bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cymbopogon Proximus Essential Oil Protects Against Isoproterenol Induced‐Cardiac Hypertrophy in Rats
Authors: Althurwi Hassan , Abdel‐kader Maged , Alharthy Khalid , Al‐salkini Mohamad , Albaqami Faisal 
Published: June 2021

Cymbopogon proximus (Halfabar), a wild plant that is usually used in folk medicine due to its diuretic and antispasmodic effects, was shown to exhibit several cardiovascular protective actions such as antidiabetic, antihypertensive, antioxidant, and antinflammatory effects. However, no reports are available regarding the investigation of the role of Cymbopogon proximus essential oil on cardiac hypertrophy. Therefore, the goals of the present study were to find whether Cymbopogon proximus could alleviate isoproterenol induced‐cardiac hypertrophy and to determine the underlying molecular mechanisms. For this purpose, male albino rats were treated daily with either Cymbopogon proximus essential oil (800 μl/kg/day, ip), isoproterenol (5 mg/kg/day, ip), or the combination of both. Oil administration was started four days prior to isoproterenol administration and continued concurrently thereafter for another three days. All animal groups were euthanized 24 hours after the last dose of treatment. Thereafter, the hearts were harvested and heart weight to body weight (HW:BW) ratios were measured and sections of hearts were stained with Masson's trichrome and H&E to assess cardiac fibrosis and morphology. Our results showed that isoproterenol alone resulted in a significant increase in HW:BW ratio and marked myocardial fibrosis in treated rats. On the other hand, treatment with Cymbopogon proximus essential oil significantly reduced the isoproterenol‐mediated increase in HW:BW ratio by 55%. However, oil treatment did not affect isoproterenol mediated‐increase in myocardial fibrosis.ConclusionCymbopogon proximus essential oil partly protects against isoproterenol‐induced cardiac hypertrophy with no effect on cardiac fibrosis. These findings provide support for the promising therapeutic effects of Cymbopogon proximus on cardiac diseases.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
PREGNANCY RATE OF BUNAJI COWS IN A FIXED TIME AI SYNCHRONIZATION PROTOCOL USING OVATIDE
Authors: Ubah Simon Azubuike , Rekwot Ibrahim Peter , Adewuyi Bode Abdulmujeeb , Omontese Oakina Bobwealth , Adewale Adeyeye Ayodeji 
Published: June 2021

This study was aimed to access the reproductive performance of bunaji cows in an ovsynch protocol involving Ovatide. Bunaji cows (n=16) aged 4 – 6 years and weighing between 250 – 350kg were used. Selected cows with average body condition scores (BCS) of 2.5 – 3.5 using 0 – 5 scale from the most emaciated to the fattest. Cows were randomly assigned to 1 or 2 treatment groups for synchronization of ovulation. Treatment group 1 comprising Bunaji (n=8) received 50μg of GnRH (Cystorellin) and 25 mg of PGF2α. While, treatment group 2 comprising Bunaji (n=8) received 50μg of Ovatide and 25 mg of PGF2α. All cows from both treatment groups were inseminated at 16 hours after each second GnRH or Ovatide injections. Cows that showed mucus discharge from the vagina on the day of AI were recorded as well as those that had patent cervix. Cervical dilation was measured by taking note of the cows that had mid cervix insemination due to non‐passage of the AI gun through the cervix. Transrectal palpation was conducted twice at a month interval to select cycling cows within 5 to 12 days of the estrous cycle before initiating Ovsynch protocol. It was repeated on day 45 post – AI to confirm pregnancies in animals. Results showed that the rate of mucus discharge from the vagina and Cervical dilation for Ovatide were 37.5% and 87.5%; and GnRH (Cystorelin) 75% and 87.5% (P > 0.05) and Pregnancy Rates were 0% and 12.5% respectively. There were no significant differences between the two groups. It was concluded that treatment of bunaji cows with 50μg Ovatide in Ovsynh protocol has heat induction potentials zero pregnancy rates. It was recommended that further studies be carried out using graded doses of 50μg, 100μg and 150μg of Ovatide in a fixed time AI synchronization protocol in bunaji cows.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
AMPK Phosphorylation of FXR at Threonine Controls Hepatic Glucose Production
Authors: Han Chang Yeob 
Published: June 2021

