Picrotoxane-type sesquiterpenoids from Dendrobium improve insulin resistance and increase glucose-stimulated insulin secretion.

Twelve picrotoxane-type sesquiterpenoids were isolated from Dendrobium wardianum, of which dendrowardins K-N (1-4) are new compounds and dendrowardins O and P (9, 10) are new natural products. Notably, the structure of dendrowardin K contains the rarely observed 10,11-γ-lactone ring. The structural configurations of these compounds were determined through comprehensive 1D and 2D nuclear magnetic resonance (NMR), single-crystal X-ray diffraction, and other spectroscopic analyses.

Structure characterization and immunoactivity on dendritic cells of two neutral polysaccharides from Dictyophora rubrovalvata.

Dictyophora rubrovalvata is a valuable fungus homologous to food and medicine, and its polysaccharide have been gaining increasing attention because of its plentiful activity. However, the structure and activity of its homogeneous polysaccharide have not been studied enough. In this study, two polysaccharides DRP-I and DRP-II were purified from D.

Cutting edge: Necrosis activates the NLRP3 inflammasome.

Cells undergoing necrosis release endogenous danger signals that possess proinflammatory potential. In this study we show that mature IL-1beta and IL-18 are released by necrotic cells but not by apoptotic cells. We identify 7-bromoindirubin-3'-oxime, an indirubin oxime derivative that induces necrosis, as a potent inducer of caspase-1 activation and release of mature IL-1beta and IL-18.

Cutting edge: inflammasome activation by alum and alum's adjuvant effect are mediated by NLRP3.

Alum is the only adjuvant approved for routine use in humans, although the basis for its adjuvanticity remains poorly understood. We have recently shown that alum activates caspase-1 and induces secretion of mature IL-1beta and IL-18. In this study we show that, in human and mouse macrophages, alum-induced secretion of IL-1beta, IL-18, and IL-33 is mediated by the NLR (nucleotide-binding domain leucine-rich repeat-containing) protein NLRP3 and its adaptor ASC, but not by NLRC4.

Identification of Francisella tularensis lipoproteins that stimulate the toll-like receptor (TLR) 2/TLR1 heterodimer.

The innate immune response to Francisella tularensis is primarily mediated by TLR2, though the bacterial products that stimulate this receptor remain unknown. Here we report the identification of two Francisella lipoproteins, TUL4 and FTT1103, which activate TLR2. We demonstrate that TUL4 and FTT1103 stimulate chemokine production in human and mouse cells in a TLR2-dependent way.

Commercial peptidoglycan preparations are contaminated with superantigen-like activity that stimulates IL-17 production.

The immunomodulatory properties of peptidoglycan (PGN), a constituent of the bacterial cell wall, have been studied extensively but with contrasting results. Recent studies have demonstrated that the TLR2-mediated inflammatory responses elicited by Gram-positive PGN preparations are in fact a result of contaminating lipoproteins and lipoteichoic acid that can be removed only through sophisticated extraction procedures. Here, we report that commercial preparations of Staphylococcus aureus or Streptococcus pyogenes PGN are contaminated with bacterial superantigens (SAg).

Aluminum hydroxide adjuvants activate caspase-1 and induce IL-1beta and IL-18 release.

Aluminum hydroxide (Alum) is the only adjuvant approved for routine use in humans, although the basis for its adjuvanticity remains poorly understood. In this study, we show that Alum activates caspase-1 and induce secretion of mature IL-1beta and IL-18. Human PBMC or dendritic cells stimulated with pure TLR4 and TLR2 agonists released only traces of IL-1beta or IL-18, despite the fact that the IL-1beta mRNA was readily induced by both TLR agonists.

Innate immune response to Francisella tularensis is mediated by TLR2 and caspase-1 activation.

Francisella tularensis, a gram-negative, facultative, intracellular bacterium, is the etiologic agent of tularemia and a category A bioterrorism agent. Little is known about the mechanism of pathogenesis of tularemia. In this paper, we describe the interaction of the live vaccine strain of F.

Synthesis of complex carbohydrates and glyconjugates: enzymatic synthesis of globotetraose using alpha-1,3-N-acetylgalactosaminyltransferase LgtD from Haemophilus infuenzae strain Rd.

The lipopolysaccharide of capsule-deficient Haemophilus infuenzae strain Rd contains an N-acetylgalactosamine residue attached to the terminal globotriose moiety in the Hex5 glycoform. Genome analysis identified an open reading frame, HI1578, referred to as LgtD, whose amino acid sequence shows a significant level of similarity to those of a number of bacterial glycosyltransferases involved in lipopolysaccharide biosynthesis. To investigate its function, overexpression and biochemical characterization were performed.

Two different O-polysaccharides from Escherichia coli O86 are produced by different polymerization of the same O-repeating unit.

The structure of a new O-polysaccharide from Escherichia coli O86:K62:B7 was determined using NMR and methylation analysis. The structure is as follows: [carbohydrate: see text]. Comparison with the previously published structure from E.

Escherichia coli O86 O-antigen biosynthetic gene cluster and stepwise enzymatic synthesis of human blood group B antigen tetrasaccharide.

Previous study showed that some Gram-negative bacteria possess human blood group activity. Among them, Escherichia coli O86 has high blood group B activity and weak blood group A activity. This is due to the cell surface O-antigen structure, which resembles that of human blood group B antigen.

Identification of alpha-galactosyl epitope mimetics through rapid generation and screening of C-linked glycopeptide library.

A general methodology has been established for rapid generation and screening of combinatorial glycopeptide library and subsequent mass spectrometric sequencing to identify the mimetics of Galalpha(1,3)Gal epitopes. Using this approach, several active glycopeptide sequences were recognized and found to inhibit the binding of human natural anti-Gal antibodies with comparable IC(50)s to synthetic Galalpha(1,3)Gal oligosaccharides. The most active glycopeptides detected from the library included Gal-Tyr-Trp-Arg-Tyr, Gal-Thr-Trp-Arg-Tyr, and Gal-Arg-Trp-Arg-Tyr.

The lck promoter-driven expression of the Wilms tumor gene WT1 blocks intrathymic differentiation of T-lineage cells.

In the thymi of WT1-transgenic (Tg) mice with the 17AA+/KTS- spliced form of the Wilms tumor gene WT1 driven by the lck promoter, the frequencies of CD4-CD8- double-negative (DN) thymocytes were significantly increased relative to those in normal littermates. Of the 4 subsets of CD4-CD8- DN thymocytes, the DN1 (CD44+CD25-) subset increased in both frequency and absolute cell number, whereas the DN2 (CD44+CD25+) and DN3 (CD44-CD25+) subsets decreased, indicating the blocking of thymocyte differentiation from the DN1 to the DN2 subsets. Furthermore, CD4-CD8+ T-cell receptor (TCR) -gammadelta T-cells increased in both frequency and absolute cell number in the spleen and peripheral blood of the WT1-Tg mice relative to those of normal littermates.