bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac Inflammation and Dysfunction During Dengue Virus Infection in Mice
Authors: Kangussu Lucas , Costa Vivian , Olivon Vania , Melo Marcos , Soriani Frederico , Rachid Milene , Santos Robson , Teixeira Mauro , Souza Danielle , Bonaventura Daniella 
Published: June 2021

The aim of this study is to investigate the mechanisms involved in cardiac function alterations in animal model of Dengue. Balb/c mice were infected with adapted DENV‐3. The study was performed on 3 and 6 days after infection. We evaluated survival, hematological and inflammatory parameters, vascular permeability, and tissue damage. Systolic blood pressure and heart rate were determined. Furthermore, the oxidative stress and the cardiac function were analyzed. Infected mice died 7 days after infection. At day 3 and 6 we observed thrombocytopenia, hemoconcentration, increased levels of transaminases, neutrophil and macrophage accumulation in heart and elevated levels of TNF‐α, IFN‐α, IL‐6, IL‐1β, CXCL1, CXCL2 and IL‐18 in serum and heart. These findings were accompanied by changes in hemodynamic parameters. There was a significant reduction in GSH levels, and increased lipid peroxidation, as well as, SOD and catalase activity in heart. Impaired cardiac function was verified with reduction in cardiac output, end‐diastolic diameter, endsystolic diameter, stroke volume, end‐diastolic volume, and endsystolic volume. Infection of mice with adapted DENV‐3 induced clinical manifestations of severe dengue infection, as observed in humans. Heart is target for Dengue virus infection, inducing intense inflammatory process and oxidative stress, associate with cardiac dysfunction.Financial Support: INCT Dengue, CAPES, FAPEMIG and CNPQ.
Hyperbaric oxygen therapy effect in vascular reactivity
Authors: Estrada Norma , Guevara-Balcazar Gustavo , Villanueva-Lopez Guadalupe Cleva , Mera-Jimenez Elvia , Lara-Padilla Eleazar , Castillo-Hernandez Maria C 
Published: June 2021

IntroductionThe oxygen (O2)is a source of energy and for cellular respiratory support, deficient of oxygen delivery in tissue, can affect the cellular functions, We know that flow warranty the oxygen concentrations in tissue, is for that reason the new use of oxygen like therapy, because of we want to evaluate a possible changes with the hyperbaric oxygen therapy (HBO) in vascular reactivity, the information will be useful to suggest treatment with HBO in patients with cardiovascular problems.MethodsMale rats were used between 250–300gr, tree months old, in two groups with and without hyperbaric oxygen therapy, rats were exposed to pure oxygen at 2 atmospheres absolute during 60 min for 3, 7, 10 and 20 sessions, the aortic rings were introduce immediately in the organ bath, after that we probe phenileprine (10−9 – 10−5 M), acetylcholine (10−9 – 10−5 M) and sodium nitroprusiate (10−11–10−6 M)ResultsThe HBO increase relaxation dependent of the endothelium, after 20 sessions in the thoracic segment and early in the abdominal segment, we shown that the independent relaxation in the endothelium is mediated for sodium nitroprusiate is increase in the first days of exposition in both segments, regularization between 10 to 20 session of HBO, on the other hand phenyleprine contraction shown a decrease in the maximum effect after 20 sessions and this is related with the increment in the relaxant response in the endothelium, and this suggest a mayor ON release.
Bivalirudin Emulsions Demonstrate Efficacy of a Nanoparticle Strategy for Inhibition and Imaging of Thrombosis
Authors: Myerson Jacob Wheatley , He Li , Allen John Stacy , Williams Todd A , Tollefsen Douglas M , Lanza Gregory M , Caruthers Shelton D , Wickline Samuel A 
Published: June 2021

