Liquid chromatography-coupled mass spectrometry analysis of glutathione conjugates of oxygenated polyunsaturated fatty acids.

Glutathione (GSH) conjugates of oxygenated polyunsaturated fatty acids comprise a group of pro-inflammatory and pro-resolving lipid mediators formed in immunocompetent cells. While the pro-inflammatory conjugates such as the cysteinyl leukotrienes (cys-LTs), eoxins (EXs) and five-oxo-GSH conjugate (FOG) derive from arachidonic acid (AA), the group of conjugates in tissue regeneration (CTRs) such as maresin CTRs (MCTRs), protectin CTRs (PCTRs) and resolvin CTRs (RCTRs) are biosynthesized from docosahexaenoic acid (DHA). Here, we present a gradient UPLC-MS/MS method for the analysis of pro-inflammatory and pro-resolving GSH conjugates using positive electrospray ionization (ESI(+)) and collision-induced fragmentation for unambiguous identification and structural information, and a negative ionization (ESI(-)) mode for quantification of the GSH conjugates.

Amino Acid-Substituted Dextran-Based Non-Viral Vectors for Gene Delivery.

To form bio-inspired non-viral vectors for DNA delivery, the polysaccharide dextran is allowed to react with Boc-amino protected amino acids glycine, β-alanine, and L-lysine activated with 1,1'-carbonyldiimidazole and subsequent dextran ester deprotection. A library of such dextran esters is made available to investigate the relationship between polymer structure, complex formation, stability, toxicity, and transfection. Only dextran esters of β-alanine and L-lysine are able to efficiently interact with DNA as shown by dye exclusion assays, to form nanosized complexes (70-110 nm) with positive zeta potential.

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data.

Objective: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients.

Design: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies.

Data Sources: Medline, Embase, and Web of Science for published studies.

Functional dextran amino acid ester particles derived from N-protected S-trityl-L-cysteine.

This work describes the derivatization of dextran using N-(tert-butyloxycarbonyl)-S-(trityl)-L-cysteine in the presence of N,N'-carbonyldiimidazole (CDI) as a coupling agent. Homogeneous reactions in dimethyl sulfoxide allowed for an efficient coupling of the amino acid derivative to the polymer backbone. Derivatization was confirmed by infrared and C NMR spectroscopy, size exclusion chromatography and elemental analysis.

Metabolomics of Thrips Resistance in Pepper (Capsicum spp.) Reveals Monomer and Dimer Acyclic Diterpene Glycosides as Potential Chemical Defenses.

The development of pesticide resistance in insects and recent bans on pesticides call for the identification of natural sources of resistance in crops. Here, we used natural variation in pepper (Capsicum spp.) resistance combined with an untargeted metabolomics approach to detect secondary metabolites related to thrips (Frankliniella occidentalis) resistance.

Stress-Induced Changes in the Lipid Microenvironment of β-(1,3)-d-Glucan Synthase Cause Clinically Important Echinocandin Resistance in Aspergillus fumigatus.

is a leading cause of invasive fungal infections. Resistance to first-line triazole antifungals has led to therapy with echinocandin drugs. Recently, we identified several high-minimum-effective-concentration (MEC) clinical isolates from patients failing echinocandin therapy.

The phenotype of target pancreatic cancer cells influences cell death by magnetic hyperthermia with nanoparticles carrying gemicitabine and the pseudo-peptide NucAnt.

In this paper we show that conjugation of magnetic nanoparticles (MNPs) with Gemcitabine and/or NucAnt (N6L) fostered their internalization into pancreatic tumor cells and that the coupling procedure did not alter the cytotoxic potential of the drugs. By treating tumor cells (BxPC3 and PANC-1) with the conjugated MNPs and magnetic hyperthermia (43 °C, 60 min), cell death was observed. The two pancreatic tumor cell lines showed different reactions against the combined therapy according to their intrinsic sensitivity against Gemcitabine (cell death, ROS production, ability to activate ERK 1/2 and JNK).

The vitamin E derivative garcinoic acid from Garcinia kola nut seeds attenuates the inflammatory response.

The plant Garcinia kola is used in African ethno-medicine to treat various oxidation- and inflammation-related diseases but its bioactive compounds are not well characterized. Garcinoic acid (GA) is one of the few phytochemicals that have been isolated from Garcinia kola. We investigated the anti-inflammatory potential of the methanol extract of Garcinia kola seeds (NE) and purified GA, as a major phytochemical in these seeds, in lipopolysaccharide (LPS)-activated mouse RAW264.

Treatment of Caenorhabditis elegans with Small Selenium Species Enhances Antioxidant Defense Systems.

