bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tempol Prevents Hypertension in Maternal High Fat‐High Sucrose Diet Programmed Rats
Authors: Polson Jaimie W , Jayaratne Sachini K 
Published: June 2021

Diets high in fat and sucrose (HFS) during pregnancy program an increased risk of hypertension in the offspring. In light of accumulating evidence that oxidative stress plays an important role in the pathogenesis of hypertension, we tested the hypothesis that the superoxide dismutase mimetic 4‐hydroxy 2,2,6,6,‐tetramethyl piperidine 1‐oxyl (Tempol, 3mM) will ameliorate hypertension in HFS programmed offspring.Dams were fed a control (4.8% fat, 0% sucrose) or HFS diet (21% fat, 34% sucrose) from 4 weeks prior to mating until weaning. Consistent with our previous studies, dams did not become obese. At 3 months age, adult male offspring were assigned to one of 4 groups for the remainder of the experiment: control+water (CW), control+Tempol (CT); HFS+water (HW), HFS+Tempol (HT). After 2 weeks of treatment, rats were implanted with radiotelemetry probes and blood pressure (BP) and heart rate (HR) were measured at rest for 24 hours. Data are expressed as mean ± SEM.Resting BP was higher in HFS than control offspring (SBP, day CW, 125.6±2.9 vs HW, 135.0±2.4 mmHg; night CW, 129.1±2.1 vs HW, 137.0±2.1 mmHg, P<.05). Resting BP in HFS offspring treated with Tempol (day, 122.2±2.8 night, 125.5±1.8 mmHg) was not significantly different from either control group (CW, day, P=0.55, night, P=0.25; CT, day, 121.7±3.5, P= 0.89; night, 121.7±1.4 mmHg, P=0.25). HR was not different between groups (night, CW, 332±20 vs HW, 320±10 BPM, P=0.60) and Tempol had no effect on HR (night, CT 304±10 vs HT, 327±16 BPM, P=0.60). Sympathetic blockade with hexamethonium (50mg/kg, s.c.) reduced BP similarly in all groups (CW, 42.6±5.1; HW, −41.4±5.9; CT,41.2±5.1; HT, 34.2±5.6 mmHg, P=0.41).Tempol treatment reduced BP in a maternal HFS model of programmed hypertension, suggesting that oxidative stress may play a role in its etiology. There were no differences in the depressor response to sympathetic blockade with hexamethonium, suggesting that the effects of Tempol were not mediated by changes in sympathetic activity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Exercise Training and TrkB blockade on Cardiac BDNF‐TrkB signaling post Myocardial Infarction in Rats
Authors: Lee Heow Won , Ahmad Monir , Wang Hong‐Wei , Leenen Frans H.H. 
Published: June 2021

PurposeExercise training post myocardial infarction (MI) is beneficial for preserving cardiac function, but underlying mechanisms are still unclear. Exercise increases brain‐derived neurotrophic factor (BDNF) in the non‐infarct area of the left ventricle (LV) with an improvement of ejection fraction (EF) and LV end‐diastolic pressure (LVEDP). Whether these effects are mediated by downstream pathways of BDNF via its binding receptor tropomyosin‐related kinase B receptor (TrkB) has not yet been assessed. Therefore, impact of exercise training post MI on cardiac function and one of downstream effectors of BDNF‐TrkB signaling, Ca2+/calmodulin dependent protein kinase II (CaMKII), were investigated in exercising rats treated with vehicle or TrkB blocker, ANA‐12.MethodsAfter sham surgery (n=10) or ligation of coronary artery, surviving MI rats were divided into 3 groups: sedentary MI with vehicle (Sed‐MI‐Veh, n=17), exercise MI with vehicle (ExT‐MI‐Veh, n=17) and exercise MI with ANA‐12 (ExT‐MI‐ANA‐12, n=7). Exercise training was done for 4 weeks (5 days/week) on a motor‐driven treadmill with or without ANA‐12 (0.5 mg/kg). At the end, LV function was evaluated by echocardiography and Millar catheter, and mature BDNF (mBDNF), phospho‐CaMKII (p‐CaMKII) and CaMKII (pan) levels were assessed in the non‐infarct area of the LV by Western blotting.ResultsMI size was similar among the MI groups. ExT‐MI‐Veh showed higher EF compared to Sed‐MI‐Veh (63 ± 2 vs. 54 ± 2%, ExT‐MI‐Veh vs. Sed‐MI‐Veh). Exercise‐induced improvement of EF was inhibited by ANA‐12 (56 ± 2%). LVEDP was significantly lower in exercise MI groups (11.6 ± 0.9 and 12.8 ± 1.6 mmHg, Veh and ANA‐12) compared to Sed‐MI‐Veh (18.4 ± 0.9 mmHg). After MI, p‐CaMKII and p‐CaMKII/CaMKII (pan) were significantly decreased (0.6 ± 0.04 and 0.5 ± 0.1, fold of Sham, respectively). Exercise increased mBDNF (0.9 ± 0.1 vs. 0.7 ± 0.1 vs. fold of Sham, ExT‐MI‐Veh vs. Sed‐MI‐Veh) and p‐CaMKII (0.8 ± 0.1, fold of Sham). ANA‐12 prevented exercise‐induced increases in mBDNF (0.6 ± 0.1, fold of Sham) and p‐CaMKII (0.6 ± 0.1, fold of Sham).Conclusions: Exercise post MI increases EF and decreases LVEDP, but TrkB blockade only inhibits the improvement of EF, but not of LVEDP. Exercise increases mBDNF and p‐CaMKII in the non‐infarct area of the LV, which are attenuated by ANA‐12. This indicates that exercise‐induced improvement of EF is mediated by TrkB and downstream effector CaMKII, and BDNF‐TrkB signaling may be mainly associated with improvement in systolic function by exercise training.Support or Funding InformationFRN:MOP‐136923 from the Canadian Institutes of Health Research. Department of Cellular and Molecular Medicine, University of OttawaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Altered hormone receptor expression in rat placenta following maternal vertical sleeve gastrectomy
Authors: Grayson Bernadette Elizabeth , Himel Alexandra R. , Lawson William J. , Spann Redin A. 
Published: June 2021

