bluuebunny/crossref_metadata_2025_split huggingface dataset:
Down‐Regulation of Thioredoxin‐Interacting Protein by Repeated Non‐Invasive Limb Ischemic Preconditioning Protects Diabetic Heart from Myocardial Ischemia/Reperfusion Injury
Authors: Ye Xiaodong , Zhang Dengwen , Wang Sheng , Irwin Michael Garnet , Xia Zhengyuan 
Published: June 2021

BackgroundMyocardial ischemia/reperfusion injury (MIRI) is a major threat to human health, causing great cardiac morbidity and mortality worldwide. Yet, it's even more severe among diabetic subjects. Repeated non‐invasive limb ischemic preconditioning (rNLIP) can be effective in protecting the diabetic heart against MIRI, though the exact mechanism is still unclear. Thioredoxin‐interacting protein (TXNIP), a critical regulator with its inhibitory effect against antioxidation, is a novel target during MIRI. Also, TXNIP is found to be highly expressed concomitantly with hyperglycemia. This study aimed to investigate the role of TXNIP in the cardioprotective effect of rNLIP against MIRI in diabetes mellitus.MethodsDiabetes mellitus was induced by streptozotocin injection (65mg/kg) in Sprague‐Dawley rats. In vivo model of MIRI was established as 30 minutes occlusion of the left anterior descending coronary artery and subsequent 2 hours reperfusion. rNLIP was accomplished as three cycles of 5min ischemia (cuff inflation) and 5min reperfusion (cuff deflation) of the left hindlimb for three consecutive days before MIRI. In vitro hypoxia/re‐oxygenation (H/R) model was established as 6 hours of hypoxia and 12 hours of re‐oxygenation of H9C2 cells. Simulated remote hypoxic preconditioning (HPC), defined as three cycles of 5 min hypoxia and 5 min re‐oxygenation, was performed just 24 hours before H/R treatment to mimic the cardioprotective effect of rNLIP.ResultsThe expression of TXNIP was significantly elevated in the diabetic group, together with much greater infarct size and higher release of CK‐MB as well as lactate dehydrogenase (LDH) after MIRI, compared to non‐diabetic group. The application of rNLIP significantly reduced the infarct size, CK‐MB, and LDH release in both diabetic and non‐diabetic group. Furthermore, the expression of TXNIP, NLRP3 and IL‐1β were significantly reduced by rNLIP in both diabetic and nondiabetic group, with simultaneous suppression of apoptosis (lower cleaved caspases‐3 expression and bax/bcl‐2 ratio). In vitro study showed that TXNIP expression was significantly higher in high glucose (HG) group with concurrently greater cell injury and much higher LDH release after H/R treatment, compared to normal glucose (NG) group. HPC exhibited protective effect in both HG and NG group with reduced expression of TXNIP, NLRP3, and IL‐1β.ConclusionDown‐regulation of TXNIP and subsequent reduction of NLRP3 may represent a mechanism whereby rNLIP protects the diabetic heart from MIRI.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The β2‐Adrenergic Receptor Agonist Formoterol Decreases Fibrotic And Mitochondrial Fusion/Fission Proteins in a Mouse Model of Diabetic Nephropathy
Authors: Cleveland Kristan , Cameron Robert B , Brosius Frank C , Schnellmann Rick G 
Published: June 2021

Diabetic nephropathy (DN) is a cause of chronic kidney disease and accounts for 50% of all end‐stage renal disease. Current therapies for DN, such as glycemic and blood pressure control and renin‐angiotensin system blockade, only slow the progression of DN. Therefore, we examined the effect of formoterol, a β2‐adrenergic receptor agonist previously shown to induce mitochondrial biogenesis (MB) and promote recovery from acute kidney injury, on fibrotic and mitochondrial proteins in db/db mice, an established mouse model for studying type 2 diabetic nephropathy (T2DN). Female diabetic db/db and non‐diabetic db/m (control) mice 9 weeks of age were treated with formoterol or saline daily for three weeks. Body weight was measured weekly and renal function was measured using serum creatinine levels. Kidneys were harvested and changes in expression of mitochondrial and fibrotic proteins were measured using immunoblot analysis. At 12 weeks of age, serum creatinine increased slightly in diabetic mice and decreased in formoterol‐treated diabetic mice without altering body weight. The mitochondrial fission protein phospho‐Drp1, and profibrotic proteins TGF‐β1, phospho‐SMAD3 and α‐SMA were increased in diabetic mouse kidneys and were restored to control levels with formoterol treatment. Additionally, mitochondrial fusion proteins Mfn1 and Mfn2 were decreased in the kidneys of diabetic mice and increased to control levels with formoterol treatment. Formoterol treatment in a T2DN model decreased kidney profibrotic proteins and restored mitochondrial fusion/fission protein levels. These results suggest that formoterol could be a potential therapy for DN.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Comparison of GMP Manufactured Ovine Mucosal Enoxaparin and Branded Porcine Enoxaparin
Authors: Niverthi Manoj , Rangnekar Varun , Jeske Walter , Yao Yiming , Kouta Ahmed , Hoppensteadt Debra , Fareed Jawed 
Published: June 2021

