bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential diagnosis of cardiac tumors on a cadaveric specimen
Authors: Raja Dewan S. 
Published: June 2021

ObjectivesPrimary cardiac tumors are a relatively rare occurrence in autopsy and surgery reports of United States. Notably, around 80% of all cardiac tumors are benign. The most common cardiac tumor is myxoma, which typically hangs inside the left atrium. On a female cadaveric specimen of about 70 years of age—we recently discovered nodular masses on the heart surface in the gross anatomy laboratory. We found two rounded cardiac tumors of 2 cm and 3 cm in diameter, both on the right ventricle encroaching on the pulmonary trunk. We explored her lungs and liver, finding no tumors in or on the cadaver's other viscera. We examined the tumors macroscopically and, on palpating, found it hard. Then we incised the nodule, finding a semi‐solid blood clot and some cheesy materials. I took photographs before and after the incision.MethodsWe searched several pathology textbooks and relevant scientific literature the cause of this swelling.Result and ConclusionThe differential diagnosis includes aneurysms of the right atrium with clotted blood, lipomas, epicardial cysts and Chagas cardiomyopathy. Our discovery has subsequently drawn keen attention from faculty and students.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evidence of Endothelin‐B Receptor Dysfunction in Obesity
Authors: Derella Cassandra C , Looney Jacob , Bieck Maire Rose , Jeong Jin hee , Rodriguez‐Miguelez Paula , Tucker Matthew A , Thomas Jeffrey , Stanheqicz Anna E , Alexander Lacy M , Pollock David M , Harris Ryan A 
Published: June 2021

BackgroundThe endothelin system has been identified as a key regulator of vascular function and is comprised of two opposing receptors; a constricting A‐receptor (ETAR) and dilating B‐receptor (ETBR). Dysregulation of the ETBR and obesity both independently contribute to vascular endothelial dysfunction. However, whether obese individuals exhibit ETBR dysfunction has yet to be determined. Thus, this study sought to test the hypothesis that microvascular ETBR dysfunction is present in obesity compared to normal weight individuals.MethodsIntradermal microdialysis assessments were completed on 13 individuals (9 men; 4 women; age range: 19–38 years old). Participants were recruited according to BMI: lean (BMI ≤ 24.9 kg/m2; n = 6) or overweight/obese (BMI ≥ 25.0 kg/m2; n = 7). Two microdiaylsis fibers were inserted into the dermal layer of the right forearm where cutaneous blood flow was measured using laser speckle contrast imaging. ETBR function was determined two ways: 1) by a seven dose incremental perfusion of ET‐1 (10−20–10−8 M) combined with the selective ETAR antagonist, BQ‐123 (750 nM), and 2) by a seven dose incremental perfusion of ET‐3 (10−17–10−11 M), the isoform that has ETBR selectivity at low doses. The dose response area under the curve (AUC) for cutaneous vascular conductance was calculated for each individual.ResultsThe AUC for the ET‐1 + BQ‐123 dose response was significantly (p=0.02 reduced in the overweight/obese group (AUC = 157.0 ± 11.0 AU) when compared to the lean group (AUC = 221.8 ± 41.1 AU). The AUC for the ET‐3 dose response tended (p=0.21) to be lower in the overweight/obese group (AUC = 155.2 ± 8.5 AU) compared to the lean group (AUC = 191.3 ± 46.4 AU).ConclusionThese data suggest that ETBR function is impaired in obesity compared to normal weight individuals. The reduced ETBR function may contribute to the observed prevalence of vascular endothelial dysfunction in obesity; however, this hypothesis warrants further investigation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Angiotensin‐(1‐7) Prevents Thyroid Hormone‐induced Cardiomyocyte Hypertrophy by FOXO3 Signaling Pathway
Authors: Senger Nathalia , Santos Robson Augusto , Barreto‐Chaves Maria Luiza Morais 
Published: June 2021

