bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change over Time of Triphenyltetrazolium Measured Infarct Size in Rat Isolated Hearts
Authors: Cleveland William J , Douglas Hunter F , Salzman Michele M , Balzer Claudius , Riess Matthias L 
Published: June 2021

IntroductionInfarct size (IS) is a valuable measure used to assess damage caused by experimental ischemia/reperfusion (I/R) injury. Accurate quantification of IS is vital in determining the efficacy of treatments, and their ability to confer cardioprotection. Thus, a consistent means of assessing IS becomes necessary, in order to avoid unintentionally biased assessment of experimental parameters. Variable times at which IS is measured following 2,3,5‐triphenyltetrazolium chloride (TTC) staining may have a confounding effect on accurate measurements. The objective of this study was to determine the optimal time to measure IS following TTC staining in rat isolated hearts.MethodsLangendorff‐prepared hearts from adult male Brown Norway rats (n=17) utilized for studies of cardioprotection in I/R injury were used. For this analysis, treatments were divided into groups based on: cardioprotection (n=3), control (n=9), or abolishment of cardioprotection (n=5). Following the experimental procedure, hearts were sliced transversely in 3mm slices and stained using 1% TTC solution, which stains viable cells red. Stained heart slices were then stored in 4% formalin at 4°C, then measured repeatedly in 24‐hour increments using cumulative planimetry. IS% was plotted over time to assess the temporal effects of measurement. Regression and correlation analyses were used to determine the relationship of IS% and time, with regards to the experimental treatments used. Data are expressed as mean±SEM and r2. Statistics: one‐way Anova, p<0.05, * vs control, † vs cardioprotective.ResultsHearts showed a linear increase in measured IS% over time for all treatments. Hearts treated with a cardioprotective abolisher had higher IS% at 24‐hours (26±2.1%*†) than control (14±1.7%) and cardioprotective (10±3.5%). Additionally, hearts from the cardioprotective abolisher group had faster increases in measured IS% per day (4.3±3.4%, r2=0.91) than control (1.8±0.1%, r2=0.84) and cardioprotective (1.6±0.6%, r2=0.75).ConclusionThese data show that measured IS has a positive correlation with time when TTC staining and cumulative planimetry are used. Additionally, the data indicate that certain treatments (e.g., cardioprotective abolishers) may cause accelerated increases in measured IS% over time. Care should be taken to measure IS at a set time ~24 hours after the experiment and TTC staining to avoid biasing data. Further experiments will need to look at more narrow time points to assess measures taken under 24 hours to determine whether this will provide more optimal measures.Support or Funding InformationThis work was supported, in part, by institutional funds, NIH grant (5R01 HL123227), and a Merit Review Award (I01 BX003482) from the U.S. Department of Veterans Affairs Biomedical Laboratory R&D Service.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mitochondrial Deacetylase Sirt3 as a New Target in Cardiovascular Diseases
Authors: Dikalova Anna , Pandey Arvind , Xiao Liang , Itani Hana , Sidorova Tatiana , Verdin Eric , Auwerx Johan , Harrison David G , Dikalov Sergey 
Published: June 2021

Multiple risk factors such as aging, vascular dysfunction, metabolic disorders and hypertension contribute to the pathogenesis of heart failure. The convergent mechanism that may underlie the interplay of these major risk factors is not clear but may provide novel strategies for treatment. Clinical studies show that Sirtuin 3 (Sirt3) expression declines by 40% by age 65 and sedentary lifestyle paralleling the increased incidence of cardiovascular diseases and heart failure while aerobic exercise increases Sirt3 expression and attenuates age‐dependent Sirt3 decline. Meanwhile, the pathophysiological role of Sirt3 depletion is not clear. Mitochondrial deacetylase Sirt3 is critical in regulation of mitochondrial metabolism and it activates a key antioxidant enzyme, superoxide dismutase 2 by deacetylation