2-Methacryloyloxyethyl phosphorylcholine (MPC)-polymer suppresses an increase of oral bacteria: a single-blind, crossover clinical trial.

OBJECTIVES: The biocompatible 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymers, which mimic a biomembrane, reduce protein adsorption and bacterial adhesion and inhibit cell attachment. The aim of this study is to clarify whether MPC-polymer can suppress the bacterial adherence in oral cavity by a crossover design. We also investigated the number of Fusobacterium nucleatum, which is the key bacterium forming dental plaque, in clinical samples. MATERIALS AND METHODS: This study was a randomized, placebo-controlled, single-blind, crossover study, with two treatment periods separated by a 2-week washout period. We conducted clinical trial with 20 healthy subjects to evaluate the effect of 5% MPC-polymer mouthwash after 5 h on oral microflora. PBS was used as a control. The bacterial number in the gargling sample before and after intervention was counted by an electronic bacterial counter and a culture method. DNA amounts of total bacteria and F. nucleatum were examined by q-PCR. RESULTS: The numbers of total bacteria and oral streptcocci after 5 h of 5% MPC-polymer treatment significantly decreased, compared to the control group. Moreover, the DNA amounts of total bacteria and F. nucleatum significantly decreased by 5% MPC-polymer mouthwash. CONCLUSIONS: We suggest that MPC-polymer coating in the oral cavity may suppress the oral bacterial adherence. CLINICAL RELEVANCE: MPC-polymer can be a potent compound for the control of oral microflora to prevent oral infection.

Differential regulation of the sphere formation and maintenance of cancer-initiating cells of malignant mesothelioma via CD44 and ALK4 signaling pathways.

Malignant mesothelioma (MM) has a poor prognosis and is largely resistant to standard treatments, so it is important to seek novel therapeutic strategies for this disease. Cancer-initiating cells (CICs) were previously identified in MM using stem cell-associated markers in combination with spheroid cultures. However, the mechanisms underlying the induction and maintenance of CICs in MM remain to be fully explored. Here we showed that the CICs, which had high aldehyde dehydrogenase levels (ALDHbright) and stem cell-associated genes, were expanded in MM cells cultured under sphere-forming conditions. The MM spheroids also initiated tumors in immunodeficient mice more efficiently than did conventional adherent MM cells. In the MM spheroids, the expression of hyaluronan (HA) synthases was upregulated. Inhibiting the HA synthesis or CD44 functions by gene knockdown or neutralizing antibody abolished the formation of large-sized spheroids and the expansion of ALDHbright CICs. The expression of activin-A was also increased in the spheroids, and type I activin-A receptor subunit (ALK4) was upregulated in the ALDHbright CICs. The neutralization of activin-A or functional inactivation of ALK4 diminished the ALDHbright CICs without affecting spheroid formation. The knockdown of CD44 or ALK4 strongly suppressed the tumor growth in immunodeficient mice. These results together suggest that the HA-CD44 and activin-A-ALK4 pathways differentially regulate the spheroid formation and maintenance of ALDHbright CICs in MM cells, and that both pathways play critical roles in tumor growth in immunodeficient hosts. Our findings provide a novel therapeutic option for MM that targets signaling pathways that promote the CIC compartment through CD44 and ALK4.

Correlation between Odor Concentration and Volatile Organic Compounds (VOC) Composition of Environmental Tobacco Smoke (ETS).

We examined the correlation between the odor concentration and the chemical composition of environmental tobacco smoke (ETS). Three types of ETS samples were prepared: secondhand smoke (SHS), thirdhand smoke (THS), and field ETS samples from an outside smoking area. The odor concentrations of the ETS, SHS, and THS samples were determined by the triangle-odor-bag method, and the chemical compositions were determined by proton transfer mass spectrometry. The odor concentration of the SHS samples was three or four orders of magnitude higher than that of the field ETS samples, and three orders of magnitude higher than that of the THS samples. The concentration ratios of the constituent chemicals in THS to those in SHS were about 10-4, corresponding to the ratio of the odor concentration. The concentration ratios of the constituent chemicals in the field ETS samples were much lower than the ratios of the odor concentrations. This suggests that the main contributing components to the odor of the field ETS samples are different from those in SHS and THS. The main contributors of the odor in the field ETS samples could be acetaldehyde, acetonitrile, acetic acid, and other unknown components with a mass-to-charge ratio (m/z) of 39 and 43.

Serum soluble CD163 levels in patients with influenza-associated encephalopathy.

BACKGROUND: Influenza-associated encephalopathy (IE) is a serious complication during influenza viral infection. Common clinical symptoms of IE include seizures and progressive coma with high-grade fever. We previously reported that hypercytokinemia and monocyte/macrophage activation may play an important role in the pathogenesis of IE. CD163 is a scavenger receptor for hemoglobin-haptoglobin complexes and is expressed by monocytes/macrophages. Proteolytic cleavage of monocyte-bound CD163 by matrix metalloproteinases releases soluble CD163 (sCD163). However, there have been no reports regarding serum sCD163 levels in IE patients. METHODS: We measured serum levels of sCD163 as a marker of monocyte/macrophage activation in IE patients with poor outcomes, those without neurological sequelae, influenza patients without IE, and control subjects. RESULTS: Serum sCD163 levels were significantly higher in IE patients with poor outcomes than in those without neurological sequelae. In particular, sCD163 levels in cases of death were significantly higher than those in other cases. CONCLUSIONS: Our results suggest that monocyte/macrophage activation is related to the pathogenesis of severe IE.