Intrauterine growth restriction (IUGR) results in long term metabolic disease later in life. Our previous work using vertical sleeve gastrectomy (VSG) to surgically reduce maternal obesity prior to pregnancy results in small‐for‐gestational age offspring that develop greater metabolic disease later in life compared to obese controls. The mechanism driving this transmission of metabolic disease following bariatric surgery from mother to offspring is undetermined.VSG in humans and rodents results in elevated bile acids and glucagon like peptide‐1 and reduced ghrelin amongst a variety of other circulating hormone changes. Independent lines of research have been undertaken to determine whether these hormone changes are independently sufficient to elicit the improvements identified following surgical weight loss. Though these hormone changes are potentially beneficial in the non‐pregnant setting, in the context of pregnancy these types of hormone changes collectively may adversely affect placental development and fetal health. The present work seeks to identify if the hormone changes following VSG are sensed by the late stage placenta.Here we performed VSG or Sham‐VSG in female Long Evans rats and after 5 weeks recovery, we time‐mated them. At gestational day 19, animals were euthanized. Pregnant VSG rats exhibited elevations in plasma levels of bile acids, GLP1 and testosterone and reductions in ghrelin and leptin in comparison to controls. Placenta were also excised and processed for real‐time PCR‐based gene expression analysis. When compared to placenta from lean, body‐weight matched control dams, VSG placenta exhibited reduced mRNA expression of insulin receptors (ir), leptin receptors (obr), androgen receptors (ar) and bile salt export pump (abcb1). Furthermore, VSG placenta expressed significantly increased ghrelin O‐acyltransferase (goat) mRNA, the rate limiting enzyme for production of active ghrelin. No differences were identified in ghrelin receptor (ghsr) and glucagon‐like peptide 1 receptor (glpr).Taken together, these preliminary data suggest that during VSG pregnancy, the fetal‐placental unit responds to the altered hormonal milieu of the dam. Further work is required to determine the role of these particular hormones in the growth and development of the fetus and whether they contribute to the long‐term outcomes of VSG offspring.Support or Funding InformationThis work is partially supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number P20 GM104357, and the Mississippi Center of Excellence in Perinatal Research COBRE (P20 GM121334).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sphingosine kinase inhibition reduced KCl‐induced contractions of gastric arteries in rats
Authors: SOYDAN GURAY 
Published: June 2021

