J Med Chem. 2009 Jun 16; Zhang L, Yan Y, Liu Z, Abliz Z, Liu GIn this paper, a peptide substrate (Pep8) of TSSK1 is identified. Using Pep8 as a substrate, two homogeneous and efficient assays for TSSK1 inhibitors screening have been developed, including luminescent kinase assay and LC-MS-based high-throughput assay. Two classes of compounds were identified that are able to efficiently inhibit phosphorylation catalyzed by TSSK1.
Cancer Res. 2009 Jun 16; Jeong CH, Bode AM, Pugliese A, Cho YY, Kim HG, Shim JH, Jeon YJ, Li H, Jiang H, Dong Z[6]-Gingerol, a natural component of ginger, exhibits anti-inflammatory and antitumorigenic activities. Despite its potential efficacy in cancer, the mechanism by which [6]-gingerol exerts its chemopreventive effects remains elusive. The leukotriene A4 hydrolase (LTA4H) protein is regarded as a relevant target for cancer therapy. Our in silico prediction using a reverse-docking approach revealed that LTA4H might be a potential target of [6]-gingerol. We supported our prediction by showing that [6]-gingerol suppresses anchorage-independent cancer cell growth by inhibiting LTA4H activity in HCT116 colorectal cancer cells. We showed that [6]-gingerol effectively suppressed tumor growth in vivo in nude mice, an effect that was mediated by inhibition of LTA4H activity. Collectively, these findings indicate a crucial role of LTA4H in cancer and also support the anticancer efficacy of [6]-gingerol targeting of LTA4H for the prevention of colorectal cancer. [Cancer Res 2009;69(13):5584-91].
Naturwissenschaften. 2009 Jun 17; Baumgartner S, Wolf M, Skrabal P, Bangerter F, Heusser P, Thurneysen A, Wolf UQuantitative meta-analyses of randomized clinical trials investigating the specific therapeutic efficacy of homeopathic remedies yielded statistically significant differences compared to placebo. Since the remedies used contained mostly only very low concentrations of pharmacologically active compounds, these effects cannot be accounted for within the framework of current pharmacology. Theories to explain clinical effects of homeopathic remedies are partially based upon changes in diluent structure. To investigate the latter, we measured for the first time high-field (600/500 MHz) (1)H T(1) and T(2) nuclear magnetic resonance relaxation times of H(2)O in homeopathic preparations with concurrent contamination control by inductively coupled plasma mass spectrometry (ICP-MS). Homeopathic preparations of quartz (10c-30c, n = 21, corresponding to iterative dilutions of 100(-10)-100(-30)), sulfur (13x-30x, n = 18, 10(-13)-10(-30)), and copper sulfate (11c-30c, n = 20, 100(-11)-100(-30)) were compared to n = 10 independent controls each (analogously agitated dilution medium) in randomized and blinded experiments. In none of the samples, the concentration of any element analyzed by ICP-MS exceeded 10 ppb. In the first measurement series (600 MHz), there was a significant increase in T(1) for all samples as a function of time, and there were no significant differences between homeopathic potencies and controls. In the second measurement series (500 MHz) 1 year after preparation, we observed statistically significant increased T(1) relaxation times for homeopathic sulfur preparations compared to controls. Fifteen out of 18 correlations between sample triplicates were higher for controls than for homeopathic preparations. No conclusive explanation for these phenomena can be given at present. Possible hypotheses involve differential leaching from the measurement vessel walls or a change in water molecule dynamics, i.e., in rotational correlation time and/or diffusion. Homeopathic preparations thus may exhibit specific physicochemical properties that need to be determined in detail in future investigations.
