Search

The epithelium-associated cytokine thymic stromal lymphopoietin (TSLP) can induce OX40L and CCL17 expression by myeloid dendritic cells (mDCs), which contributes to aberrant Th2-type immune responses. Herein, we report that such TSLP-induced Th2-type immune response can be effectively controlled by Dectin-1, a C-type lectin receptor expressed by mDCs. Dectin-1 stimulation induced STAT3 activation and decreased the transcriptional activity of p50-RelB, both of which resulted in reduced OX40L expression on TSLP-activated mDCs. Dectin-1 stimulation also suppressed TSLP-induced STAT6 activation, resulting in decreased expression of the Th2 chemoattractant CCL17. We further demonstrated that Dectin-1 activation was capable of suppressing ragweed allergen (Amb a 1)-specific Th2-type T cell response in allergy patients ex vivo and house dust mite allergen (Der p 1)-specific IgE response in non-human primates in vivo. Collectively, this study provides a molecular explanation of Dectin-1-mediated suppression of Th2-type inflammatory responses and suggests Dectin-1 as a target for controlling Th2-type inflammation.

Acute pancreatitis is a complex inflammatory disease resulting in extreme pain and can result in significant morbidity and mortality. It can be caused by several factors ranging from genetics, alcohol use, gall stones, and ductal obstruction caused by calcification or neutrophil extracellular traps. Acute pancreatitis is also characterized by immune cell infiltration of neutrophils and M1 macrophages. Toll-like receptor 4 (TLR4) is a pattern recognition receptor that has been noted to respond to endogenous ligands such as high mobility group box 1 (HMGB1) protein and or exogenous ligands such as lipopolysaccharide both of which can be present during the progression of acute pancreatitis. This receptor can be found on a variety of cell types from endothelial cells to resident and infiltrating immune cells leading to production of pro-inflammatory cytokines as well as immune cell activation and maturation resulting in the furthering of pancreatic damage during acute pancreatitis. In this review we will address the various mechanisms mediated by TLR4 in the advancement of acute pancreatitis and how targeting this receptor could lead to improved outcomes for patients suffering from this condition. [ABSTRACT FROM AUTHOR]

A study was conducted to characterize the asymmetric synthesis of the C9-C21 area of the aplysiatoxin and oscillatoxin marine natural products. Thin-layer chromatography was carried out using silica gel coated onto aluminum plates. Nuclear magnetic resonance spectra were then determined from solutions in CDCl3. Results indicated that the triethylsilyl ether group at C11 can be removed without affecting the SEM ether group at C20.

An addition reaction between ((CH3)3NH)(nido-7,8-C2B9H12) and 2.5 equiv of I2 produces the diiodocompound ((CH3)3NH)(nido-9,11-I2-7,8-C2B9H10). X-ray studies of the anion of the diiodo compound reveal the presence of an endo B-H bond in the open five-membered face. X-ray studies of the crystal structure of the corresponding monoiodo species reveal the presence of a B-H-B bridge at the B(10) and B(11) positions.

An ordinary antomated DNA synthesizer is used in the rapid and facile preparations of massive functionalized boron-rich oligophosphate trailers that are very hydrophilic and homogeneous. These trailers are relevant to the immunoprotein-mediated boron neutron capture therapy of cancer. The standard reagents or processes can remain unaltered when using boron-rich phosphoramidite on automated DNA synthesis tools to prepare boron-rich oligophosphates.

An efficient solution-phase synthesis of boron-10-rich peptides is described. The process involves a progressive segment condensation that is able to form an octapeptide in 50% yield after the second cycle. Condensation is achieved during the selective double-deprotection (carbonyl and amino) step from a basic glycine-containing peptide structure derived from the coupling of a carboranylpropyl iodide with a monoalkyl imine. The oligopeptide is a potentially rich source of boron-10 for boron nuclear capture therapy.

Beta cell replacement therapy, the transplantation of isolated pancreatic islets by intraportal infusion, offers patients with brittle type 1 diabetes blood glucose regulation with a minimally invasive technique. Chemical modification of islets prior to transplantation, providing a nanothin barrier that potentially includes active protective compounds, has been proposed as a strategy to minimize the inflammatory and immune reactions that often significantly limit graft function and duration. Chemical modification also has the potential to allow the use of alternative sources of islets, such as porcine islets, for transplantation. This investigation compared three orthogonal covalent islet modification techniques across three species (human, porcine, and murine), using multiple measures to determine biocompatibility and effectiveness. All three conjugation chemistries were well tolerated, and the overall efficiency, gross uniformity, and stability of the surface modifications were dependent upon the conjugation chemistry as well as the islet source (human, porcine, or murine). Notably, the reductive modification of surface disulfides was shown to afford intense and long-lasting modification of human islets. This study demonstrates that murine, human, and porcine islets tolerate a variety of covalent modifications, that these modifications are relatively stable, and that the murine islet model may not be predictive for some chemical contexts. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 869-877, 2015. [ABSTRACT FROM AUTHOR]