bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remote limb ischemic preconditioning improves post‐resuscitation long term survival in a rat fixed pressure hemorrhagic shock model
Authors: Dai Wangde , Shi Jianru , Carreno Juan , Hale Sharon , Kloner Robert A. 
Published: June 2021

BackgroundWe investigated whether bilateral lower limb remote ischemic preconditioning (RIP) could improve long‐term survival in a rat model of hemorrhagic shock/resuscitation.MethodsSprague Dawley rats (both genders) were anesthetized with intraperitoneal ketamine and xylazine, and were intubated and ventilated with room air. Rats were randomly assigned to RIP (n= 26; induced by inflating small bilateral pressure cuffs to 200 mmHg around the femoral arteries for 5 minutes, followed by 5 minute release of the cuffs, repeated 4 times) or control group (n= 27; the blood pressure cuffs are inflated only to 30 mmHg). After heparinization, hemorrhagic shock was induced by withdrawing blood from the left carotid artery to a fixed mean blood pressure of 30 mmHg for 30 minutes, followed by 30 min of resuscitation with shed blood. Rats remained anesthetized for one hour during which hemodynamics were monitored (femoral artery catheter); and then allowed to survive for 6 weeks.ResultsThe survival rate at 6 weeks was 5 out of 27 rats in the control group (18.5%), and 13 out of 26 rats in the RIP group (50%; p<0.05 by Fisher's exact test). Recovery of blood pressure during the early resuscitation phase was significantly improved and the heart rate was significantly lower in the RIP group compared to the control group (Figure below). At 6 weeks, all of the surviving rats were neurologically intact. Histochemistry/histologic staining was performed in the tissues from 9 survived rats, and showed brain infarction in 1 out of 3 rats in control and 1 out of 6 rats in RIP group; no evidence of myocardial or kidney infarction were detected.ConclusionsRIP markedly and significantly improved long term survival after experimental hemorrhagic shock/resuscitation and improved recovery of blood pressure in the early phase of resuscitation.Support or Funding InformationThis work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Peer Reviewed Medical Research Program under Award No.W81XWH‐16‐1‐0606. Opinions, interpretations, conclusion and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Improving Accuracy of Falling Drop Hemoglobin Method via Modifications to Column Length
Authors: Rupprecht William , Randolph Tim 
Published: June 2021

Anemia is a common blood disorder characterized by a depletion of red blood cells. This condition is prevalent in third world countries and in areas with scarce resources. There are numerous types of anemia, which can range from treatable and mild to untreatable and life‐threatening. In underdeveloped settings, even iron‐deficiency anemia can be fatal if left untreated. An estimated 32.9% of the global population suffered from anemia in 2010, principally due to malnutrition. Before anemia can be effectively treated, it must be predicated by an accurate diagnosis. Contemporary methods for determining anemia are common in developed countries, but many poverty‐stricken regions do not have the necessary infrastructure to perform them – to include funding, stable electricity, refrigeration, climate control, waste removal, well‐trained laboratory technicians, and clean water. These barriers demonstrate the need for a technique of hemoglobin measurement to diagnose anemia that is simple, accurate, inexpensive, and independent of electricity/batteries. The Falling Drop Hemoglobin Method, developed in our laboratory, entails releasing a blood droplet onto a solution of 4.58% copper sulfate in a vertical column. The hemoglobin concentration has been shown to have an inverse, linear relationship with the blood droplet descent time in the column. However, correlation to existing methods was lower than expected due to the shallow slope of the linear regression curve. This finding necessitated modifications to the system: the specific aim of this study. It was hypothesized that a longer column length would improve correlation to existing methods by steepening of the standard curve. Two additional columns of increasing length (46 cm and 61 cm) were compared to the original column length (31 cm), using the method previously established in our laboratory. Venous blood was collected from members of the research team into potassium oxalate/sodium fluoride anticoagulant tubes. Dilutions of venous blood in autologous plasma were made to match eight different hematocrit values (i.e. 15%, 20%, 25%…50%), and the descent time of each hematocrit sample was timed. The slope of the regression curve using the original 31 cm column was −0.3235. The slope of the curve using the 46 cm column was −0.5196, and the 61 cm tube produced a slope of −0.7397. Data indicate that increasing the column length decreases descent time variability (SD61 cm tube = 1.481) and increases the slope of the standard curve – potentially improving the correlation with “gold standard” techniques. Experiments are underway to correlate this method, using the 61 cm column, to four standard methods of hemoglobin measurement.Support or Funding InformationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Growth, Ageing of Coronary Arterial Trees Obey Scaling Laws
Authors: Pei Niu , Yunlong Huo 
Published: June 2021