ObjectiveLow Molecular Weight Heparins (LMWH) such as Enoxaparin are currently derived from porcine mucosal heparin (PMH). The same depolymerization methods that retrieve this enoxaparin from unfractionated heparin can be used from other sources, including from sheep, resulting in ovine enoxaparin. Previous studies have compared non‐good manufacturing practice (GMP) batches of ovine enoxaparin and comparing them to porcine mucosal enoxaparin. The purpose of this study is to compare the pharmacokinetics of GMP ovine mucosal enoxaparin (OME) with that of porcine mucosal enoxaparin (PME).Materials and MethodsBranded Enoxaparin (Lovenox, Sanofi‐Aventis, Bridgewater, NJ) and three batches of GMP OME were used. Individual batches of GMP or branded Lovenox were administered subcutaneously (SC) to groups of primates (macaca mulatta) at a dose of 1 mg/kg. Blood samples were collected at baseline and post‐injection times of 2,4, and 6 hours. Plasma samples were frozen for batch analysis. aPTT was measured using clot‐based methods and amidolytic anti‐Xa and anti‐thrombin assays were used to calculate circulating levels of heparin. Individual calibration curves for each the GMP product and branded product were constructed, and the concentrations of drugs were measured at time points in terms of micrograms per milliliter. Drug levels and PK parameters were determined using anti‐Xa and anti‐thrombin assays. The batches of the GMP products were compared among each other and grouped means of all batches were compared with the branded Enoxaparin.ResultsIn the in‐vitro calibration studies, using the aPTT, anti‐Xa and, anti‐IIa assays, despite minor variations, the GMP batches composite values compared well with that of the branded Lovenox. In the PK/PD studies, the three batches of GMP‐produced ovine enoxaparin compared well within the group and the composite mean was similar to that of the branded Lovenox.DiscussionAt a 1 mg/kg SC dosage, three GMP OME preparations produced comparable anti‐Xa and anti‐IIa effects which were similar to the ones observed with PME. The PK parameters calculated based on this data were also comparable for both groups. It is concluded that the SC pharmacokinetics of the three batches of OME were not only comparable between batches but were also similar to the branded Lovenox.Support or Funding InformationNone.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Lactobacillus bulgaricus Reduces the Expression of Toll‐like 4 Receptor on Dendritic Cells and Attenuates the Airway Inflammation in Asthmatic Mice
Authors: Aimbire Flavio , Sá Ana Karolina , Olimpio Fabiana , Brito Aurileia , Albertini Regiane , Keller Alexandre 
Published: June 2021

