Involvement of N-acetyl-D-galactosamine-specific lectin in biofilm formation by the periodontopathogenic bacterium, Eikenella corrodens

Eikenella corrodens is known not only as one of the periodontopathogenic bacteria but also as a pathogen associated with many infectious diseases of humans. Dental plaque is a complex biofilm community comprised of many bacterial species. E. corrodens has a lectin on its cell surface that is thought to be involved in its pathogenicity. In this study, we found that E. corrodens forms a biofilm on a polystyrene surface. A biofilm was formed at the bottom of the wells in microtiter plates after 24 h. Microcolonies were observed as the amount of biofilm became larger. When anaerobic respiration was repressed due to nitrate limitation, the biofilm formed only at the air-water interface. Strain 1073 and HU, which have higher lectin activity, formed a biofilm more effectively than other strains. Biofilm formation was repressed by the addition of N-acetyl-D-galactosamine. These results suggest that the lectin on the surface of E. corrodens might be involved in biofilm formation.     

Memory Deficit in Mice Administered Aluminum–maltolate Complex

Recently, aluminum (Al) has been identified as one of the environmental factors responsible for cause certain nerve degeneration diseases, particularly, Alzheimer’s disease (AD). However, the relationship between Al and AD is controversial. We previously examined whether Al induced neurotoxin in the brain of mice when aluminum–maltolate complex (ALM) was administered daily for 120 days. Our results revealed that Al accumulated in the brain induced oxidative stress, and the nerve degeneration was detected in the brain of the ALM-treated group. On the basis of these results, we have tried to examine whether the incorporated Al affects memory in mice with regard to an indicator of spatial memory deficits depending on the chemical forms of Al, namely, as an ion (AlCl₃) and in the form of a complex (ALM). We administered saline, AlCl₃, and ALM at a concentration of 40 μmol Al/kg body weight to mice by daily ip injections for 60 days. We assessed spatial memory by a water maze task and determined the Al levels in the brain of the mice by the neutron activation analysis method. Spatial memory deficit as an indicator of the swimming time was related to Al accumulation in the brain of mice; the chemical form of the Al compound was important in order to exhibit the memory deficit in mice; the uptake of Al is higher in mice when it is administered in a complex form than in an ionic form.     

The ATR-Chk1 pathway plays a role in the generation of centrosome aberrations induced by Rad51C dysfunction

Rad51C is a central component of two complexes formed by five Rad51 paralogs in vertebrates. These complexes are involved in repairing DNA double-strand breaks through homologous recombination. Despite accumulating evidence suggesting that the paralogs may prevent aneuploidy by controlling centrosome integrity, Rad51C's role in maintaining chromosome stability remains unclear. Here we demonstrate that Rad51C deficiency leads to both centrosome aberrations in an ATR-Chk1-dependent manner and increased aneuploidy in human cells. While it was reported that Rad51C deficiency did not cause centrosome aberrations in interphase in hamster cells, such aberrations were observed in interphase in HCT116 cells with Rad51C dysfunction. Caffeine treatment and down-regulation of ATR, but not that of ATM, reduced the frequency of centrosome aberrations in the mutant cells. Silencing of Rad51C by RNA interference in HT1080 cells resulted in similar aberrations. Treatment with a Chk1 inhibitor and silencing of Chk1 also reduced the frequency in HCT116 mutants. Accumulation of Chk1 at the centrosome and nuclear foci of γH2AX were increased in the mutants. Moreover, the mutant cells had a higher frequency of aneuploidy. These findings indicate that the ATR-Chk1 pathway plays a role in increased centrosome aberrations induced by Rad51C dysfunction.     

Serum metabolomics as a novel diagnostic approach for pancreatic cancer

Pancreatic cancer is one of the leading causes of cancer-related death, and there is currently little hope of a cure because there are no effective biomarkers for its early detection. Therefore, the search for novel biomarkers that would allow the early detection of pancreatic cancer is ongoing. In this study, the differences between the metabolomes of pancreatic cancer patients with Stage III, Stage IVa, or Stage IVb disease (n = 20) and healthy volunteers (n = 9) were evaluated by metabolomics, which is the endpoint of the Omics cascade and therefore the last step in the cascade before the phenotype. In our experimental conditions using gas chromatography mass spectrometry (GC/MS), a total of 60 metabolites were detected in serum, and the levels of 18 of the 60 metabolites were significantly changed in pancreatic cancer patients compared with those in healthy volunteers. Then, Principal Component Analysis (PCA), which is a basic form of Multiple Classification Analysis, was performed, and the PCA scores plots based on the 60 metabolites highlighted the metabolomic differences between the pancreatic cancer patients and healthy volunteers. The differences between different stages of pancreatic cancer were also assessed by Partial Least Squares Discriminant Analysis (PLS-DA), which is one of Multiple Classification Analysis, and we found that it was possible to discriminate among the Stage III, Stage IVa, and Stage IVb groups. In addition, values of the 9 metabolites in 1 Stage I pancreatic cancer patient were similar to those obtained from the Stage III, Stage IVa, and Stage IVb pancreatic cancer patients. Our findings will aid the discovery of novel biomarkers that allow the early detection of pancreatic cancer by metabolomic approaches.     