of specific lysine residues. We hypothesized that Sirt3 plays critical role in vascular dysfunction and hypertension. To test this hypothesis, we have developed new tamoxifen‐inducible endothelium specific Sirt3 knockout (EcSirt3KO), endothelial Sirt3 overexpressing (EcSirt3OX), smooth muscle Sirt3 knockout (SmcSirt3KO), smooth muscle Sirt3 overexpressing (SmcSirt3OX) and global Sirt3 overexpressing (Sirt3OX) mice on C57Bl/6J background, and examined the effect of Sirt3 expression on vascular dysfunction and angiotensin II‐induced hypertension. Sirt3 depletion in EcSirt3KO and SmcSirt3KO mice raises basal vascular permeability in the heart by 2‐fold, reduces endothelial NO, increases blood pressure and accelerates vascular aging compared with wild‐type mice. Angiotensin II infusion in EcSirt3KO and SmcSirt3KO mice caused vascular hyperpermeability, increased vascular hypertrophy, exacerbated endothelial dysfunction and hypertension. Meanwhile, Sirt3 overexpression attenuates vascular aging, normalizes vascular permeability, diminishes vascular inflammation, inhibits vascular oxidative stress, preserves endothelial‐dependent relaxation, reduces vascular hypertrophy and attenuates hypertension in Sham and angiotensin II‐infused EcSirt3OX and SmcSirt3OX mice compared with the wild‐type littermates. We suggest that Sirt3 is central in redox and metabolic regulations of smooth muscle and endothelial cells. As vascular permeability increases, the access of cytokines, inflammatory cells and LDL to tissue is greater contributing to cardiac inflammation, altered tissue remodeling, hypertrophy and dysfunction. Our data support a therapeutic potential of targeting Sirt3 in cardiovascular dysfunction and hypertension which can improve treatment of the heart failure.Support or Funding InformationThis work was supported by funding from National Institute of Health (NHLBI 1R01HL124116) and American Heart Association (16GRNT31230017).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Prediction of cadet basic training physical performance outcomes
Authors: Ploch Christopher , Thomas Diana M , Adams Bryan , Turner Dusty , Hug Adam , Suby Jason , Palmer John E. , Bigelman Kevin 
Published: June 2021

BackgroundEntry to the United States Military Academy requires submission of scores on the Cadet Fitness Assessment. The cadet fitness assessment consists of push‐ups, crunches, kneeling basketball throw, shuttle run, and 1‐mile run. Upon arrival for Cadet Basic Training, cadets are assessed on the components of the Army Physical Fitness Test; push‐ups, sit‐ups and a 2‐mile run. Additionally all cadets are assessed on a swim test. Records of stress‐fractures incurred during Cadet Basic Training are also retained.ObjectiveTo apply supervised and unsupervised machine learning to describe Cadet Basic Training and Cadet Fitness Assessment data compiled from the graduating classes of 2012 to 2021.MethodsSimple data‐analysis plots, linear regression models, and unsupervised k‐means cluster analysis were developed to predict Cadet Basic Training performance. Models were generated to identify the relationship between body mass index (BMI), age and gender on 2‐mile run performance to replicate past Army results.ResultsA total N=8886 (82% male) cadets were retained for analysis. The relationship between 2‐mile run performance and BMI was weak (R2=0.07), with age, BMI, and gender representing significant predictors (p<0.01). Similar results were found for all performance outcomes except pull‐ups. The relationship between pull‐up performance and BMI was stronger (R2=0.47). The cluster analysis revealed four clusters. One cluster was identified to poor 2‐mile run performance while a second cluster was identified with poor swim, push‐up, and sit‐up performance. Scatterplots did not indicate any relationship between cluster assignments and BMI.ConclusionsBMI and even waist circumference may be poor predictors of performance on military physical fitness test outcomes. Machine learning could offer more precision for identifying poor performers early and provide novel opportunities for remediation.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.
