Stress Granule Assembly in Pulmonary Arterial Hypertension.

The role of stress granules (SGs) in pulmonary arterial hypertension (PAH) is unknown. We hypothesized that SG formation contributes to abnormal vascular phenotypes, and cardiac and skeletal muscle dysfunction in PAH. Using the rat Sugen/hypoxia (SU/Hx) model of PAH, we demonstrate the formation of SG puncta and increased expression of SG proteins compared to control animals in lungs, right ventricles, and soleus muscles.

Perinatal Factors Associated with Successful Pharmacologic Closure of the Patent Ductus Arteriosus in Premature Infants.

The patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. While pharmacologic closure of the PDA is common and effective, it can be difficult to identify which patients will respond. As such, the objective of this study was to identify factors associated with successful pharmacologic closure of the PDA.

An essential role for EROS in redox-dependent endothelial signal transduction.

The chaperone protein EROS ("Essential for Reactive Oxygen Species") was recently discovered in phagocytes. EROS was shown to regulate the abundance of the ROS-producing enzyme NADPH oxidase isoform 2 (NOX2) and to control ROS-mediated cell killing. Reactive oxygen species are important not only in immune surveillance, but also modulate physiological signaling responses in multiple tissues.

D-Amino acid oxidase-derived chemogenetic oxidative stress: Unraveling the multi-omic responses to in vivo redox stress.

Chemogenetic approaches have been developed to define the mechanisms whereby the intracellular oxidant hydrogen peroxide (HO) modulates both physiological and pathological responses. Recombinant yeast D-amino acid oxidase (DAAO) can be exploited to modulate H₂O₂ in target cells and tissues. In vitro studies using cultured cells expressing recombinant DAAO have provided critical new information on the intracellular transport and metabolism of HO with great temporal and spatial resolution.

Predictors of successful extubation from volume-targeted ventilation in extremely preterm neonates.

Objective: To identify variables associated with extubation success in extremely preterm neonates extubated from invasive volume-targeted ventilation.

Study Design: We retrospectively evaluated 84 neonates ≤28 weeks' gestational age, on their first elective extubation. The primary outcome of successful extubation was defined as non-reintubation within seven days.

Sensory ataxia and cardiac hypertrophy caused by neurovascular oxidative stress in chemogenetic transgenic mouse lines.

Oxidative stress is associated with cardiovascular and neurodegenerative diseases. Here we report studies of neurovascular oxidative stress in chemogenetic transgenic mouse lines expressing yeast D-amino acid oxidase (DAAO) in neurons and vascular endothelium. When these transgenic mice are fed D-amino acids, DAAO generates hydrogen peroxide in target tissues.

Differential endothelial hydrogen peroxide signaling via Nox isoforms: Critical roles for Rac1 and modulation by statins.

Statins have manifold protective effects on the cardiovascular system. In addition to lowering LDL cholesterol levels, statins also have antioxidant effects on cardiovascular tissues involving intracellular redox pathways that are incompletely understood. Inhibition of HMG-CoA reductase by statins not only modulates cholesterol synthesis, but also blocks the synthesis of lipids necessary for the post-translational modification of signaling proteins, including the GTPase Rac1.

Skeletal Muscle Dysfunction in Experimental Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is a serious, progressive, and often fatal disease that is in urgent need of improved therapies that treat it. One of the remaining therapeutic challenges is the increasingly recognized skeletal muscle dysfunction that interferes with exercise tolerance. Here we report that in the adult rat Sugen/hypoxia (SU/Hx) model of severe pulmonary hypertension (PH), there is highly significant, almost 50%, decrease in exercise endurance, and this is associated with a 25% increase in the abundance of type II muscle fiber markers, thick sarcomeric aggregates and an increase in the levels of FoxO1 in the soleus (a predominantly type I fiber muscle), with additional alterations in the transcriptomic profiles of the diaphragm (a mixed fiber muscle) and the extensor digitorum longus (a predominantly Type II fiber muscle).

Metabolomic and transcriptomic signatures of chemogenetic heart failure.

The failing heart is characterized by elevated levels of reactive oxygen species. We have developed an animal model of heart failure induced by chemogenetic production of oxidative stress in the heart using a recombinant adeno-associated virus (AAV9) expressing yeast d-amino acid oxidase (DAAO) targeted to cardiac myocytes. When DAAO-infected animals are fed the DAAO substrate d-alanine, the enzyme generates hydrogen peroxide (HO) in the cardiac myocytes, leading to dilated cardiomyopathy.

Dissecting in vivo and in vitro redox responses using chemogenetics.

Hydrogen peroxide (HO) is the most abundant reactive oxygen species (ROS) within mammalian cells. At low concentrations, HO serves as a versatile cell signaling molecule that mediates vital physiological functions. Yet at higher concentrations, HO can be a toxic molecule by promoting pathological oxidative stress in cells and tissues.

Acetazolamide Improves Right Ventricular Function and Metabolic Gene Dysregulation in Experimental Pulmonary Arterial Hypertension.

Right ventricular (RV) performance is a key determinant of mortality in pulmonary arterial hypertension (PAH). RV failure is characterized by metabolic dysregulation with unbalanced anaerobic glycolysis, oxidative phosphorylation, and fatty acid oxidation (FAO). We previously found that acetazolamide (ACTZ) treatment modulates the pulmonary inflammatory response and ameliorates experimental PAH.

Carbonic anhydrase inhibition improves pulmonary artery reactivity and nitric oxide-mediated relaxation in sugen-hypoxia model of pulmonary hypertension.

