Thiocarbohydrazone and Chalcone-Derived 3,4-Dihydropyrimidinethione as Lipid Peroxidation and Soybean Lipoxygenase Inhibitors.

The potential of the 4,6-diphenyl-3,4-dihydropyrimidine-2(1)-thione (abbreviated as ) and ()-'-benzylidenehydrazinecarbothiohydrazide (abbreviated as ) compounds as possible drug leads is investigated. and are synthesized in high yield of up to 97%. Their structure, binding in the active site of the LOX-1 enzyme, and their toxicity are studied via joint experimental and computational methodologies.

Structure and synthesis of a vaccine and diagnostic target for Enterocloster bolteae, an autism-associated gut pathogen - Part II.

Enterocloster bolteae (formerly known as Clostridium bolteae) is a gastro-intestinal pathogenic bacterium often detected in the fecal microbiome of children in the autism spectrum. E. bolteae excretes metabolites that are thought to act as neurotoxins.

Serum metabolomic profiling identifies potential biomarkers in arthritis in older adults: an exploratory study.

Background: Seronegative elderly-onset rheumatoid arthritis (EORA) and polymyalgia rheumatica (PMR) have similar clinical characteristics making them difficult to distinguish based on clinical features. We hypothesized that the study of serum metabolome could identify potential biomarkers of PMR vs. EORA.

The effects of simvastatin and fenofibrate on malondialdehyde and reduced glutathione concentrations in the plasma, liver, and brain of normolipidaemic and hyperlipidaemic rats.

The objective of study was to investigate the effects of different doses of simvastatin and fenofibrate on malondialdehyde (MDA) and reduced glutathione (GSH) in the plasma, liver, and brain tissue of male normolipidaemic and hyperlipidaemic rats. Normolipidaemic (Wistar) rats were receiving 10 or 50 mg/kg a day of simvastatin or 30 or 50 mg/kg a day of fenofibrate. Hyperlipidaemic (Zucker) rats were receiving 50 mg/kg/day of simvastatin or 30 mg/kg/day of fenofibrate.

Cross-Platform Comparison of Amino Acid Metabolic Profiling in Three Model Organisms Used in Environmental Metabolomics.

Environmental metabolomics is a promising approach to study pollutant impacts to target organisms in both terrestrial and aquatic environments. To this end, both nuclear magnetic resonance (NMR)- and mass spectrometry (MS)-based methods are used to profile amino acids in different environmental metabolomic studies. However, these two methods have not been compared directly which is an important consideration for broader comparisons in the environmental metabolomics field.

Efficiency of Neat and Quaternized-Cellulose Nanofibril Fillers in Chitosan Membranes for Direct Ethanol Fuel Cells.

In this work, fully polysaccharide based membranes were presented as self-standing, solid polyelectrolytes for application in anion exchange membrane fuel cells (AEMFCs). For this purpose, cellulose nanofibrils (CNFs) were modified successfully with an organosilane reagent, resulting in quaternized CNFs (CNF (D)), as shown by Fourier Transform Infrared Spectroscopy (FTIR), Carbon-13 (C13) nuclear magnetic resonance (C NMR), Thermogravimetric Analysis (TGA)/Differential Scanning Calorimetry (DSC), and ζ-potential measurements. Both the neat (CNF) and CNF(D) particles were incorporated in situ into the chitosan (CS) membrane during the solvent casting process, resulting in composite membranes that were studied extensively for morphology, potassium hydroxide (KOH) uptake and swelling ratio, ethanol (EtOH) permeability, mechanical properties, ionic conductivity, and cell performance.

Structural polymorphism driven by a register shift in a CGAG-rich region found in the promoter of the neurodevelopmental regulator AUTS2 gene.

The AUTS2 gene has been shown to influence brain development by controlling the number of neurons, promoting the growth of axons and dendrites and regulating neuronal migration. The expression of two isoforms of AUTS2 protein is precisely regulated and misregulation of their expression has been correlated with neurodevelopmental delay and autism spectrum disorder. A CGAG-rich region, which includes a putative protein binding site (PPBS), d(AGCGAAAGCACGAA), was found in the promoter region of AUTS2 gene.

NMR-Based Metabolite Profiling and the Application of STOCSY toward the Quality and Authentication Assessment of European EVOOs.

Extra virgin olive oil (EVOO) possesses a high-value rank in the food industry, thus making it a common target for adulteration. Hence, several methods have been essentially made available over the years. However, the issue of authentication remains unresolved with national and food safety organizations globally struggling to regulate and control its market.

singlet state filtered nuclear magnetic resonance: towards monitoring toxic responses inside living organisms.

In line with recent paradigm shifts in toxicity testing, nuclear magnetic resonance (NMR) is a powerful tool for studying the biological impacts and perturbations caused by toxicants in living organisms. However, despite the excellent molecular insights that can be obtained through this technique, NMR applications are hampered by considerable experimental challenges such as poor line shape and spectral overlap. Here, we demonstrate the application of singlet-filtered NMR to target specific metabolites and facilitate the study of metabolite fluxes in living , an aquatic keystone species and model organism.

Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro.

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a relentlessly progressive neurodegenerative disorder caused by mutations in the gene. C19orf12 has been implicated in playing a role in lipid metabolism, mitochondrial function, and autophagy, however, the precise functions remain unknown. To identify new robust cellular targets for small compound treatments, we evaluated reported mitochondrial function alterations, cellular signaling, and autophagy in a large cohort of MPAN patients and control fibroblasts.