Late‐In‐Life Treadmill‐Training Ameliorates the Decline in Cardiac Autophagy Associated with Aging in Mice
Authors: Cho Jae Min , Ramous Caroline , Mattera Maria Sara , Hansen Michele , Pires Karla Maria , Ferhat Maroua , Whitehead Kevin , Carter Kandis , Buffolo Marcio , Park Seul‐Ki , Boudina Sihem , Symons J. David 
Published: June 2021

Protein aggregates accumulate and organelles become damaged and/or dysfunctional during the process of aging. A progressive loss of the cellular quality control mechanism autophagy contributes to this age‐associated decline in cellular function in many organs. Evidence for an age‐associated repression in cardiac autophagy is not consistent. We hypothesized that 24‐month old (old) male C57Bl6/J mice exhibit repressed autophagosome formation in the heart, myocardial dysfunction, and reduced exercise capacity vs. 6‐month old (adult) mice. First, cardiac lysates from old mice displayed reduced (p<0.05) accumulation of LC3II/GAPDH and degradation of p62 vs. adult animals (n=12 per group). Second, the lysosomal acidification inhibitor chloroquine (CQ) induced accrual (p<0.05) of LC3II/GAPDH and p62 in hearts from adult but not old mice (n=7 per group). Third, left ventricular mass was greater (p<0.05), and indices of systolic, diastolic, and global left ventricular function (transthoracic echocardiography) were impaired, in old vs. adult animals (n=12 per group). Finally, maximal workload performed during a treadmill‐test was less (p<0.05) in aged (n=11) vs. adult (n=12) mice. To determine whether late‐in‐life exercise training induces cardiac autophagy, separate cohorts of male mice completed a progressive‐resistance treadmill‐running program (old‐ETR) or remained sedentary (old‐SED) from 21–24 months. Body composition, exercise performance during a maximal workload test, soleus muscle citrate synthase (CS) activity, indices of cardiac antioxidant enzyme activity, markers of cardiac autophagy, and indices of myocardial function, all improved (p<0.05) in old‐ETR (n=11) vs. old‐SED (n=12) mice. These data are the first to demonstrate that markers of cardiac autophagy are elevated, and indices of myocardial function are improved, in old mice that complete a treadmill‐training regimen that is sufficient to increase skeletal muscle CS activity and maximal exercise capacity. These data provide strong proof of concept to evaluate cause and effect relationships among exercise‐training, myocardial.Support or Funding InformationUU Research Fellowship (JMC); APS UGRF (CR); AHA17POST33670663 (SKP); NIHRO1DK098646‐01A1, NIHRO1DK099110, AHA16GRANT30990018 (SB); AHA16GRNT31050004, NIH RO3AGO52848, NIH RO1HL141540 (JDS).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Obesogenic diet in aging mice disrupts gut microbe composition and alters neutrophil:lymphocyte ratio leading to inflamed milieu in acute heart failure
Authors: Kain Vasundhara , Van Der Pol William , Mariappan Nithya , Ahmad Aftab , Eipers Peter , Morrow Casey , Gibson Deanna L , Gladine Cecile , Vigor Claire , Durand Thierry , Halade Ganesh V 
Published: June 2021

Calorie dense obesogenic diet (OBD) is a prime risk factor for cardiovascular disease in aging. However, increasing age coupled with changes in the diet can affect the interaction of intestinal microbiota impacting immune system that can lead to chronic inflammation. How the age and calorie enriched OBD interact with microbial flora and impacts leukocyte profiling is currently under‐investigated. Here, we tested whether OBD in young and aging mice alters the gut microbe composition and the splenic leukocyte profile in acute heart failure. Young (2 month‐old) and aging (18 month‐old) mice were supplemented with STD‐(standard chow diet ~4% safflower oil diet) and OBD‐(obesogenic diet‐10% safflower oil) diet for 2 months and then subjected to coronary artery ligation to induce myocardial infarction (MI). Fecal samples were collected pre‐ and post‐diet and the microbial flora analyzed using 16S V4 rRNA gene DNA sequencing and QIIME informatics. The STD and OBD in aging mice resulted in an expansion of the genus Allobaculum in the fecal microbiota. However, we found a pathological change of neutrophil: lymphocyte ratio in aging mice in comparison to their young counterparts. Thus, calorie‐enriched OBD dysregulated splenic leukocytes by decreasing immune responsive F4/80+/CD169+ macrophages in aging. OBD programmed neutrophil swarming with an increase in isoprostanes levels with dysregulation of