Pd nanostructures have been synthesized by electrochemical deposition in a highly diluted solution. The morphology of the as-synthesized Pd nanostructures can be solely controlled by depositing potentials because the driving force for variable crystal nucleation and growth is only correlated with overpotentials. The as-prepared Pd nanostructures deposited at -0.25 V show a 3D feather-like dendritic morphology with a nanoscale structure, which exhibits high electrocatalysis activity towards ethanol electro-oxidation in alkaline media. Moreover, the present electrochemical method can be easily applied to fabricate other noble metal nanostructures.

RNA virus infection is recognized by retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), RIG-I, and melanoma differentiation-associated gene 5 (MDA5) in the cytoplasm. RLRs are comprised of N-terminal caspase-recruitment domains (CARDs) and a DExD/H-box helicase domain. The third member of the RLR family, LGP2, lacks any CARDs and was originally identified as a negative regulator of RLR signaling. In the present study, we generated mice lacking LGP2 and found that LGP2 was required for RIG-I- and MDA5-mediated antiviral responses. In particular, LGP2 was essential for type I IFN production in response to picornaviridae infection. Overexpression of the CARDs from RIG-I and MDA5 in Lgp2(-/-) fibroblasts activated the IFN-beta promoter, suggesting that LGP2 acts upstream of RIG-I and MDA5. We further examined the role of the LGP2 helicase domain by generating mice harboring a point mutation of Lys-30 to Ala (Lgp2(K30A/K30A)) that abrogated the LGP2 ATPase activity. Lgp2(K30A/K30A) dendritic cells showed impaired IFN-beta productions in response to various RNA viruses to extents similar to those of Lgp2(-/-) cells. Lgp2(-/-) and Lgp2(K30A/K30A) mice were highly susceptible to encephalomyocarditis virus infection. Nevertheless, LGP2 and its ATPase activity were dispensable for the responses to synthetic RNA ligands for MDA5 and RIG-I. Taken together, the present data suggest that LGP2 facilitates viral RNA recognition by RIG-I and MDA5 through its ATPase domain.

Viral infections are detected by sensor molecules, which initiate innate antiviral responses, including the activation of type I interferons (IFNs) and proinflammatory cytokines. These cytokines are responsible for not only inhibiting viral replication in infected cells but also regulating the induction of adaptive immunity, leading to the swift eradication of viruses. Recent advances in the identification of pathogen receptors in the innate immune system have revealed that distinct types of sensors play a role in the detection of viral nucleic acids in different ways; Toll-like receptors (TLRs), which detect viral DNA or RNA in endosomal compartments in immune cells, retinoic acid inducible gene-I (RIG-I)-like receptors (RLRs), which recognise viral RNA in the cytoplasm, and DNA sensors, which detect cytoplasmic viral DNA. Since these sensors have to exclusively recognise viral infections, it is intriguing to understand how they distinguish self nucleic acids from foreign viral ones. Here, we review the current knowledge of the recognition of viral nucleic acids by these sensor molecules and the signal transduction machinery. Copyright (c) 2009 John Wiley & Sons, Ltd.

4-Alkylidenehydrazino-1H-pyrazolo[3,4-d]pyrimidines, 4-arylmethylidenehydrazino-1H-pyrazolo[3,4-d]pyrimidines, and 2-substituted 7H-pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidines as potential xanthine oxidase inhibitors were docked into the active site of the bovine milk xanthine dehydrogenase using two scoring functions involved in AutoDock 3.05 and the CAChe 6.1.10. The correlation coefficiency obtained between the AutoDock binding energy and IC(50) of the inhibitors was better than that obtained by the CAChe-PMF docking score. Many ligands exhibited one to four hydrogen bonds within the active site, where the detected hydrogen bonds by CAChe was identified quantitatively in the docked conformation by using MOPAC 2002. These ligands were docked into a long, narrow channel of the enzyme leading to the molybdopterin active moiety, with hydrogen bonding and electrostatic interaction between the planar aromatic moiety of the ligand and the enzyme. Furthermore, SAR among inhibitors was investigated, which revealed that the oxo group of pyrazolopyrimidine analogs is essential for its activity and the tricyclic derivatives are shown to be more potent than bicyclic ones. The mode of interaction of the docked inhibitors was described in details.

