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Viable Target (viable + target)
Selected AbstractsIs Atrial Remodeling a Viable Target for Prevention of Atrial Fibrillation Recurrence?JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2004STANLEY NATTEL M.D. [source] Roles of the novel interleukin-12-associated cytokine, interleukin-23, in the regulation of T-cell-mediated immunityHEPATOLOGY RESEARCH, Issue 2007Masanori Matsui Interleukin (IL)-12 is a heterodimeric proinflammatory cytokine formed by a 35-kDa light chain (p35) and a 40-kDa heavy chain (p40). This cytokine is a key regulator of cell-mediated immunity, and therefore should have therapeutic potential in infectious diseases and tumors. Recently, a novel IL-12-associated cytokine, IL-23 has been discovered. IL-23 is also a heterodimer that consists of the p40 subunit of IL-12 and a novel subunit, p19. Several studies have shown that IL-23 possesses immunoadjuvant activity against tumor and infectious diseases as well as IL-12. On the other hand, there is increasing evidence that IL-12 and IL-23 have discrete roles in the regulation of T-cell-mediated immunity despite their structural similarities. IL-12 leads to the development ofinterferon-,-producing T-helper type 1 (Th1) cells, whereas IL-23 amplifies and stabilizes a new CD4+ T-cell subset, Th17 producing IL-17. The IL-23/Th17 axis rather than the IL-12/Th1 axis contributes to several immune-mediated inflammatory autoimmune diseases. Furthermore, IL-23/IL-17 promotes tumor incidence and growth. Therefore, IL-23 and Th17 are attracting considerable attention at present. Taken together, these findings suggest that IL-23 may be an immunoadjuvant against infectious diseases and tumors, and a viable target for the treatment of inflammatory diseases. [source] Perfect planar tetracoordinate carbon in neutral unsaturated hydrocarbon cages: A new strategy utilizing three-dimensional electron delocalizationJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 13 2009Yang Wang Abstract A new series of unsaturated pure and boron-substituted hydrocarbons containing a perfect planar tetracoordinate carbon (ptC) have been proposed by performing density functional computations. The ptC is effectively stabilized through three-dimensional delocalization of ptC's lone pair into ,-conjugated systems, by utilizing a new strategy opening a brand new way of designing ptC structures. Compared to previously proposed ptC-containing hydrocarbon cage compound, a neutral hydrocarbon designed here might be a more viable target for synthetic attempts. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009 [source] Identification of small peptides mimicking the R2 C -terminus of Mycobacterium tuberculosis ribonucleotide reductaseJOURNAL OF PEPTIDE SCIENCE, Issue 3 2010Daniel J. Ericsson Abstract Ribonucleotide reductase (RNR) is a viable target for new drugs against the causative agent of tuberculosis, Mycobacterium tuberculosis. Previous work has shown that an N -acetylated heptapeptide based on the C -terminal sequence of the smaller RNR subunit can disrupt the formation of the holoenzyme sufficiently to inhibit its function. Here the synthesis and binding affinity, evaluated by competitive fluorescence polarization, of several truncated and N -protected peptides are described. The protected single-amino acid Fmoc-Trp shows binding affinity comparable to the N -acetylated heptapeptide, making it an attractive candidate for further development of non-peptidic RNR inhibitors. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. [source] Role of interleukin-1, in postoperative cognitive dysfunctionANNALS OF NEUROLOGY, Issue 3 2010Mario Cibelli MD Objective: Although postoperative cognitive dysfunction (POCD) often complicates recovery from major surgery, the pathogenic mechanisms remain unknown. We explored whether systemic inflammation, in response to surgical trauma, triggers hippocampal inflammation and subsequent memory impairment, in a mouse model of orthopedic surgery. Methods: C57BL/6J, knock out (lacking interleukin [IL]-1 receptor, IL-1R,/,) and wild type mice underwent surgery of the tibia under general anesthesia. Separate cohorts of animals were tested for memory function with fear conditioning tests, or euthanized at different times to assess levels of systemic and hippocampal cytokines and microglial activation; the effects of interventions, designed to interrupt inflammation (specifically and nonspecifically), were also assessed. Results: Surgery caused hippocampal-dependent memory impairment that was associated with increased plasma cytokines, as well as reactive microgliosis and IL-1, transcription and expression in the hippocampus. Nonspecific attenuation of innate immunity with minocycline prevented surgery-induced changes. Functional inhibition of IL-1,, both in mice pretreated with IL-1 receptor antagonist and in IL-1R,/, mice, mitigated the neuroinflammatory effects of surgery and memory dysfunction. Interpretation: A peripheral surgery-induced innate immune response triggers an IL-1,-mediated inflammatory process in the hippocampus that underlies memory impairment. This may represent a viable target to interrupt the pathogenesis of postoperative cognitive dysfunction. ANN NEUROL 2010;68:360,368 [source] | |||||||||||||