lipoxygenases and cytokines. In summary, calorie dense OBD in aging mice disrupted the composition of the gut microbiota that correlates with the development of integrative and system‐wide non‐resolving inflammation in acute heart failure.Support or Funding InformationAuthors acknowledge the support from National Institutes of Health (NIH)‐NCCIH (formerly known as NCCAM) AT006704, HL132989‐01 to GVH and American Heart Association postdoctoral fellowship [POST31000008] to V. K. The authors also acknowledge support of Microbiome Resource at the University of Alabama at Birmingham: Comprehensive Cancer Center (P30AR050948), Center for Clinical Translational Science (UL1TR001417), University‐Wide Institutional Core, Heflin Center for Genomic Sciences and Microbiome Center to CMThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Gamma‐mangostin of Garcinia mangostana peels ameliorates hyperglycemia in synergism of insulin
Authors: Chen Shi‐Pei , Lue Sheng‐I , Fu Yaw‐Syan , Cheng Hui‐Wen , Wang Chun‐erh , Weng Ching‐Feng 
Published: June 2021

Type II diabetes mellitus is diagnosed because of obese having high sugar, high salt and high fat in diet, and is a heterogeneous group of disorders characterized by hyperglycemia due to an absolute or relative deficit in insulin synthesis or action. Mangostins, isolated from Garcinia mangostana peels, contain various isoforms α, β and γ, however, the medicinal values of γ‐mangostin particular in anti‐diabetic as an alternative medicine or folk medicine remain to be explored. This study attempted to investigate hypoglycemic efficacy of γ‐mangostin through execution in cellular and mouse levels. In vitro, the vascular smooth cells isolated from the external carotid artery of SD rat and FL83B mouse hepatocytes were applied to determine the cytotoxicity and glucose uptake. The cell viability data showed that 0.5 μM, 2.5 μM and 5 μM γ‐mangostin had non‐toxicticity in both cell types. The hypoglycemic effectiveness of 5 μM γ‐mangostin treatment was greater than those of 0.5 and 2.5 μM γ‐mangostin during two hours test of two cell types. Compared with 10−7 M insulin, the potency of γ‐mangostin plus insulin in synergistic glucose uptake reached plateau within 90 min. Furthermore, the hypoglycemic efficacy of oral administration 0.1, 0.2 and 0.4 mg γ‐mangostin was similar to 0.2 U insulin intraperitoneal injection and oral 50 mg/kg metformin for 120 min of oral glucose tolerance test (OGTT) in diet‐induced diabetic ICR mice. The hypoglycemic ability of oral 0.4 mg γ‐mangostin was more effective than that of 12 mg/kg Acarbose for 180 min in oral starch tolerance test. Diabetic ICR mice were daily fed 0.2 mg γ‐mangostin, 0.4 mg γ‐mangostin and vehicle for 4 weeks, the data revealed that γ‐mangostin caused the lowing blood glucose at fasting level and OGTT. Taken altogether, γ‐mangostin plays an insulin sensitizer to dampen the hyperglycemia with non‐ cytotoxicity in cell line tested.Support or Funding InformationMinistry of Science and Technology (107‐2813‐C‐259‐061‐B), Taiwan.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Melatonin Supplementation Decreases Inflammatory Adipokines Expression from Adipose Tissue of Obese Animals
Authors: da Silva Mendes Farias Talita , Paixão Regislane Ino , Cruz Maysa Mariana , Dourado Roberta 
Published: June 2021

The incidence of obese people worldwide is increasing every year and accumulating evidence indicates that dysregulated expression of adipokines, caused by excess adiposity and adipocyte dysfunction, has been linked to the pathogenesis of obesity‐linked complications. Melatonin, a hormone responsible for the synchronization of mammalian circadian rhythms, is related to beneficial effects on the control of obesity and its complications. In this work we evaluated the effects of melatonin supplementation on the production of adipokines in epididydimal (EPI) and inguinal (ING) fat depots from obese animals induced by a high‐fat‐diet (HFD). Male C57Bl/6j mice were divided into 3 groups: CO, animals fed with control diet; Obese, animals fed with HFD and Obese + melatonin, animals fed with HFD and supplemented with melatonin (1mg/kg). Melatonin presented a preventive effect on body weight gain and slowed down the effects on food and energy efficiency triggered by HFD. Adiponectin, IL‐6, leptin, and TNF‐α gene expression in ING and EPI fat depots were analysed. It was observed an increase (by 55 %, p <0.05) in adiponectin mRNA in ING depot when the animals received