ObjectiveDespite the well‐known design principles of vascular systems, it is unclear whether the vascular arterial tree in a given species satisfies some scaling constraints during normal growth and ageing.MethodBasing on the micro‐computed tomography measurements of coronary arterial trees in mice at different ages (one week to more than eight months), we present a constant exponent of 3/4, but age‐dependent scaling coefficients in a length–volume scaling law.ResultsThe constant 3/4 exponent represents the self‐similar fractal‐like branching pattern (i.e. basic mechanism to regulate the development of vascular trees for a certain species), whereas the age‐dependent scaling coefficients characterize the structural growth or resorption of vascular trees during normal growth or ageing, respectively.ConclusionsThis study helps to understanding of age‐associated changes in vascular structure and function.Support or Funding InformationThis research is supported in part by the Natural Science Foundation of China grant No.11372010 (Y.L.H.) and the China MOST grant No.2014DFG32740 (Y.L.H.).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Targeted Gene Therapy with RXFP1 Attenuates Myocardial Infarction and Preserves Left Ventricular Function in Mice
Authors: Devarakonda Teja V. , Kohlbrenner Erik , Cain Chad , Das Anindita , Hajjar Roger J. , Salloum Fadi N. 
Published: June 2021

BackgroundSeveral studies have shown that recombinant relaxin targets various mechanisms of cell injury and is protective in models of ischemia/reperfusion (I/R) by reducing oxidative stress, calcium overload, neutrophil activity, NLRP3 inflammasome, endothelial adhesive protein expression, mast cell degranulation, apoptosis, platelet adhesion, as well as improving coronary blood flow. However, there is no information on the role of relaxin receptor 1 (RXFP1) signaling in the heart in the context of myocardial infarction (MI). We sought to determine the effect of RXFP1 gain‐of‐function using novel cardiotropic AAV9 vectors as a therapeutic modality against MI.MethodsRXFP1 cDNA (pCMV6 backbone) was purchased from Origene technologies and introduced into AAV9 cis plasmids following KpnI and AgeI digestion. Plasmids were transformed into NEB stable E. Coli and following propagation, they were transfected into 293T cells with the helper plasmid pDG‐9 to produce AAV9‐RXFP1. Viral particles were isolated post cell lysis and purified. 1.0 × 1011 viral genomes in 100μL were intravenously administered to 8‐week‐old CD1 male mice through tail vein. Four weeks later, a subset of mice was sacrificed and cardiac tissue was extracted for qPCR, western blot, or adult cardiomyocyte isolation. Another subset of mice was subjected to LAD ligation for 30 minutes followed by 24 hours of reperfusion. Cardiac function was assessed via echocardiography prior to sacrifice and infarct size was subsequently determined using triphenyl tetrazolium (TTC) staining.ResultsCardiac tissue from mice injected with AAV9‐RXFP1 showed increased mRNA and protein levels of RXFP1 (Fig. A&B). qPCR analysis also revealed overexpression of RXFP1 in adult cardiomyocytes isolated from mice that received AAV9‐RXFP1 (Fig. C). Phosphorylation of P44/42 MAP kinase downstream of RXFP1 activation was also evident in hearts overexpressing RXFP1 (Fig. D). Moreover, gene therapy with RXFP1 reduced infarct size and preserved cardiac function following MI as compared to control (Fig. E&F).ConclusionOur novel AAV9 construct successfully upregulates cardiac RXFP1, which in turn attenuates infarct size and preserves cardiac function. These findings provide strong rationale for investigating the therapeutic potential of gene therapy with RXFP1 in a more clinically relevant model of established ischemic HF.Support or Funding InformationNHLBI (R01HL133167) and NIA (R21AG053654) to Dr. Salloum.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Involvement of NO and ROS in Organ Culture‐induced Vascular Damage. Influence of Androgenic Function
Authors: Ferrer Mercedes , Rivas Juan Gómez , Villalpando Diva M. , de Bethencourt Fermin R. 
Published: June 2021