IntroductionProbiotics can be considered nonspecific adjuvants of innate immune response by modulating the Th1/Th2 response in different pathological conditions. Our goal is to investigate the probiotic Lactobacillus bulgaricus (Lb) anti‐inflammatory effect in experimental asthma.MethodsBALB/c‐mice were sensitized with ovalbumin (OVA) on days 0 and 7 and then were challenged from day 14–28 (3‐times/week) with aerosolized OVA. From seventh day before the sensitization until day 28, mice were treated 3‐times/ week with Lb via gavage. All measurements were performed 24 hours after the last OVA challenge.ResultsThe CD86 molecules expression as well as the toll‐like 4 receptor on dendritic cells was increased after oral administration of Lb. In addition, Lb attenuated the eosinophils infiltration, mucus production and the ovalbumin‐specific IgE concentration in serum. Moreover, Lb inhibited the secretion of asthma‐related inflammatory molecules such as IL‐4, IL‐5, IL‐13 and eotaxin in bronchoalveolar lavage fluid (BALF). On the contrary, the IL‐10 level in BALF was reduced by Lb. The analysis of lung tissue using real‐time PCR revealed that Lb inhibited the local transcription of asthma‐associated genes such as GATA3 and STAT6, and the otherwise Lb increased the expression of T‐bet.ConclusionThe results contribute to the understanding of the probiotic modulator activities for the control of allergic diseases.Support or Funding InformationCAPESThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Omental Arteries from Diabetic Hypertensive Subjects are Larger and Stiffer than those from Non‐Diabetic Normotensives
Authors: Quinones Mariana Morales , Bloksgaard Maria , Ramirez‐Perez Francisco Ignacio , Padilla Jaume , Martinez‐Lemus Luis Arturo 
Published: June 2021

Diabetes and hypertension are associated with structural and mechanical changes of the resistance vasculature that contribute to cardiovascular disease development and progression. We have previously reported that in mouse isolated resistance arteries prolonged vasoconstriction leads to vascular inward remodeling and stiffening, through a process that requires smooth muscle actin polymerization. We hypothesized that human arteries from diabetic hypertensive subjects would be inwardly remodeled and stiffer than those from non‐diabetic normotensives. We also hypothesized that actin stress fiber disruption would dilate and soften the arteries from diabetic hypertensives. To test these hypotheses, omental samples were obtained from patients undergoing abdominal surgery at The University of Missouri Hospital. Small arteries were isolated, cannulated and analyzed using pressure myography. Vascular luminal diameters and wall‐thicknesses were monitored by videomicroscopy at different levels of intraluminal pressure (5–120mmHg) under passive conditions (calcium‐free buffer with 100μM adenosine and 2mM EGTA) in the absence or presence of Mycalolide‐B (2uM) to disrupt the actin cytoskeleton. Investigators were blinded to the subject condition throughout the experimental procedures. Data were used for assessment of vascular remodeling and characterization of vascular wall mechanical properties. Subsequently, the arterial parameters obtained were compared across groups according to diabetic and hypertensive status retrieved from medical records. Results indicate that small omental arteries from diabetic hypertensive (N=10) subjects have larger diameters and are stiffer than those from non‐diabetic normotensives (N=22, P<0.05). Data also show that disruption of the actin cytoskeleton had no significant effects on their mechanical properties. We conclude that small omental arteries from diabetic and hypertensive subjects undergo a process of outward remodeling that results in them becoming larger and stiffer and that, at the single time point of our sampling, this is not dependent on vascular cell actin stress fibers.Support or Funding InformationNational Institutes of Health grants: R01 HL137769 (JP), R01 HL088105 (LM‐L).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Genetic Expression Profile of Cerebrovascular Endothelium During Development of Alzheimer's Disease
Authors: Nye Phoebe P. , Behringer Erik J. 
Published: June 2021

