Anti-Inflammatory Effects of Auranamide and Patriscabratine—Mechanisms and In Silico Studies

Auranamide and patriscabratine are amides from Melastoma malabathricum (L.) Smith. Their anti-inflammatory activity and nuclear factor erythroid 2-related factor 2 (NRF2) activation ability were evaluated using Escherichia coli lipopolysaccharide (LPSEc)-stimulated murine macrophages (RAW264.7) and murine hepatoma (Hepa-1c1c7) cells, respectively. The cytotoxicity of the compounds was assessed using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The anti-inflammatory activity was determined by measuring the nitric oxide (NO) production and pro-inflammatory cytokines (Interleukin (IL)-1β, Interferon (IFN)-γ, tumour necrosis factor (TNF)-α, and IL-6) and mediators (NF-κB and COX-2). NRF2 activation was determined by measuring the nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) quinone oxidoreductase 1 (NQO1), nuclear NRF2 and hemeoxygenase (HO)-1. In vitro metabolic stability was assessed using the mouse, rat, and human liver microsomes. The compounds were non-toxic to the cells at 10 μM. Both compounds showed dose-dependent effects in downregulating NO production and pro-inflammatory cytokines and mediators. The compounds also showed upregulation of NQO1 activity and nuclear NRF2 and HO-1 levels. The compounds were metabolically stable in mouse, rat and human liver microsomes. The possible molecular targets of NRF2 activation by these two compounds were predicted using molecular docking studies and it was found that the compounds might inhibit the Kelch domain of KEAP1 and GSK-3β activity. The physicochemical and drug-like properties of the test compounds were predicted using Schrodinger small molecule drug discovery suite (v.2022-2).     

Novel and Efficient Method for the Synthesis of Racemic Fexofenadine

Fexofenadine is a selective H₁-histamine receptor antagonist, which is an attractive alternative treatment for allergy symptoms. An efficient and environmentally friendly synthetic approach for the preparation of fexofenadine was developed from commercially available cumene. The method involves the Friedel–Craft's reaction, substitution, reduction, bromination, and the Grignard reaction.

Nanostructured block-random copolymers with tunable magnetic properties

It was recently shown that block copolymers (BCPs) produced room-temperature ferromagnetic materials (RTFMs) due to their nanoscopic ordering and the cylindrical phase yielded the highest coercivity. Here, a series of metal-containing block-random copolymers composed of an alkyl-functionalized homo block (C(16)) and a random block of cobalt complex- (Co) and ferrocene-functionalized (Fe) units was synthesized via ring-opening metathesis polymerization. Taking advantage of the block-random architecture, the influence of dipolar interactions on the magnetic properties of these nanostructured BCP materials was studied by varying the molar ratio of the Co units to the Fe units, while maintaining the cylindrical phase-separated morphology. DC magnetic measurements, including magnetization versus field, zero-field-cooled, and field-cooled, as well as AC susceptibility measurements showed that the magnetic properties of the nanostructured BCP materials could be easily tuned by diluting the cobalt density with Fe units in the cylindrical domains. Decreasing the cobalt density weakened the dipolar interactions of the cobalt nanoparticles, leading to the transition from a room temperature ferromagnetic (RTF) to a superparamagnetic material. These results confirmed that dipolar interactions of the cobalt nanoparticles within the phase-separated domains were responsible for the RTF properties of the nanostructured BCP materials.     

Biochemical Characterization of Novel Bioactive Protein from Silkworm (Bombyx mori L) Fecal Matter

In this study, complete purification and biochemical characterization of protein is presented. The protein was purified by using Sephadex G-75 gel filtration column followed by reverse-phase high-performance liquid chromatography in a C18 column. The molecular weight of the protein was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, mass spectrum matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) and liquid chromatography-electrospray ionization tandem mass spectrometry. Protein was fragmented by trypsin based on the m/z values obtained by MALDI-TOF-MS analysis. The peptide fragments sequence showed homology with DEAD-box-ATP-dependent RNA helicase 45, present in a public domain, National Centre for Biotechnology Information. The protein exhibited antibacterial activity against selected Gram +/? bacteria. The analgesic activity was determined by conducting acetic-acid-induced writhing test in mice.     

A Hybrid Taguchi–Immune approach to optimize an integrated supply chain design problem with multiple shipping

Supply chain network design is considered a strategic decision level problem that provides an optimal platform for the effective and efficient supply chain management. In this research, we have mathematically modeled an integrated supply chain design. To ensure high customer service levels, we propose the inclusion of multiple shipping/transportation options and distributed customer demands with fixed lead times into the supply chain distribution framework and formulated an integer-programming model for the five-tier supply chain design problem considered. The problem has been made additionally complex by including realistic assumptions of nonlinear transportation and inventory holding costs and the presence of economies of scale. In the light of aforementioned facts, this research proposes a novel solution methodology that amalgamates the features of Taguchi technique with Artificial Immune System (AIS) for the optimum or near optimum resolution of the problem at hand. The performance of the proposed solution methodology has been benchmarked against a set of test instances and the obtained results are compared against those obtained by Genetic Algorithm (GA), Hybrid Taguchi–Genetic Algorithm (HTGA) and AIS. Simulation results indicate that the proposed approach can not only search for optimal/near optimal solutions in large search spaces but also has good repeatability and convergence characteristics, thereby proving its superiority.     

Exploring the effect of sialic acid orientation on ligand-receptor interactions

Here, we present the synthesis of two sialo-micelles to validate the significance of sialic acid orientation during specific carbohydrate-protein and carbohydrate-carbohydrate interactions. Our data clearly suggest that orientation of carboxylic acid and glycerol side chains of sialic acid moieties exert fine tuning of ligand-receptor interactions.