Inhibitory Activity of 4-O-Benzoyl-3'-O-(OMethylsinapoyl) Sucrose from Polygala tenuifolia on Escherichia coliß-Glucuronidase.

Bacterial ß-glucuronidase in the intestine is involved in the conversion of 7-ethyl-10- hydroxycamptochecin glucuronide (derived from irinotecan) to 7-ethyl-10-hydroxycamptothecin, which causes intestinal bleeding and diarrhea (side effects of anti-cancer drugs). Twelve compounds (1-12) from Polygala tenuifolia were evaluated in terms of ß-glucuronidase inhibition in vitro. 4-O-Benzoyl-3'-O-(O-methylsinapoyl) sucrose (C3) was highly inhibitory at low concentrations. C3 (an uncompetitive inhibitor) exhibited a ki value of 13.4 µM; inhibitory activity increased as the substrate concentration rose. Molecular simulation revealed that C3 bound principally to the Gln158-Tyr160 enzyme loop. Thus, C3 will serve as a lead compound for development of new ß- glucuronidase inhibitors.

Influence of Thermal Processing on Free and Bound Forms of Phenolics and Antioxidant Capacity of Rice Hull (Oryza sativa L.).

The objective of this study was to evaluate the effects of heat treatment on the phenolics and antioxidant activity of rice hull. Heat treatment was performed at temperatures 80∼140°C for 1∼5 h, and the heated rice hull was extracted with 80% (v/v) methanol in an ultrasonic bath. The highest total polyphenol and flavonoid content (10.68 mg gallic acid equivalents/g and 1.83 mg catechin equivalents/g, respectively) occurred in rice hull heated at 130°C for 5 h. During heat treatment, the content of free phenolic acids increased compared with that of the bound phenolic acids. The highest 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity and reducing power was observed in rice hull heated at 140°C for 3 h. The highest OH radical scavenging activity was 75.30% in rice hull heated at 140°C for 5 h. These results suggested that heat treatment was an efficient method to enhance the antioxidant characteristics of rice hull.

Chemically Activated Covalent Triazine Frameworks with Enhanced Textural Properties for High Capacity Gas Storage.

Chemical activation of porous/nonporous materials to achieve high surface area sorbents with enhanced textural properties is a very promising strategy. The chemical activation using KOH, however, could lead to broad distribution of pores originating from the simultaneous pore deepening and widening pathways. Accordingly, establishing correlation between the chemical/textural properties of starting porous/nonporous materials and various pore formation mechanisms is quite critical to realize superior porosity and gas uptake properties. Here, we show that the chemical and textural properties of starting porous organic polymers, that is, covalent triazine frameworks (CTF), have profound effect on the resulting porosity of the frameworks. The chemical activation of microporous CTF-1 using KOH at 700 °C enabled the preparation of chemically activated CTF-1, caCTF-1-700, which predominantly showed pore deepening, leading to an increased surface area of 2367 m2 g-1 and significantly enhanced gas adsorption properties with CO2 uptake capacities up to 6.0 mmol g-1 at 1 bar and 1.45 mmol g-1 at 0.15 bar and 273 K along with a isosteric heats of adsorption (Qst) of 30.6 kJ mol-1. In addition, a remarkable H2 uptake capacity of 2.46 and 1.66 wt % at 77 and 87 K, 1 bar along with the Qst value of 10.95 kJ mol-1 at zero coverage was also observed for the caCTF-1-700. Notably, the activation of mesoporous CTF-2 under the same conditions was accompanied by a decrease in its surface area and also in the conversion of mesopores into the micropores, thus leading to a pore deepening/narrowing rather than widening. We attributed this result to the presence of reactive weak spots, triazine moieties, for the chemical activation reaction within the CTF backbone. These results collectively suggest the critical role of chemical and pore characteristics of porous organic polymers in chemical activation to realize solid-sorbents for high capacity gas storage applications.

Decursin from Angelica gigas Nakai Inhibits B16F10 Melanoma Growth Through Induction of Apoptosis.

