Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Successful Ag activation of naive T helper cells requires at least two signals consisting of TCR and CD28 on the T cell interacting with MHC II and CD80/CD86, respectively, on APCs. Recent evidence demonstrates that a third signal consisting of proinflammatory cytokines and reactive oxygen species (ROS) produced by the innate immune response is important in arming the adaptive immune response. In an effort to curtail the generation of an Ag-specific T cell response, we targeted the synthesis of innate immune response signals to generate Ag-specific hyporesponsiveness. We have reported that modulation of redox balance with a catalytic antioxidant effectively inhibited the generation of third signal components from the innate immune response (TNF-alpha, IL-1beta, ROS). In this study, we demonstrate that innate immune-derived signals are necessary for adaptive immune effector function and disruption of these signals with in vivo CA treatment conferred Ag-specific hyporesponsiveness in BALB/c, NOD, DO11.10, and BDC-2.5 mice after immunization. Modulating redox balance led to decreased Ag-specific T cell proliferation and IFN-gamma synthesis by diminishing ROS production in the APC, which affected TNF-alpha levels produced by CD4(+) T cells and impairing effector function. These results demonstrate that altering redox status can be effective in T cell-mediated diseases such as autoimmune diabetes to generate Ag-specific immunosuppression because it inhibits the third signal necessary for CD4(+) T cells to transition from expansion to effector function.
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PMID:Disruption of innate-mediated proinflammatory cytokine and reactive oxygen species third signal leads to antigen-specific hyporesponsiveness. 1720 52

An unusually large expansion upon solvent adsorption occurs without apparent bond breaking in the network of a series of isoreticular chromium(III) or iron(III) diarboxylates labeled MIL-88A to D [dicarbox = fumarate (88A); terephthalate (1,4-BDC) (88B); 2,6-naphthalenedicarboxylate (2,6-NDC) (88C); and 4-4'-biphenyldicarboxylate (4-4'-BPDC) (88D)]. This reversible "breathing" motion was analyzed in terms of cell dimensions (extent of breathing), movements within the framework (mechanism of transformation), and the interactions between the guests and the skeleton. In situ techniques show that these flexible solids are highly selective absorbents and that this selectivity is strongly dependent on the nature of the organic linker.
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PMID:Role of solvent-host interactions that lead to very large swelling of hybrid frameworks. 1739 25

A three-dimensional microporous metal-organic framework Zn(BDC)(Dabco)0.5 (BDC = 1,4-benzenedicarboxylate, Dabco = 1,4-diazabicyclo [2,2,2]octane), having two types of intersecting pores to encapsulate linear hexane and to block branched hexanes, and thus exhibiting highly selective sorption with respect to n-hexane, has been successfully applied to the kinetic separation of hexane isomers by fixed-bed adsorption.
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PMID:Kinetic separation of hexane isomers by fixed-bed adsorption with a microporous metal-organic framework. 1750 May 57

Due to the poor prognosis and limited management options for perihilar cholangiocarcinoma (CC) the development of alternatives for treatment is an important topic. Photodynamic therapy (PDT) with porfimer as palliative or neoadjuvant endoscopic treatment of non-resectable perihilar CC has improved quality of life and survival time, but cannot eradicate the primary tumors because of inadequate tumoricidal depth (4 mm only around the tumor stenoses). The use of meta-tetrahydroxyphenyl chlorin (mTHPC) and photoactivation at higher wavelengths (650-660 nm) provides high tumoricidal depth (10 mm) for PDT of pancreatic cancer and should yield similar tumoricidal depth in CC. This study investigates the photodynamic characteristics of mTHPC in solvent-based formulation (Foscan) and in liposomal (water soluble) formulation (Foslip) in an in vitro model system consisting of two biliary cancer cell lines (GBC, gall bladder cancer and BDC, bile duct cancer cells). Dark toxicity, photodynamic efficiency, time-dependent uptake and retention and intracellular localization of Foscan and Foslip were studied. The results prove mTHPC as a potent photosensitizing agent with high phototoxic potential in biliary cancer cells as a concentration of 600 ng ml(-1) and irradiation with 1.5 J cm(-2) (660 +/- 10 nm) is sufficient for about 90% cell killing. Addition of foetal bovine serum (FBS) to the incubation medium and analysis of the uptake and phototoxic properties reveals that both photosensitizer formulations bind to serum protein fractions, i.e. no difference between Foscan and Foslip can be found in the presence of FBS. Laser scanning fluorescence microscopy indicates a similar pattern of perinuclear localization of both sensitizers. This study demonstrates the potential of mTHPC for treatment of bile duct malignancies and provides evidence that Foslip is an equivalent water-soluble formulation of mTHPC that should ease intravenous application and thus clinical use of mTHPC.
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PMID:Comparative characterization of the efficiency and cellular pharmacokinetics of Foscan- and Foslip-based photodynamic treatment in human biliary tract cancer cell lines. 1754 63