In 2018 alone, seven‐hundred thousand Americans of age 65 years and older will have a form of Alzheimer's disease (AD) by the end of their lives. Emerging evidence demonstrates the association of AD with impaired delivery of blood oxygen and nutrients to and throughout the brain. Cerebral arteries coordinate vasodilation through endothelium‐derived hyperpolarization (EDH); sequentially entailing stimulation of G protein‐coupled receptors (GPCRs), increases in intracellular Ca2+, activation of small‐ and intermediate‐conductance Ca2+‐activated K+ channels (SKCa/IKCa), and spread of negative intracellular charge (“hyperpolarization”) through cell‐to‐cell gap junctions. Thus, we tested the hypothesis that the genetic expression of EDH vasodilatory components may decline during progression of age‐related AD in mouse cerebrovascular endothelium. We used the triple mutation mouse model of AD (3xTgAD) to examine cerebrovascular genetic profiles for young control (YC; 1 to 2 mo), mild cognitive impairment (MCI; 4 to 5 mo), amyloid‐β plaques (Aβ; 6 to 8 mo), and plaques + neurofibrillary tangles (Aβ+Tau; ≥12 mo); 3 male and 3 female mice/group. Quantitative polymerase chain reaction (qPCR) and RNA sequencing were used to examine genetic expression of isolated cerebral artery endothelium and purified brain vessels respectively. The qPCR results demonstrate mixed expression of respective isoforms of purinergic receptors as indicated by no changes for P2ry1 (transcript for P2Y1) but ~35% and ~65% upregulation of P2ry2 (P2Y2) during Aβ and Aβ+Tau respectively. In contrast, the expression of ion channel mRNA in the form of major K+ channels (Kcnn3/Kcnn4, SKCa/IKCa & Kcnj2, inward rectifying KIR2.1) and transient receptor potential channels (Trpv4, TRPV4) remains relatively stable throughout the life of the animal. Further, with the exception of Gja1 (Cx43), the expression of connexins composing gap junctions (Gja4, Cx37 & Gja5, Cx40) increased by ≥ 20% during Aβ and Aβ+Tau. Finally, RNAseq data and pathway analysis demonstrate a >two‐fold upregulation of genes integral to cardiovascular remodeling during Aβ+Tau vs. YC. Overall, these data indicate profound genetic alterations underlying cerebral blood vessel function corresponding to moment‐to‐moment regulation of blood flow and chronic maintenance of vascular structure. Pairing new found knowledge of vascular “signatures” with developmental phases of AD may offer unprecedented opportunities to maintain a healthy mind throughout the entirety of a standard lifespan (~80 to 100 years).Support or Funding InformationThis research is supported by Loma Linda University School of Medicine new faculty start‐up funds and National Institutes of Health grants R00AG047198 & R56AG062169 (EJB).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ultrastructural Changes of the Microcirculation with Aging
Authors: Mortensen Stefan P , Finsen Stine H 
Published: June 2021

IntroductionAging is associated with an increase in capillary basement membrane (BM) thickness which may contribute to the decreased working capacity in elderly. The aim of this study was to elucidate if age‐related changes is present in both the upper and lower extremities, and to what extent endurance training can reduce BM thickness.MethodsFive healthy older men (66±3 yr.) completed 8 weeks of one‐legged knee extensor training (3x/week). Muscle biopsies were obtained from the m. vastus lateralis (VL) and the deltoid muscle before the training intervention. After the training intervention, biopsies from VL of both the trained leg and the control leg was obtained. The capillary‐to‐fiber (C/F) ratio was determined with light microscope, and morphometry analysis was completed after transmission electron microscopy (TEM). Data were analyzed by one‐way repeated measures ANOVA.ResultsAt baseline, the BM thickness was higher in the VL compared to the deltoid muscle (p<0.05), whereas there was no difference on the C/F ratio. After 8 weeks of training, the BM thickness was decreased in the VL of the trained leg (~24%, p<0.05), and it was thinner compared to the control leg (p<0.05). The C/F ratio was higher in the trained leg compared to the control leg (p<0.05).ConclusionThese preliminary results indicate that the age‐related alterations in BM thickness are more pronounced in the lower extremities of healthy aged men and that exercise training results in a local thinning of the BM.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Vascular function in the facial skin circulation is significantly correlated with age
Authors: Miyaji Akane , Hayashi Naoyuki 
Published: June 2021

