Obesity exacerbates imiquimod‐induced psoriasis‐like epidermal hyperplasia and interleukin‐17 and interleukin‐22 production in mice

Psoriasis is a chronic inflammatory skin disorder that is accompanied by an imbalance between the proliferation and differentiation of keratinocytes. A number of studies have suggested an association between obesity and severe psoriasis; however, it remains to be clarified whether obesity exacerbates psoriasis. To address this unsolved question, we induced psoriasiform dermatitis in mouse models for obesity. We found that obesity exaggerated the severity of psoriasiform dermatitis induced by topical application of the Toll‐like receptor (TLR) 7 agonist, imiquimod. Ear swelling and epidermal hyperplasia were more prominent in the obese mice than in the control mice. When compared to imiquimod‐treated control mice, imiquimod‐treated obese mice expressed higher levels of psoriasis mediators, interleukin‐17A (IL‐17A) and IL‐22 in the skin. Food intake restriction partially abrogated enhanced ear swelling and cytokine overproduction in obese mice. Furthermore, the obesity environment and imiquimod treatment synergistically induced an IL‐17A downstream molecule, regenerating islet‐derived 3γ (Reg3γ), which is a critical molecule for psoriatic epidermal hyperplasia. Palmitic acid, one of the fatty acids released by subcutaneous adipocytes, increased the expression of REG3A (a human homologue of mouse Reg3γ) in both the HaCaT keratinocyte cell line and normal human keratinocytes. Taken together, these results strongly suggest that obesity exacerbates psoriasiform dermatitis in mice by upregulating IL‐17A, IL‐22 and Reg3γ.     

Conformational Change Observed in the Active Site of Class C β-Lactamase MOX-1 upon Binding to Aztreonam

We solved the crystal structure of the class C β-lactamase MOX-1 complexed with the inhibitor aztreonam at 1.9Å resolution. The main-chain oxygen of Ser315 interacts with the amide nitrogen of aztreonam. Surprisingly, compared to that in the structure of free MOX-1, this main-chain carboxyl changes its position significantly upon binding to aztreonam. This result indicates that the interaction between MOX-1 and β-lactams can be accompanied by conformational changes in the B3 β-strand main chain.     

Evaluation of the antiviral potential of the soluble forms of glycoprotein D receptors on ocular herpes caused by HSV-1 and HSV-2 infections in a transgenic mouse model

Ocular herpes, caused by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections, remains an important corneal disease, which may result in loss of vision. Because the frequency of acyclovir resistance in HSV has increased, novel antiviral agents are needed for therapeutic approaches to ocular herpes. Several studies have demonstrated that fusion proteins containing entire ectodomain of HSV glycoprotein D receptors, including herpesvirus entry mediator A (HVEM), nectin-1 and nectin-2, and the Fc portion of human IgG (HVEMIg, nectin-1Ig, and nectin-2Ig, respectively), can exert antiviral effects in vitro and in vivo. Here, to evaluate the antiviral potential of HVEMIg, nectin-1Ig, and nectin-2Ig against ocular infections with HSV, transgenic mice expressing these fusion proteins were ocularly inoculated with HSV-1 and HSV-2. Transgenic mouse lines expressing HVEMIg and nectin-1Ig showed marked resistance to ocular herpes; on the other hand, mouse lines expressing nectin-2Ig did not. Furthermore, to investigate the therapeutic effects of nectin-1Ig, which can neutralize HSVs in vitro against ocular disease, transgenic mouse serum containing nectin-1Ig was dropped into the eyes of wild-type mice after HSV infection. Reduction of severe symptoms could be observed in mice treated with nectin-1Ig serum. These results warrant further study of soluble HVEM and nectin-1 products as preventive and therapeutic agents against ocular herpes caused by HSV-1 and HSV-2 infections, especially nectin-1Ig as a new eye drop.     

Evaluation of 2 thione primers and 3 resin adhesives for silver-palladium-copper-gold alloy bonding.

OBJECTIVE: The purpose of this study was to evaluate 2 thione primers and 3 resin adhesives for enhancement of bonding strength to a silver-palladium-copper-gold alloy. METHOD AND MATERIALS: Two different sized disk specimens (10- and 8-mm diameter by 2.5-mm thick) were prepared from a silver-palladium-copper-gold alloy (Castwell M.C. 12, GC). The specimens were airborne-particle abraded with 50-microm-grain alumina, conditioned either with a thiouracil primer (Metaltite, Tokuyama Dental) or with a triazine dithione primer (V-Primer, Sun Medical), and then bonded with 1 of 3 acrylic resins: a benzoyl peroxide-amine redox-initiated resin adhesive (Multi-Bond, Tokuyama Dental) or a tri-nbutylborane-initiated resin adhesive (Super-Bond C&B and Super-Bond Quick, Sun Medical). For each adhesive, unprimed specimens were prepared as experimental controls. Shear bond strength was determined after thermocycling (100,000 cycles). RESULTS: Use of primers significantly (P < .05) enhanced the bond strength of specimens in all adhesives. Irrespective of the type of primer, the strength of Multi-Bond adhesive was significantly (P < .05) lower than that of Super-Bond C&B and Super-Bond Quick adhesives. The strength of the 2 tri-n-butylborane-initiated adhesives did not differ significantly (P > .05). The mean strength of the Super-Bond C&B adhesive was 40.4 MPa with Metaltite and 37.8 MPa with V-Primer; that of Super-Bond Quick adhesive was 40.9 MPa with Metaltite and 36.5 MPa with V-Primer. CONCLUSION: Use of thione primers effectively enhanced the strength of the bond to the silver-palladium-copper-gold alloy. Furthermore, the combinations of primers and tri-n-butylborane-initiated adhesives were found to be more efficient for bonding.     

Interaction of structural isomers of sucrose in the reaction between sucrose and glucosyltransferases from mutans streptococci

Structural isomers of sucrose, i.e. disaccharides composed of glucose and fructose molecules with different glucosidic linkages, were examined for their effect on the reaction between sucrose and various glucosyltransferases (GTases) from Streptococcus mutans MT8148 and Streptococcus sobrinus 6715. Trehalulose (alpha 1-1), turanose (alpha 1-3), maltulose (alpha 1-4), and palatinose (alpha 1-6) were used as the sucrose analogues. Mutans streptococci were found not to utilize these sucrose analogues. Analysis of enzymatic products of GTase and sucrose with thin layer chromatography clearly revealed that glucan synthesis from [14C]sucrose by the various purified GTase preparations from S. mutans and S. sobrinus was inhibited in the presence of these sucrose analogues except turanose, resulting in the release of increased amounts of [14C]fructose and [14C]oligosaccharides. It was also found that the fructose residues in the oligosaccharides were derived from those of sucrose analogues but not sucrose itself. The Lineweaver-Burk plots of the substrate saturation kinetics of GTase vs sucrose indicated increased Km and Vmax in the presence of sucrose analogue, as compared with sucrose alone. Finally, these sucrose analogues except turanose inhibited sucrose dependent cellular adherence of S. sobrinus 6715 to a glass surface, while they scarcely inhibited the adherence of S. mutans MT8148. Among the analogues, maltulose appeared the most effective inhibitor against GTases in general.