IntroductionSphingolipids are responsible for several physiological and pathological processes in digestive system. Sphingosine‐1‐phosphate (S1P) is generated by sphingosine kinases (SPH) within the cell. S1P may also signal as a second messenger and may be involved in excitation‐contraction coupling. We aimed to investigate the effects of SPK inhibitors on the contractile responses of gastric fundus strips to 5‐HT, acethylcholine, KCl and isolated gastric arteries to KCl‐induced depolarization.MethodsGastric fundus strips and gastric arteries of rats were isolated and mounted into a organ bath and wire myograph system, respectively. Both were incubated with dimethylsphingosine (DMS) or SPK II (SPK inhibitor) and contractile responses were evaluated.ResultsKCl‐induced contractions were significantly decreased in the presence of SPK II in gastric arteries. These contractions did not change after DMS incubation. Conractile responses to KCl, ACh and 5‐HT did not show significant difference after DMS or SPK II incubation.ConclusionsOur results suggest that KCl‐induced contractions decreased after SPK inhibition and SPK may have a regulatory role in gastric artery contractionsSupport or Funding InformationThis study was funded by Hacettepe University Scientific Research Projects Coordination UnitThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glycemic and Insulinemic Response to Ingestion of a Novel Food Bar Containing Whey Protein and Isomalto‐Oligosaccharides
Authors: Grubic Tyler Joseph , Kreider Richard B , Sowinski Ryan , Dalton Ryan , Favot Christopher , Greenwood Mike , Earnest Conrad P , Reyes Aimee , Rasmussen Chris 
Published: June 2021

This study examined the glucose and insulin response of ingesting whey protein bars using a plant fiber (isomalto‐oligosaccharides, IMO) as the carbohydrate source. In a randomized and crossover manner, 10 healthy men and women (4 female, 6 male; BMI <24.9 kg/m2) donated fasting blood samples prior to ingesting two food bars (FB) each containing 20 g of a whey protein blend, 25 g of carbohydrate (13 g IMO, 4 g sugar, 8 g fiber), and 7 g of fat (1.5g saturated) or 50 g of dextrose (PLA). The experiment was repeated 7 to 10 days later while ingesting the alternative treatment. Blood samples were taken at 10, 20, 30, 60, 90, and 120 min post‐ingestion while subjective ratings related to appetite and hypoglycemia were obtained at 0, 60 and 120 min. Data were analyzed by general linear model statistics and are presented as mean [95% CI] changes from baseline. Results revealed that the glycemic response to ingestion of the FB was significantly lower during the first 60 min following ingestion in comparison to the dextrose PLA. Glucose and insulin levels peaked 30 minutes after ingestion; interestingly FB ingestion only marginally increased glucose from baseline for ten minutes. The overall AUC for glucose was significantly lower in FB treatment (530 ± 48, PLA 697 ± 67 mmol‐h/L, p<0.001). No significant differences were observed between treatments in the overall insulin AUC (FB 4,185 ± 1,934, PLA 3,888 ± 707 μIU/mL‐h/L, p=0.65). The glucose integrated AUC (iAUC) change from baseline was significantly lower with FB ingestion (FB 65 [49, 82], PLA 209 [170, 244] mmol‐h/L, p<0.001) while no differences were observed between treatments in insulin iAUC responses. In comparison to the dextrose standard, the FB had an iAUC derived glycemic index (GI) of 34 [CI 23, 46] and a glycemic load (GL) of 8.5 [CI 5.6, 11.6]. Participants also reported significantly less subjective ratings of appetite and hunger and greater satisfaction from food and feeling of fullness in both studies. No significant differences over time or between treatments were observed in ratings of symptoms of hypoglycemia. Results indicate that ingestion of a whey protein bar using IMO as the source of carbohydrate elicited a low glycemic response in comparison to a reference carbohydrate in healthy individuals. Thus, this FB may serve as a low glycemic food option for individuals on a low glycemic diet and/or athletes interested in optimizing nutrient availability around exercise.Support or Funding InformationExercise and Sport Nutrition Lab, Human Clinical Research Facility, Department of Health & Kinesiology, Texas A&M University, College Station, Texas, USAThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Structural Characterization of Vitiligo Associated T Cell Receptor: Towards the Development of Improved Melanoma Immunotherapy
Authors: Smith Angela R , Eby Jonathan M , Ankney Christopher M , Cosgrove Cormac , Henning Steven W , Nishimura Michael I , Le Poole Caroline , Baker Brian M 
Published: June 2021