A thrombin‐inhibiting perfluorocarbon nanoparticle (PFC NP), functionalized by PPACK (Phe(D)‐Pro‐Arg‐Chloromethylketone), was recently presented as a prototype for a novel class of targeted antithrombotic. Here, a NP functionalized with Bivalirudin (BVR), was compared to BVR and the PPACK NP.PPACK or BVR were covalently attached to PFC NPs. Optical assay verified that PPACK and BVR selectivity and activity against thrombin was not diminished on the NPs. In vivo activity was assessed for PPACK NPs, PPACK, BVR, BVR NPs, heparin, non‐functionalized NPs, or saline in C57BL6 mice subjected to laser injury of the carotid artery. Time to thrombotic occlusion of the injured artery was assessed via Doppler flow measurement. Selected arteries were excised to assess NP retention via 19F magnetic resonance (MR). 3T MRI of thrombosis following administration of PPACK NPs was also demonstrated in cholesterol‐fed rabbits.Previously, PPACK NPs outperformed both heparin (p=.001) and PPACK (p=.0006) in delaying occlusion of the carotid artery. PPACK or non‐functionalized NPs failed to delay occlusion of the carotid artery. BVR NPs significantly delayed occlusion (p=.02) whereas an equivalent dose of free BVR (120 mg/kg) did not (figure 1a). 19F MR captured thrombin‐specific PFC NP retention in occluded arteries of mice (figure 1b) and rabbits (figure 2).
Macrophage pro‐angiogenic miRNA, miR‐27b, is under NF‐kB transcription regulation
Authors: Pan Hua , Clarke Bradley , Wickline Samuel A 
Published: June 2021

Atherosclerosis is the common trigger of cardiovascular diseases, which is a leading cause of mortality in US. It exhibits plaque development with chronic inflammation as a prominent feature. The NF‐κB signaling pathway is a pivotal mediator of the chronic inflammatory process that drives atherosclerotic plaque development, and has been proposed as a therapeutic target for clinical management. Additionally, microRNA species are rapidly being uncovered as equally prominent components of atherosclerosis. But little is known about the interplay between NF‐κB signaling and microRNA in this context. Here, we report that pro‐angiogenic miRNA, miR‐27b, is regulated by NF‐κB signaling in RAW267.4 cells under TNF‐α stimulation.First, we evaluated the dose and time dependence of TNF‐α stimulated NF‐κB signaling activation in RAW267.4 cells. We found that the nuclear translocation of NF‐kB protein, p65, peaked 30 minutes after treatment with 10 ng/ml TNF‐α. To investigate the interplay between NF‐κB signaling and microRNA, we specifically inhibited TNF‐α stimulated NF‐κB activation by treating TNF‐α activated RAW264.7 cells with Bay 11‐7082. The time dependent evaluation demonstrated that 30 minutes 5 μM Bay 11‐7082 inhibited TNF‐α induced NF‐κB activation in RAW264.7 cells. We then treated RAW264.7 with or without 10 ng/ml TNF‐α for 30 minutes and with or without Bay 11‐7082. Then total small RNA was extracted by using TRIzol reagent and evaluated for the expressions of 88 inflammation‐related microRNAs by polymerase chain reaction (PCR)‐based arrays. Among those 88 inflammation‐related microRNAs, miR19a, miR‐27b, and miR 195 are significantly upregulated (more than 7‐fold increase) after TNF‐α stimulated. After Bay 11‐7082 inhibition, miR‐27b expression level is not significantly different from the control cells. These results suggest that miR‐27b may represent a therapeutic target for clinical management of inflammation in atherosclerosis.
Resveratrol protects against diabetes‐induced endothelial dysfunction in high‐fat diet fed mice
Authors: Li Dai-Er , Hung Li-Man 
Published: June 2021

