Hydroxy-Porphyrin as an Effective,Endogenous Molecular Clamp during Early Stages of Amyloid Fibrillization

Amyloid fibril formation of proteins is of great concern in neurodegenerative disease and can be detrimental to the storage and stability of biologics. Recent evidence suggests that insulin fibril formation reduces the efficacy of type II diabetes management and may lead to several complications. To develop anti-amyloidogenic compounds of endogenous origin, we have utilized the hydrogen bond anchoring, π stacking ability of porphyrin, and investigated its role on the inhibition of insulin amyloid formation. We report that hydroxylation and metal removal from the heme moiety yields an excellent inhibitor of insulin fibril formation. Thioflavin T, tyrosine fluorescence, Circular Dichorism (CD) spectroscopy, Field emission scanning electron microscopy (FESEM) and molecular dynamics (MD) simulation studies suggest that hematoporphyrin (HP) having hydrogen bonding ability on both sides is a superior inhibitor compared to hemin and protoporphyrin (PP). Experiments with hen egg white lysozyme (HEWL) amyloid fibril formation also validated the efficacy of endogenous porphyrin based small molecules. Our results will help to decipher a general therapeutic strategy to counter amyloidogenesis.     

Growth and liver histology of Channa punctatus exposed to a common biofertilizer

Mustard oil cake (MOC) is widely used as biofertilizer in the field of agriculture and aquaculture. Channa punctatus was exposed to 0.42 g.L^?1 sublethal concentration for 4, 7, 14, 21 and 28 days. Due to such exposure, body growth and histological changes in liver were observed. It was revealed that weight, length and breadth of fish were gradually increased with the days of exposure in compare to control fish, whereas, liver showed an increase in sinusoidal space and lipidosis during early days, followed by a recovery from the stress of MOC on the 28th day.     

Synthesis and structural characterization of copper(II) and vanadium(V) complexes of pyridyl/pyrimidyl–pyrazole derived Schiff base ligands – Metal specific adjustment of ligand binding mode

Two mononuclear copper(II) complexes [Cu(L₁)ClO₄] (1), [Cu(L₂)ClO₄] (3) and two mononuclear vanadium(V) complexes [{VO(L₁)(OCH₃)(CH₃OH)}{VO(L₁)(OCH₃)}] (2) and [VO(L₂) (OCH₃)(CH₃OH)] (4) have been synthesized using two Schiff base ligands HL₁ [N′-(2-hydroxybenzylidene)-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-3-carbohydrazide] and HL₂ [1-(4,6-dimethylpyrimidin-2-yl)-N′-(2-hydroxybenzylidene)-5-methyl-1H-pyrazole-3-carbohydrazide]. These two similar ligands HL₁ and HL₂ in their ‘ketoimine’ form function as mononegative NNNO tetradentate ones towards the Cu(II) centre forming square planar part of the square pyramidal geometry. Where as the same ligands in their ‘imineol’ form behave as binegative ONO tridentate ones to form their V(V) analogues. In the asymmetric unit of 2, there are two independent V(V) complex molecules differing in their conformations as well as in coordination environment – octahedral V(V) in ‘unit A’ is hexa-coordinated while that in ‘unit B’ being penta-coordinated is square pyramidal. Vanadium atom in 4 is in octahedral geometry with NO₅ chromophore. The ligands HL₁ and HL₂ have been synthesized for the first time in our laboratory and characterized by X-ray crystallography and spectroscopy. The complexes (1, 2 and 4) are also characterized by X-ray crystallography, spectroscopic and electrochemical studies.     

Ionic Liquid-Assisted Fabrication of Bioactive Heterogeneous Magnetic Nanocatalyst with Antioxidant and Antibacterial Activities for the Synthesis of Polyhydroquinoline Derivatives

