bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Methanol Extracts from Roots, Leaves, and Fruits of the Lebanese Strawberry Tree (Arbutus andrachne) on Cardiac Function Together with their Antioxidant Activity
Authors: Abidi Emna , Habib Jean , Chahine Nathalie , Mahjoub Touhami , Elkak Assem 
Published: June 2021

CONTEXTSeveral plant‐derived natural products have been used in clinical phase for applications in neurological, cardiovascular, and inflammatory diseases. Arbutus andrachne L. (Ericacea) is an evergreen shrub native to the Mediterranean region. Traditionally, the fruits and leaves of Arbutus tree are well known and used as antiseptics, diuretics, blood tonic, and laxatives.OBJECTIVEData regarding the biological effects of compounds derived from the Lebanese Arbutus andrachne are not available. In the present work, we studied the antioxidant activity of methanol extracts of leaves, fruits, and roots of the plant against electrolysis; together with their effects on the cardiodynamics of isolated perfused rabbit hearts.MATERIALS AND METHODSIn vitro electrolysis of the different root, leaves, and fruits methanol extracts was evaluated by the amount of free radicals that has been reduced by increasing the concentration of root extracts ranging from 0.5 to 2 mg after 1, 2, 3, and 4 min. Left ventricular pressure (LVP), heart rate (HR), and coronary flow (CR) were investigated in isolated rabbit heart after administration of 0.5, 1, 2, and 2 mg of each methanol extracts plotted against time (0, 0.5, 1.5, 5, and 10 min), according to the Langendorff method. Lipid peroxidation study was performed by the colorimetric method on myocard tissue after incubation with 500 μl of the different methanol extracts. The amount of MDA was determined at 500 nm absorbance after 5 min incubation.RESULTSAmong the different methanol extracts, the roots showed the highest in vitro antioxidant activity, particularly observed at concentration of 2 mg which completely inhibits free radical generation after 4 min. LVP decreases by 32% at the dose of 2 mg of root extracts after 5 min. No significant effect was observed by the three tested extracts on the heart rate. The three methanol extracts did not show any significant effect on the coronary flow. Moreover, the roots show an increase in the coronary flow at a concentration of 1 and 2 mg/ml during 1 min. Electrolysis on heart tissue treated with the roots extracts shows a decrease in the MDA level from 70.51 ± 6.71 to 48.58 ± 4.15 nmole/g of tissue.DISCUSSION AND CONCLUSIONMethanol extracts of the roots possess antihypertensive effect that may result from its ability to decrease the LVP together with its protective role by inhibiting free radical generation and significantly decreasing the MDA level of heart tissue.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Applied Predictive Modeling of Coronary Microvascular Disease using Coronary Doppler and Cardiac Echocardiography
Authors: Patel Kishan U. , Sunyecz Ian L. , McCallinhart Patricia E. , Bartlett Christopher W. , Trask Aaron J. 
Published: June 2021