Androgen deprivation may induce vascular dysfunction by altering the release and action of different factors, such as nitric oxide (NO) and reactive oxygen species (ROS), that maintained along the time lead to cardiovascular diseases. On the other hand, vascular damage can be induced by organ‐culture system, which has been reported as a valid model to study the phenotypic changes that occur in several cardiovascular pathologies. Since there are no studies analyzing the impact of androgenic loss on vascular vulnerability, the objective of this study was to analyze the preventive role of sex hormones on the vascular damage induced by organ‐cultured, as well as the involvement of NO and ROS on the acetylcholine‐ (ACh) induced relaxation. For this purpose, aortic segments from control and orchidectomized rats were incubated for 20 hours at 37°C in serum‐free culture medium, and the following parameters were studied: i) the release of NO and the expression of iNOS; ii) the production of hydrogen peroxide and the activity of peroxidase; iii) the vasodilator responses induced by acetylcholine (ACh), sodium nitroprusside (SNP), a NO donor, and 8Br‐cGMP, a cell‐permeable analog of cGMP; and iv) the effect of L‐NAME or Tempol (inhibitor of NOS or ROS scavenger, respectively) on the ACh‐induced response. The results showed that organ culture‐induced vascular damage increased NO release, iNOS expression and the production of hydrogen peroxide in similar extent in arteries from control or orchidectomized rats, while the increase in peroxidase activity was greater in arteries from orchidectomized than in those of control rats. Organ‐culture decreased the ACh‐induced response and did not modify the SNP‐ or 8Br‐cGMP‐induced responses in arteries from control rats, while enhanced the SNP‐induced response in arteries from orchidectomized rats. L‐NAME and Tempol decreased the ACh‐induced response in cultured arteries from orchidectomized rats, while that induced by SNP was increased. These results show that organ culture promotes oxidative stress and vascular inflammation in arteries from both control or orchidectomized rats in which the increased NO and hydrogen peroxide production are involved, although the action of theses mediators seems to be less in arteries from control rats. Overall, these results indicate that the androgenic function protects against organ cultured‐induced vascular damage by minimizing the effect of NO and ROS as well as the alteration in the endothelium‐dependent vasodilator response.Support or Funding InformationSupported from 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.
Hypotestosteronemia‐Induced Hypertension in Male Sprague‐Dawley Rats is Reversed by Testosterone Replacement Therapy, Which is a Non‐Genomic, Estrogen‐Independent Effect
Authors: Hanson Andrea E. , Garcia Nikolas W. , McKenna Joshua M. , Perusquia Mercedes , Stallone John N. 
Published: June 2021

Acutely, testosterone (TES) and other androgens are efficacious vasodilators, both in vitro and in vivo; however, their long‐term effects on arterial blood pressure (BP) are unclear. We previously reported that castration (CsX) produced hypertension in male rats, and that TES replacement therapy (TRT) was antihypertensive and normalized BP via inhibition of renin‐angiotensin system function. Thus, long‐term effects of endogenous TES and exogenous TRT on BP were studied in male Sprague‐Dawley (SD) and Testicular‐feminized male (Tfm, androgen receptor defective) rats. 12–13 wk old male rats were castrated (CsX) and weekly measurements of systolic BP (tail cuff plethysmography) revealed a progressive rise in BP over 10 wks in CsX‐SD (109.5 ± 1.3 vs. 139.1 ± 0.4 mmHg) and in CsX‐Tfm (108 ± 0.9 vs. 138.4 ± 0.3 mmHg). During the next 5 weeks, TRT with 5α‐dihydro‐TES‐enanthate (1.00 mg/kg 2X/wk) gradually reduced BP to normal in CsX‐SD rats (111.4 ± 1). TRT of CsX‐Tfm rats over 5 weeks with TES‐enanthate (1.75 mg/kg 2X/wk) reduced BP to a similar extent. 24 hr urine output (UO) in intact SD was 48.3 ml/kg at baseline, 34.3 at 10 wks, 38.4 at 12 wks, and 34.8 at 15 wks. UO in CsX‐SD was 47.6, 30.3, 25.2, and 27.7; UO in CsX+TRT was 46.1, 29.2 36.2, and 29.5. Plasma TES in SD rats (radioimmunoassay, RIA) was 0.40 ng/ml in intact rats, <0.1 ng/ml in CsX, and 1.05 ng/ml in CsX+TRT. Plasma estrogen in SD (RIA) was 15.1 pg/ml in intact rats, 15.2 in CsX, and 15.4 in CsX+TRT. These data suggest that: 1) TES exerts antihypertensive effects in male SD and Tfm rats; 2) the antihypertensive effect of TES appear to involve a diuretic effect on the kidney, which is non‐genomically mediated and independent of TES aromatization to estrogen. (State of Texas).Support or Funding InformationState of TexasThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Proteomics Reveals Context‐Dependent Activation of Rictor Signaling by TGFβ in Vascular Smooth Muscle Cells
Authors: Parker Sarah Josepha , Stotland Aleksandr , Orosco Amanda , Wilson Nicole Parker Dietz , MacFarlane Elena , Madrid Kyle , Gottlieb Roberta , Dietz Harry C. , Van Eyk Jennifer 
Published: June 2021