Epidemiological studies have shown that red wine consumption is associated with reduced in cardiovascular mortality in the general population and diabetic patients. The present study was designed to investigate whether resveratrol (RSV, a red wine antioxidant) can attenuate diabetes progression, improves diabetes‐related vescular endothelial dysfunctions, and delineated further its underlying mechanisms.Male C57Bl/6 mice were fed with high‐fat diet (HFD) for 17 weeks. Animals developed type 2 diabetes characterized by elevated body weight, hyperglycemia, hyperinsulinemia, and hyperlipidemia. Oral gavage fed with RSV (5 or 10 mg/kg/day for 17 weeks) significantly reduced body weight, plasma glucose, insulin, and triglyceride compared to non‐treated HFD mice. RSV treatment also attenuated plasma glucose elevation and improved insulin responses during glucose tolerance test. Furthermore, HFD diabetic mice exhibited an increasing the numbers of leukocyte rolling, adhering, and transmigrating in the post‐capillary venules of cremaster muscle. In contrast, treatment of RSV significantly attenuated leukocyte rolling, adhesion, and transmigration in HFD diabetic mice. The phenylephrine (PE)‐induced vasoconstriction was dramatically attenuated in HFD diabetic mice; whereas, RSV treatment significantly improved the vessel responsiveness to PE. Our result also shows that the phosphorylated AMPK (5′AMP‐activated protein kinase), Akt, and eNOS (endothelial nitric oxide synthase) protein levels were significantly reduced in aorta of HFD mice. Consistence with the observation on improvement of blood vessel responsiveness, RSV also elevated AMPK, Akt, and eNOS protein phosphorylation levels. Taking together, these results indicate that RSV attenuated diabetes‐related vascular endothelial dysfunctions, at least in part, by elevation of AMPK, Akt, and eNOS proteins phosphorylation.
Role of NO and Superoxide in Hyperhomocysteinemia Induced Cardiac Metabolic Dysfunction in Pregnant Cystathionine Beta‐synthase Heterozygote Mice
Authors: Song Su , Kertowidjojo Elizabeth , Ojaimi Caroline , KandhiI Sharath , Wolin Michael , Hintze Thomas H 
Published: June 2021

Genetic defects in cystathionine beta‐synthase (CBS) can cause severe hyperhomocysteinemia (HHcy). HHcy causes cardiovascular dysfunction and is associated with many complications during pregnancy related to reduced NO bioactivity. This study assessed the mechanisms of HHcy on the NO‐dependent control of cardiac O2 consumption in pregnant CBS heterozygote (HET) mice. Pregnant CBS HET mice (n=8) were fed low‐folate diet for 20 days to increase plasma Hcy (8.2±0.5 of WT to 17.9±2.2 uM of HET). As compared to wild type (WT) (n=10), while heart weight/body weight increased by 18.2%, ejection fraction decreased from 85.7±0.8% to 80.3±1.8% in HET. Systolic blood pressure was significantly increased from 92.5±3.6 mmHg of WT to 114.5±4.0 mmHg in HET, and MBP from 66.8±9.2 mmHg to 82.9±5.5 mmHg, without hypertension. The total peripheral resistance significantly increased by 42.1%. The ability of bradykinin to reduce myocardial O2 consumption in vitro was impaired by 56% in heart. The response was restored by ascorbic acid, tempol and apocynin. O2− production was increased by 2.7 folds in Hcy heart using lucigenin chemiluminescence.ConclusionCBS deficiency caused HHcy during pregnancy, impairs cardiac function, increases O2− production and reduces the ability of NO to regulate myocardial O2 consumption probably through NADPH oxidase stimulation.
GLOBAL GENE EXPRESSION PROFILE IN RENAL ISCHEMIA/REPERFUSION INDUCED CARDIAC HYPERTROPHY
Authors: Nakama Karina Kaori , Carneiro-Ramos Marcela Sorelli 
Published: June 2021

ObjectivesThe heart is a target organ in many regulatory systems, such as hormones, neuronal and immunological systems, modulating heart trophism. This study aimed to determine changes in gene expression of hypertrophied cardiac tissue in a renal ischemia‐induced systemic inflammation model.MethodsC57BL/6 mice were submitted to unilateral occlusion of left renal pedicle for 60 min, followed by reperfusion of 5, 8, 15 and 20 days. The software dChip and GeneMAPP were used to separate and group genes in signaling pathways which had shown significant increase or decrease in expression. Three genes (H2‐Oa, Crtam and Ifnz) of very modulated pathways associated with immune response (MHC class II, Positive Regulation of Natural Killer Cell and Cytokine Activity Pathways, respectively) were selected. To validate array results, real time PCR was performed.ResultsThe analysis results indicated 17,413 up‐regulated and 18,297 down‐regulated genes, and 405 up‐regulated and 300 down‐regulated pathways. According to the array analysis and real time PCR results the three selected genes were up regulated and showed a greater increase after 8 days of reperfusion.ConclusionValidation of H2‐Oa, Crtam and Ifnz indicates a possible relationship of these genes in the development of cardiac hypertrophy due to a systemic condition of inflammation caused by renal failure.
Mutations of HOMEZ gene in Congenital Heart Diseases
Authors: XUAN Chao , JIA Ke-Gang , WANG Bin-Bin , BAI Xiao-Yan , GAO Ge , YANG Qin , LIU Xiao-Cheng , MA Xu , HE Guo-Wei 
Published: June 2021