Visible light-induced water oxidation catalyzed by molybdenum-based polyoxometalates with mono- and dicobalt(III) cores as oxygen-evolving centers.

The Mo-based polyoxometalates containing mono- and dicobalt(III) catalyst cores, [CoMo(6)O(24)H(6)](3-) and [Co(2)Mo(10)O(38)H(4)](6-), were found to serve as O(2)-evolving catalysts in a system consisting of tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)(3)(2+)) and sodium persulfate (S(2)O) in an aqueous borate buffer solution at pH 8.0. Kinetics of O(2) evolution reveals that the higher cobalt nuclearity is not necessary to attain the highly active nature of the catalyst.

Intraneuronal amyloid ß oligomers cause cell death via endoplasmic reticulum stress, endosomal/lysosomal leakage, and mitochondrial dysfunction in vivo.

Intraneuronal accumulation of amyloid ß (Aß) is an early pathological change in Alzheimer's disease. Previously, we showed that the E693Δ mutation (referred to as the "Osaka" mutation) of amyloid precursor protein (APP) caused intracellular accumulation of Aß oligomers and apoptosis in transfected COS-7 cells. We also showed that transgenic mice expressing APP(E693Δ) (APP(OSK) ) displayed both an age-dependent accumulation of intraneuronal Aß oligomers from 8 months of age and apparent neuronal loss in the hippocampus at 24 months of age. These findings indicate that intraneuronal Aß oligomers cause cell death, but the mechanism of this process remains unclear. Accordingly, here we investigated the subcellular localization and toxicity of intraneuronal Aß oligomers in APP(OSK) -transgenic mice. We found Aß oligomer accumulation in the endoplasmic reticulum (ER), endosomes/lysosomes, and mitochondria in hippocampal neurons of 22-month-old mice. We also detected up-regulation of Grp78 and HRD1 (an E3 ubiquitin ligase), leakage of cathepsin D from endosomes/lysosomes into cytoplasm, cytochrome c release from mitochondria, and activation of caspase-3 in the hippocampi of 18-month-old mice. Collectively, our findings suggest that intraneuronal Aß oligomers cause cell death by inducing ER stress, endosomal/lysosomal leakage, and mitochondrial dysfunction in vivo. © 2011 Wiley-Liss, Inc.

Photochemical and thermal hydrogen production from water catalyzed by carboxylate-bridged dirhodium(II) complexes.

A series of dinuclear Rh(II) complexes, [Rh(2)(µ-OAc)(4)(H(2)O)(2)] (HOAc = acetic acid) (1), [Rh(2)(µ-gly)(4)(H(2)O)(2)] (Hgly = glycolic acid) (2), [Rh(2)(µ-CF(3)CO(2))(4)(acetone)(2)] (3), and [Rh(2)(bpy)(2)(µ-OAc)(2)(OAc)(2)] (4), were found to serve as H(2)-evolving catalysts in a three-component system consisting of tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)(3)(2+)), methylviologen (MV(2+)), and ethylenediaminetetraacetic acid disodium salt (EDTA). It was also confirmed that thermal reduction of water into H(2) by MV(+)˙, in situ generated by the bulk electrolysis of MV(2+), is effectively promoted by 1 as a H(2)-evolving catalyst. The absorption spectra of the photolysis solution during the photocatalysis were monitored up to 6 h to reveal that the formation of photochemical or thermal byproducts of MV(+)˙ is dramatically retarded in the presence of the Rh(II)(2) catalysts, for the H(2) formation rather than the decomposition of MV(+)˙ becomes predominant in the presence of the Rh(II)(2) catalysts. The stability of the Rh(II)(2) dimers was confirmed by absorption spectroscopy, (1)H NMR, and ESI-TOF mass spectroscopy. The results indicated that neither elimination nor replacement of the equatorial ligands take place during the photolysis, revealing that one of the axial sites of the Rh(2) core is responsible for the hydrogenic activation. The quenching of Ru*(bpy)(3)(2+) by 1 was also investigated by luminescence spectroscopy. The rate of H(2) evolution was found to decrease upon increasing the concentration of 1, indicating that the quenching of Ru*(bpy)(3)(2+) by the Rh(ii)(2) species rather than by MV(2+) becomes predominant at the higher concentrations of 1. The DFT calculations were carried out for several possible reaction paths proposed (e.g., [Rh(II)(2)(µ-OAc)(4)(H(2)O)] + H(+) and [Rh(II)(2)(µ-OAc)(4)(H(2)O)] + H(+) + e(-)). It is suggested that the initial step is a proton-coupled electron transfer (PCET) to the Rh(II)(2) dimer leading to the formation of a Rh(II)Rh(III)-H intermediate. The H(2) evolution step is suggested to proceed either via the transfer of another set of H(+) and e(-) to the Rh(II)Rh(III)-H intermediate or via the homolytic radical coupling through the interaction of two Rh(II)Rh(III)-H intermediates.