IntroductionType 2 diabetic (T2DM) coronary resistance microvessels (CRMs) show early inward hypertrophic remodeling and reduced wall stiffness, which are associated with decreased blood flow (CBF), coronary flow reserve, and disrupted flow patterns. These data may suggest that coronary microvascular disease (CMD) underlies the early pathophysiology of T2DM. Furthermore, distinct correlations have been identified between the Doppler coronary flow pattern in both normal and T2DM mice, potentially allowing for a predictive relationship between coronary flow patterns and CMD. Currently, CMD is extremely difficult to diagnose due to lack of non‐invasive methods. The goal of this study was to develop an applied predictive model for CMD non‐invasively in early T2DM using CBF combined with functional and structural measurements of the heart.MethodsCBF of the left main coronary artery, aortic flow, E & A wave, left ventricular structural dimensions, and aortic diameter were recorded using high frequency, high resolution non‐invasive Doppler echocardiography (Vevo2100, Visual Sonics, Toronto, Canada) in 37 normal heterozygous Db/db mice and 36 T2DM homozygous db/db mice. Coronary flow patterns were analyzed using a Matlab program developed in our laboratory to identify 13 distinct parameters. All other flow patterns and structural and functional features were manually measured in the Vevo2100 software resulting in 13 additional parameters. All the parameters were feature engineered, and a factor analysis model was created and tested using various machine learning algorithms.ResultsPhysiological data were subjected to a variety of machine learning models, and the “glmnet algorithm” in R software (generalized linear regression via penalized maximum likelihood) best predicted CMD with a cross validation accuracy of 80.19% and test dataset accuracy to date of 84.84%.ConclusionAn applied predictive model for CMD in T2DM was developed using 73 mice, which shows a promising ability to accurately predict CMD in T2DM. Further studies will be undertaken to improve the predictive accuracy of the model to be suitable for clinical diagnostics and/or decision support.Support or Funding InformationSupported by the National Institutes of Health (R00 HL‐116769 to AJT) and Nationwide Children's Hospital (to AJT and CWB).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Blood Pressure and Vascular Function in Hypertensive Individuals: Partitioning cause and effect
Authors: La Salle D. Taylor , Broxterman Ryan M. , Ratchford Stephen M. , Richardson Russell S. , Trinity Joel D. 
Published: June 2021

IntroductionVascular dysfunction is a hallmark of hypertension and contributes to an increased risk of cardiovascular disease. Pharmacological interventions to treat hypertension generally result in improved blood pressure status and concomitant improvements in vascular function. However, recent findings have challenged this notion as vascular dysfunction appears to persist despite blood pressure control with antihypertensive medications. Importantly, medications differ in their vasoactive properties and may have direct effects on the vasculature independent of their impact on blood pressure. Therefore, it is difficult to discern if the potential improvements in vascular function are associated with lower blood pressure or a direct effect on vascular function. Utilizing the dietary approach of salt restriction this study examined the impact of reducing blood pressure on vascular function and peripheral hemodynamics in individuals with essential hypertension.MethodsHypertensive adults (male n=14, female n=8, 50±10 yr) completed two dietary phases: liberal sodium (LS) (200 mmol/d) followed by restricted sodium (RS) (10 mmol/day) diet for five days, respectively. Antihypertensive medications were withdrawn 2 weeks before the first intervention. Following each dietary phase, measurements of systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MAP), arterial diameter and blood velocity (Doppler ultrasound) were assessed at rest, during brachial artery (BA) flow mediated dilation (FMD), and during progressive handgrip (HG) exercise performed at 15, 30 and 45% of maximal voluntary contraction (MVC).ResultsRS significantly lowered SBP (LS: 140±3, RS: 123±3 mmHg), DBP (LS: 85±2, RS: 79±2 mmHg) and MAP (LS: 103±2, RS: 94±2 mmHg) (all p<0.05). Despite improvements in blood pressure, conduit artery function, as measured by FMD, was similar between conditions (LS: 4.6±0.4%; RS: 5.1±0.5%). Similarly, the hyperemic response during FMD, an assessment of microvascular function, was not different between conditions (LS: 548±43; RS: 615±44 ml). During HG exercise, MAP was lower at all exercise intensities during RS compared to LS (15% MVC; LS: 109±2 vs. RS: 102±2 mmHg; 30% MVC; LS: 113±2 vs. RS: 105±2 mmHg; 45% MVC; LS: 122±3 vs. RS: 112±3 mmHg) while vascular conductance and BA vasodilation were not different between LS and RS (p>0.05).ConclusionDespite improvements in blood pressure at rest and during exercise, both conduit artery and microvascular function measured during FMD and HG exercise‐induced vasodilation were not improved. These findings support recent evidence that vascular dysfunction persists in individuals with hypertension independent of blood pressure status.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 Spirulina Extracts on Vasodilator Function of Arteries from Hypertensive Rats
Authors: Villalpando Diva M. , Verdasco Carlos , Plaza Ignacio , Rivas Juan Gómez , de Bethencourt Fermin R. , Otero Cristina , Ferrer Mercedes 
Published: June 2021