Farnesoid X receptor (FXR) controls the expression of genes involved in the regulation of energy metabolism. Nonetheless, the regulatory signal of FXR in glucose‐lowering effect and the underlying mechanisms are largely unknown. Based on the functional link between SIRT1 and AMPK, this study explored the effect of AMPK on the phosphorylation of FXR and its role for SIRT1‐mediated hepatic glucose metabolism. SIRT1 overexpression increased the transcriptional activities of FXR response reporter gene, whereas a loss of SIRT1 had the opposite effect. SIRT1‐mediated FXR transactivation was significantly blocked by the inhibition of AMPK. The impact of SIRT1 and AMPK on the regulation of FXR function was strengthened by the pharmacological effect of ajoene. We also found that AMPK directly phosphorylated FXR at Thr156 residue as shown by in vitro kinase, oligopeptide competition and point‐mutation analyses. The overexpression of FXR‐T156A mutant attenuated AMPK‐mediated FXR phosphorylation and the binding of FXR to coactivator. The inhibition of glucose‐6‐phosphatase expression or hepatocyte glucose production by CA‐AMPK or ajoene was abrogated by either FXR knockdown or FXR‐T156A mutant overexpression. Finally, ajoene treatment diminished hyperglycemia and sensitized insulin signaling in high fat diet‐induced obese mice. In conclusion, AMPK phosphorylates FXR at Thr156 downstream of SIRT1, which may contribute to the inhibition of hepatic glucose production.Support or Funding InformationThis research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF‐2015R1A2A1A10052663) and the Basic Science Research Program through NRF funded by the Ministry of Education (2017R1D1A1B03028272).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Investigating the Role of Vascular Endothelial Growth Factor in Hematopoietic Stem Cell Driven Perivascular Niche Remodeling
Authors: Bubenheimer Rebecca K. , Tamplin Owen J. 
Published: June 2021

Hematopoiesis is the process that produces the entirety of mature blood cells. A balance between the quiescence and proliferation of hematopoietic stem cells (HSC) is essential to maintain the blood supply. During development, HSCs expand exponentially in an intermediate niche before migration to the adult bone marrow. In zebrafish, the intermediate niche is the caudal hematopoietic tissue (CHT), a vascular plexus in the tail of the embryo, and in mice it is the fetal liver. Previous work by Tamplin et al. 2015 showed that arrival of an HSC triggers endothelial cells (EC) in the CHT niche to remodel and form a pocket around the HSC. Our goal is to uncover the function of the EC pocket and the mechanism of its formation. One candidate for this signaling cascade is vascular endothelial growth factor C (VEGF‐C) and its receptors VEGFR2 and VEGFR3. Within all hematopoietic lineages, VEGF‐C is highly expressed in HSC. VEGFR2/3 are expressed on sinusoidal endothelial cells of the CHT and fetal liver niches. Previous studies have shown a decrease in hematopoietic progenitor numbers when VEGFR3 is knocked out in mouse embryos (Hamada, 2000). Our preliminary data in zebrafish embryos have agreed with these findings. We have seen a decrease in hematopoietic stem and progenitor cells in vivo marked by the transgenic reporter cd41:gfp and in whole mount in situ with c‐myb probe after knocking down VEGFR3 alone as well as in combination with VEGFR2. To further confirm this phenotype, we administered pan VEGFR inhibitor, Semaxinib, and saw a similar decrease in cd41:gfp+ progenitors. We plan to further investigate this phenotype with a variety of small molecule inhibitors, genetic mutants, and synthetic oligo “morpholino” knockdown. Once we establish the mechanism for VEGF signaling in the remodeling of the perivascular EC niche, we plan to investigate the downstream targets. Uncovering the signals that govern the interaction between HSCs and their perivascular niche is clinically applicable in improving the efficiency of HSC transplants.Support or Funding InformationDepartment of Pharmacology, Lung and Vascular Biology Training Grant; NIH T32 HL027829This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Complex Interactions of excitatory and inhibitory stimuli in the vascular endothelium
Authors: Ratnayake Manuela , Wilson Calum , Lee Matthew D. , Girkin John M. , Saunter Christopher M. , McCarron John G. 
Published: June 2021