Four two-dimensional coordination polymers containing the uranyl cation (UO2(2+)), (NH4)UO2(BDC)1.5 . 2.5H2O (1), KUO2(NDC)1.5 . 2H2O (2), [C(NH2)3]UO2(NDC)1.5 . 2H2O (2b), and UO2(HBDC-Br)2 (3) (BDC = 1,4-benzenedicarboxylate, NDC = 1,4-naphthalenedicarboxylate, BDC-Br = 2-bromoterephthalate) have been synthesized by hydrothermal reactions. Compounds 1-2b have the same honeycomb (6,3) net but with two-fold interpenetration in 1 and without interpenetration in 2 and 2b. The use of 2-bromoterephthalate yields compound 3 with a (4,4) net. The structures of 2 and 2b show that the interpenetration can be prevented by the addition of a bulky substituent to the ligand. Maintaining the desired topology, however, requires a careful choice of the substituent group. Compounds 1, 2, and 2b have a similar structural arrangement to that of benzenetricarboxylic acid (trimesic acid, H3BTC). In H3BTC, the six rings are formed by hydrogen bonding and the interpenetration is more complex than that in 1. Crystal data: 1, triclinic, space group P, a = 10.453(8) A, b = 12.316(9) A, c = 13.441(10) A, alpha = 78.49(1) degrees , beta = 82.17(1) degrees , gamma = 85.57(1) degrees , and Z = 4; 2, monoclinic, space group C2/c, a = 12.7795(9) A, b = 19.728(1) A, c = 15.379(1) A, beta = 92.247(1) degrees , and Z = 8; 2b, monoclinic, space group C2/c, a = 12.7214(8) A, b = 19.645(1) A, c = 17.065(1) A, beta = 98.896(1) degrees , and Z = 8; 3, monoclinic, space group P21/c, a = 7.873(5) A, b = 18.358(14) A, c = 6.893(5) A, beta = 115.96(2) degrees , and Z = 2.
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PMID:(6,3)-honeycomb structures of uranium(VI) benzenedicarboxylate derivatives: the use of noncovalent interactions to prevent interpenetration. 1762 40

The octanuclear complex [Eu8L4(1,4-BDC)2Cl8(MeOH)12].4Cl.2MeOH.18H2O (2) was obtained from the reaction of the tetranuclear Eu(III) species [Eu4L2Cl2(OH)4(H2O)4(MeOH)2].2Cl.7MeOH.2H2O (1) and 1,4-H2BDC (H2L = bis(5-bromo-3-methoxysalicylidene)ethylene-1,2-phenylenediamine, 1,4-H2BDC = 1,4-benzenedicarboxylic acid). Both 1 and 2 were structurally characterized by X-ray crystallography, and their luminescence properties were determined. The cagelike structure of 2 encapsulates two chloride anions via MeOH...Cl hydrogen bonding. In the solid state, 2 has an open three-dimensional network with extended channels and is capable of reversible MeOH adsorption.
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PMID:Synthesis of an octanuclear Eu(III) cage from Eu(4)(2+): chloride anion encapsulation, luminescence, and reversible MeOH adsorption via a porous supramolecular architecture. 1762 44

Foxp3-expressing regulatory T (T reg) cells derive primarily from selection in the thymus. Yet conversion of mature conventional CD4(+) T (T conv) cell lymphocytes can be achieved in several conditions, such as transforming growth factor beta treatment, homeostatic expansion, or chronic exposure to low-dose antigen. Such conversion might provide a means to generate peripheral tolerance by "converting" potentially damaging T cells that react to self-antigens. We tested this hypothesis in mice transgenic for the BDC2.5 T cell receptor (TCR), which is representative of a diabetogenic specificity that is naturally present in NOD mice and reactive against a pancreatic self-antigen. In the thymus, before any exposure to antigen, clonotype-positive T reg and T conv cells express a second TCRalpha chain derived from endogenous loci. High-throughput single-cell sequencing of secondary TCRs of the Valpha2 family showed their joining CDR3alpha regions to be very different in T reg and T conv cell thymocytes. These specific CDR3alpha motifs, thus, provided a "tag" with which to test the actual impact of T conv to T reg cell conversion in response to peripheral self-antigen; should the autoreactive clonotypic TCR induce T conv to T reg cell conversion upon encounter of cognate antigen in the pancreas or draining lymph node, one would expect to detect tag CDR3alpha motifs from T conv cells in the T reg cell populations. Sequencing large numbers of peripheral BDC(+)Valpha2(+) cells showed that little to no conversion occurs in response to this pancreatic autoantigen.
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PMID:TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets. 1772 31