Summary Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K(1)), menaquinone (vitamin K(2)) and menadione (vitamin K(3)). Recently, it was reported that vitamin K, especially vitamins K(1) and K(2), exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K(3) in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K(3) inhibited the tumour necrosis factor (TNF)-alpha-evoked translocation of nuclear factor (NF)-kappaB into the nucleus, although vitamins K(1) and K(2) did not. Vitamin K(3) also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-kappaB and production of TNF-alpha in mouse macrophage RAW264.7 cells. Moreover, the addition of vitamin K(3) before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K(3) also suppressed the LPS-induced increase in the serum TNF-alpha level and inhibited the LPS-evoked nuclear translocation of NF-kappaB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K(3) may be an effective therapeutic strategy against acute lung injury including ARDS.

A hybrid library of the marine natural products dictyostatin and discodermolide, incorporating the taxol or taxotere side chains, were synthesised; preliminary biological evaluation in the PANC-1 cancer cell line revealed significant antiproliferative activity, demonstrating that a macrolide scaffold is an effective surrogate for the baccatin core of taxol.

BACKGROUND: Clinicopathological features of remnant gastric cancers after gastrectomy for synchronous multiple gastric cancers have not been fully addressed. In this study we evaluated the potential risk factors attributable to the development of remnant gastric cancers after initial gastrectomy for multiple gastric cancers. METHODS: We retrospectively analyzed 3042 patients diagnosed with gastric cancers who underwent a gastrectomy. Of these, 922 total gastrectomy cases were excluded and the remaining 2120 cases were clinicopathologically investigated. RESULTS: Among the 2120 patients, 1967 patients were histopathologically diagnosed with a solitary lesion and 153 patients with multiple lesions. The incidence of remnant gastric cancers was higher in patients with multiple lesions at initial surgery than in those with a solitary lesion (7/153 [4.5%] vs. 9/1967 [0.45%], p < 0.05). Among the patients with remnant gastric cancer, the percentages of cases with a combination of undifferentiated-type carcinoma (Type C), differentiated-type carcinoma (Type A), and differentiated- and undifferentiated-type carcinoma (Type B) as initial lesions were 15.0, 3.3, and 2.7%, respectively. Compared with those with no remnant gastric cancer, the incidence of the combination of undifferentiated-type carcinoma (Type C) as an initial lesion was significantly associated with a higher (p < 0.05) incidence of remnant gastric cancer. CONCLUSION: As initial lesions, a combination of undifferentiated-type carcinoma was a potential risk factor for the development of remnant gastric cancers after initial gastrectomy.

A 36-year-old woman with systemic lupus erythematosus (SLE) and nephrotic syndrome showed massive ascites. She was admitted to our hospital because of edema in both legs and a remarkably distended non-tender abdomen. On admission, massive ascites was observed in the abdominal CT scan findings. Laboratory examination of the ascites showed low levels of total protein (1.5 g/dL), albumin (0.5 g/dL) and LDH (89 IU/L), which were characterized as ascites per diapedesis. In addition, she was diagnosed with SLE and nephrotic syndrome from the clinical and laboratory findings. We treated her with steroid therapy, including methylprednisolone plus therapy. Although the serological abnormalities with SLE had normalized and urinary protein almost disappeared on the 51th hospital day, the ascites had not improved at all. These findings indicated that she had suffered from chronic lupus peritonitis, complicated with nephrotic syndrome and we had continued to treat her with prednisolone for a long time. The ascites was remarkably diminished at 220 days after admission. We believe that in addition to nephrotic syndrome, impaired vascular circulation caused by chronic lupus peritonitis might have contributed to accumulation of the massive ascites.