melatonin. There was an increase (3,7‐fold, p <0.05) in the IL‐6 mRNA expression in the EPI depot (but not in ING) in HFD group, that was prevented by melatonin supplementation. The same increase was observed on leptin expression in EPI adipose depot (6‐fold, p <0.05) from animals fed with HFD. Again, melatonin supplementation completely abolished this effect. Similarly, there was an increase (by 23‐fold, p <0.05) in the expression of this gene in the ING depot from HFD animals, and herein, we observed only a prevention trend (p = 0.0514) by melatonin on leptin mRNA in this fat depot. In both, EPI and ING depots, TNF‐α mRNA was significantly increased (by 5‐fold and 7‐fold respectively, p <0.05) in the HFD as compared to the CO group, but the melatonin supplementation not decreased this parameter. The protein analysis in these tissues (ING and EPI) performed by Elisa, showed that IL‐6 protein was increased (68%, p <0.05) in EPI fat depot from HFD group when compared to CO. This elevation was completely prevented when the animals were supplemented with melatonin. By the other side, no changes were observed between the groups concerning IL‐6 secretion in ING depot. The results obtained herein suggest that melatonin supplementation improves the adipokines expression in animais with obesity induced by a HFD, that is, it increases adiponectin while reducing the expression of inflammatory cytokines in adipose tissues. Together, these results show that melatonin supplementation had an protetive action on obesity complicationsSupport or Funding InformationFapesp (2015/03554‐2)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cardiovascular Effects of Pyridoxamine in Type 1 Diabetic Female Rats
Authors: Delbin Maria A , Passos Matheus P , Ruberti Olivia M , Jarrete Aline P , Sousa Andressa S 
Published: June 2021

The formation of advanced glycation end products (AGEs) is an important pathway involved in cardiovascular complications of diabetes mellitus (DM). The pharmacologic approaches in clinical use have remained unsatisfactory in preventing the diabetic cardiovascular complications and more innovative therapies are needed. Therefore, the aim of the study was to investigate the coronary vascular responsiveness and oxidative stress in the left ventricle in type 1 diabetic female rats and the effects of the combined treatment with insulin and pyridoxamine (AGEs inhibitor). This study was approved by the Ethical Committee for Animal Research Use (CEUA UNICAMP 4532/2017). Female Wistar rats (180–200g) were divided into four groups: control (CTR), type 1 DM (DM1, alloxan 170 mg/kg IP), DM1 treated with insulin (DM1+INS, 2U morning + 4U evening SC/day) and DM1 treated with insulin and pyridoxamine (DM1+INS+PDX, 180 mg/kg/day oral gavage). One week after DM1 induction the DM1+INS and DM1+INS+PDX groups initiated the respective treatment that lasted for three weeks. Concentration‐response curves to acetylcholine (ACh), sodium nitroprusside (SNP) and thromboxane A2 analog (U46619) were obtained in septal coronary artery. The generation of reactive oxygen species (ROS) were evaluated in left ventricle in basal condition and in the presence of superoxide dismutase mimetic (MnTMPyP). Biochemical parameters were measured. One‐way ANOVA followed by a Tukey's test was performed. As expected, the body weight was reduced and the blood glucose was increased in DM1 as compared with CTR group. In DM1+INS and DM1+INS+PDX groups the blood glucose was reduced and the body weight values were normalized. The maximal response (EMAX) to ACh was decreased in DM1 (72±6%) and DM1+INS (78±8%) groups compared with CTR (97±8%), the combined treatment in DM1+INS+PDX (99±5%) restored this alteration with no changes in potency (pEC50). Neither the EMAX nor pEC50 were modified for SNP and U46619 in all experimental groups. At basal condition, ROS measurement in the left ventricle was not modified in all groups. However, the reduction of ROS generation in the presence of MnTMPyP was impaired in DM1 group (approximately 50%) as compared with CTR group. Only the combined treatment with insulin and pyridoxamine was effective in preventing this alteration in DM1+INS+PDX group. In conclusion, our results show that insulin associated with pyridoxamine treatment prevented the coronary dysfunction and cardiac oxidative stress in type 1 diabetic female rats.Support or Funding InformationFAPESP (2016/16351‐5; 2017/22670‐9) and CAPES.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.