The endothelium is the single, innermost, layer of cells in blood vessels and it controls almost all cardiovascular functions. The endothelium regulates immune responses, blood coagulation, angiogenesis, vessel repair, and vascular permeability. To regulate function, the endothelium continuously monitors multiple chemicals that are circulating in the blood or derived from nearby cells (e.g. endocrine, paracrine, autocrine or neurotransmitter signals). These chemicals each provide cues to physiological status. The chemicals are detected and processed selectively by the endothelium to direct resources that adjust physiological function. Some chemicals provide conflicting signals to the endothelium such as those which promote or inhibit vascular tone. How conflicting signals are detected and managed by the endothelium is not understood. The present study was undertaken to determine how the endothelium selectively processes conflicting information. To monitor the behaviour of the endothelium, changes in endothelial cytosolic Ca2+ concentration were measured in ~200 endothelial cells in small mesenteric arteries using the indicator Cal‐520 and high‐resolution imaging. Changes in cytosolic Ca2+ concentration underlies virtually all endothelial functions and so provides a useful measure of endothelial activity. The vasodilator substance acetylcholine evoked Ca2+ increases that initiated in small clusters of cells. As the concentration of acetylcholine increased, the amplitude of the Ca2+ rise and the number of activated cells increased. To examine the interaction of excitatory and inhibitory inputs, acetylcholine (as an excitatory input) at an EC75 (15nM) was used. In the first series of experiments the vasoconstrictor alpha‐adreneric agonist phenylephrine was used. Phenylephrine (10 μM) did not itself evoke any detectable Ca2+ signals in the endothelium. However, phenylephrine inhibited the Ca2+ rise evoked by acetylcholine (15 nM). Phenylephrine inhibited the amplitude of the response in each activated cell and the number of cells activated. By inhibiting endothelial activity, phenylephrine will increase the contractile response operating on the smooth muscle cells. The vasoconstrictor agonist angiotensin (10 μM) did not evoke Ca2+ increases when applied by itself. However, angiotensin increased the amplitude of the Ca2+ response to acetylcholine in each activated cell. The number of cells activated did not change. This effect of angiotensin on the endothelium may serve to limit a vasoconstrictor response. Together these data reveal complex interaction occur between excitatory and inhibitory stimuli acting on the endothelium.Support or Funding InformationSupported by the Wellcome Trust and British Heart FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Alamandine Counteracts Inflammation in the Central Nervous System of Hypertensive Animals.
Authors: Campagnole‐Santos Maria Jose , Souza Lucas AC. , Kangussu Lucas M. , Santos Robson AS. , Bader Michael 
Published: June 2021

