‐responders: ‐0.63±2.2 mEq/L). 24‐hr BPs were recorded during the last day of each diet (every 20‐30 min/24 hrs); the standard deviation (SD) of SBP was used as an index of variability. During the high dietary sodium condition, SBP variability was greater in the s[Na+] responders compared to the s[Na+] non‐responders (13.8±3.2 vs. 10.8±1.6, mmHg, p < 0.01). Moreover, the change in SBP variability going from LS to HS diet was greater in the s[Na+] responders compared to the s[Na+] non‐responders (Δ3.0±2.2 vs. Δ‐0.90±2.4 mmHg, p < 0.01). Linear regression analysis across all subjects supported a modest relation between s[Na+] and SBP variability (r2=0.32, p < 0.01). These data suggest that dietary sodium loading can increase SBP variability in salt resistant adults, but only in those that have a diet‐induced increase in s[Na+].Grant Funding Source: NIH Grant R01 HL104106