Scope: Small selenium (Se) species play a key role in Se metabolism and act as dietary sources of the essential trace element. However, they are redox-active and trigger pro- and antioxidant responses. As health outcomes are strongly species-dependent, species-specific characteristics of Se compounds are tested in vivo.

Genome-wide association study suggests impact of chromosome 10 rs139401390 on kidney function in patients with coronary artery disease.

Chronic kidney disease (CKD) is an independent risk factor for onset and progression of coronary artery disease (CAD). Discovery of predisposing loci for kidney function in CAD patients was performed using a genome-wide association approach. Inclusion criteria were CAD with ≥50% stenosis (≥1 coronary artery) and a creatinine-based estimated glomerular filtration rate (eGFR) of 30-75 ml/min/1.

Short communication: Changes under low ambient temperatures in the milk lipodome and metabolome of mid-lactation cows after dehorning as a calf.

Horns are living tissue and cows can use their horns for thermoregulatory purposes. We investigated the effect of the presence of horns on the metabolome of milk serum and lipidome of milk fat, to assess the physiological effect of dehorning. Milk sampling took place at low ambient temperatures of -6 to 2°C.

Different Routes to Ampholytic Polydehydroalanine: Orthogonal versus Simultaneous Deprotection.

Polydehydroalanine (PDha) is a polyampholyte featuring both a -NH and a -COOH in every repeat unit and with that presents a rather high charge density. The synthesis and polymerization of two monomers, benzyl 2-tert-butoxycarbonylaminoacrylate and methyl 2-benzyloxycarbonylaminoacrylate is herein reported, which feature different protective groups and, after polymerization, the resulting PtBABA and PBOMA can be transformed into PDha using polymer-analogous modification reactions. More important, the current choice of protective groups allows either simultaneous deprotection in one step in both cases, but also the orthogonal deprotection of either -NH or -COOH moiety for PtBABA, given that appropriate conditions are chosen.

Effect of Genetically Low 25-Hydroxyvitamin D on Mortality Risk: Mendelian Randomization Analysis in 3 Large European Cohorts.

The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes (rs12794714, rs10741657) and (rs12785878, rs11234027), were combined in two allelic scores.

Society of Thoracic Surgeons Risk Score and EuroSCORE-2 Appropriately Assess 30-Day Postoperative Mortality in the STICH Trial and a Contemporary Cohort of Patients With Left Ventricular Dysfunction Undergoing Surgical Revascularization.

Background: The STICH trial (Surgical Treatment for Ischemic Heart Failure) demonstrated a survival benefit of coronary artery bypass grafting in patients with ischemic cardiomyopathy and left ventricular dysfunction. The Society of Thoracic Surgeons (STS) risk score and the EuroSCORE-2 (ES2) are used for risk assessment in cardiac surgery, with little information available about their accuracy in patients with left ventricular dysfunction. We assessed the ability of the STS score and ES2 to evaluate 30-day postoperative mortality risk in STICH and a contemporary cohort (CC) of patients with a left ventricle ejection fraction ≤35% undergoing coronary artery bypass grafting outside of a trial setting.

Where cone snails and spiders meet: design of small cyclic sodium-channel inhibitors.

A 13 aa residue voltage-gated sodium (Na) channel inhibitor peptide, Pn, containing 2 disulfide bridges was designed by using a chimeric approach. This approach was based on a common pharmacophore deduced from sequence and secondary structural homology of 2 Na inhibitors: Conus kinoshitai toxin IIIA, a 14 residue cone snail peptide with 3 disulfide bonds, and Phoneutria nigriventer toxin 1, a 78 residue spider toxin with 7 disulfide bonds. As with the parent peptides, this novel Na channel inhibitor was active on Na1.

A 5‑lipoxygenase-specific sequence motif impedes enzyme activity and confers dependence on a partner protein.

Leukotrienes (LT) are lipid mediators of the inflammatory response that play key roles in diseases such as asthma and atherosclerosis. The precursor leukotriene A (LTA) is synthesized from arachidonic acid (AA) by 5‑lipoxygenase (5-LOX), a membrane-associated enzyme, with the help of 5‑lipoxygenase-activating protein (FLAP), a nuclear transmembrane protein. In lipoxygenases the main chain carboxylate of the C-terminus is a ligand for the non-heme iron and thus part of the catalytic center.

Achievable Central Nervous System Concentrations of the Green Tea Catechin EGCG Induce Stress in Glioblastoma Cells in Vitro.