Chemical speciation of insulinomimetic VO(IV) complexes of pyridine-N-oxide derivatives: binary and ternary systems

In order to estimate the impact of the low-molecular-mass (l.m.m.) VO(IV) binders of blood serum on the potentially insulin-enhancing compound VO(HPO)(2) (HPO, 2-hydroxypyridine-N-oxide): and VO(MPO)(2) (MPO, 2-mercaptopyridine-N-oxide), the speciation in the binary system VO(IV)-HPO and VO(IV)-MPO and in the ternary systems VO(IV)-HPO(MPO)-ligand B (B=oxalate, lactate, citrate or phosphate) was studied by pH-potentiometry. The stability constants of the complexes formed were determined in aqueous solution at I=0.2 M (KCl) and T=25 degrees C. The most probable binding modes of the complexes were determined by EPR method. The pyridine-N-oxides were found to form very stable bis complexes, which are predominant in the pH range 2-7. The results in the ternary systems demonstrate that only the citrate is a strong enough VO(IV) binder to compete with the carrier ligands. The binding ability of the high-molecular-mass (h.m.m.) serum proteins albumin and transferrin were also assessed and transferrin was found to be an efficient binder molecule. The actual solution state of these compounds in blood serum is compared with that of other insulin-mimic VO(IV) complexes.     

Fine structure of the eggs of blowflies Aldrichina grahami and Chrysomya pacifica (Diptera: Calliphoridae)

We report here the fine structure of the eggs of blowflies Aldrichina grahami (Aldrich) and Chrysomya pacifica Kurahashi. For A. grahami, the plastron is wide and extends to almost the entire length of the eggs. The plastron near the micropyle is truncated. The polygonal patterns of chorionic sculpture bear a distinct swollen boundary. Regarding C. pacifica, the plastron is narrow and extends to almost the entire length of the eggs. The plastron near the micropyle bifurcates to a Y-shape, but the arms of the 'Y' are short. Information presented herein allows some distinctive features to differentiate among eggs of blowfly species.     

The action mechanism of zinc(II) complexes with insulinomimetic activity in rat adipocytes

Zinc (Zn), an essential trace element, and its complexes have recently been known to exhibit insulinomimetic activities. However, the action mechanism of Zn(II) has yet been obscure. The purpose of the present study was to estimate the action mechanism of the Zn(II) complexes. We found first that Zn given in the chemical forms such as Zn(maltolate)2 and Zn(threoninate)2 complexes is highly uptaken in the isolated rat adipocytes compared with that of Zn(picolinate)2. Then, the action mechanism for the insulinomimetic activities was examined in terms of free fatty acid release from the adipocytes. Four Zn(II) compounds, ZnSO4, Zn(picolinate)2, Zn(maltolate)2, and Zn(threoninate)2, inhibited the free fatty acid release from the adipocytes treated with epinephrine (adrenaline). By using several inhibitors for fatty acids and glucose metabolisms in the adipocytes, the following results were obtained. (1) Zn(picolinic acid)2 complex acts on the insulin receptor and PI3-k, which relate to the glucose uptake, as indicated by the experiments using hydroxy-2-naphthalenylmethyl phosphonic acid tris acetoxy methyl ester (HNMPA-(AM)3) and wortmannin, respectively. (2) ZnSO4, and Zn(maltolate)2 and Zn(threoninate)2 complexes affect a glucose transporter 4 (GLUT 4), which is involved in the glucose uptake as indicated by the results using cytochalasin B. (3) Four Zn(II) compounds affect the activation of the phosphodiesterase as indicated by the experiments using cilostamide. These results indicate that the Zn(II) compounds promote the glucose uptake into the adipocytes by affecting at least three sites in the adipocytes, which in turn normalize the blood glucose levels in the experimental diabetic animals.     

Biodegradable stents as a platform to drug loading

Despite technical and mechanical improvement in coronary stents the incidence of restenosis caused by in-stent neointimal hyperplasia remains high. Oral administration of numerous pharmacological agents has failed to reduce restenosis after coronary stenting in humans, possibly owing to insufficient local drug concentration. Therefore, drug-eluting stents were developed as a vehicle for local drug administration. The authors developed a new drug-eluting polymer stent that is made of poly-l-lactic acid polymer mixed with tranilast, an anti-allergic drug that inhibits the migration and proliferation of vascular smooth muscle cells induced by platelet-derived growth factor and transforming growth factor->1. Polymer stents might be superior to polymer-coated metallic stents as local drug delivery stents in terms of biodegradation and the amount of loaded drug. Drug-mixed polymer stents can be loaded with a larger amount of drug than can drug-coated metallic stents because the polymer stent struts can contain the drug. Clinical application is required to assess the safety and efficacy of drug-eluting polymer stents against stent restenosis.