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.

Modulation of physico-chemical and technofunctional properties of quinoa protein isolate: Effect of precipitation acid.

The typically low solubility and gelation capacity of plant proteins can impose challenges in the design of high-quality plant-based foods. The acid used during the precipitation step of plant protein isolate extraction can influence protein functionality. Here, acetic acid and citric acid were used to extract quinoa protein isolate (QPI) from quinoa flour, as these acids are more kosmotropic than the commonly used HCl, promoting the stabilisation of the native protein structure.

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.

TKPlate 1.0: An Open-access platform for toxicokinetic and toxicodynamic modelling of chemicals to implement new approach methodologies in chemical risk assessment.

This publication is linked to the following EFSA Supporting Publications articles: http://onlinelibrary.wiley.com/doi/10.

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.

Atypical phase behaviour of quinoa protein isolate in mixture with maltodextrin.

Consumers are increasingly looking for new plant-based alternatives to substitute animal proteins in their diets but for some applications it can be difficult to achieve the desired product microstructure using only plant proteins. One approach to facilitate structuring is to mix these plant-based ingredients with a polysaccharide. Here, the phase behaviour and microstructure of quinoa protein isolate (QPI) in mixture with maltodextrin (MD) of two dextrose equivalents (DE 7 and 2) were investigated.

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.

Propolis particles incorporated in aqueous formulations with enhanced antibacterial performance.

In recent years, the use of natural bioactives in food, pharmaceutical and cosmetic industries has emerged as a global formulation development trend. Although natural bioactives exhibit promising properties, they are also associated with chemical instability or poor aqueous solubility. One such bioactive with beneficial functionalities but limited industrial applicability within industry is propolis.

Formulation design, production and characterisation of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the encapsulation of a model hydrophobic active.

Lipid nanoparticles have been widely investigated for their use as either carriers for poorly water soluble actives or as (Pickering) emulsion stabilisers. Recent studies have suggested that the fabrication of lipid nanostructures that can display both these performances concurrently, can enable the development of liquid formulations for multi-active encapsulation and release. Understanding the effects of different formulation variables on the microstructural attributes that underline both these functionalities is crucial in developing such lipid nanostructures.

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.

Lower oxygen saturation targets in preterm infants are not associated with increased rates of pulmonary hypertension.

Background: The optimal oxygen saturation target in preterm infants is not known. In this study, we aimed to assess the effect of lower oxygen saturation targets on the rate of bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and pulmonary hypertension (PH) in preterm infants.

Methods: Retrospective cohort study comparing BPD, ROP, and PH incidence among two cohorts of infants born at≤32 weeks gestation with different oxygen saturation targets at≥34 weeks post-menstrual age (PMA): cohort 1, 94-98% (n = 126); cohort 2, 92-97% (n = 121).

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.

Independent co-delivery of model actives with different degrees of hydrophilicity from oil-in-water and water-in-oil emulsions stabilised by solid lipid particles via a Pickering mechanism: a-proof-of-principle study.

Hypothesis: The development of vehicles for the co-encapsulation of actives with diverse characteristics and their subsequent controllable co-delivery is gaining increasing research interest. Predominantly centred around pharmaceutical applications, the majority of such co-delivery approaches have been focusing on solid formulations and less so on liquid-based systems. Simple emulsions can be designed to offer a liquid-based microstructural platform for the compartmentalised multi-delivery of actives.

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.

A flow velocity dependence of dynamic surface tension in Plateau borders of foam.

Hypothesis: Liquid drainage through foams is a multiscale process, that primarily occurs through channels known as Plateau borders (PBs). Recent experimental studies of isolated PBs have observed variations in channel surface tension, γ, with liquid flow rate, Q, for systems containing soluble low molecular weight surfactant (LMWS). The current study proposes that the dynamic surface tension (DST) could be responsible for this effect, where the residence time of surfactant molecules in the PB is similar to the time required for their adsorption to the channel interface.