Aortic aneurysm describes abnormal growth and remodeling of the aorta and predisposes to fatal vascular dissection and rupture. Marfan syndrome (MFS) is a hereditary disorder caused by deficiency of extracellular fibrillin‐1, with multiple characteristic phenotypes including highly penetrant aneurysm. The discovery that deficiency of fibrillin‐1 lead to excessive activation of transforming growth factor β (TGFβ) signaling has led to major advances in the understanding of AA in MFS, though many details regarding the molecular mechanisms remain unclear. To describe molecular changes correlating with aneurysm development in a mouse model of MFS, proteomic analysis was performed on ascending aorta from young (10‐weeks; N=3 WT, N=3 MFS) and aged (12 months, N=3 WT, N=4 MFS) mice. We identified 425 proteins with altered abundance (e.g., Log2FC > |0.8| and < 1% FDR) in the MFS mice relative to WT, with 71 and 297 specific to young and aged mice, respectively, and 57 consistently altered at either age. Pathway analysis predicted TGFβ as a dominantly activated upstream regulator at both ages. Interestingly, in comparison to their WT counterparts, aged MFS mice showed markedly lower mitochondrial protein expression and a reversal in predicted activation status of the mTOR2 component rictor, with predicted inhibition in young MFS mice and strong activation in the aged MFS mice. Immunoblotting revealed increased phosphorylation of rictor and activation of its downstream signaling target Akt in aged MFS aorta. In cultured aortic vascular smooth muscle cells (VSMCs), TGFβ promoted both rictor and Akt phosphorylation, which could be blocked by inhibition of Integrin linked Kinase. Interrogation of integrin expression patterns implicated altered expression of integrin alpha v/beta 3 and its ligand vitronectin as uniquely upregulated in aged MFS aorta, leading to a hypothesis that the αv/β3 integrin may modulate TGFβ‐induced rictor signaling. Indeed, overexpression of ITβ3 enhanced while inhibition of ITβ3 blocked TGFβ‐induced rictor phosphorylation in cultured VSMCs. Altered physiology in ITβ3‐overexpressing VSMCs included increased migration/proliferation and altered TGFβ‐mediated effects on mitochondrial respiration. These results suggest that after additional in vivo validation, ITβ3 and/or mTOR2/Rictor signaling may represent novel targets for therapeutic intervention for aneurysm caused by MFS.Support or Funding Information1K99HL12878‐01A1 ‐ PI: Sarah ParkerThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Pansteatitis Induced Differential Expression of Inflammatory and Apoptosis Genes in Adipose Tissue: A Glimpse into Pathophysiology of the Condition in the Nile Crocodile.
Authors: Azeez Odunayo Ibraheem , Myburgh Jan , Meintjes Roy , Bosman Anna‐Mari , Featherstone Jonathan , Oosthuizen Marinda , Chamunorwa Joseph Panashe 
Published: June 2021

