Specific S100 Proteins Bind Tumor Necrosis Factor and Inhibit Its Activity

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here, we report that among eighteen representatives of the multifunctional S100 protein family, only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (K_d) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The apparent K_d values for the complexes of multimeric sTNF with S100A11/A12 estimated from fluorimetric titrations are 0.1–0.3 µM. S100A12/A13 suppress the cytotoxic activity of sTNF against Huh-7 cells, as evidenced by the MTT assay. Structural modeling indicates that the sTNF-S100 interactions may interfere with the sTNF recognition by the therapeutic anti-TNFs. Bioinformatics analysis reveals dysregulation of TNF and S100A11/A12/A13 in numerous disorders. Overall, we have shown a novel potential regulatory role of the extracellular forms of specific S100 proteins that may affect the efficacy of anti-TNF treatment in various diseases.     

Interfacial interactions and properties of filled polymers. II: Dispersion of filler particles

The specific interaction characteristics and the inherent agglomeration of variously surface coated rutile pigments have been assessed, respectively, by inverse gas chromatographic and powder rheological methods. Standardized methods were used to disperse the pigments in polyethylene and chlorinated polyethylene. Measurements were made of energy requirements for dispersion and of the quality of dispersion attained. It was found that in the non-polar polyethylene matrix, dispersion processes depended on the strength of pigment agglomerates, but not on the specific interaction potential of the solids. Conversely, in the acidic chlorinated polyethylene, acid/base interactions influenced dispersion but the process was independent of inherent pigment agglomeration.     

Time-dependent response of aramid-epoxy-aluminum sheet,ARALL, laminates

Selected results of an ongoing investigation aimed at characterizing the timedependent response of an aramid-epoxy-aluminum sheet laminate and its constitutents at 121°C are outlined in this paper. This laminate is a recently developed hybrid composite developed by the Aluminum Company of America, marketed under the ARALL-4 tradename. The paper addresses the time-dependent response of the above hybrid composite under creep loading. It is illustrated that ARALL-4 laminates may exhibit substantial creep effects at stress levels below the proportional limit. The creep response is a nonlinear function of time and the applied stress level and is primarily due to the creep characteristics of the aluminum layers. An analytical model based on the assumptions of the classical lamination theory developed to model the time-dependent response of these laminates under creep and thermal loading is shown to yield good correlation with the experimental data. It is also illustrated that the residual state of stress can influence the extent of creep. This offers the possibility of minimizing the creep effects by altering the state of residual stress with mechanical prestraining.     

The modelling of networks with frequently changing topology whilst maintaining a constant system matrix

This paper describes a novel technique with which a system with changing topology can be modelled whilst maintaining a constant system matrix. This technique employs a new transmission-line switch model which has a constant characteristic impedance, irrespective of its state. The method is explained, compared with the switched-resistance method and demonstrated by two examples. It has been found that the proposed method offers substantial advantages in the formulation of the problems and in the efficiency of computation.     

Preparation,Characterisation, and Rheological Behaviour of Starch-Sodium Trimetaphosphate Hydrogels

Ionic biopolymer hydrogels were prepared by the cross-linking of starches with sodium trimetaphosphate in alkaline medium at 40°C for 2 hours. The swelling capacity is relatively high — up to 310 g H₂0/g polymer. Salt solutions have a marked influence, and result in shrinkage but not in a total collapse. The effect of both the cross-linker and substrate concentrations on the swelling and rheological properties was investigated. The influence of temperature and NaOH concentration on the rheological behaviour suggests that they are both significant in determining the gel properties because of the readiness of the diester phosphate bonds to undergo hydrolysis. The molecular weight between two entanglement points (M_e) and the effectiveness of cross-linking [n_e(r)/n_e(t)] were estimated from the observed G_p′ values, and those calculated from complete conversion of the cross-linker. The effectiveness of cross-linking lay between 0.2 and 2.74% for 10% wlw gels, and reached a maximum of 48.1% at the higher substrate concentration of 20% wlw. ¹³C-NMR signals from the anhydroglucose units became broader and decreased in intensity with rising cross-linker concentration due to the restricted motion arising from the additional bonding.     

4-Acetylantroquinonol B Suppresses Prostate Cancer Growth and Angiogenesis via a VEGF/PI3K/ERK/mTOR-Dependent Signaling Pathway in Subcutaneous Xenograft and In Vivo Angiogenesis Models

Prostate cancer is a major cause of cancer-related mortality in men in developed countries. The compound, 4-acetylantroquinonol B (4AAQB), is isolated from Antrodia cinnamomea (commonly known as Niu-Chang-Chih), which has been shown to inhibit cancer growth. However, the anticancer activity of 4AAQB has not previously been examined in prostate cancer. This study aimed to investigate the effect of 4AAQB on cancer and angiogenesis, as well as to explore its mechanism of action. Human prostate cancer cells (PC3) and human umbilical vein endothelial cells (HUVEC) were used in cell viability, cell migration, and cell cycle functional assays to evaluate the anticancer and antiangiogenic efficacy of 4AAQB in vitro. The effects of 4AAQB in vivo were determined using xenograft and angiogenesis models. The signaling events downstream of 4AAQB were also examined. The 4AAQB compound inhibited PC3 cell growth and migration, and reduced in vivo cancer growth, as shown in a subcutaneous xenograft model. Furthermore, 4AAQB inhibited HUVEC migration, tube formation, and aortic ring sprouting; it also reduced neovascularization in a Matrigel implant angiogenesis assay in vivo. The 4AAQB compound also decreased metastasis in the PC3 prostate cancer model in vivo. Serum or vascular endothelial growth factor (VEGF)-induced VEGF receptor 2 (VEGFR2), phosphoinositide 3-kinase (PI3K)/Ak strain transforming (Akt), and extracellular signal-regulated kinase ½ (ERK ½) phosphorylation were attenuated by 4AAQB in both PC3 and HUVEC. In conclusion, 4AAQB is a potential candidate for prostate cancer therapy.