Toxicol In Vitro. 2009 Aug 1; Lu N, Zhou G, Pei D, Yi L, Gao ZThe major pathways of protein tyrosine nitration in vivo include peroxynitrite (ONOO(-)) and heme peroxidase -NO(2)(-)-H(2)O(2) dependent reaction in which free radicals and iron catalysis are involved. In this paper, we chose three classic antioxidants (GSH, a major intracellular antioxidant; Trolox, a phenolic antioxidant without chelating effect; and DFO, a good iron chelator), to study their efficiencies against ONOO(-) or Heme/NaNO(2)/H(2)O(2) - mediated nitrative/oxidative damage to human plasma proteins in vitro. Protein nitration was efficiently inhibited by the three antioxidants regardless of nitration pathways, whereas the efficiencies of antioxidants on protein oxidation depended on the concentration of antioxidants and categories of oxidant. In both models, GSH exhibited protective activity in protein oxidation and Trolox promoted the formation of plasma protein carbonyl groups at lower concentration (0.01mM and 0.1mM). DFO dose-dependently inhibited ONOO(-)-induced protein oxidation, while it enhanced Heme/NaNO(2)/H(2)O(2)-triggered protein oxidation at lower concentration. However, both DFO and Trolox exhibited protective effect on protein carbonyl formation when the higher concentration was used. The pro-oxidant or anti-oxidant effect for these antioxidants at different concentration, may provide useful information about the selection of the suitable antioxidant and dosage in experimental and clinical application.

PLoS One. 2009; 4(8): e6520Yang HZ, Cui B, Liu HZ, Mi S, Yan J, Yan HM, Hua F, Lin H, Cai WF, Xie WJ, Lv XX, Wang XX, Xin BM, Zhan QM, Hu ZWBACKGROUND: Metastasis is the most pivotal cause of mortality in cancer patients. Immune tolerance plays a crucial role in tumor progression and metastasis. METHODS AND FINDINGS: In this study, we investigated the potential roles and mechanisms of TLR2 signaling on tumor metastasis in a mouse model of intravenously injected B16 melanoma cells. Multiple subtypes of TLRs were expressed on B16 cells and several human cancer cell lines; TLR2 mediated the invasive activity of these cells. High metastatic B16 cells released more heat shock protein 60 than poor metastatic B16-F1 cells. Importantly, heat shock protein 60 released by tumor cells caused a persistent activation of TLR2 and was critical in the constitutive activation of transcription factor Stat3, leading to the release of immunosuppressive cytokines and chemokines. Moreover, targeting TLR2 markedly reduced pulmonary metastases and increased the survival of B16-bearing mice by reversing B16 cells induced immunosuppressive microenvironment and restoring tumor-killing cells such as CD8(+) T cells and M1 macrophages. Combining an anti-TLR2 antibody and a cytotoxic agent, gemcitabine, provided a further improvement in the survival of tumor-bearing mice. CONCLUSIONS AND SIGNIFICANCE: Our results demonstrate that TLR2 is an attractive target against metastasis and that targeting immunosuppressive microenvironment using anti-TLR2 antibody is a novel therapeutic strategy for combating a life-threatening metastasis.

Homeopathy. 2009 Jul; 98(3): 165-8Waisse-Priven S, Jurj G, Lima Thomaz LC, Tierno SA, Filho WL, Sos ABThis paper describes the successful outcome of homeopathic treatment in a case of resistant livedoid vasculopathy (LV). LV is a rare disease characterized by chronic recurrent and painful ulceration of the lower limbs, frequently associated to atrophie blanche (AB), probably due to procoagulant conditions. Most literature reports single or very few cases; response to treatment is difficult, even resistant. This patient suffered LV for 7 years before seeking homeopathic treatment; ulcers recurred frequently, at intervals less than 3 months, in spite of continual use of pentoxyfilline. Configuration of signs and symptoms strongly pointed out to the prescription of homeopathic remedy Sepia succus that promptly elicited significant improvement of LV and the patient's overall state (non suppressive treatment). Considerations are made on the value of single case reports and the reliability of prescriptions grounded on consistent signs and coherence among the manifold features of individual disease.

Rapid Commun Mass Spectrom. 2009 Jul 28; 23(17): 2724-2732Wang Y, Ding C, Du K, Xiao Y, Wu C, Zhang J, Qin H, Du GXiao-xu-ming decoction (XXMD) prescription is a traditional Chinese prescription that has been widely used to treat theoplegia and the sequela of theoplegia. Modern pharmacological research has also indicated that the active fraction from XXMD is able to treat cardiovascular diseases and Alzheimer's disease. In the study reported here, high-performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (HPLC/FTICR-MS) was developed to identify active compounds and their metabolites after oral administration of active fraction from Xiao-xu-ming decoction to rats, using parent mass list triggered data-dependent multiple-stage mass analysis at a resolving power of 100 000 in the external calibration mode. The mass accuracies obtained for full-scan MS were within 2 ppm in most cases. Fifteen constituents were identified in the active fraction from XXMD and the biological samples of rats. The fragmentation behaviors of these constituents were summarized which would be helpful for structural characterization. The profiles of the constituents in the active fraction and biological samples of rats were obtained which provided us with much information for a better understanding of the chemical basis of the pharmacologic actions of XXMD. Copyright (c) 2009 John Wiley & Sons, Ltd.