Melanoma‐associated vitiligo is a notable example of the intersection between tumor immunity and autoimmunity. Normal melanocytes and melanoma cells present many of the same differentiation antigens which may explain why vitiligo can develop as a side effect in melanoma patients with active tumor immune responses. Most interestingly, it has been shown that vitiligo‐derived T cells can kill melanoma cells, suggesting that vitiligo may be a useful source of T cells for adoptive T cell therapy against melanoma.T cell receptors (TCRs) are responsible for the antigen specificity of T cells and are the major component of new cell‐based immunotherapies. TCRs are restricted to the recognition of antigen peptides presented by major histocompatibility complex (MHC) proteins. The SILv44 TCR was isolated from a vitiligo patient's skin infiltrating T cells and has shown superior inhibition of tumor growth in a mouse model. A structural and biophysical characterization of SILv44 compared to two melanoma‐derived TCRs (R6C12 and T4H2) that recognize the same peptide‐MHC (gp100209‐2M/HLA‐A2) will allow us to assess the TCR properties best associated with anti‐melanoma immunity. Interestingly, all three TCR transduced CD8 T cells elicited different cytokine expression profiles. Despite possessing the strongest anti‐tumor immunity, SILv44 has the weakest affinity for its antigen compared to R6C12 and T4H2. When expressed in primary CD8 T cells and exposed to antigen‐presenting cells, all receptors elicited interferon‐gamma (IFN‐γ) responses which correlated with TCR affinity and inversely correlated with tumor growth suppression. These results suggest that TCR affinity and IFN‐γ secretion may not be the key factors in productive T cell recognition of shared tumor antigens. The SILv44 crystal structure indicates that the global positioning of SILv44 over this peptide‐MHC (pMHC) is similar to other HLA‐A2 bound TCR complexes. SILv44 predominantly uses its β chain to engage this pMHC. Crystal structure determinations of R6C12 and T4H2 complexes are in progress and will be compared to the SILv44 complex.Support or Funding InformationWalther Cancer Foundation Interdisciplinary Interface Training ProjectThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inhibition of HDAC8 Ameliorates Pulmonary Fibrosis
Authors: Saito Shigeki , Zhuang Yan , Lasky Joseph 
Published: June 2021

Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative lung disease with high mortality, and fibroblast‐myofibroblast differentiation (FMD) is thought to be a key event in the pathogenesis of IPF. Histone deacetylase 8 (HDAC8) has been shown to associate with α‐smooth muscle actin (α‐SMA; a marker of FMD) and regulates cell contractility in vascular smooth muscle cells. However, the role of HDAC8 in FMD or pulmonary fibrosis has never been investigated. This study investigated the role of HDAC8 in pulmonary fibrosis, with a focus on FMD. We observed that HDAC8 expression was increased in IPF lung tissue as well as TGF‐β1‐treated normal human lung fibroblasts (NHLFs). Our immunoprecipitation experiments revealed that HDAC8 associated with α‐SMA in TGF‐β1‐treated NHLFs. HDAC8 inhibition with NCC170 (HDAC8‐ selective inhibitor) repressed TGF‐β1‐induced fibroblast contraction and α‐SMA protein expression in NHLFs cultured in collagen gels. HDAC8 inhibition with HDAC8 siRNA also repressed TGF‐β1‐induced expression of CTGF and PAI‐1, and increased PPAR‐γ expression in NHLFs. Chromatin immunoprecipitation quantitative PCR (ChIP‐qPCR) using an antibody against H3K27ac (histone H3 acetylated at lysine 27; a known HDAC8 substrate and a marker for active enhancers) suggested that HDAC8 inhibition with NCC170 ameliorated TGF‐β1‐ induced loss of H3K27ac at the PPAR‐γ gene enhancer. Furthermore, NCC170 treatment significantly decreased fibrosis measured by Ashcroft score as well as type‐1 collagen expression in bleomycin‐treated mouse lungs. In conclusion, these data suggest that HDAC8 contributes to pulmonary fibrosis and that there is a therapeutic potential for HDAC8 inhibitors to treat IPF as well as other fibrotic lung diseases.Support or Funding InformationWetmore Foundation: Shigeki Saito M1: 555007G1; Louisiana Clinical and Translational Science (LA CaTS) Center: Shigeki Saito 1 U54 GM104940This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Long‐term endurance exercise coactivates autophagy/mitophagy and anabolic signaling
Authors: Quintin Stephan , Jang Yongchul , Kwon Insu , Song Wankeun , Cosio‐Lima Ludmila M. , Lee Youngil 
Published: June 2021