Genome‐wide linkage analysis revealed that a potential congenital heart disease (CHD) susceptibility locus on Homeodomain leucine zipper‐encoding (HOMEZ) gene in a South Indian population. We aimed to identify potential pathogenic mutations for HOMEZ in isolated VSD in the Chinese population. Case‐control mutational analysis was performed in 400 patients with isolated VSD and 400 healthy controls by using PCR and sequencing. Two novel heterozygous missense mutations (c.116 C>T; c. 630T>A) were identified in HOMEZ gene exon‐2. The two mutations lead to alanine to valine substitution at the position 39 and serine to arginine at position 210 which are highly conservative among many species. The hydropathicity of the valine and arginine residue at the position 39 and 210 were significantly different from the wild type. We have identified two novel heterozygous missense mutations in HOMEZ gene exon‐2 in isolated VSD patients and have found that these two mutations resulted in alteration of the hydropathicity of the HOMEZ protein. Therefore, the two missense mutations of HOMEZ gene are directly linked with the etiology of isolated VSD in the Chinese population.Supported by National Basic Research Program of China 2010CB529502; International S&T Cooperation Program of China 2009DFB30560; Tianjin Municipal S&T Com 09ZCZDSF04200 & 10JCYBJC26400; NSFC 81170148; GRF CUHK4789/09M; CUHK2041688
Uterine artery vasoconstriction during exercise in rat pregnancy
Authors: OˈHagan Kathleen P , Lashley Christopher , Supik David A , Atkinson James T , Murphy Robert J 
Published: June 2021

Dynamic exercise initiates a decrease in uterine artery conductance (UtC) that is reduced at term pregnancy in rabbits [−40% (SD20) vs. −7% (SD15)]. We hypothesized that a gestational attenuation of the uterine vasoconstrictor response occurs in rats, a common model for pregnancy research. Nonpregnant (8NP) and pregnant (12P) rats were familiarized w/treadmill running and instrumented with a left carotid arterial catheter to measure blood pressure (BP) and a Transonic flowprobe for measurement of right UtBF. At day20 gestation (7–10d postsurgery), rats underwent exercise at 7 m/min (6%grade) for 5 min. Values are mean (SD). Pre‐exercise BP was lower [126 (13) vs. 111 (13) P=0.02], HR similar [456 (34) bpm] and UtBF [0.46 (0.25) vs 2.1 (1.6) ml/min, P<0.01] and UtC [0.35 (0.17) vs. 2.1 (1.7) ml‐min−1/mmHg × 10−2P<0.01] elevated in the P rats. BP and HR increased with exercise in P and NP. Averaged over min 2–5 of exercise, the reduction in UtBF [−47% (12) vs. −25% (20), P=0.02)] and UtC [−49% (12) vs. −30% (20), P=0.02] was mildly attenuated in the P rats. Similar to rabbits, P rats demonstrate a reduced uterine vasoconstrictor response to dynamic exercise, although it appears less pronounced in the rat.Supported by MWU.
NOS1‐dependent S‐nitrosylation of cardiac calcium‐handling proteins (RyR2, SERCA, and L‐type Ca2+ channel) modulates basal contractility and adrenergic inotropism
Authors: Vielma Alejandra Z , Eller Gisela , González Daniel R , Boric Mauricio P 
Published: June 2021

