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The primary goal of this research is to study the Cattaneo-Christov heat flux model on the impacts of mass and energy transit of MHD Casson-Carreu nanofluid through a permeable vertical accelerating plate with Soret and Dufour mechanism. The non-Newtonian fluids flowed over the porous vertical plate to reach the boundary layer in this investigation. In order to understand the physical model, partial differential equations (PDEs) are used. To get a linked nonlinear set of ordinary differential equations (ODEs), we reduced this set of PDEs by using similarity variables. SHAM, a spectrum basis technique, was utilized to solve these modified equations to understand the physical significance. A good method is to utilize SHAM to decouple the coupled nonlinear ODE systems and divide them into linear and nonlinear equation sets since this helps to separate the systems. As a result, the two non-Newtonian fluids (Carreu and Cassin) flow together through the vertical wall and into the boundary layer, where different parameters’ impacts are scrutinized. The current results showed that an upturn in the Casson parameter (β) degenerates the boundary layer velocity and the total thickness. Upturn in the Weissenberg number (We) on the other hand, raises the velocities and temperatures in both directions. Additionally, increasing the Soret and Dufour parameters sped up the velocity graph.

Objective— Oxidative stress contributes to the pathogenesis of many diseases, including atherosclerosis and sepsis. We have previously described a novel class of therapeutic compounds with antioxidant and antiinflammatory properties. However, at present, the intracellular targets of these compounds have not been identified. The purpose of this study was to elucidate the mechanism by which 2 structurally-related antioxidants (AGI-1067 and AGI-1095) inhibit LPS induction of tissue factor (TF) expression in human monocytic cells and endothelial cells. Methods and Results— We found that succinobucol (AGI-1067) and AGI-1095 inhibited LPS induction of TF expression in both monocytic cells and endothelial cells. These compounds also reduced LPS induction of nuclear AP-1 and expression of Egr-1 without affecting nuclear translocation of NF-κB. Importantly, these antioxidants inhibited LPS activation of the redox-sensitive kinase, apoptosis signal-regulating kinase-1 (ASK1) and the mitogen-activated protein kinases (MAPKs) p38, ERK1/2, and JNK1/2. Conclusions— AGI-1067 and AGI-1095 inhibit TF gene expression in both monocytic cells and endothelial cells through a mechanism that involves the inhibition of the redox-sensitive MAP3K, ASK1. These compounds selectively reduce the activation/induction of MAPK, AP-1, and Egr-1 without affecting NF-κB nuclear translocation.

We examined induced expression of the 5-lipoxygenase-activating protein (FLAP), which is critical for leukotriene synthesis in mononuclear phagocytes. Prolonged exposure to the bacterial component, lipopolysaccharide (LPS), increased FLAP gene transcription, mRNA expression, and protein expression in the human monocyte-like THP-1 cell line. Activation and inhibition of the NF-kappaB pathway modulated LPS induction of FLAP gene expression. An NF-kappaB-mediated mechanism of action was supported by overexpression of dominant-negative IkappaBalpha and p50/p65 proteins. EMSA/supershift and DNase I footprint analyses revealed that p50 binds to an NF-kappaB site located in the proximal FLAP promoter, while chromatin immunoprecipitation assays demonstrated that LPS induced binding of p50 but not of p65. Moreover, EMSA/supershift analyses demonstrated that LPS induced time-dependent binding of THP-1 nuclear extracts (containing p50) to this promoter region. Mutation of the NF-kappaB site decreased basal promoter activity and abolished the p50- and p65-associated induction. EMSA/supershift analyses also demonstrated that LPS induced binding of THP-1 nuclear extracts [containing CCAAT/enhancer binding protein (C/EBP)-alpha, -delta, and -epsilon] to a C/EBP site located adjacent to the NF-kappaB site in the FLAP promoter. We conclude that LPS enhances FLAP gene expression via both NF-kappaB- and C/EBP-mediated transcriptional mechanisms in mononuclear phagocytes.

Glucocorticoids, such as dexametha- sone (Dex), are used clinically in the treatment of various inflammatory diseases. Dex acts by inhib- iting the expression of inflammatory mediators, such as tumor necrosis factor (TNF-) and monocyte chemoattractant protein-1 (MCP-1). It is surprising that Dex enhances bacterial lipopoly- saccharide (LPS) induction of tissue factor (TF) expression in human monocytic cells. TF is a trans- membrane glycoprotein that activates the coagula- tion protease cascade. In this study, we analyze the mechanism by which Dex enhances LPS-induced TF expression in human monocytic cells. We found that Dex reduced LPS-induced TF gene transcrip- tion but increased the stability of TF mRNA. Dex decreased the stability of MCP-1 mRNA and did not affect TNF- mRNA stability. Finally, we showed that Dex increased the stability of a tran- script consisting of the final 297 nucleotides of the TF mRNA in in vitro decay assays. This region contains AU-rich elements that regulate mRNA sta- bility and may mediate the Dex response. There- fore, despite an inhibition of TF gene transcrip- tion, Dex enhances TF expression in human mono- cytic cells by increasing the stability of TF mRNA. J. Leukoc. Biol. 76: 145-151; 2004.

