Showing papers in "Biochemical Pharmacology in 2006"

TL;DR: Evidence is presented that numerous agents identified from fruits and vegetables can interfere with several cell-signaling pathways and the active principle identified in fruit and vegetables and the molecular targets modulated may be the basis for how these dietary agents not only prevent but also treat cancer and other diseases.

TL;DR: This review critically review the recent data highlighting the role of ROS in NF-κB activation by proinflammatory cytokines (TNF-α and IL-1β) and lipopolysaccharide (LPS), two major components of innate immunity.

TL;DR: The critical link between inflammation and cancer is described and observations imply that anti-inflammatory agents that suppress NF-kappaB or NF- kappaB-regulated products should have a potential in both the prevention and treatment of cancer.

TL;DR: The recent data suggest that dietary polyphenols can work as modifiers of signal transduction pathways to elicit their beneficial effects during oxidative stress, their metabolism and bioavailability.

TL;DR: Calprotectin expression and potential cytokine-like function in inflammation and in cancer suggests that S100A8/A9 may play a key role in inflammation-associated cancer.

TL;DR: The history of NFkappaB began with the TLR4 ligand lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria, since this was the stimulus first used to activate NFKappaB in pre-B-cells.

TL;DR: The emerging concept of protein-S-thiolation, protein- S-nitrosation and protein-SH (formation of sulfenic, sulfinic and sulfonic acids) in redox signaling during normal physiology and under oxidative stress in controlling the cellular processes is discussed.

TL;DR: Second-generation programs have been initiated and show early promise to significantly improve the clinical usefulness of currently available and future antibiotics against otherwise recalcitrant Gram-negative infections.

TL;DR: It is demonstrated that most of the flavonoids assayed reduce macrophage M-CSF-induced proliferation without affecting cellular viability and some flavonoid also inhibit TNFalpha production as well as iNOS expression and NO production in LPS-activated macrophages, an effect that has been associated with the inhibition of the NF-kappaB pathway.

TL;DR: Inhibition of the alternative pathway is potentially associated to a wide range of disorders like rheumatoid arthritis, ulcerative colitis or B cell lymphomas and could be valuable tools for the treatment of inflammatory disorders and cancers.

TL;DR: It is proposed that new antibacterial assays which combine cell-based screening with molecular targets could offer better prospects for lead discovery.

TL;DR: The hypothesis is emerging that the diverse tissue-specific, TCDD-mediated toxicities are due to sustained and inappropriate AhR activation leading to deregulated physiologic functions, and recent observations in the context of some TCDDs toxic responses are discussed.

TL;DR: The success in exploiting DHFR as a drugable target as exemplified by trimethoprim (TMP) and the development of several new diaminopyrimidines is described and several examples of anti-DHFR antibacterial compounds in pre-clinical development are described.

TL;DR: The malate-aspartate shuttle and the glycerol phosphate shuttle act to transfer reducing equivalents from NADH in the cytosol to the mitochondria since the inner mitochondrial membrane is impermeable to NADH and NAD+.

TL;DR: Understanding on the molecular mechanisms underlying the anti-inflammatory and anti-cancer activities of celastrol and celastro-containing medicinal plant is extended, which would be a valuable candidate for the intervention of NF-kappa B-dependent pathological conditions.

TL;DR: The discovery of oncogenic partner in this signaling pathway, more especially in diverse hematologic malignancies support a prominent role of deregulated pathways in the pathogenesis of diseases.

TL;DR: This commentary provides an overview of current antibiotic leads and their mechanism of action, and highlights tools that can be applied to the discovery of new antibiotics.

TL;DR: Gallidermin shows most promise as a therapeutic agent, with relatively low cytotoxicity and potent antimicrobial activities, and Melittin, while showing little potential as an antimicrobial agent, may have potential in delivery of poorly bioavailable drugs.

TL;DR: The impact of microbial biodiversity, the influence of growth conditions on the production of secondary metabolites, the choice of the best approach at the screening step and the challenges faced during the isolation and identification of the active compounds are examined in this review as the critical factors contributing to success in the effort of antibiotic discovery from microbial natural products.

TL;DR: The present commentary is a survey of data concerning the role of GGT in tumor cell biology and the mechanisms of its potential involvement in tumor drug resistance.

TL;DR: Whereas traditional pharmacokinetic/pharmacodynamic models assume that the amount of the drug-target complex is negligible relative to the total amount of drug in the body, integrated mechanism-based models of TMDD incorporate the binding and stoichiometry of drug- target binding.

TL;DR: Intrinsic clearance values generated using human liver microsomes under-predict in vivo hepatic clearance, and in vivo clearances of glucuronidated drugs are generally under-predicted by CL(int) values from human hepatocytes, but to a lesser extent than observed with the microsomal model.

TL;DR: Biochemical evidence that phytochemicals (curcumin and sesquiterpene lactone) inhibit both ligand-induced and lig and-independent dimerization of TLR4 is reported, demonstrating that small molecules with non-microbial origin can directly inhibit TLRs-mediated signaling pathways at the receptor level.

TL;DR: The various mechanisms by which NF-kappaB activation blunts TNF-induced JNK activation are discussed, including the induction of JNK inhibitory proteins and controlling the levels of reactive oxygen species (ROS).

TL;DR: Underlying mechanisms as well as some structural features with a focus on Jak1 and two of the signal transducing receptor subunits of interleukin (IL)-6 type cytokines, gp130 and OSMR are discussed.

TL;DR: Current evidence points to an antidepressant mechanism that is independent of monoaminergic facilitation that is driven by neurogenesis, a process facilitated by increased BDNF expression, but alternative hypotheses need to be considered given uncertainties in the relationship between BDNF increases and the effects of conventional antidepressant medications.

TL;DR: It is demonstrated that AMD3100 is a specific antagonist of CXCR4, is not cross-reactive with other chemokine receptors, and is not an agonist of C XCR4.

TL;DR: Recent findings deciphering the diverse functions of NF-kappaB in NS development and activity are described, which range from the control of cell growth, survival and inflammatory response to synaptic plasticity, behavior and cognition.

TL;DR: Evaluated ERalpha and ERbeta selectivity of 19 known estrogens and antiestrogens using reporter cell lines previously developed in the laboratory demonstrate the usefulness of stably transfected cell lines to characterize ER ligands and indicate that treatments combining agonist/antagonist ligands produce full-ER beta selectivity.

TL;DR: Data underpin the anti-tumor property of Rg3 through its angiosuppressive activity.