Antibacterial materials have obtained much attention in recent years due to the presence of hazardous agents causing oxidative stress and observation of pathogens. However, materials with antioxidant and antibacterial activities can cause toxicity due to their low biocompatibility and safety profile, urging scientists to follow new ways in the synthesis of such materials. Ionic liquids have been employed as a green and environmentally solvent for the fabrication of electrically conductive polymers. In the present study, an antibacterial poly(p-phenylenediamine)@Fe₃O₄ (PpPDA@Fe₃O₄) nanocomposite was fabricated using [HPy][HSO₄] ionic liquid. The chemical preparation of PpPDA@Fe₃O₄ nanocomposite was initiated through the oxidative polymerization of p-phenylenediamine by ammonium persulfate in the presence of [HPy][HSO₄]. The PpPDA@Fe₃O₄ nanocomposite exhibited antibacterial properties against Gram-negative (Escherichia coli) and Gram-positive (Bacillus subtilis) bacteria. The PpPDA@Fe₃O₄ nanocomposite was employed as a heterogeneous nanocatalysis for one-pot synthesis of polyhydroquinoline derivatives using aromatic aldehyde, dimedone, benzyl acetoacetate, and ammonium acetate. Polyhydroquinoline derivatives were synthesized in significant yields (90–97%) without a difficult work-up procedure in short reaction times. Additionally, PpPDA@Fe₃O₄ nanocatalyst was recycled for at least five consecutive catalytic runs with a minor decrease in the catalytic activity. In this case, 11 derivatives of polyhydroquinoline showed in vitro antioxidant activity between 70–98%.     

Moisture Absorption Effects on the Mechanical Properties of Sandwich Biocomposites with Cork Core and Flax/PLA Face Sheets

The aim of this study was to evaluate the moisture absorption behaviour and its influence on the mechanical properties of newly developed sandwich biocomposites with flax fibre-reinforced poly-lactic acid (PLA) face sheets and soft cork as the core material. Three different types of sandwich biocomposite laminates comprised of different layup configurations, namely, non-woven flax/PLA (Sample A), non-woven flax/PLA and cork as core (Sample B) and non-woven flax/paper backing/PLA, cork as core (Sample C), were fabricated. In order to evaluate the influence of moisture ingress on the mechanical properties, the biocomposites were immersed in seawater for a period of 1200 h. The biocomposites (both dry and water immersed) were then subjected to tensile, flexural and low-velocity falling weight impact tests. It was observed from the experimental results that the moisture uptake significantly influenced the mechanical properties of the biocomposites. The presence of the cork and paper in sample C made it more susceptible to water absorption, reaching a value of 34.33%. The presence of cork in the core also has a considerable effect on the mechanical, as well as energy dissipation, behaviours. The results of sample A exhibited improved mechanical performance in both dry and wet conditions compared to samples B and C. Sample A exhibits 32.6% more tensile strength and 81.4% more flexural strength in dry conditions than that in sample C. The scanning electron microscopy (SEM) and X-ray micro-CT images revealed that the failure modes observed are a combination of matrix cracking, core crushing and face core debonding. The results from this study suggest that flax/PLA sandwich biocomposites can be used in various lightweight applications with improved environmental benefits.     

The Relation Between Position and Chemical Composition of Bis-Indole Substituents Determines Their Interactions with G-Quadruplex DNA

G-quadruplex (G4) DNA structures are linked to fundamental biological processes and human diseases, which has triggered the development of compounds that affect these DNA structures. However, more knowledge is needed about how small molecules interact with G4 DNA structures. This study describes the development of a new class of bis-indoles (3,3-diindolyl-methyl derivatives) and detailed studies of how they interact with G4 DNA using orthogonal assays, biophysical techniques, and computational studies. This revealed compounds that strongly bind and stabilize G4 DNA structures, and detailed binding interactions which for example, show that charge variance can play a key role in G4 DNA binding. Furthermore, the structure–activity relationships generated opened the possibilities to replace or introduce new substituents on the core structure, which is of key importance to optimize compound properties or introduce probes to further expand the possibilities of these compounds as tailored research tools to study G4 biology.     

High-content and high-throughput identification of macrophage polarization phenotypes

Macrophages are plastic cells of the innate immune system that perform a wide range of immune- and homeostasis-related functions. Due to their plasticity, macrophages can polarize into a spectrum of activated phenotypes. Rapid identification of macrophage polarization states provides valuable information for drug discovery, toxicological screening, and immunotherapy evaluation. The complexity associated with macrophage activation limits the ability of current biomarker-based methods to rapidly identify unique activation states. In this study, we demonstrate the ability of a 2-element sensor array that provides an information-rich 5-channel output to successfully determine macrophage polarization phenotypes in a matter of minutes. The simple and robust sensor generates a high dimensional data array which enables accurate macrophage evaluations in standard cell lines and primary cells after cytokine treatment, as well as following exposure to a model disease environment.

Phenotyping macrophage activation states using an array-based sensor. FRET complex assembly selectively interacts with the macrophage surface, generating a fingerprint for each polarization state that is further used to identify the activation state.