Alamandine, a new peptide of the renin‐angiotensin system (RAS), has shown similar biological actions of angiotensin‐(1‐7). In SD rats, alamandine produced stimulatory effects when microinjected into medullary areas involved in sympathetic control. On the other hand, lateral ventricle (ICV) infusion of alamandine improved the baroreflex sensitivity of normotensive rats. We investigated the effect of long‐term central increase of alamandine on the arterial pressure (AP) of transgenic TGR(mREN2)27 (TG) hypertensive rats. Twelve weeks old SD and TG rats (Protocol 239/2016, CEUA/UFMG) instrumented with telemetry probes for AP measurement, underwent 28 days of ICV infusion of alamandine (TG+Ala, 200 ng/h) or saline (TG+Sal and SD+Sal; Control; 0.25 μL/h) through osmotic mini‐pumps. The levels of inflammatory cytokines (TNF‐α, IL‐6, IL‐1β, and IL‐10) in hypothalamus and medulla oblongata was determined by ELISA. Long‐term ICV infusion of alamandine produced a small decrease in Mean AP (ΔMAP: −16±8 mmHg, n=5, p<0.05) of TG rats from the first week of treatment, while control rats (TG+Sal) presented an increase in the AP during the same period of time (ΔMAP: +17±7 mmHg, n=5, p<0.05). Alamandine infusion did not alter baseline heart rate or the circadian rhythm of AP or heart rate in TG rats. Further, TG+Sal presented increased levels of TNF‐α, IL‐6, and IL‐1β in the hypothalamus and medulla oblongata. Interestingly, long‐term ICV infusion of alamandine attenuated levels of TNF‐α (SD+Sal: 29.2±3.1 pg/100 mg of protein; TG+Sal: 73.1±2.9 pg/100 mg of protein; and TG+Ala: 49.3±0.4 pg/100 mg of protein; n=4–7, p<0.001) and IL‐6 (SD: 26.8±1.2 pg/100 mg of protein; TG+Sal: 65.5±4.3 pg/100 mg of protein; and TG+Ala: 42.3±1.8 pg/100 mg of protein; n=4–7, p<0.001) in the hypothalamus and the levels of TNF‐α (SD: 23.5±2.0 pg/100 mg of protein; TG+Sal: 56.9±4.5 pg/100 mg of protein; and TG+Ala: 40.2±1.2 pg/100 mg of protein; n=4–7, p<0.01) in the medulla oblongata of TG hypertensive rats. Treatment with alamandine also increased the levels of IL‐10 (SD: 20.0±0.7 pg/100 mg of protein; TG+Sal: 19.2±0.52 pg/100 mg of protein; and TG+Ala: 24.2±1.4 pg/100 mg of protein; n=4–7, p<0.05) in the hypothalamus of TG rats. Our data show that long‐term ICV infusion of alamandine has anti‐inflammatory effect in areas related to cardiovascular control in transgenic hypertensive rats. This effect was associated with a decrease in AP of these animals. Our data suggest alamandine as an alternative route for the RAS in the central control of AP.Support or Funding InformationFAPEMIG, CNPq, INCT‐Nanobiofar, CAPES/DAAD (PROBRAL), and FAPEMIG/CNPq (Universal Projects to MJC‐S)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evaluation of cardiovascular hemodynamics in response to recumbent positions by using magnetic resonance imaging
Authors: Sasaki Konosuke , Ota Hideki , Kimura Tomoyoshi , Onuma Tomoya , Nagasaka Tatsuo , Saiki Yoshikatsu , Maruyama Ryoko 
Published: June 2021

Limited research has been performed to clarify hemodynamic response to different positions, namely the supine, left recumbent, and right recumbent positions. In general, magnetic resonance imaging (MRI) has been reported to be more reliable and reproducible technique than an ultrasound scan for accurate assessment of hemodynamics. Our aim was to evaluate whether the left and right recumbent positions affect cardiovascular hemodynamics compared with the supine position by using MRI assessment. Between June 2017 and August 2017, 12 healthy men aged 26.8 ± 3.1 years were recruited in this study. We measured the following parameters in each posture: heart rate (HR), stroke volume index (SI), cardiac index (CI) in the left ventricle using cine‐MRI, and blood flow velocity and blood volume in the superior vena cava (SVC) and inferior vena cava (IVC) using phase‐contrast MRI. After lying in the supine position, the participants maintained each recumbent position in random order at an angle of approximately 45°. The HR in the left recumbent position and SI in the right recumbent position were observed to be the lowest among those in the other positions. In both recumbent positions, CI tended to decrease compared to that in the supine position. In the right recumbent position, blood volume in the SVC and IVC was significantly lower than that in the supine position. These results suggest that a low HR in the left recumbent position and low blood volume in the right recumbent position result in a decrease in CI in both the right and left recumbent positions.Support or Funding InformationThis work was supported in part by a grant from North Japan Academy of Nursing Science.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High fat diet induces early diastolic dysfunction and cardiac hypertrophy in mice
Authors: Utreras‐Mendoza Yildy Priscilla , Peña Juan Pedro , Montesinos Luis , Sánchez Gina , Donoso Paulina 
Published: June 2021