Three indium-oxide organic frameworks, In(2)O(1,3-BDC)(2), 1; In(OH)(2,6-NDC)(H(2)O), 2; and In(OH)(2,7-NDC)(H(2)O), 3 (BDC = benzene dicarboxylic acid and NDC = naphthalene dicarboxylic acid), were synthesized and characterized by thermogravimetric analysis, infrared spectroscopy, and single-crystal X-ray diffraction. Previously, we reported the structure of In(OH)(1,4-BDC).(0.75H(2)BDC), 0, where the framework is built by interconnecting In-OH-In chains with the BDC anions to form large diamond-shaped one-dimensional channels filled with guest molecules. Compounds 0-3 all contain In-O(H) chains, but the coordination and geometry depend on the nature of the dicarboxylate ligand. Compound 0 contains In-O octahedral centers that connect to form a single trans octahedral chain, while in compound 1, they connect to form a more complex double chain of octahedra. Both compounds 2 and 3 contain chains of connected pentagonal bipyramidal InO(6)(OH(2)) units. In 2, these units share trans vertices that are cross-linked by chelating 2,6-NDC anions, whereas in compound 3, cis vertices are shared to form chains that are linked by the 2,7-NDC anions.
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PMID:Influence of ligand geometry on the formation of In-O chains in metal-oxide organic frameworks (MOOFs). 1788 66

Reaction of 1,4-benzenedicarboxylic acid (1,4-H2BDC) with EuCl(3).6H2O in MeOH in the presence of Et3N and MeCN gives a mixture of the 3-D metal-organic-framework (MOF) materials [Eu2(1,4-BDC)3(MeOH)4].8MeOH (1) and 2-D [Eu(1,4-BDC)(MeOH)4].Cl.MeOH.0.25H2O (2). Similar reactions afforded the isomorphous Gd (3) and Tb (4) analogs of 2. Reaction of 1,4-H2BDC with Ln(NO3)(3).6H2O under similar conditions gave [Ln(BDC)NO3(MeOH)2].MeCN.H2O (Ln = Eu (5) and Gd (6)), which have 2-D framework structures. The structures of 1-6 were determined by single crystal X-ray crystallographic studies and the luminescence properties of 1 and 4 in DMF solution were determined.
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PMID:Syntheses, structures and luminescent properties of new lanthanide-based coordination polymers based on 1,4-benzenedicarboxylate (bdc). 1789 91

Adoptive transfer of diabetogenic CD4 Th1 T cell clones into young NOD or NOD.scid recipients rapidly induces onset of diabetes and also provides a system for analysis of the pancreatic infiltrate. Although many reports have suggested a role for macrophages in the inflammatory response, there has been little direct characterization of macrophage activity in the pancreas. We showed previously that after migration to the pancreas, diabetogenic CD4 T cell clones produce a variety of inflammatory cytokines and chemokines, resulting in the recruitment of macrophages. In this study, we investigated mechanisms by which macrophages are recruited and activated by T cells. Analysis of infiltrating cells after adoptive transfer by the diabetogenic T cell clone BDC-2.5 indicates that large numbers of cells staining for both F4/80 and CD11b are recruited into the pancreas where they are activated to make IL-1beta, TNF-alpha, and NO, and express the chemokine receptors CCR5, CXCR3, and CCR8. Diabetogenic CD4 T cell clones produce several inflammatory chemokines in vitro, but after adoptive transfer we found that the only chemokine that could be detected ex vivo was CCL1. These results provide the first evidence that CCR8/CCL1 interaction may play a role in type 1 diabetes through macrophage recruitment and activation.
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PMID:Recruitment and activation of macrophages by pathogenic CD4 T cells in type 1 diabetes: evidence for involvement of CCR8 and CCL1. 1794 48


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