We examined expression of the 5-lipoxygenase activating protein (FLAP), which is critical for inflammatory cell leukotriene synthesis. A 3.4-kb segment of the FLAP gene 5'-untranslated region accounted for a 22-fold increase in promoter activity when transfected into the monocyte-like cell line, THP-1, and demonstrated no activity in non-inflammatory cells. Virtually all of the promoter activity was mediated by the first 134 bp upstream of the transcription start site, a region that contains CCAAT/enhancer-binding proteins (C/EBP) consensus binding sites, at -36 to -28 bp (distal) and -25 to -12 bp (proximal). DNase I footprint analyses demonstrated THP-1 nuclear extract proteins bind to the proximal site. Electrophoretic mobility shift assay analyses revealed that C/EBP alpha, delta, and epsilon bind to the proximal site and C/EBP alpha and epsilon bind to the distal site, constitutively. Transfection studies indicated that mutation of both the proximal and distal sites decreased constitutive FLAP promoter activity. Overexpression of C/EBP alpha, beta, and delta transactivated promoter activity and increased native FLAP mRNA accumulation. Mutation of both C/EBP sites essentially abolished promoter induction by C/EBP overexpression. Tumor necrosis factor (TNF) alpha induced FLAP mRNA expression, FLAP promoter activity, and C/EBP alpha, delta, and epsilon binding to the proximal and distal promoter consensus sites. Chromatin immunoprecipitation assays demonstrated that C/EBP alpha, delta, and epsilon bound to this region of the 5'-untranslated region, whereas C/EBP beta does not bind even under conditions of overexpression and stimulation. We conclude that the FLAP gene is transactivated by members of the C/EBP family of transcription factors in inflammatory cells and that these factors play an important role in FLAP gene induction by TNFalpha.

We examined expression of the 5-lipoxygenase activating protein (FLAP), which is critical for inflammatory cell leukotriene synthesis. A 3.4-kb segment of the FLAP gene 5'-untranslated region accounted for a 22-fold increase in promoter activity when transfected into the monocyte-like cell line, THP-1, and demonstrated no activity in non-inflammatory cells. Virtually all of the promoter activity was mediated by the first 134 bp upstream of the transcription start site, a region that contains CCAAT/enhancer-binding proteins (C/EBP) consensus binding sites, at -36 to -28 bp (distal) and -25 to -12 bp (proximal). DNase I footprint analyses demonstrated THP-1 nuclear extract proteins bind to the proximal site. Electrophoretic mobility shift assay analyses revealed that C/EBP alpha, delta, and epsilon bind to the proximal site and C/EBP alpha and epsilon bind to the distal site, constitutively. Transfection studies indicated that mutation of both the proximal and distal sites decreased constitutive FLAP promoter activity. Overexpression of C/EBP alpha, beta, and delta transactivated promoter activity and increased native FLAP mRNA accumulation. Mutation of both C/EBP sites essentially abolished promoter induction by C/EBP overexpression. Tumor necrosis factor (TNF) alpha induced FLAP mRNA expression, FLAP promoter activity, and C/EBP alpha, delta, and epsilon binding to the proximal and distal promoter consensus sites. Chromatin immunoprecipitation assays demonstrated that C/EBP alpha, delta, and epsilon bound to this region of the 5'-untranslated region, whereas C/EBP beta does not bind even under conditions of overexpression and stimulation. We conclude that the FLAP gene is transactivated by members of the C/EBP family of transcription factors in inflammatory cells and that these factors play an important role in FLAP gene induction by TNFalpha.

Leukotrienes formed by the action of 5-lipoxygenase on arachidonic acid are a group of endogenous compounds active in hypersensitivity reactions and inflammation. In this report the formation of LTB4 from LTA4 was measured by incubating lung microsomes from normal and exercised rats to determine whether LTB4 may have a role in the mediation of exercise-induced oxidant stress. Exhaustive exercise in the form of swimming results in the enhanced production of LTB4 in lung microsomes. Further, free radicals measured by ESR spectroscopy were also significantly increased in lung tissue from exercised rats. These results suggest a role for LTB4 in the mediation of lung tissue damage during exercise-induced oxidative stress.

The synthesis and characterisation of ruthenium(II) complexes with 2-amidobenzimidazoles are reported. The complexes RuCl2(DMSO)4 and RuCl2(PPh3) react with 2-(acetamido)benzimidazole (AB) and 2-(benzamido)benzimidazole (BB) it acetone to give products of the type [Ru(L)2(N−O)2]Cl2 [L=DMSO, PPh3, N−O=AB, BB). The displacement reactions are faster in the case of methyl (AB) than phenyl (BB) substituted ligands. The ligands are bifunctional chelating agents coordinating through the tertiary nitrogen of benzimidazole ring and amide oxygen. The complexes are characterised based on their elemental analysis, conductivity data, infrared,1H and31P nmr spectra. Acis-geometry is proposed for all the complexes reported.