Chemokine Receptor 5 Antagonism Causes Reduction in Joint Inflammation in a Collagen-Induced Arthritis Mouse Model

Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly affecting the synovial joints. A highly potent antagonist of C-C chemokine receptor 5 (CCR5), maraviroc (MVC), plays an essential role in treating several infectious diseases but has not yet been evaluated for its potential effects on RA development. This study focused on evaluating the therapeutic potential of MVC on collagen-induced arthritis (CIA) in DBA/1J mice. Following CIA induction, animals were treated intraperitoneally with MVC (50 mg/kg) daily from day 21 until day 35 and evaluated for clinical score and histopathological changes in arthritic inflammation. We further investigated the effect of MVC on Th9 (IL-9, IRF-4, and GATA3) and Th17 (IL-21R, IL-17A, and RORγT) cells, TNF-α, and RANTES in CD8+ T cells in the spleen using flow cytometry. We also assessed the effect of MVC on mRNA and protein levels of IL-9, IL-17A, RORγT, and GATA3 in knee tissues using RT-PCR and western blot analysis. MVC treatment in CIA mice attenuated the clinical and histological severity of inflammatory arthritis, and it substantially decreased IL-9, IRF4, IL-21R, IL-17A, RORγT, TNF-α, and RANTES production but increased GATA3 production in CD8+ T cells. We further observed that MVC treatment decreased IL-9, IL-17A, and RORγt mRNA and protein levels and increased those of GATA3. This study elucidates the capacity of MVC to ameliorate the clinical and histological signs of CIA by reducing pro-inflammatory responses, suggesting that MVC may have novel therapeutic uses in the treatment of RA.     

Lagrangian PTV in 3D flows

Particle Tracking Velocimetry (PTV) is one of the evolving techniques which can cover the increasing need for measurements in a Lagrangian frame. Here some recent developments and the validation of the tracking scheme on the Kinematic Simulation Inertial Model (KSIM) test flow field is presented.     

Synthesis,Crystal Structure and Spectroscopic Properties of 1,2-Benzothiazine Derivatives:An Experimental and DFT Study

1,2-Benzothiazine derivatives methyl 3-methoxy-4-oxo-3,4-dihydro-2H-benzo[e] [1,2]thiazine-3-carboxylate 1,1-dioxide(1) and methyl 2-ethyl-3-hydroxy-4-oxo-3,4-dihydro-2Hbenzo[e][1,2]thiazine-3-carboxylate 1,1-dioxide(2) were synthesized, and characterized by spectroscopic techniques; 1H-NMR and infrared(IR) spectroscopy. Crystals of 1 and 2 were grown by slow evaporation of methanol and ethyl acetate, respectively and their crystal structures were investigated by single-crystal X-ray diffraction analysis. Geometric properties were calculated by the B3 LYP method of density functional theory(DFT) at the 6-31G+(d) basis set to compare with the experimental data. Simulated properties were found in strong agreement with the experimental ones. Intermolecular forces have also been modeled in order to investigate the strength of packing and strong hydrogen bonding was observed in both compounds 1 and 2. Electronic properties such as Ionization Potential(IP), Electron Affinities(EA) and coefficients of the highest occupied molecular orbital(HOMO) and the lowest unoccupied molecular orbital(LUMO) of com- pounds 1 and 2 were simulated for the first time.     

Divergent Strain-Release Amino-Functionalization of [1.1.1]Propellane with Electrophilic Nitrogen-Radicals

Herein we report the development of a photocatalytic strategy for the divergent preparation of functionalized bicyclo[1.1.1]pentylamines. This approach exploits, for the first time, the ability of nitrogen-radicals to undergo strain-release reaction with [1.1.1]propellane. This reactivity is facilitated by the electrophilic nature of these open-shell intermediates and the presence of strong polar effects in the transition-state for C−N bond formation/ring-opening. With the aid of a simple reductive quenching photoredox cycle, we have successfully harnessed this novel radical strain-release amination as part of a multicomponent cascade compatible with several external trapping agents. Overall, this radical strategy enables the rapid construction of novel amino-functionalized building blocks with potential application in medicinal chemistry programs as p-substituted aniline bioisosteres.     

Generalized Jordan derivations on Lie ideals associate with Hochschild 2-cocycles of rings

Let R be a 2-torsion free ring and L be a Lie ideal of R. In this paper we initiate the study of generalized derivations on Lie ideals associate with Hochschild 2-cocycles and prove that every generalized derivation associate with a Hochschild 2-cocycle on L is a generalized derivation on L under certain conditions.     

Arbutin derivatives from the seeds of Madhuca latifolia

A new arbutin derivative, madhuglucoside (1), along with three known arbutin derivatives were isolated from the seeds of Madhuca latifolia in addition to seven other known constituents. Their structures were established on the basis of spectral analysis. Compounds 1a, 2a and 3a were obtained in a pure state after acetylation of the mother fraction and characterized as their acetyl derivatives.     

Simulation of peristaltic flow of chyme in small intestine for couple stress fluid

In this article couple stress fluid have been considered for the peristaltic flow of chyme in intestine. Problem under consideration have been formulated assuming that two non-periodic sinusoidal wave of different wavelength propagate with same speed c along the outer wall of the tube. Governing equations have been simplified under the assumptions of long wavelength and low Reynolds number approximation (such assumption are consistent that Re (Reynold number) is very small and long wavelength approximation also exists in the small intestine). Exact solutions have been evaluated for velocity and pressure rise. Physical behaviour of different parameter of couple stress fluid have been presented graphically for velocity, pressure rise, pressure gradient and frictional forces. The stream lines are also made against different parameters.