It is well‐known that high levels of thyroid hormone promote cardiomyocyte hypertrophy, which in part is mediated by activation of Renin‐Angiotensin System (RAS). Recent study of our group demonstrated that the contralateral RAS axis (ACE2/Angiotensin‐(1–7)/Mas receptor) is also involved in this cardiac hypertrophy model and that transgenic rats overexpressing circulating levels of Angiotensin‐(1‐7) (Ang‐(1‐7)) present an improvement of cardiac function and attenuation of cardiac hypertrophy. However, the molecular mechanisms involved in these Ang‐(1‐7) actions have not been fully elucidated. The aim of this study was to investigate if the anti‐hypertrophic effect of Ang‐(1‐7) also occurs in isolated cardiomyocytes, as well as the involvement of the Foxo3 signaling pathway for these effects. All experiments were approved by the Ethics Committee on Animal Experimentation of ICB‐USP (n030/12/CEUA). Primary cardiomyocytes cultures obtained from neonatal rats were treated with triiodothyronine (T3) (15nM) and/or Angiotensin‐(1‐7) (Ang‐(1‐7)) (100nM). All data were analyzed by ANOVA followed by Tukey's post hoc test, and values of P<0.05 were considered statistically significant. The Ang‐(1‐7) treatment prevented the cardiomyocyte hypertrophy induced by T3, which was confirmed by reduction cell surface area, L‐[3,4,5‐3H] leucine incorporation and BNP gene expression. Combined treatment with the MAS receptor antagonist (A779, 100nM) impaired the anti‐hypertrophic effect of Ang‐(1‐7). Regarding molecular mechanisms, although Ang‐(1‐7) treatment did not impair the rapid activation of Akt promoted by T3, Ang‐(1‐7) treatment reduced the phosphorylation of Foxo3 (inactive form) and promoted the nuclear accumulation of Foxo3 in cardiomyocytes, indicating the activation of this protein. Collectively, these findings indicate an important cardioprotective effect of Ang‐(1‐7) in isolated cardiomycoytes treated with T3, occurring via MAS receptor and with possible participation of Foxo3.Support or Funding InformationFoundation for the Support of Research in the State of São Paulo (FAPESP) and National Council of Technological and Scientific Development (CNPq).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Antiarrhythmic Effects of Chronic Melatonin Treatment Are Not Associated with Its Antioxidative Action in Rat Myocardial Ischemia/Reperfusion Model
Authors: Azarov Jan E , Efremova Yulia , Bernikova Olesya , Pliss Michael , Lopatina Ekaterina , Vaykshnorayte Marina , Sedova Ksenia 
Published: June 2021

IntroductionMelatonin was proposed as a potential antiarrhythmic agent, and its antioxidative properties are considered to be the basis for the antiarrhythmic effect. The present study was aimed at the evaluation of association between ventricular tachycardia and/or ventricular fibrillation (VT/VF) incidence, oxidative stress parameters and electrophysiological changes in myocardial ischemia/reperfusion setting.Methods18 rats were treated by melatonin (10 mg/kg/day, orally) for 7 days, while 13 control animals were given placebo. The left anterior descending artery was reversibly ligated for 5 min to induce ischemia and subsequent reperfusion in the anesthetized animals. Unipolar electrograms were recorded from ventricular epicardium with a 64‐lead array connected to a custom‐made high‐resolution (4 kHz) mapping system. Local activation and repolarization times were measured as instants of dV/dt min during QRS complexes and dV/dt max during T waves in unipolar electrograms, respectively. Local repolarization durations and dispersion of repolarization were calculated. After experiments, the hearts were excised, and parameters of the oxidative stress were determined in ventricular myocardium.ResultsVT/VF incidence was less in the animals given melatonin as compared to controls (6/18 vs 9/13, p=0.047, respectively). Superoxide dismutase activity was higher in the melatonin group as compared to the control group (69.6±0.5 vs 60.2±2.0 inhibition rate %, p=0.001, respectively), while total antioxidant capacity, 4‐HNE adduct and total glutathione content did not differ in the studied groups. No parameters of oxidative stress were associated with arrhythmia susceptibility. Among the studied ventricular epicardial electrophysiological parameters, local activation times at the baseline (preischemic) state were both reduced by melatonin treatment (9.39±0.26 vs 10.58±0.33 ms, p=0.012) and associated with VT/VF incidence (B=1.872, 95% CI 1.106–3.169, p=0.020) in logistic regression analysis. No association between parameters of ventricular electrical excitation and oxidative stress were found.ConclusionThough chronic melatonin treatment enhanced enzymatic antioxidant activity, its antiarrhythmic action in ischemia/reperfusion model was associated with its direct effect on ventricular activation pattern.Support or Funding InformationThe study was supported by Russian Science Foundation (RSF 18‐15‐00309).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exogenous MG53 Protects Adult Mouse Cardiomyocytes by Preventing Mitochondria Damage in Response to Oxidative Stress
Authors: Gumpper Kristyn Nicole , Ko Jae‐Kyun , Xu Li , Han Renzhi , Zhou Hua , Lin Pei‐Hui , Ma Jianjie 
Published: June 2021