Synthesis and Cytotoxicity Evaluation of Novel Coumarin-Palladium(II) Complexes against Human Cancer Cell Lines.

Two newly synthesized coumarin-palladium(II) complexes (C1 and C2) were characterized using elemental analysis, spectroscopy (IR and H-C NMR), and DFT methods at the B3LYP-D3BJ/6-311+G(d,p) level of theory. The in vitro and in silico cytotoxicity of coumarin ligands and their corresponding Pd(II) complexes was examined. For in vitro testing, five cell lines were selected, namely human cervical adenocarcinoma (HeLa), the melanoma cell line (FemX), epithelial lung carcinoma (A549), the somatic umbilical vein endothelial cell line (EA.

SASSY NMR: Simultaneous Solid and Solution Spectroscopy.

Synergism between different phases gives rise to chemical, biological or environmental reactivity, thus it is increasingly important to study samples intact. Here, SASSY (SimultAneous Solid and Solution spectroscopY) is introduced to simultaneously observe (and differentiate) all phases in multiphase samples using standard, solid-state NMR equipment. When monitoring processes, the traditional approach of studying solids and liquids sequentially, can lead to information in the non-observed phase being missed.

Children gut microbiota exhibits a different composition and metabolic profile after exposure to and increases its sporulation.

infection (CDI) is one of the main public health concerns in adults, while children under 2 years of age are often colonized asymptomatically. In both adults and children, CDI is strongly associated with disturbances in gut microbiota. In this study, an model of children gut microbiota was challenged with vegetative cells or a conditioned media of six different toxigenic strains belonging to the ribotypes 027, 078, and 176.

Optical Rotation-A Reliable Parameter for Authentication of Honey?

The controversial question of whether optical rotation data can be used to distinguish floral from honeydew honey was investigated. Specific optical rotation angles were determined for 41 honey samples, including floral, honeydew, and adulterated honey, indicating that moderate to high positive optical rotation angles were found for all adulterated samples measured. A strong correlation between the sugar profile and the specific optical rotation angle of honey was confirmed, and a method based on C NMR metabolomics was proposed to calculate specific optical rotation angles with good correlation with the experimental values.

In Silico Prediction of the Toxicity of Nitroaromatic Compounds: Application of Ensemble Learning QSAR Approach.

In this work, a dataset of more than 200 nitroaromatic compounds is used to develop Quantitative Structure-Activity Relationship (QSAR) models for the estimation of in vivo toxicity based on 50% lethal dose to rats (LD). An initial set of 4885 molecular descriptors was generated and applied to build Support Vector Regression (SVR) models. The best two SVR models, SVR_A and SVR_B, were selected to build an Ensemble Model by means of Multiple Linear Regression (MLR).

An investigation of metabolome in blood in patients with chronic peripheral, posttraumatic/postsurgical neuropathic pain.

Neuropathic pain (NP) is a chronic pain condition resulting from a lesion or disease in the somatosensory nervous system. The aim of this study was to investigate the metabolome in plasma from patients with chronic peripheral, posttraumatic/postsurgical NP compared to healthy controls. Further, we aimed to investigate the correlation between pain intensity and the metabolome in plasma.

DNA damage independent inhibition of NF-κB transcription by anthracyclines.

Anthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning and to eviction of histones from select sites in the genome. Here, we show that the extensively used anthracyclines Doxorubicin, Daunorubicin, and Epirubicin decrease the transcription of nuclear factor kappa B (NF-κB)-dependent gene targets, but not interferon-responsive genes in primary mouse () macrophages.

NMR spectrum reconstruction as a pattern recognition problem.

A new deep neural network based on the WaveNet architecture (WNN) is presented, which is designed to grasp specific patterns in the NMR spectra. When trained at a fixed non-uniform sampling (NUS) schedule, the WNN benefits from pattern recognition of the corresponding point spread function (PSF) pattern produced by each spectral peak resulting in the highest quality and robust reconstruction of the NUS spectra as demonstrated in simulations and exemplified in this work on 2D H-N correlation spectra of three representative globular proteins with different sizes: Ubiquitin (8.6 kDa), Azurin (14 kDa), and Malt1 (44 kDa).

Targeting the phosphoserine phosphatase MtSerB2 for tuberculosis drug discovery, an hybrid knowledge based /fragment based approach.

Tuberculosis is currently still one of the leading causes of death from a treatable pathogen. The proportion of cases of resistance to common antibiotics is frequently increasing and the development of new drugs with new therapeutic targets is becoming necessary. The Mycobacterium tuberculosis phosphoserine phosphatase MtSerB2 is an interesting enzyme to target in drug design because of its ability to allow immune evasion of the bacteria.

Computational Studies on Selected Macrolides Active against Combined with the NMR Study of Tylosin A in Deuterated Chloroform.

Although many antibiotics are active against Gram-positive bacteria, fewer also show activity against Gram-negative bacteria. Here, we present a combination of in silico (electron ion-interaction potential, molecular docking, ADMET), NMR, and microbiological investigations of selected macrolides (14-membered, 15-membered, and 16-membered), aiming to discover the pattern of design for macrolides active against Gram-negative bacteria. Although the conformational studies of 14-membered and 15-membered macrolides are abundant in the literature, 16-membered macrolides, and their most prominent representative tylosin A, have received relatively little research attention.