We tested the hypothesis that NOS‐1 activity regulates basal and β‐adrenergic‐stimulated cardiac contractility by S‐nitrosylation of Ca2+‐handling proteins.We used the isolated rat heart preparation and biotin‐switch assay, to study the effect of selective NOS‐1 inhibitor (S‐methyl‐L‐thiocitrulline, SMTC) on the contractile response to isoproterenol (ISO) and S‐nitrosylation of sarcoplasmic Ca2+ channel (RyR2) and pump (SERCA2), L‐type Ca2+ channel (LTCC), and unspecific total cardiac proteins (TCP).SMTC (300nM, 20‐min) significantly decreased basal contractility (−15%) and the S‐nitrosylation of RYR2 (−70%), SERCA2 (−50%), LTCC (−80%), and TCP (−55%). ISO (10nM, 3‐min) increased S‐nitrosylation of RyR2 (+140%) and TCP (+30%), but did not change S‐nitrosylation of SERCA2 and LTCC. In the presence of SMTC, ISO caused proportionally similar changes in S‐nitrosylation of all these proteins, but the maximal inotropic response was reduced (−30%). Furthermore, in isolated mice cardiomyocytes, SMTC reduced ISO‐elicited maximal sarcomere shortening (−50%) and [Ca2+]i transient amplitude (−50%), and increased the time‐constant for [Ca2+]i decay (+30%).Thus, rapid and reversible NOS‐1 dependent S‐nitrosylation of specific Ca2+‐handling proteins is essential to keep basal cardiac contractility, and to accomplish a full inotropic response.Supported by Grants Fondecyt 1090757 & Anillos‐ACT71
Iron supplementation during lactation increases hemoglobin without an increase in iron status or oxidative stress
Authors: Jorgensen Josh M , Yang Zhenyu , Lonnerdal Bo , Chantry Caroline J , Allen Lindsay H , Dewey Kathryn G 
Published: June 2021

The RDA for iron (Fe) decreases to 9 mg/d during lactation, yet breastfeeding women are counseled to continue taking prenatal vitamin‐mineral supplements (PNV) postpartum. Our objective was to examine the effect of Fe‐containing PNV taken postpartum on biomarkers of Fe status and oxidative stress. Lactating women (n=114) were randomly assigned to consume daily one Fe‐free PNV plus either 27 mg of Fe (as Fe sulfate) or placebo for 3 mo. The placebo group took the tablets between meals, while those in the Fe group took the tablets either with (Fe‐with) or between meals (Fe‐between). Blood and urine samples were collected before and after the supplementation period to analyze hemoglobin (Hb), Fe status (ferritin, hepcidin, transferrin saturation (TfSat), and total plasma Fe) and oxidative stress (isoprostane and 8‐ hydroxy‐2‐deoxyguanosine (8‐OHdG)). The change from baseline in Hb was greater in the Fe‐with and Fe‐between groups compared to placebo (0.04, 0.25, and −0.37g/dL, respectively; P=0.027), yet only 1 woman in the placebo group had Hb < 12 g/dL at the end of the intervention period. There were no significant differences in ferritin (P=0.09), hepcidin (P=0.84), TfSat (P=0.08), or total plasma Fe (P=0.07). There were no group‐wise differences in isoprostane (P=0.64) or 8‐OHdG (P=0.67). Fe consumption during lactation increased Hb without a significant increase in Fe status and did not affect oxidative stress.Grant Funding Source: Center for Health and Nutrition Research at UC Davis
Titin is not the weak link in the Z‐disk streaming induced by plyometric exercise
Authors: Macaluso Filippo , Isaacs Ashwin W , Myburgh Kathy H 
Published: June 2021

The purpose was to analyze the skeletal muscle changes induced by an acute bout of plyometric exercise (PlyEx) before and after a PlyEx training.Healthy untrained individuals (N=13) completed an acute bout of PlyEx (10×10 squat‐jumps, 1 min rest). Thereafter, 8 subjects completed 8 weeks of PlyEx, while 5 subjects were instructed to refrain from doing any jumping activity for 8 weeks. Seven days after the last training session all subjects repeated a second acute bout of PlyEx.The first acute bout of PlyEx induced a rise of creatine kinase activity (CK = 2421 ± 4978 U/l), Z‐line streaming mainly in fast twitch fibers, a stretch of the c‐terminus of titin (observed by immunogold) not limited to fast twitch fibers, and an increase in calpain‐3 autolysis. The second acute bout of PlyEx in the trained group did not induce: a rise of CK (110 ± 58 U/l), Z‐line streaming, or calpain‐3 activation; while in the control group only two subjects exhibited Z‐line streaming, although all subjects presented a stretch of titin.Eccentric explosive exercise induced a stretch of titin, which is not responsible for the weakness of the sarcomere and of the calpain‐3 activation involved in sarcomeric remodelling.Grant Funding Source: Claude Leon Foundation, National Research Foundation (NRF)
Human skeletal muscle microvascular blood volume: effects of ageing, feeding and exercise training
Authors: Phillips Bethan , Varadhan Krishna , Atherton Philip , Rennie Michael , Smith Kenneth , Williams John 
Published: June 2021