Pulmonary hypertension (PH) is a serious disease with pulmonary arterial fibrotic remodeling and limited responsiveness to vasodilators. Our data suggest that mild acidosis induced by carbonic anhydrase inhibition could ameliorate PH, but the vascular mechanisms are unclear. We tested the hypothesis that carbonic anhydrase inhibition ameliorates PH by improving pulmonary vascular reactivity and relaxation mechanisms.

Adipokines and Metabolic Regulators in Human and Experimental Pulmonary Arterial Hypertension.

Pulmonary hypertension (PH) is associated with meta-inflammation related to obesity but the role of adipose tissue in PH pathogenesis is unknown. We hypothesized that adipose tissue-derived metabolic regulators are altered in human and experimental PH. We measured circulating levels of fatty acid binding protein 4 (FABP-4), fibroblast growth factor -21 (FGF-21), adiponectin, and the mRNA levels of FABP-4, FGF-21, and peroxisome proliferator-activated receptor γ (PPARγ) in lung tissue of patients with idiopathic PH and healthy controls.

Echocardiographic markers of pulmonary hemodynamics and right ventricular hypertrophy in rat models of pulmonary hypertension.

Echocardiography is the gold standard non-invasive technique to diagnose pulmonary hypertension. It is also an important modality used to monitor disease progression and response to treatment in patients with pulmonary hypertension. Surprisingly, only few studies have been conducted to validate and standardize echocardiographic parameters in experimental animal models of pulmonary hypertension.

Bronchopulmonary Dysplasia: An Update of Current Pharmacologic Therapies and New Approaches.

Bronchopulmonary dysplasia (BPD) remains the most prevalent long-term morbidity of surviving extremely preterm infants and is associated with significant health care utilization in infancy and beyond. Recent advances in neonatal care have resulted in improved survival of extremely low birth weight (ELBW) infants; however, the incidence of BPD has not been substantially impacted by novel interventions in this vulnerable population. The multifactorial cause of BPD requires a multi-pronged approach for prevention and treatment.

Segregation of Tetragenococcus halophilus and Zygosaccharomyces rouxii using W/O/W double emulsion for use in mixed culture fermentation.

Antagonism in mixed culture fermentation can result in undesirable metabolic activity and negatively affect the fermentation process. Water-oil-water (W/O/W) double emulsions (DE) could be utilized in fermentation for segregating multiple species and controlling their release and activity. Zygosaccharomyces rouxii and Tetragenococcus halophilus, two predominant microbial species in soy sauce fermentation, were incorporated in the internal W and external W phase of a W/O/W, respectively.

A comparative study on the capacity of a range of food-grade particles to form stable O/W and W/O Pickering emulsions.

Whilst literature describing edible Pickering emulsions is becoming increasingly available, current understanding of these systems still suffers from a lack of consistency in terms of the (processing and formulation) conditions within which these structures have been studied. The current study aims to provide a comparative analysis of the behaviour of different edible Pickering candidates and their ability to stabilise emulsion droplets, under well-controlled and uniform experimental conditions, in order to clearly identify the particle properties necessary for successful Pickering functionality. More specifically, an extensive investigation into the suitability of various food-grade material to act as Pickering particles and provide stable oil-in-water (O/W) and water-in-oil (W/O) emulsions was carried out.

Short Stature in Chronic Kidney Disease Treated with Growth Hormone and an Aromatase Inhibitor.

We describe an alternative strategy for management of severe growth failure in a 14-year-old child who presented with advanced chronic kidney disease close to puberty. The patient was initially treated with growth hormone for a year until kidney transplantation, followed immediately by a year-long course of an aromatase inhibitor, anastrozole, to prevent epiphyseal fusion and prolong the period of linear growth. Outcome was excellent, with successful transplant and anticipated complete correction of height deficit.

Self-structuring foods based on acid-sensitive low and high acyl mixed gellan systems to impact on satiety.

This study investigated the acid-induced gelation of mixed systems of two biopolymers; low acyl and high acyl gellan gum. Rheological and texture analysis showed that these mixed gels displayed textures that lay between the material properties exhibited for the low and high acyl variants. DSC analysis showed that mixtures of the low acyl and high acyl forms exhibit two separate conformational transitions at temperatures coincident with each of the individual biopolymers.

Investigation into the potential ability of Pickering emulsions (food-grade particles) to enhance the oxidative stability of oil-in-water emulsions.

In this study the potential ability of food-grade particles (at the droplet interface) to enhance the oxidative stability was investigated. Sunflower oil-in-water emulsions (20%), stabilised solely by food-grade particles (Microcrystalline cellulose (MCC) and modified starch (MS)), were produced under different processing conditions and their physicochemical properties were studied over time. Data on droplet size, surface charge, creaming index and oxidative stability were obtained.

The effect of interfacial microstructure on the lipid oxidation stability of oil-in-water emulsions.

A novel approach to reduce lipid oxidation in oil-in-water emulsions has been taken and involves the manipulation of the emulsions' interfacial microstructure. Oil-in-water emulsions stabilised by sodium caseinate (CAS), Tween 20 and silica particles were prepared and their lipid oxidation stability was assessed over a week. Lipid oxidation was monitored by measuring the concentration of primary lipid oxidation product, using the peroxide value method and secondary lipid oxidation products formation were evaluated with the p-anisidine technique.

W1/O/W2 double emulsions stabilised by fat crystals--formulation, stability and salt release.

Water/oil (W(1)/O) emulsions containing fat crystals have been incorporated into an aqueous phase containing 1% na-caseinate as emulsifier to create stable water/oil/water (W(1)/O/W(2)) double emulsions. The W(1)/O primary emulsion was stabilised exclusively with monoglyceride and triglyceride crystal "shells", and contained 30% W(1) aqueous phase as well as KCl. The stability of the double emulsions was monitored over the course of 6 weeks.