Hydrogels were prepared by contacting air containing 10-50 ppm HO with an aqueous solution containing polymer(s) possessing phenolic hydroxyl (Ph) moieties (polymer-Ph) and horseradish peroxidase (HRP). In this system, HRP catalyzes cross-linking of the Ph moieties by consuming HO diffused from the air. The hydrogelation rate and mechanical properties of the resultant hydrogels can be tuned by controlling the HO concentration in air, the exposure time of the air containing HO to the solution containing polymer-Phs and HRP, and the HRP concentration. The shortest hydrogelation time of the solution stirred in air containing 16 ppm HO was 6 s. Based on these findings, this hydrogelation system was applied to microextrusion bioprinting, in which bioink containing polymer-Phs, HRP, and cells were extruded into air containing HO. The superior cytocompatibility of the bioprinting method was confirmed by more than 90% viability, migration, and the spreading of mouse fibroblast 10T1/2 cells enclosed in the bioprinted hydrogels composed of derivatives of hyaluronic acid and gelatin, both possessing Ph moieties. These results demonstrate the great potency of HRP-catalyzed hydrogelation consuming HO supplied in surrounding air for various biomedical applications, especially bioprinting.

The pregnane X receptor (PXR) is understood to be the key regulator for gene expression of such drug-metabolizing enzymes and transporters as multidrug-resistant protein 1 (MDR1) and the cytochrome P450 (CYP) family. We examined the effect of dietary phytochemicals on the PXR-dependent transcriptional activity in human intestinal LS180 cells by using a reporter assay. Among approximately 40 kinds of phytochemicals, tangeretin and ginkgolides A and B markedly induced the PXR-dependent transcriptional activity and also the activity of the human MDR1 promoter. The expression levels of MDR1 mRNA as well as of CYP3A4 mRNA, another gene regulated by PXR, were significantly increased by these phytochemicals. Furthermore, an increase was observed of the MDR1 protein and its functional activity by tangeretin and by ginkgolides A and B. These findings strongly suggest that tangeretin and ginkgolides A and B activated PXR, thereby regulating detoxification enzymes and transporters in the intestines.

Since 1986, the authors have been conducting conservative treatment for idiopathic scoliosis with the combination of brace treatment and physical treatment (side shift exercise and hitch exercise). A total of 328 female patients with adolescent idiopathic scoliosis who were at least 10 years of age at the first visit, with Cobb angle of 10 degrees at the minimum and followed until after 15 years of age or skeletal maturity were included. The average Cobb angle was 32.4 degrees and the average age was 13.8 years at the first visit. Surgery was recommended when curvature progressed to >50 degrees. Twenty of 328 patients (6.1%) with more severe curves to begin with (mean Cobb angle at admission of 48.5 +/- 9.3 degrees ) progressed to 62.2 +/- 8.5 degrees and were treated with spinal fusion by the age of 16.0 +/- 2.6 years. The remaining 308 patients, of comparable age at inception of treatment but with a smaller original mean Cobb angle (32.4 +/- 11.1 degrees ), showed no significant increase in magnitude of curvature (mean 33.6 +/- 11.5 degrees ) by the time of discharge (18.6 +/- 3.1 years). The fact that curvature magnitude was maintained at <35 degrees means that these patients will have a good prognosis for avoiding dramatic progression during adulthood.

The total cross sections were measured for coherent double neutral-pion photoproduction on the deuteron at incident energies below 0.9 GeV for the first time. No clear resonancelike behavior is observed in the excitation function for W γd = 2.38-2.61 GeV, where the d * (2380) dibaryon resonance observed at COSY is expected to appear. The measured excitation function is consistent with the existing theoretical calculation for this reaction. The upper limit of the total cross section is found to be 0.034 µb for the dibaryon resonance at W γd = 2.37 GeV (90% confidence level) in the γd → π 0 π 0 d reaction.

Neuronal plasticity in the pain-processing pathway is thought to be a mechanism underlying pain hypersensitivity and negative emotions occurring during a pain state. Recent evidence suggests that the activation of astrocytes in the anterior cingulate cortex (ACC) contributes to the development of negative emotions during pain hypersensitivity after peripheral inflammation. However, it is unknown whether these activated astrocytes contribute to neuronal plasticity in the ACC. In this study, by using optical imaging with voltage- and Ca(2+)-sensitive dyes, we examined the long-term facilitation of neuronal excitation induced by high-frequency conditioning stimulation (HFS) in ACC slices of control mice and mice with peripheral inflammation induced by the injection of complete Freund adjuvant (CFA) to the hind paw. Immunoreactivity of glial fibrillary acidic protein in laminae II-III of the ACC in the CFA-injected mice was higher than in the control mice. Neuronal excitation in ACC slices from the CFA-injected mice was gradually increased by HFS, and the magnitude of this long-term facilitation was greater than in the control mice. The long-term facilitation in the CFA-injected mice was inhibited by the astroglial toxin, the N-methyl-d-aspartate (NMDA) receptor antagonist and NMDA receptor glycine binding site antagonist. The increase of intracellular Ca(2+) concentration in astrocytes during HFS was higher in the CFA-injected mice than in the control mice and was inhibited by l-α-aminoadipate (l-α-AA). These results suggest that the activation of astrocytes in the ACC plays a crucial role in the development of negative emotions and LTP during pain hypersensitivity after peripheral inflammation.