Decursin, a bioactive phytochemical isolated from Angelica gigas Nakai (danggwi), has shown preclinical anticancer efficacy in various cancer models. However, the antitumor effect of decursin in melanoma models remains undefined. The antitumor activities of decursin were investigated in B16F10 cells in vitro and in vivo. In this study, we show that treatment with decursin inhibited cell proliferation in a dose-dependent manner in B16F10 cells, but not in normal cells. Decursin also induced apoptosis in B16F10 cells, as determined by annexin V-staining assay and transferase-mediated nick-end labeling (TUNEL) staining assay. Decursin increased the phosphorylation of p38 as well as the expression of Bax while decreasing the phosphorylation of extracellular signaling-regulated kinase (ERK) and the expression of Bcl-2 in B16F10 cells. Moreover, decursin activated caspase-3 in B16F10 cells and xenograft tumor tissue. Together, these findings support further investigations into the potential use of decursin in the treatment of melanoma cells.

A Case of Organizing Pneumonia Associated with FOLFIRI Chemotherapy.

The combination chemotherapy of irinotecan with 5-fluorouracil and leucovorin (FOLFIRI regimen) was recently proven to be beneficial in patients with advanced colorectal cancer. Pulmonary toxicity is very rare in adverse effects of irinotecan. No case of organizing pneumonia (also known as bronchiolitis obliterans organizing pneumonia) associated with FOLFIRI chemotherapy has been reported. We experienced a case of a 62-year-old man who presented persistent dry cough and progressive dyspnea after receiving chemotherapy with FOLFIRI regimen. After surgical lung biopsy, the patient was diagnosed with FOLFIRI chemotherapy-induced organizing pneumonia which was successfully treated with steroid therapy.

Forced expression of programmed death-1 gene on T cell decreased the incidence of type 1 diabetes.

Programmed death-1 (PD-1) is a co-inhibitory receptor of the CD28/CTLA-4 family which is expressed on activated T cells and inhibits T cell activation after binding to PD-1 ligands. In animal models, PD-1 regulates autoimmune disease and induces tolerance in pancreas. In this study the effects of PD-1 on type 1 diabetes were examined using PD-1 transgenic mice (Tg). The incidence of autoimmune diabetes induced by multiple low dose of streptozotocin (STZ) was reduced in PD-1 Tg mice. Although the expression of CTLA-4, PD-1 and FoxP3, which are inhibitory molecules of activated T cells, is reduced only on STZ injected wild type (WT) mice, CD4, CD8 and regulatory T cell populations were not changed in all experimental groups. When splenocytes were re-stimulated in ex vivo, the production of IL-2 and IFN-γ and the T cell proliferation were increased in all STZ injected mice, but the increment rate was less in PD-1 Tg groups. Interestingly, macrophages were observed in splenocytes of STZ injected PD-1 Tg at somewhat lower level than macrophage in diabetic wild type mice. In this research, we found out that total numbers of T cell in the experimental groups are not changed, but T cell function is changed, and FoxP3 expression is decreased in pancreas and spleen of diabetes-induced groups. Macrophage frequency might also affects on type 1 diabetes. Although more experimental evidence needs to be provided, these results suggest that ligation of PD-1 and PD-L1/2 may have an effect on macrophages as well as does T cells.

Molecular mechanisms of MHC class I-antigen processing: redox considerations.

Major histocompatibility complex (MHC) class I molecules present antigenic peptides to the cell surface for screening by CD8(+) T cells. A number of ER-resident chaperones assist the assembly of peptides onto MHC class I molecules, a process that can be divided into several steps. Early folding of the MHC class I heavy chain is followed by its association with beta(2)-microglobulin (beta(2)m). The MHC class I heavy chain-beta(2)m heterodimer is incorporated into the peptide-loading complex, leading to peptide loading, release of the peptide-filled MHC class I molecules from the peptide-loading complex, and exit of the complete MHC class I complex from the ER. Because proper antigen presentation is vital for normal immune responses, the assembly of MHC class I molecules requires tight regulation. Emerging evidence indicates that thiol-based redox regulation plays critical roles in MHC class I-restricted antigen processing and presentation, establishing an unexpected link between redox biology and antigen processing. We review the influences of redox regulation on antigen processing and presentation. Because redox signaling pathways are a rich source of validated drug targets, newly discovered redox biology-mediated mechanisms of antigen processing may facilitate the development of more selective and therapeutic drugs or vaccines against immune diseases.