Organofluorine Hydrazone Derivatives as Multifunctional Anti-Alzheimer's Agents with CK2 Inhibitory and Antioxidant Features

A set of novel hydrazone derivatives were synthesized and analyzed for their biological activities. The compounds were tested for their inhibitory effect on the phosphorylating activity of the protein kinase CK2, and their antioxidant activity was also determined in three commonly used assays. The hydrazones were evaluated for their radical scavenging against the DPPH, ABTS and peroxyl radicals. Several compounds have been identified as good antioxidants as well as potent protein kinase CK2 inhibitors. Most hydrazones containing a 4-N(CH₃)₂ residue or perfluorinated phenyl rings showed high activity in the radical-scavenging assays and possess nanomolar IC₅₀ values in the kinase assays.     

A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion

Direct allorecognition is the earliest and most potent immune response against a kidney allograft. Currently, it is thought that passenger donor professional antigen-presenting cells (APCs) are responsible. Further, many studies support that graft ischemia-reperfusion injury increases the probability of acute rejection. We evaluated the possible role of primary human proximal renal tubular epithelial cells (RPTECs) in direct allorecognition by CD4+ T-cells and the effect of anoxia-reoxygenation. In cell culture, we detected that RPTECs express all the required molecules for CD4+ T-cell activation (HLA-DR, CD80, and ICAM-1). Anoxia-reoxygenation decreased HLA-DR and CD80 but increased ICAM-1. Following this, RPTECs were co-cultured with alloreactive CD4+ T-cells. In T-cells, zeta chain phosphorylation and c-Myc increased, indicating activation of T-cell receptor and co-stimulation signal transduction pathways, respectively. T-cell proliferation assessed with bromodeoxyuridine assay and with the marker Ki-67 increased. Previous culture of RPTECs under anoxia raised all the above parameters in T-cells. FOXP3 remained unaffected in all cases, signifying that proliferating T-cells were not differentiated towards a regulatory phenotype. Our results support that direct allorecognition may be mediated by RPTECs even in the absence of donor-derived professional APCs. Also, ischemia-reperfusion injury of the graft may enhance the above capacity of RPTECs, increasing the possibility of acute rejection.     

Optimization of flow in additively manufactured porous columns with graded permeability

Chemical engineering systems often involve a functional porous medium, such as in catalyzed reactive flows, fluid purifiers, and chromatographic separations. Ideally, the flow rates throughout the porous medium are uniform, and all portions of the medium contribute efficiently to its function. The permeability is a property of a porous medium that depends on pore geometry and relates flow rate to pressure drop. Additive manufacturing techniques raise the possibilities that permeability can be arbitrarily specified in three dimensions, and that a broader range of permeabilities can be achieved than by traditional manufacturing methods. Using numerical optimization methods, we show that designs with spatially varying permeability can achieve greater flow uniformity than designs with uniform permeability. We consider geometries involving hemispherical regions that distribute flow, as in many glass chromatography columns. By several measures, significant improvements in flow uniformity can be obtained by modifying permeability only near the inlet and outlet.     

Role of Endocrine-Disrupting Chemicals in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: A Comprehensive Review

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder, affecting around 25% of the population worldwide. It is a complex disease spectrum, closely linked with other conditions such as obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, which may increase liver-related mortality. In light of this, numerous efforts have been carried out in recent years in order to clarify its pathogenesis and create new prevention strategies. Currently, the essential role of environmental pollutants in NAFLD development is recognized. Particularly, endocrine-disrupting chemicals (EDCs) have a notable influence. EDCs can be classified as natural (phytoestrogens, genistein, and coumestrol) or synthetic, and the latter ones can be further subdivided into industrial (dioxins, polychlorinated biphenyls, and alkylphenols), agricultural (pesticides, insecticides, herbicides, and fungicides), residential (phthalates, polybrominated biphenyls, and bisphenol A), and pharmaceutical (parabens). Several experimental models have proposed a mechanism involving this group of substances with the disruption of hepatic metabolism, which promotes NAFLD. These include an imbalance between lipid influx/efflux in the liver, mitochondrial dysfunction, liver inflammation, and epigenetic reprogramming. It can be concluded that exposure to EDCs might play a crucial role in NAFLD initiation and evolution. However, further investigations supporting these effects in humans are required.     

Botulinum Toxin: From Poison to Possible Treatment for Spasticity in Spinal Cord Injury

Botulism has been known for about three centuries, and since its discovery, botulinum toxin has been considered one of the most powerful toxins. However, throughout the 20th century, several medical applications have been discovered, among which the treatment of spasticity stands out. Botulinum toxin is the only pharmacological treatment recommended for spasticity of strokes and cerebral palsy. Although its use as an adjuvant treatment against spasticity in spinal cord injuries is not even approved, botulinum toxin is being used against such injuries. This article describes the advances that have been made throughout history leading to the therapeutic use of botulinum toxin and, in particular, its application to the treatment of spasticity in spinal cord injury.     

Hall current effects on MHD flow of chemically reacting fluid through a porous medium with heat source

We considered the magnetohydrodynamic (MHD) free convective flow of an incompressible electrically conducting viscous fluid past an infinite vertical permeable porous plate with a uniform transverse magnetic field, heat source and chemical reaction in a rotating frame taking Hall current effects into account. The momentum equations for the fluid flow during absorbent medium are controlled by the Brinkman model. Through the undisturbed state, both the plate and fluid are in a rigid body rotation by the uniform angular velocity perpendicular to an infinite vertical plate. The perpendicular surface is subject to the homogeneous invariable suction at a right angle to it and the heat on the surface varies about a non-zero unvarying average whereas the warmth of complimentary flow is invariable. The systematic solutions of the velocity, temperature, and concentration distributions are acquired systematically by utilizing the perturbation method. The velocity expressions consist of steady-state and fluctuating situations. It is revealed that the steady part of the velocity field has a three-layer characteristic while the oscillatory part of the fluid field exhibits a multi-layer characteristic. The influence of various governing flow parameters on the velocity, temperature, and concentration are analyzed graphically. We also discuss computational results for the skin friction, Nusselt number, and Sherwood number in the tabular forms.