The polyphenolic compounds present in green tea are preventative against cancer in several animal tumor models. However, direct cytotoxic effects on cancer cells have also been reported. In order to determine whether drinking of green tea has chemopreventive or cytotoxic effects on brain cancer cells, we investigated the effect of the major green tea polyphenol EGCG as a pure substance and as tea extract dietary supplement on primary human glioblastoma cell cultures at the CNS-achievable concentration of 100 nM reported in the literature.

Validation of a simplified in vitro Transwell model of the alveolar surface to assess host immunity induced by different morphotypes of Aspergillus fumigatus.

Interactions between fungal pathogens such as Aspergillus fumigatus with host alveolar epithelium and innate immune cells are crucial in the defense against opportunistic fungal infections. In this study a simplified Transwell system with a confluent layer of A549 cells acted as a model for the alveolar surface. A.

Sphingosine-1-phosphate (S1P) induces potent anti-inflammatory effects in vitro and in vivo by S1P receptor 4-mediated suppression of 5-lipoxygenase activity.

Sphingosine-1-phosphate (S1P) is involved in the regulation of important cellular processes, including immune-cell trafficking and proliferation. Altered S1P signaling is strongly associated with inflammation, cancer progression, and atherosclerosis; however, the mechanisms underlying its pathophysiologic effects are only partially understood. This study evaluated the effects of S1P in vitro and in vivo on the biosynthesis of leukotrienes (LTs), which form a class of lipid mediators involved in the pathogenesis of inflammatory diseases.

Development of hydrophilic gels containing coenzyme Q-loaded liposomes: characterization, stability and rheology measurements.

Objective: The aim of this study was to develop, characterize and evaluate stability of a gel containing coenzyme Q (Q)-loaded liposomes, and enhance the stability of Q in the nanocarrier-containing gel compared to the conventional gel.

Methods: Q-loaded liposome dispersions prepared from unsaturated or saturated lecithin, were characterized for particle size, polydispersity index (PDI), zeta-potential, pH value, oxidation index, Q-content and morphology, and incorporated into carbomer gel. Liposome gels and liposome-free gel were analyzed for flow properties, pH values, Q-content, and liposomes size and PDI (liposome gels), 48 h after preparation and in predetermined time intervals during 6 months storage at different temperatures in order to predict their long term stability.

Multisensory stimulation modulates perceptual and post perceptual face representations: Evidence from event-related potentials.

Seeing a face being touched in spatial and temporal synchrony with the own face produces a bias in self-recognition, whereby the other face becomes more likely to be perceived as the self. The present study employed event-related potentials to explore whether this enfacement effect reflects initial face encoding, enhanced distinctiveness of the enfaced face, modified self-identity representations, or even later processing stages that are associated with the emotional processing of faces. Participants were stroked in synchrony or asynchrony with an unfamiliar face they observed on a monitor in front of them, in a situation approximating a mirror image.

Bottom-up Layer-by-Layer Assembling of Antibacterial Freestanding Nanobiocomposite Films.

In this study, freestanding nanobiocomposite films were obtained by the sequential deposition of biopolymer-capped silver nanoparticles (AgNPs) and hyaluronic acid (HA). At first, dispersions of AgNPs decorated with chitosan (CS) or aminocellulose (AC) were synthesized by applying high intensity ultrasound. These polycationic nanoentities were layer-by-layer assembled with the HA polyanion to generate stable 3D supramolecular constructs, where the biopolymer-capped AgNPs play the dual role of active agent and structural element.

Structural insight into the optimization of ethyl 5-hydroxybenzo[g]indol-3-carboxylates and their bioisosteric analogues as 5-LO/m-PGES-1 dual inhibitors able to suppress inflammation.

The release of pro-inflammatory mediators, such as prostaglandines (PGs) and leukotrienes (LTs), arising from the arachidonic acid (AA) cascade, play a crucial role in initiating, maintaining, and regulating inflammatory processes. New dual inhibitors of 5-lipoxygenase (5-LO) and microsomal prostaglandin E synthase-1 (mPGES-1), that block, at the same time, the formation of PGE and LTs, are currently emerged as a highly interesting drug candidates for better pharmacotherapie of inflammation-related disorders. Following our previous studies, we here performed a detailed structure-based design of benzo[g]indol-3-carboxylate derivatives, disclosing several new key factors that affect both enzyme activity.

The Chara Genome: Secondary Complexity and Implications for Plant Terrestrialization.

Land plants evolved from charophytic algae, among which Charophyceae possess the most complex body plans. We present the genome of Chara braunii; comparison of the genome to those of land plants identified evolutionary novelties for plant terrestrialization and land plant heritage genes. C.