No previous study investigated whether the condition in facial skin vessels change with age, though it is well known that conditions in facial skin, i.e., the elastic property, thickness, and echogenicity, decrease with age (Takema et al. 1994; Pellacani and Seidenari 1999). Vessels are important organs to supply nutrition and oxygen to cells, and thus may keep skin cells function properly. Previous studies reported the age‐related decline in the vascular function (Celermajer et al. 1994; Seals et al. 2008). The age‐related decline in the facial vascular function is expected but no previous study demonstrated that. In fact, the method for evaluation of the vascular function in the facial skin circulation has not been established. Laser speckle flowgraphy (LSFG) can assess blood flow in superficial tissues non‐invasively. The blowout time (BOT) calculated from the pulse‐wave analysis of ocular blood flow velocity is an index of vascular flexibility. Previous studies reported that the BOT in ocular circulation is negatively related to age (Shiba et al. 2011; Miyaji et al. 2016). It has not been investigated whether the BOT in skin circulation also be related to age. Thus the objective of this study was to investigate whether the BOT in facial skin is related to age. We assessed the BOT in whole face, eyelid, cheek, nose, upper lip, and lower lip in 29 young (17 ± 4 years, range 11 to 27 years of age), and 15 middle and old subjects (54 ± 11 years, range 39 to 77 years of age) by using LSFG. BOTs in whole face, cheek, and upper lip was significantly greater in young group than middle and old group (whole face: 68 ± 2 vs. 62 ± 2; cheek: 67 ± 2 vs. 58 ± 3; upper lip: 61 ± 2 vs. 52 ± 2, P<0.05). The BOT in whole face, eyelid, cheek, and upper lip were related to age of all subjects negatively (whole face: r=−0.34; eyelid: r=−0.30; cheek: r=−0.34; upper lip: r=−0.41, P<0.05, respectively). This relationship was observed solely in females (n=27, whole face: r=−0.45; eyelid: r=−0.44; cheek: r=−0.56; upper lip: r=−0.46, P<0.05, respectively). The BOT in nose and lower lip did not change with age. These results suggested an age‐related change in facial vascular function and regional difference in the age‐related change.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Integrin‐mediated Vasoconstrictor Function Declines with Age in Skeletal Muscle Resistance Arteries
Authors: Shin Song Yi , Trache Andreea , Woodman Christopher 
Published: June 2021

IntroductionVasoconstrictor responses decline with age in skeletal muscle resistance arteries. The mechanism for functional regulation of resistance artery contractility is not fully understood but has been proposed to involve impaired integrin signaling in vascular smooth muscle.ObjectiveThe purpose of this study was to test the hypothesis that RGD binding integrin‐mediated constrictor responses decline with age in skeletal muscle resistance arteries.MethodsSoleus muscle feed arteries (SFA) were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats. SFA were cannulated with glass micropipettes and pressurized to 90 cm H2O for assessment of vasoconstrictor function. Vasoconstrictor responses were assessed using an a1 selective adrenergic agonist (phenylephrine; PE). To test the role of integrin signaling, constrictor responses were assessed in the absence or presence of an integrinblocking peptide (RGD) or a control peptide (RGE).ResultsConstrictor responses to PE were significantly impaired in old SFA relative to young SFA. In the presence of the RGD soluble peptide, constrictor responses to PE were significantly reduced in young SFA such that the young SFA responded like control (no treatment) old SFA. In the presence of the RGD peptide, constrictor responses to PE were further reduced in old SFA. Constrictor responses to PE were not altered by RGE in young or old SFA.ConclusionThe results of this study indicate that RGD binding integrin‐mediated constrictor function declines with age in SFA.Support or Funding InformationResearch support: National Institute on Aging, Sydney and J.L. Huffines Institute of Sports Medicine and Human Performance.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hemodynamics of Capillary Networks in Sickle Cell Disease
Authors: Feng Feng , Huo Yunlong 
Published: June 2021

ObjectiveSickle cell disease (SCD) is a complex hereditary blood disorder that can significantly affect the rheological properties of patients. Researches on the change of the rheological properties of blood and hemodynamics in a single capillary vessel have been carried out in recent three decades. The target of this work is to explore the hemodynamic behavior of diseased capillary networks based on anatomical data, in order to provide advice on the generation and prevention of the vaso‐occlusive crisis of patients with sickle cell disease.MethodIn this work, we use numerical simulations to calculate the sickle RBC velocity, blood hematocrit and blood viscosity in capillary bifurcations and networks based on mesenteric anatomical data. Then, the model predictions are discussed with reported clinical manifestations and compared with normal networks.ResultsThe predictions from our simulations show agreement with clinical manifestations. Compared with the properties of normal capillary networks, the blood flow in diseased micro vessel networks has 10%–25% larger hematocrit, slower RBC velocity and larger blood viscosity, which can lead to the vaso‐occlusive crisis and the pain of patients with sickle cell disease.ConclusionsThis study helps us to understand the blood flow properties of capillary networks of patients with sickle cell disease, and may help us to prevent the vaso‐occlusive crisis. To improve our study, we can use capillary networks from the diseased part of sickle cell patients instead.Support or Funding InformationThis research is supported by Shenzhen Science and Technology Innovation Institution (China) Grant JCYJ20160427170536358 (Y Huo).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.