Obesity is a major risk factor for the development of cardiovascular diseases including cardiac hypertrophy. Mice fed with a high fat diet (HFD) become obese after 7–8 weeks and eventually develop cardiac hypertrophy. Yet, the time course of the development of the diet‐induced cardiac hypertrophy is largely unknow.To study the initial events leading to hypertrophy we fed mice (C57BL/6) with a HFD (60% fat, 20% proteins and 20% carbohydrates) and measured cardiac dimension and function by echocardiography‐doppler after 8 and 12 weeks on this diet. We also determined the mRNa expression for hypertrophic markers such as BNP and RCAN1.4 and since obesity induces the expression of NADPH oxidase in several tissues, we also measured the expression of NOX2 and NOX4, the two isoforms of NAPDH oxidase expressed in the heart.We found that after 8 weeks on a HFD, mice show normal cardiac dimensions but a decrease in the ratio of the peak velocity in early diastole (Early filling: E) to peak velocity flow in late diastole (Active filling: A) (E/A ratio), indicating the presence of diastolic dysfunction. By 12 weeks E/A ratio is normalized (pseudo normalization) but there is a significant increase in the thickness of the interventricular septum, the left ventricular posterior wall and the heart weight/tibia length ratio, all signals of hypertrophy. At the molecular level, other signs of hypertrophy were significant increases in the mRNa expression of BNP and RCAN1.4. We also found an increase in the expression of NOX4 from 8 weeks but NOX2 expression was unchanged. Until 12 weeks, however, there were no signs of oxidative stress such as a decrease in total glutathione concentration or GSH/GSSG ratio or an increase in carbonylated proteins in the heart.These results suggest that cardiac hypertrophy develops at 12 weeks as a compensatory response to the diastolic dysfunction induced by the HFD. Redox signaling involving NOX4 may underlie this responseSupport or Funding InformationFunded by Fondecyt grant 1160704 (PD) and Doctoral fellowship 21160378 (YUM)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Nuclear Receptor NR4A2 Coordinates Transcriptional Remodeling of Metabolic, Calcium, and Growth Signaling Networks in Adult Rat Ventricular Myocytes
Authors: Ashraf Sadia , Harmancey Romain 
Published: June 2021

Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and contractile dysfunction in heart failure. Better understanding of β‐adrenergic signaling regulation in cardiomyocytes should provide therapeutic insights for heart failure management. The orphan nuclear receptor NR4A2 is an immediate early response gene activated in the heart under various stress conditions. The goal of this study was to identify the transcriptional networks regulated by NR4A2 in cardiomyocytes and their effect on cellular remodeling induced by sustained β‐adrenergic stimulation. Isoproterenol (ISO; 10 μM) induced a transient increase in NR4A2 mRNA levels in H9c2 cardiomyoblasts (5‐fold) and in isolated adult rat ventricular cardiomyocytes (ARVM; 80‐fold) that peaked after 1 hour before returning to baseline levels within 24 hours of stimulation. In addition, ISO induced rapid and transient nuclear localization of NR4A2 as visualized by immunofluorescence. Total RNA sequencing revealed that adenovirus‐mediated overexpression of NR4A2 in ARVM led to the regulation of genes associated with cAMP signaling, cell growth and proliferation, glucose metabolism, and calcium homeostasis. These transcriptional events were accompanied by the down‐regulation of genes encoding pro‐hypertrophic transcription factors implicated in pathological remodeling of the stressed heart (Nfatc2, Nfatc3, Gata4, Gata6, and Stat5a). In ARVM chronically treated with ISO for 48 hours, NR4A2 overexpression prevented both the up‐regulation of the pathologic hypertrophic marker BNP and an overall increase in protein synthesis rates as determined by measurement of [3H]leucine incorporation. The overexpression of NR4A2 also prevented ISO‐induced increase in cell surface area for both ARVM and H9c2 cardiomyoblasts. In conclusion, the results expose NR4A2 as a potential regulator of cardiomyocyte metabolic and functional remodeling under stress conditions. NR4A2 may promote antihypertrophic pathways to counteract the detrimental effects of excessive sympathetic system activity.Support or Funding InformationSupported by grants R00 HL112952, P01 HL051971, and P20 GM104357 from the National Institutes of HealthThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.