Perfusion of the skeletal muscle microvasculature in response to hyperaemic stimuli such as feeding and exercise is crucial for whole‐body (e.g. glycaemia) and local (e.g. protein turnover) metabolic control, and in the case of exercise; performance, recovery and adaptation. Using the novel technique of contrast‐enhanced ultrasound (CEUS) we explored the effects of feeding on muscle microvascular blood volume (MBV) in 10 young (23 y, BMI; 24 kg·m2) and 12 older (71 y, BMI; 26 kg·m2) men, and in a sub‐group of 4 older men (73 y, BMI; 26 kg·m2) after 20 wk resistance exercise training (RET). Under both postabsorptive and postprandial (IV Glamin 102 mg·kg·h−1 and 20% dextrose; blood glucose at ~7 mmol·l−1) conditions, femoral artery leg blood flow (LBF) was measured over 40 min, before infusion of Definity™perflutren microbubbles to assess regional quadriceps MBV by CEUS. Increases in LBF were evident only in the young men after feeding (0.51±0.02 vs. 0.57±0.04 l.min−1, P<0.05). Similarly, increases in MBV after feeding were observed in young (+25±10%, P<0.05) but not older men (+5.3±6%; P>0.05). Intriguingly, in older men, RET faithfully restored youth‐like increases in MBV after feeding (+31±24%, P<0.05). We conclude that: (i) RET rejuvenates age‐related declines in postprandial microvascular hyperaemia and (ii) RET‐induced improvements in MBV may underlie some of the established metabolic benefits of exercise.This work was supported the Dunhill Medical Trust.
TNF‐α‐induced loss of IKK‐α in skeletal muscle: implications for skeletal muscle oxidative phenotype
Authors: Remels Alexander , Langen Ramon , Schols Annemie , Gosker Harry 
Published: June 2021

Molecular mechanisms underlying lower limb muscle dysfunction in chronic inflammatory disorders, e.g. chronic obstructive pulmonary disease (COPD), are unclear. Here we describe that IKK‐α, a key kinase in the alternative NF‐κB pathway, is a novel regulator of skeletal muscle oxidative phenotype (OXPHEN), which is targeted by inflammation. In C2C12 myotubes, IKK‐α knock‐down decreased myosin heavy chain (MyHC) slow protein and MyHC I and IIA (oxidative) mRNA levels while MyHC IIB (glycolytic) mRNA levels increased. Conversely, IKK‐α overexpression increased MyHC slow protein. Importantly, IKK‐α knock‐down decreased PGC‐1α and PGC‐1β mRNA levels, two key regulators of muscle OXPHEN. We previously demonstrated that TNF‐α potently impairs skeletal muscle OXPHEN (Remels et. al. FASEB J 2010). Interestingly, TNF‐α reduced IKK‐α protein, mRNA and promoter activity and diminished phosphorylation of the down‐stream target of IKK‐α in the alternative NF‐κB pathway (P100) in a classical NF‐κB dependent manner. IKK‐α protein levels in skeletal muscle tissue of COPD patients (n=34) were lower (−50%) compared to healthy controls (n=10). This data shows that IKK‐α controls skeletal muscle OXPHEN and suggests that TNF‐α‐induced loss of IKK‐α protein may contribute to loss of muscle OXPHEN in COPD.This study was supported by the Netherlands Asthma Foundation (3.2.09.068) and ENIGMA grant QLK6‐CT‐2002‐02285.