Ischemic heart disease is a major cause of mortality and morbidity world‐wide and its incidence is continually increasing as other health factors, such as diabetes type II and obesity, climb. Ischemic injury of any tissue causes a loss of healthy mitochondria, due to an increase in reactive oxygen species leading to oxidative stress. MG53, also known as TRIM72, is highly expressed in skeletal muscle and modestly in other tissues and is essential to repair damage to plasma membrane by acting as a myokine. We have previously shown that MG53's membrane repair function is associated with changes in oxidative state inside the cell. Moreover, we have shown that mg53−/− mice are more susceptible to ischemia‐reperfusion injury, whereas treatment with exogenous recombinant human MG53 (rhMG53) reduces both infarct damage and fibrosis and restores cardiac function. We hypothesize that in addition to cell membrane repair, exogenous MG53 enters cardiomyocytes and can act as a myokine to protect cardiomyocytes by maintaining mitochondrial function through control of oxidative‐stress induced mitophagy. In this study, MG53 protection of cardiomyocyte mitochondria was assessed by subjecting HL‐1 cells (an immortalized mouse atrial cardiomyocyte cell line) to oxidative stress followed by analysis for mitochondrial structure and function. Overall, we show that treatment with rhMG53 allowed cells to maintain a healthy mitochondrial membrane potential to protect mitochondrial function. We are currently dissecting the mechanism that facilitates the endocytic uptake of MG53 from the circulation into the cardiomyocytes as well as downstream signaling pathways that mediate the protection of the mitochondria function. The novelty of this study is that it shows exogenous MG53 can protect mitochondria in cardiomyocytes upon oxidative stress. This provides a mechanism behind how rhMG53 treatment may be a clinically relevant strategy to reduce cardiomyocyte injury and maintain cardiac function in patients after ischemic injuries.Support or Funding InformationResearch Support: R01 grants (DK106394 and AR070752) from NIH to J. M and AHA predoctoral fellowship (18PRE34030430) to K.G.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Regulation of Brown Adipose Tissue Function by HuR
Authors: Anthony Sarah R. , Lanzillotta Lindsey , Guarnieri Adrienne , Green Lisa , Slone Sam , Helsley Robert N. , Brown J. Mark , Civelek Mete , Owens A. Phillip , Tranter Michael 
Published: June 2021

Stimulating the metabolic function of brown adipose tissue (BAT) and/or inducing the beiging of white adipocytes (WAT) to BAT‐like cells represent potential therapeutic strategies for increasing energy expenditure and reducing obesity. HuR (ELAVL1) is an RNA binding protein that mediates gene expression through stabilization of mRNA targets and is highly expressed in both WAT and BAT. We identified an inverse correlation between HuR expression and obesity in humans via the METabolic Syndrome In Men study of Finnish men. Thus, we hypothesized that HuR expression in adipocytes plays a critical role in maintaining metabolic homeostasis.Our results show that, compared to control littermates, adipocyte‐specific HuR‐null (adipo‐HuR−/−) mice display a lean phenotype with decreased fat mass and increased energy expenditure, independent of diet. Interestingly, adipo‐HuR−/− mice also show a disruption of BAT structure and function, with increased lipid droplet size, decreased BAT density, and an inability to thermoregulate when subjected to cold. Examination of skeletal muscle suggests that the lean phenotype in adipo‐HuR−/− mice is due to compensatory shivering to thermoregulate in the absence of functional BAT, a result consistent with UCP1−/− mice. Surprisingly, we found no difference in basal expression of UCP1 in BAT from control and adipo‐HuR−/− mice. However, HuR is activated downstream of β3 adrenergic stimulation and appears to play a role in cold/β3 induced UCP1 expression. Additionally, adipo−HuR−/− mice show a decrease in mitochondrial density in both BAT and subcutaneous (sc) WAT, as well as a decrease in brown/beige adipocyte marker genes (PRDM16, Elovl3) in scWAT.In conclusion, our results demonstrate that HuR plays a central role in the structure and function of BAT. Work is ongoing to identify the transcriptome wide changes in HuR‐dependent gene expression as well as the potential role of HuR in beiging of WAT.Support or Funding InformationThis work was partially funded by a University of Cincinnati Heart, Lung, and Vascular Institute Pilot Grant (MT, APO).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Genistein and Exercise Reverse Hyperglycemia and Hyperinsulinemia Induced by High Fat/High Sucrose Diet via Influences on Hepatic Gluconeogenesis in Mice
Authors: St Aubin Chaheyla , Fisher Amy , Broderick Thomas , Al‐Nakkash Layla 
Published: June 2021