Growing evidence has identified that autophagy plays an important role in sustaining normal cellular function. Endurance exercise (EE) is a potent inducer of autophagy in multiple tissues. However, the exact underlying signaling pathways responsible for exercise‐induced autophagy in brain has not been fully understood yet. In this study, we investigated potential signaling pathways involved in EE‐induced autophagy and mitochondrial dynamics in the cortex of the brain. C57BL/6 male mice were randomly assigned to a control group (CON, n=12) and an endurance exercise group (EXE, n=12). Our data demonstrated that EE‐induced autophagy evidenced by upregulation of autophagy‐related proteins (e.g., LC3 II, BECLIN1, ATG7, LAMP2, CATHEPSIN L and TFEB) coincides with increased anabolic signaling state (p‐AKT, p‐mTOR and p‐p70S6K). Furthermore, we revealed that EE promoted mitophagy evidenced by increases in LC3 II, p62, BNIP3, PINK, DRP1 in isolated mitochondrial fraction). We attempted to examine if low degree of oxidative stress would be a potential factor involved in EE‐induced autophagy. As opposed to our postulation, oxidative stress was not the case since EE did not increase protein oxidation, but rather enhanced antioxidative capacity (CATALASE and PRX III). Taken together, our results indicate that EE‐induced autophagy/mitophagy concomitant with anabolic signaling activation may be a novel protective signaling that mediates facilitation of healthy brain.Support or Funding InformationThis project was supported by a research grant from the University of West Florida though Office of Research and Sponsored Programs (R0062) and UWF Florida Research Fellowship to YL (CF6672 and CR0070).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Electromyostimulation with Blood Flow Restriction Enhances Activation of mTOR and MAPK Signalling Pathways in Rat Gastrocnemius Muscles
Authors: Natsume Toshiharu , Yoshihara Toshinori , Naito Hisashi 
Published: June 2021

AimNeuromuscular electrical stimulation (NMES) combined with blood flow restriction (BFR) can induce muscle hypertrophy. However, cellular mechanisms underlying the muscle hypertrophy induced by NMES combined with BFR remain unclear. Thus, the purpose of this study was to elucidate the signalling pathways involved in NMES with BFR induced muscle hypertrophy.MethodsAge‐matched male Wistar rats (6 months old, n=7 per group) were assigned randomly into control, BFR alone (BFR), NMES alone (NMES) and NMES combined with BFR (NMES/BFR) groups. NMES induced 25 isometric contractions lasting 8 s with a 4 s resting period between each contraction in the gastrocnemius muscle. Four sets in total were performed, with 1‐min intervals between each set. Latex cuff was placed on the proximal portion of hind limb and BFR was conducted in four sets (each set 5 min) with 1‐min rest intervals in between at 200 mmHg. Venous blood was collected from the lateral tail vein to determine pH, H+, lactic acid concentration before and immediately after the treatments. Expression levels of proteins related to muscle hypertrophy were determined by western blot analysis.ResultsThe application of NMES combined with BFR encouraged muscle fatigue more than NMES alone. NMES/BFR induced greater changes in accumulation of metabolites and increase in the weight of gastrocnemius muscle. The phosphorylation of mTOR and MAPK signalling related proteins also enhanced following NMES combined with BFR, compared with other conditions.ConclusionsWe elucidated that NMES enhanced the activation of mTOR and MAPK signalling pathways when combined with BFR.Support or Funding InformationThis work was supported by Japan Society for Promotion of Science (JSPS) KAKENHI Grant No. 16K16564 (T. Natsume) and Grant No. 17K01765 (T. Yoshihara). Grants from the MEXT‐Supported Program for Strategic Research Foundation at Private Universities also supported this research.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inter‐hemispheric analysis of compensatory neural activity in deep brain stimulation patients
Authors: Uy Daniel R , Thompson John R , Abosch Aviva 
Published: June 2021

Parkinson's disease is a progressive neurodegenerative disorder that is chiefly marked by the progressive loss of dopaminergic neurons, resulting in motor and some non‐motor (e.g., olfactory dysfunction) symptoms (Calabresi et al., 2015). The motor related symptoms are a result of the reduction of dopamine caused by the decline in the population of dopamine producing neurons in the substantia nigra of the basal ganglia. Deep brain stimulation (DBS) is a symptom management treatment for pharmaceutically unmanageable Parkinson's disease because of its ability to improve motor functions and thus quality of life (Martinez‐Ramirez et al., 2015). Individuals will typically have two procedures, one hemisphere per surgery, and thus have electrodes implanted in both hemispheres of the brain. Given the necessity for electrophysiological evaluation of implant target, the DBS procedure provides one of the few opportunities to examine changes in neural networks in the human brain. This study sought to examine whether there were compensatory changes in neural activity within basal ganglia structures as a function of surgical disruption. The current results suggest that there is a compensatory increase in contralateral neural activity within basal ganglia structures following surgery.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.