Hypertension is a multifactorial disorder that is considered one of the major causes of premature death worldwide. This pathology is associated with functional and structural vascular alterations in which oxidative stress and decreased nitric oxide (NO) bioavailability are involved. On the other hand, the use of natural compounds, including extracts of microalgae, for the treatment of cardiovascular diseases is gaining attention. Based on the anti‐oxidant and anti‐inflammatory properties of Spirulina, the aim of this study was to investigate the effect of aqueous Spirulina extract on the release and function of NO, as well as on the expression of the antioxidant protein hemoxygenase‐1 (HO‐1), phosphorylated Akt (p‐Akt) and phosphorylated eNOS (p‐eNOS) that regulate the production of NO. For this purpose, aortic segments from male Spontaneously Hypertensive rats (SHR) and its normotensive counterparts, Wistar‐Kyoto (WKY) rats, were isolated. Aortic segments exposed to the aqueous Spirulina extract (0.1 % w/v, for 3 h) and those not exposed were used to analyze the following parameters: (i) the release of NO; (ii) the NO‐dependent response to acetylcholine (ACh) and the vasodilator response to the NO donor, sodium nitroprusside (SNP); and (iii) the expression of HO‐1, p‐eNOS and p‐Akt. The results showed that Spirulina extracts increased the release of NO more in arteries from SHR than that of WKY rats. Spirulina extracts also increased the ACh‐ and SNP‐induced response in arteries from both WKY and SHR. Additionally, Spirulina increased the expression of HO‐1, p‐Akt and p‐eNOS in arteries from SHR. These results suggest that Spirulina extracts exert benefits for the treatment of hypertension by increasing the release and function of NO in which the increased levels of HO‐1, p‐eNOS and p‐Akt can be involved.Support or Funding InformationSupported by Comunidad de Madrid (S2013/ABI‐2783, “INSPIRA1‐CM”) and Fondo Europeo de Desarrollo Regional.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Distinct Biaxial Mechanical Properties between Right and Left Ventricles in Healthy Adult Sheep
Authors: Nguyen‐Truong Michael , Labus Kevin M. , Liu Wenqiang , McGilvray Kirk , Puttlitz Christian M. , Wang Zhijie 
Published: June 2021

Right ventricle failure (RVF) is a serious disease with a 40% mortality rate where the right heart is unable to sufficiently pump blood to the body. RVF is associated with biomechanical changes such as extracellular matrix deposition and right ventricle (RV) wall stiffening. It has been well established that the RV is distinct from the left ventricle (LV) in embryologic origin, anatomy and function, and the two chambers' pathologies are significantly different. However, unlike left ventricle failure (LVF), the mechanisms of RVF are not well understood and it is partly due to the lack of knowledge in the difference in biomechanical properties and mechanobiology between the two chambers.To investigate the mechanical properties of the LV and RV, ex vivo biaxial tensile mechanical tests were performed in adult, healthy sheep hearts. Using homogenous, square slices of fresh ovine ventricles, 1:1 biaxial tests were performed and the stress‐strain responses were recorded. The elastic modulus at high and low strain regions were then derived as E1 and E2, respectively. The LV and RV showed distinct anisotropic mechanical properties: the longitudinal elastic moduli are larger than those of circumferential axis in the RV, while the opposite trend was observed in the LV. Moreover, we found that the RV was stiffer than the LV in the longitudinal direction (which is parallel to the outflow tract direction), whereas in the circumferential direction the RV was more compliant than the LV (Figure and Table). To our knowledge this is the first characterization and comparison of biaxial mechanical properties of LV and RV in a large animal model. Future work will test more heart samples and examine the histology to correlate structure to mechanical function. Overall, our finding that the healthy RV was stiffer than the healthy LV in the outflow tract direction may shed light on the biomechanical changes under pathological conditions, such as pressure overload induced RVF.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Albumin and palmitate overload increases osteopontin production in renal tubule epithelial cells
Authors: Cobbs Alyssa , Ballou Kristopher , Chen Xiaoming , George Jasmine , Zhao Xueying 
Published: June 2021