Consumption of a high fat/high sugar (HFHS) diet has not only been identified as risk factor for obesity, but it also predisposes towards type 2 diabetes mellitus (T2DM), by resulting in hyperglycemia and impaired insulin signaling. A targeted metabolic pathway for treatment of T2DM is hepatic gluconeogenesis. Gluconeogenesis is responsible for maintaining blood glucose levels during times of exercise, fasting, and stress. Insulin is responsible for suppressing gluconeogenic activity. However, as the liver becomes insulin resistant, hepatic gluconeogenesis becomes over activated exacerbating T2DM pathology. We aimed to assess whether genistein and/or exercise regulate hepatic gluconeogenesis. C57BL/6J male and female mice aged 5–6 weeks were randomly assigned to one of the following groups (n=8–10/group): lean control (Ln), high fat/high sucrose diet (HFHS), HFHS+Gen (genistein), HFHS+Ex (exercise), and HFHS+Gen+Ex. The HFD consisted of 60% saturated fat, 20% carbohydrate, 20% protein and included sucrose and fructose (42 g/L) in the drinking water. Exercise consisted of daily moderate treadmill running for a total duration of 150 minutes/week for 12 weeks. Genistein dose was 600 mg genistein/kg HF diet. C57BL/6J mice fed HFHS exhibited phenotypes seen in T2DM pathology; including rapid weight gain, hyperinsulinemia and hyperglycemia. Our results demonstrate that serum glucose and insulin levels in males were rescued by Gen+Ex treatment combined compared to controls. Corticosterone levels were significantly elevated in females fed HFHS diet (2755±375 pg/mL, n=6) compared to Ln controls (1449 ± 275 pg/mL, n=7), with significant recovery by Gen+Ex (964±234 pg/mL, n=7). Measures of total protein expression of renal 11βHSD2 (responsible for the conversion of active cortisol to inactive cortisone) however, showed no significant difference indicating that 11βHSD2 may not be playing a role in corticosterone deactivation. We are currently determining total protein expression levels of hepatic 11βHSD1 (responsible for the conversion of corticosterone to its active form). Current studies are also evaluating the roles of two rate limiting enzymes; phosphoenolpyruvate carboxykinase (PEPCK) and glucose‐6‐phosphotase (G6Pase). These studies provide evidence of the protective role that genistein and exercise may provide to ameliorate diabetic‐obesity induced by HFHS diet.Support or Funding InformationSupport: Layla Al‐Nakkash, Tom Broderick were supported by Midwestern‐Arizona Alzheimer's Consortium and Midwestern University Intramural Funds. Chaheyla St Aubin and Amy Fisher were supported by the Department of Biomedical Sciences.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Gene and protein expression of exercise pressor reflex‐related molecular receptors in dorsal root ganglion of spontaneous‐hypertensive and normotensive rats
Authors: Weavil Joshua C , Kwon Oh Sung , Hughen Ronald W , Zhang Jie , Richardson Russell S , Light Alan R , Amann Markus 
Published: June 2021