In the quest to understand the pathophysiology of pansteatitis in the Nile crocodile, a condition that was attributed to the recent crocodile die off at the Olifant river, Mpumalanga, the whole transcriptome of the Nile crocodile was sequenced and assembled using whole transcriptome shotgun sequencing data by Illumina RNAseq from RNA obtained from fat body and other adipose tissues.Total RNA, from abdominal fat body and other adipose tissue from normal farmed Nile crocodiles and samples collected from Nile crocodiles that had died of pansteatitis, were extracted and purified using Qiagen RNA mini prep (Qiagen, USA). RNA samples library were prepped using the Truseq stranded total RNA sample preparation and sequenced on the Illumina Hiseq 2500 with v4 SBS chemistry. Reads were assembled using Tophat (http://tophat.cbcb.umd.edu/) and aligned with reference transcriptome from Crocodylus porosus using Cufflinks (http://cufflinks.cbcb.umd.edu/) for downstream analysis while the differential gene expression analysis was done using Cuffdiff and RSEM (http://deweylab.github.io/RSEM/).A total of 13,329 genes were identified out which 1541 genes related to inflammatory response and apoptosis were identified. A total of 641 genes were up regulated in the pansteatitis samples as compared to normal adipose tissues using a fold change of 16.0. A total of 70 inflammatory genes were up regulated in the pansteatitis samples including, PDCD5 (programmed cell death 5), NFIL3 (nuclear factor, interleukin 3 regulated protein), HSP90B1 (heat shock protein 90kDa beta (Grp94), member 1), VCAM1 (vascular cell adhesion molecule 1), IL1R1 (interleukin 1 receptor, type I), TNIP1 (TNFAIP3 interacting protein 1), JAK1 (Janus kinase 1), TNFAIP2 (tumor necrosis factor, alpha‐induced protein 2) IL6ST (interleukin 6 signal transducer (gp130, oncostatin M receptor)) CFD (complement factor D (adipsin) and PPARG (peroxisome proliferator‐activated receptor gamma) among others. These genes are responsible for inflammation, apoptosis, regulation of Toll‐like receptors in inflammatory response, leucocyte migration and fibrosis in chronic inflammation.We present for the first time in the Nile crocodile, a comprehensive lists of inflammatory response genes that are expressed and up regulated in pansteatitis in the Nile crocodile.Support or Funding InformationPart of the study was funded by Tertiary Education Trust Fund (TETFund) AST and D, Nigeria and Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa.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 Role of the Unfolded Protein Response in Mediating Adaptations to Exercise Responsiveness”
Authors: Hart Corey R. , Koh Jin‐Ho , Dasari Surendra , Lalia Antigoni Z. , Lanza Ian R. 
Published: June 2021

Aging is associated with altered mitochondrial physiology and exercise responsiveness in skeletal muscle. Activation of the unfolded protein response in the endoplasmic reticulum (UPRER) and mitochondria (UPRMT) is linked with exercise‐induced adaptations in skeletal muscle, but the possibility that these processes impact exercise responsiveness and mitochondrial function in older humans has not been fully elucidated. The purpose of this study was to evaluate age‐related changes in UPRER and UPRMT gene transcripts and protein abundance in response to a single bout of exercise. Muscle biopsies were obtained from 12 young (27±5 yr) and 12 older (75±5 yr) well‐matched, healthy men and women before exercise and 18h following a single bout of unilateral leg extension. Before exercise, a gene set enrichment analysis (GSEA) revealed that 27 genes associated with the UPRER were upregulated in the older subjects compared to the young (enrichment false discovery rate [FDR] = 0.0842). After exercise, GSEA indicated upregulated UPRER genes in both the young (FDR = 0.0405) and older subjects (FDR = 0.0619), however, pathway activation analysis revealed significantly greater activation of UPRER and UPRMT gene transcripts post‐exercise in the younger subjects (P < 0.05). In contrast, age did not affect key UPR‐regulatory protein abundance 18h post‐exercise. Interestingly, statistically significant correlations were observed in the young subjects between the mitochondrial transcriptional coactivator, peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α) and key regulatory genes associated with the UPRER (GRP78, R = 0.67; ATF6, R = 0.70) and the UPRMT (HSPE1, R = 0.61; HSPD1, R = 0.55; and HSPA9, R = 0.79), which were not evident in the older subjects. In conclusion, transcriptomic analysis revealed an age‐related decline in the adaptive UPRER and UPRMT transcriptional response following a single bout of exercise that could potentially explain, in part, impaired exercise responsiveness and mitochondrial dysfunction with age.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.