Intrinsic atomic-level forces in polymer networks exhibiting non-gaussian effects: relationship with the limited chain extensibility

Intrinsic atomic-level forces for networks exhibiting non-Gaussian effects were evaluated during the integration of the equations of motion using the Verlet algorithm. The forces acting on the junction points of the cross-linking chains and the elastomeric chains of unimodal and bimodal network arrangements showed no apparent change as a consequence of the network variation. The forces acting on the short chains in a bimodal network cross-linked using sulfur atoms and relatively long polyquinone chains had much higher values than those in a unimodal network arrangement. Nevertheless, the intrinsic forces acting on the polyquinone atoms decreased dramatically as a result of the formation of bimodal networks. The presence of relatively long polyquinone chains in bimodal networks caused the short sulfur chains to stretch to their maximum extensibility and they can no longer increase their end-to-end separation by simple rotations about their skeletal bonds. Limited chain extensibility of the short chains resulting from the deformation of the bond angles and bond lengths led to much higher potential energies, as determined using the dynamic quenching technique. This resulted in the non-Gaussian effects known for bimodal networks and their subsequent anomalous mechanical properties. The dynamical behavior of the nuclei bending and torsional angles was also investigated for the unimodal and bimodal networks.     

Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect

A new series of quinoline derivatives of combretastatin A-4 have been designed, synthesised and demonstrated as tubulin polymerisation inhibitors. These novel compounds showed significant antiproliferative activities, among them, 12c exhibited the most potent inhibitory activity against different cancer cell lines (MCF-7, HL-60, HCT-116 and HeLa) with IC₅₀ ranging from 0.010 to 0.042 µM, and with selectivity profile against MCF-10A non-cancer cells. Further mechanistic studies suggest that 12c can inhibit tubulin polymerisation and cell migration, leading to G₂/M phase arrest. Besides, 12c induces apoptosis via a mitochondrial-dependant apoptosis pathway and caused reactive oxygen stress generation in MCF-7 cells. These results provide guidance for further rational development of potent tubulin polymerisation inhibitors for the treatment of cancer.

Highlights

• A novel series of quinoline derivatives of combretastatin A-4 have been designed and synthesised.
• Compound 12c showed significant antiproliferative activities against different cancer cell lines.
• Compound 12c effectively inhibited tubulin polymerisation and competed with [³H] colchicine in binding to tubulin.
• Compound 12c arrested the cell cycle at G₂/M phase, effectively inducing apoptosis and inhibition of cell migration.

     

Interferon-β Is a Potent Promoter of Nerve Growth Factor Production by Astrocytes

Abstract: Recent clinical evidence has suggested that interferon-β is efficacious in the treatment of the demyelinating disease, multiple sclerosis. The mechanism of its efficacy remains unclear, and suggested modes of action have focused on immune modulation. Nonimmune effects of interferon-β may also contribute to its efficacy. Given that astrocytes produce a range of neurotrophic factors, we examined the possibility that interferon-β could increase the astrocytic production of nerve growth factor (NGF), which has been reported to cause oligodendrocytes to proliferate and to extend their processes; these phenotypes can impact favorably on remyelination. When the recombinant form of mouse interferon-β was added to mouse astrocyte cultures, a dose-dependent increase in NGF mRNA was obtained. The 40-fold increase in NGF mRNA elicited by 1,000 U/ml interferon-β was far more potent than that produced by other NGF-elevating agents in this study. In concordance, the protein for NGF was elevated by interferon-β. The production of NGF by interferon-β may be relevant to its clinical efficacy in multiple sclerosis. Furthermore, we suggest the potential utility of interferon-β in Alzheimer's disease.     

Amylin,Food Intake,and Obesity

Amylin, also known as islet amyloid polypeptide, identified in 1987, is a naturally occurring hormone, released by the β cells of the pancreas and consists of 37 amino acids. Amylin seems to decrease food intake through both central and peripheral mechanisms and indirectly by slowing gastric emptying. The mean basal amylin concentration is higher in obese than in lean human subjects. The amylin response to oral glucose is also greater in obese subjects, whether or not they have impaired glucose tolerance. The elevated amylin levels in obesity may lead to down-regulation of amylin receptors and lessen the impact of postprandial amylin secretion on satiety and gastric emptying. Amylin administration may overcome resistance at target tissues, delay gastric emptying, and have potential for inducing weight loss in obese individuals.     

Contamination level and risk assessment of heavy metal deposited in street dusts in Khamees-Mushait city,Saudi Arabia

Abstract

The levels of some potentially toxic metals (Cr, Mn, Fe, Co, Cu, Zn, Cd, and Pb) were quantified in 60 street dust samples from Khamees-Mushait city, Saudi Arabia. Samples were taken from three locations at each functional area (total 18 including traffic, industrial, residential, and workshops) and at each control area (total two including a park and a new domestic planner). Heavy metals concentrations were quantified in less than 106 µm particle-size using inductively-coupled plasma-optical emission spectrometer after microwave wet digestion. The total concentrations (µg/g) were in the ranges of Cr 128.48–277.53, Mn 589.43–1091.45, Fe 43478.26–99151.63, Co 23.04–55.22, Cu 10.46–176.13, Cd 0.30–1.99, and Pb 9.36–340.56. The accuracy of results was examined using standard quality control samples, spiking, and a certified reference material. The overall recovery was in the range of 86.2–113.3%. The enrichment factors and the geoaccumulation indices, besides principal component analysis, reveal various levels of enrichment by Fe, Cu, Zn, and Pb from functional areas of congested traffic, commercial activities, and metallic workshops activities. In contrast, no significant enrichment by Cr, Mn, and Co was recorded. The cluster analysis revealed that the metallic workshops and the vehicle scrap workshops are the hottest functional areas.