Anti-Inflammatory and Anti-Rheumatic Potential of Selective Plant Compounds by Targeting TLR-4/AP-1 Signaling: A Comprehensive Molecular Docking and Simulation Approaches

Plants are an important source of drug development and numerous plant derived molecules have been used in clinical practice for the ailment of various diseases. The Toll-like receptor-4 (TLR-4) signaling pathway plays a crucial role in inflammation including rheumatoid arthritis. The TLR-4 binds with pro-inflammatory ligands such as lipopolysaccharide (LPS) to induce the downstream signaling mechanism such as nuclear factor κappa B (NF-κB) and mitogen activated protein kinases (MAPKs). This signaling activation leads to the onset of various diseases including inflammation. In the present study, 22 natural compounds were studied against TLR-4/AP-1 signaling, which is implicated in the inflammatory process using a computational approach. These compounds belong to various classes such as methylxanthine, sesquiterpene lactone, alkaloid, flavone glycosides, lignan, phenolic acid, etc. The compounds exhibited different binding affinities with the TLR-4, JNK, NF-κB, and AP-1 protein due to the formation of multiple hydrophilic and hydrophobic interactions. With TLR-4, rutin had the highest binding energy (−10.4 kcal/mol), poncirin had the highest binding energy (−9.4 kcal/mol) with NF-κB and JNK (−9.5 kcal/mol), respectively, and icariin had the highest binding affinity (−9.1 kcal/mol) with the AP-1 protein. The root means square deviation (RMSD), root mean square fraction (RMSF), and radius of gyration (RoG) for 150 ns were calculated using molecular dynamic simulation (MD simulation) based on rutin’s greatest binding energy with TLR-4. The RMSD, RMSF, and RoG were all within acceptable limits in the MD simulation, and the complex remained stable for 150 ns. Furthermore, these compounds were assessed for the potential toxic effect on various organs such as the liver, heart, genotoxicity, and oral maximum toxic dose. Moreover, the blood–brain barrier permeability and intestinal absorption were also predicted using SwissADME software (Lausanne, Switzerland). These compounds exhibited promising physico-chemical as well as drug-likeness properties. Consequently, these selected compounds portray promising anti-inflammatory and drug-likeness properties.     

In Silico Comparative Exploration of Allergens of Periplaneta americana,Blattella germanica and Phoenix dactylifera for the Diagnosis of Patients Suffering from IgE-Mediated Allergic Respiratory Diseases

The burden of allergic illnesses is continuously rising, and patient diagnosis is a significant problem because of how intricately hereditary and environmental variables interact. The past three to four decades have seen an outbreak of allergies in high-income countries. According to reports on the illness, asthma affects around 300 million individuals worldwide. Identifying clinically important allergens for the accurate classification of IgE-mediated allergy respiratory disease diagnosis would be beneficial for implementing standardized allergen-associated therapy. Therefore, the current study includes an in silico analysis to identify potential IgE-mediated allergens in date palms and cockroaches. Such an immunoinformatic approach aids the prioritization of allergens with probable involvement in IgE-mediated allergic respiratory diseases. Immunoglobulin E (IgE) was used for molecular dynamic simulations, antigen–antibody docking analyses, epitope identifications, and characterizations. The potential of these allergens (Per a7, Per a 1.0102, and Bla g 1.0101) in IgE-mediated allergic respiratory diseases was explored through the evaluation of physicochemical characteristics, interaction observations, docking, and molecular dynamics simulations for drug and vaccine development.     

Trans‐ and cis‐ Cobalt(III), Iron(III), and Chromium(III) Complexes Based on α‐ and γ‐Diimine Schiff Base Ligands: Synthesis and Evaluation of the Complexes as Catalysts for Oxidation of L‐Cysteine

The synthesis of a new series of trans and racemic cis isomers of cobalt(III)‐, iron(III)‐, and chromium(III)‐based complexes with the α‐ and γ‐diimine Schiff base ligands, N,N′‐bis(X)‐2,3‐butandiimine and N,N′‐bis(X)‐1,2‐phenyldiimine (X = cyclohexyl, 2‐isopropylphenyl, 1‐naphthyl) is described. To confirm the identity of the complexes prepared in the present study, a variety of techniques including elemental analysis, magnetic susceptibility, infrared‐, mass‐ (EI), and UV/Vis‐ spectroscopy have been utilized. Some of the isolated complexes have been evaluated as catalysts for the oxidation of L‐cysteine. Preliminary results showed that the metal atoms, geometry of the complexes, auxiliary substituents, and the backbone of the ligand influenced the rate of oxidation reaction.     

Synthesis,characterization of V2O5 nanoparticles and determination of catalase mimetic activity by new colorimetric method

Journal of Thermal Analysis and Calorimetry - This paper deals with an advanced colorimetric method used to determine the catalase mimetic activity of V2O5 nanoparticles by measuring the decrease...     

Developing imprinted polymer nanoparticles for the selective separation of antidiabetic drugs

In this study, new molecularly imprinted polymer (MIP) nanoparticles are designed for selective recognition of different drugs used for the treatment of type 2 diabetes mellitus, i.e. sitagliptin (SG) and metformin (MF). The SG‐ and MF‐imprinted polymer nanoparticles are synthesized by free‐radical initiated polymerization of the functional monomers: methacrylic acid and methyl methacrylate; and the crosslinker: ethylene glycol dimethacrylate. The surface morphology of resultant MIP nanoparticles is studied by atomic force microscopy. Fourier transform infrared spectra of MIP nanoparticles suggest the presence of reversible, non‐covalent interactions between the template and the polymer. The effect of pH on the rebinding of antidiabetic drugs with SG‐ and MF‐imprinted polymers is investigated to determine the optimal experimental conditions. The molecular recognition characteristics of SG‐ and MF‐imprinted polymers for the respective drug targets are determined at low concentrations of SG (50–150 ppm) and MF (5–100 ppm). In both cases, the MIP nanoparticles exhibit higher binding response compared to non‐imprinted polymers. Furthermore, the MIPs demonstrate high selectivity with four fold higher responses toward imprinted drugs targets, respectively. Recycled MIP nanoparticles retain 90% of their drug‐binding efficiency, which makes them suitable for successive analyses with significantly preserved recognition features.     

Discrete lattice simulation of transient motions in elastic and viscoelastic composites

Discrete viscous lattices are studied in order to mathematically simulate the propagation of general disturbances in semi-infinite, elastic and viscoelastic periodic composites. Integral transform techniques are employed to derive exact and approximate solutions for the cases in which viscosity is introduced to the elastic lattice by adding dash pots in both series and parallel with the springs connecting adjacent particles. Solutions for the continuum models (for vanishing lattice spacings) are also derived either directly or as special cases. It is demonstrated that the effect of the periodic discretization in these systems induces oscillation about the continuum solutions. Comparison of the exact and approximate results shows excellent correlation, particularly near the wave front.     

Magnetic Field Effects on Spacetime Around?a?Magnetized Spherical Star

We investigate the effects of magnetic field on the background spacetime of a spherically symmetric relativistic star. Using the general relativistic Maxwell equations coupled to the Einstein field equations for the gravitational field, it is shown that not only the backreaction of the spacetime modifies the magnetic field of the star, but also the magnetic field of the star molds the spacetime in its vicinity. The part played by the poloidal as well as the toroidal components of the magnetic field on the exterior spacetime are investigated.