Osteopontin (OPN) is one of the proinflammatory cytokines upregulated in the kidneys of diabetic animals and patients with diabetic nephropathy (DN). An increase in albuminuria and albumin‐bound fatty acids presents a proinflammatory environment to the proximal tubules in proteinuric kidney diseases including DN. This study was designed to examine if fatty acid overload or albumin itself could stimulate OPN production by renal tubular epithelial cells. Renal tubular OPN expression and secretion were examined in Zucker diabetic (ZD) rats and NRK‐52E cell line exposure to bovine serum albumin (BSA) or BSA overloaded with saturated fatty acid palmitate. Gene microarray and real‐time PCR confirmed an albuminuria‐associated upregulation of OPN transcripts in kidney cortex of ZD rats at the age of 7–20 weeks. Immunofluorescence staining of kidney sections revealed an increase in OPN protein in damaged proximal tubules of diabetic rats. Western blot analysis detected a progressive increase in urinary OPN levels in the ZD rats, which was prevented by antiproteinuric treatment with losartan, an angiotensin II receptor blocker. When exposed to fatty acid‐free bovine serum albumin (BSA, 10 mg/ml), NRK‐52E cells exhibited an increase in OPN protein expression. Palmitate (250 μM) further enhanced albumin‐induced OPN in NRK‐52E cells. These results demonstrate a stimulatory effect of albumin and its conjugated fatty acids on OPN expression in renal tubule epithelial cells. Thus, besides lowering albuminuria/proteinuria, mitigating circulating fatty acid levels may be an important factor in preventing renal inflammation in proteinuric diseases.Support or Funding InformationNIH SC1DK112151, NIH/NCRR/RCMI 8G12MD007602 & 8U54MD007588This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Organelle Segregation and Quality Control during Meiotic Differentiation
Authors: Ünal Elçin , Sawyer Eric , King Grant , Goodman Jay 
Published: June 2021

Meiotic differentiation is a complex developmental program that involves extensive cellular remodeling. In budding yeast, under nutrient deprived conditions, a diploid mother cell undergoes two successive meiotic divisions to generate four nuclei. After meiosis, the four nuclei are packaged with a subset of the organelles and cytoplasm originating from the mother to form four haploid gametes. Our lab has found that during the latter process, certain components of the mother cell are not inherited by the gametes and are subsequently produced de novo. For example, the nuclear pore complexes and components of the nucleoli do not segregate with any of the four nuclei, whereas only a subset of the mitochondria is inherited by the gametes. A programmed pathway that entails vacuole permeabilization subsequently degrades the excluded cellular materials. We posit that the restricted inheritance of organelles and other cellular sub‐compartments is required for cellular rejuvenation that occurs as part of gametogenesis.Support or Funding InformationPew Charitable Trusts (00027344), Damon Runyon Cancer Research Foundation (35‐15), March of Dimes (5‐FY15‐99), National Institute of Health (DP2 AG055946‐01) and Glenn Foundation for Medical ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cold‐Inducible RNA Binding Protein (CIRP) In Inflammation and Breast Cancer
Authors: Lujan Daniel A. , Perrone‐Bizzozero Nora , Beswick Ellen J. , Kusewitt Donna F. , Hartley Rebecca S. 
Published: June 2021