BACKGROUNDThe exercise pressor reflex (EPR), mediated by mechano‐ and metabosensitive skeletal muscle afferent feedback, is exaggerated in spontaneously hypertensive rats. This cardiovascular reflex dysfunction could be the result of disease‐related abnormalities in the expression and/or sensitivity of molecular receptors located on the terminal end of these muscle afferents, altered central integration of muscle afferent feedback, and/or altered end‐organ responsiveness to a given sympathetic activity.PURPOSETo examine dorsal root ganglion (DRG) gene and protein expression of molecular receptors recognized to be significant determinants of the EPR in control (CTRL) and spontaneous hypertensive rats (SHR).METHODSTwelve lumbar DRGs (6 left, 6 right) were harvested from each of the ten CTRL (mean arterial blood pressure (MAP): 99 ± 2 mmHg) and the ten SHR (MAP: 146 ± 3 mmHg) male rats. DRGs from the right side were quickly frozen for later extraction and RNA sequencing. All mRNA values were normalized to transcripts per million (TPM). DRGs from the left were quickly frozen and later assessed for protein expression by Western Blot. All protein was normalized to GAPDH. Analyses were focused on the transient receptor potential cation channel 1 (TRPV1), acid‐sensing ion channel 3 (ASIC3), purinergic receptor 2X3 (P2X3), and prostaglandin E2 receptor 4 (EP4).RESULTSmRNA content was similar between SHR and CTRL animals (TRPV1: 113 ± 9 TPM vs 110 ± 13 TPM; ASIC3: 39 ± 9 vs 44 ± 7; P2X3: 246 ± 16 vs 246 ± 26; EP4: 10 ± 1 vs 9 ± 1, respectively; all P > 0.18). In contrast, SHR animals demonstrated a greater protein expression for all receptors measured compared to CTRL animals (TRPV1: 1.47 ± 0.20% vs 0.86 ± 0.06%; ASIC3: 1.36 ± 0.09 vs 0.77 ± 0.07; P2X3: 1.49 ± 0.11 vs 1.18 ± 0.11; EP4: 1.36 ± 0.21 vs 1.11 ± 0.13; all P < 0.01).CONCLUSIONIn the face of an equivalent mRNA content in the SHR and CRTL DRG, the substantially greater receptor protein content in the SHR supports the potential for a dysregulated expression of muscle receptor protein in the hypertensive rats. Furthermore, these findings suggest an abnormally increased content of EPR‐related molecular receptors as a potential mechanism contributing to the exaggerated EPR which characterizes these animals.Support or Funding InformationHL‐116579This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Central Administration of Hydrogen Sulfide Alleviates Rodent Angiotensin II Hypertension
Authors: Donertas Basak , Malphurs Wendi L. , Baekey David M. , Julian David , Sirmagul Basar , Zubcevic Jasenka 
Published: June 2021

IntroductionActivation of autonomic neural pathways plays a significant role in pathogenesis of hypertension (HTN). Hydrogen sulfide (H2S) is an endogenous neuro‐ and immunomodulatory molecule that is reportedly reduced in both rodent and human HTN. However, central role of H2S in HTN is not well understood. We hypothesized that chronic intracerebroventricular (ICV) infusion of sodium hydrosulfide (NaHS), an H2S donor, will alleviate rodent angiotensin II (Ang II) HTN.MethodsAdult male Sprague Dawley rats were implanted with radiotelemetry transmitters (DSI) in the descending aorta. Following baseline BP measurements, rats were randomly divided into three groups: (i) ICV NaHS; (ii) HTN; and (iii) ICV NaHS‐treated HTN rats. HTN was induced by chronic infusion of Ang II (200 ng/kg/min s.c.) for four weeks using mini‐osmotic pumps. ICV NaHS (30 nmol/h) or ICV saline was administered simultaneously with s.c. Ang II or saline infusion. At endpoint, H2S levels were measured in plasma samples of all rats.ResultsAt week four, mean arterial pressure (MAP) was significantly reduced in the ICV NaHS‐treated HTN group when compared with HTN group (104±7 vs. 166±5 mmHg, respectively; P< 0.01). This was associated with a lower MAP at night in the ICV NaHS‐treated HTN vs. HTN group (Delta MAP from day to night: 15.29±4 vs. 31.37±17 mmHg, respectively), suggesting reduced sympathetic drive following treatment with NaHS. Interestingly, this also reflected in significantly higher plasma H2S levels in the ICV NaHS‐treated HTN vs. HTN group (0.070±0.000 AU vs. 0.067±0.000 AU, respectively; P<0.05).ConclusionThese results support our hypothesis that alterations in central H2S signaling are associated with HTN, as centrally administered NaHS alleviated rodent Ang II HTN via reduction of sympathetic tone at night.Support or Funding InformationTUBITAK 2214‐A and UF CVM.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.