RNA binding proteins (RBPs) post‐transcriptionally regulate gene expression by associating with the regulatory sequences in the untranslated regions of mRNAs. RBPs are often disrupted in cancer, but current knowledge of their role in regulating cancer‐associated genes is largely based on in vitro studies. This study seeks to determine the in vivo role of cold‐inducible RBP (CIRP), which is overexpressed in some human breast cancers. CIRP promotes cell proliferation and survival and inhibits apoptosis in vitro and promotes inflammation in vivo, all hallmarks of cancer. We tested the hypothesis that CIRP promotes breast tumorigenesis in vivo by crossing a transgenic mouse overexpressing CIRP in the mammary epithelium with the PyMT mouse model of breast cancer. Effects on both early (7‐week‐old mice) and late (14‐week‐old mice) tumorigenesis were assessed. Unexpectedly, mammary glands from 7‐week‐old CIRP/PyMT mice had 50% fewer mammary intraepithelial neoplasias than PyMT mice. Consistent with this, histopathological analysis showed decreased mitosis and increased apoptosis in CIRP/PyMT vs. PyMT mammary glands. Late stage tumorigenesis was also inhibited. CIRP/PyMT mice had slower tumor growth kinetics, smaller tumors, decreased tumor burden and decreased pulmonary metastasis compared to PyMT mice. To assess the mechanism of inhibition, mammary glands from 7 and 14‐week‐old mice were incubated in medium overnight and Luminex cytokine assays were performed on the medium. Results showed a decrease in cytokines that promote inflammation, angiogenesis and metastasis. Altogether, our results suggest that CIRP inhibits proliferation and promotes apoptosis in vivo to suppress early tumorigenesis, potentially via decreasing a protumorigenic inflammatory response.Support or Funding InformationThis work was funded by the University of New Mexico Research Allocation Committee, the American Association of Anatomists Fellows Grant Award Program and by the National Institutes of Health under the Ruth L. Kirschstein National Research Service Award (1 F31 CA213933‐01A1)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reduced Renal Primary Cilia Expression in Humanized Sickle Cell Mice
Authors: Taylor Crystal Monique , Kasztan Malgorzata , Yoder Bradley , Pollock Jennifer S. , Pollock David 
Published: June 2021

Sickle cell disease (SCD) is an autosomal recessive hematologic disorder that afflicts millions of people across the globe. As longevity improves due to therapeutic advancements, end‐organ damage, namely sickle cell nephropathy (SCN), has emerged as a major contributor to mortality and morbidity in these patients. Renal primary cilia are mechanosensory organelles that extend from the apical membrane of epithelial cells throughout the nephron and contribute to structural homeostasis. Studies have shown that renal primary cilia display alterations in response to renal ischemic injury and are essential in the epithelial repair process. Defects in renal primary cilia expression and signaling have been shown to contribute to the development of renal cystogenesis. In addition, recent studies have demonstrated an increased prevalence of renal cyst formation in sickle cell disease patients. Therefore, we hypothesized that renal primary cilia expression is reduced in a mouse model of sickle cell disease. We further predicted that acute hypoxia challenge will reduce renal primary ciliogenesis in SCD animals compared to controls. Male 14‐week old humanized sickle cell mice (HbSS) and their genetic controls (HbAA) were subjected to 3 hr exposure to hypoxia (10% O2) prior to the assessment of renal primary cilia formation. Cilia formation was assessed using Western blot analysis on kidney section lysates. Prior to hypoxia exposure, acetylated □‐tubulin expression, a protein involved in cilia architecture, was reduced in the cortex of HbSS mice compared to the genetic controls (0.45 ± 0.02 vs. 1 ± 0.02 a.u. [arbitrary units], respectively, p= 0.03, n=4). In addition, IFT88 expression, a protein involved in cilia assembly, was also reduced in the cortex of HbSS mice compared to HbAA mice (0.59 ± 0.00 vs. 1 ± 0.001, respectively, p= 0.02, n=4). After a 3 hr hypoxia challenge, HbSS mice maintained a significant reduction in cortical acetylated □‐tubulin expression compared to hypoxia‐ challenged HbAA mice (0.38 ± 0.02 vs. 1 ± 0.03 a.u., respectively, p= 0.008, n=5). However, there was no significant difference in cortical IFT88 expression in HbSS mice compared to controls following hypoxia (1.1± 0.002 vs. 1 ± 0.002 a.u., respectively, p= 0.69, n=5). These data suggest that renal primary cilia expression is reduced in SCD and acute hypoxia exposure may promote renal ciliogenesis. These findings provide a potential mechanism by which renal injury is potentiated in SCN.Support or Funding InformationWilliam Townsend Porter Pre‐ doctoral Fellowship from the American Physiological Society to C. TaylorU01 HL117684 to DMPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.