Development of Injectable Polydactyly-Derived Chondrocyte Sheets

We are conducting a clinical study of the use of allogeneic polydactyly-derived chondrocyte sheets (PD sheets) for the repair of articular cartilage damage caused by osteoarthritis. However, the transplantation of PD sheets requires highly invasive surgery. To establish a less invasive treatment, we are currently developing injectable fragments of PD sheets (PD sheets-mini). Polydactyly-derived chondrocytes were seeded in RepCell™ or conventional temperature-responsive inserts and cultured. Cell counts and viability, histology, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR), and flow cytometry were used to characterize PD sheets-mini and PD sheets collected from each culture. To examine the effects of injection on cell viability, PD sheets-mini were tested in four experimental conditions: non-injection control, 18 gauge (G) needle, 23G needle, and syringe only. PD sheets-mini produced similar amounts of humoral factors as PD sheets. No histological differences were observed between PD sheets and PD sheets-mini. Except for COL2A1, expression of cartilage-related genes did not differ between the two types of PD sheet. No significant differences were observed between injection conditions. PD sheets-mini have characteristics that resemble PD sheets. The cell viability of PD sheets-mini was not significantly affected by needle gauge size. Intra-articular injection may be a feasible, less invasive method to transplant PD sheets-mini.     

Daily Ingestion of Aloe Vera Gel Powder Containing Aloe Sterols Prevents Skin Photoaging in OVX Hairless Mice

Estrogen deficiencies associated with menopause accelerate spontaneous skin aging and stimulate the ultraviolet (UV) irradiation‐induced photoaging of skin. However, food compositions with the potential to ameliorate the UV irradiation‐induced acceleration of skin aging with menopause have not yet been investigated in detail. In the present study, we examined the ability of plant sterols derived from Aloe vera gel to prevent the UV irradiation‐induced acceleration of skin aging in ovariectomized mice. Skin transepidermal water loss (TEWL) was significantly higher in the ovariectomy group than in the sham operation group following UVB irradiation, whereas skin elasticity was significantly lower. Ultraviolet B (UVB) irradiation induced greater reductions in skin hyaluronic acid levels and more severe collagen fiber damage in the derims in the ovariectomy group than in the sham group. The intake of AVGP significantly ameliorated this acceleration in skin aging by reducing the expression of matrix metalloproteinases (MMPs) and increasing that of epidermal growth factor (EGF) and hyaluronan synthase (HAS) in the skin. These results indicate that AVGP supplementation prevents skin damage induced by UVB irradiation and ovariectomy in part by inhibiting damage to the extracellular matrix.     

Synthesis and Crystal Structure of a New Layered Carbide ZrAl4C4

A new ternary layered carbide, ZrAl₄C₄, has been synthesized and characterized by X-ray powder diffraction. The crystal structure was successfully determined using direct methods and further refined by the Rietveld method. The crystal is trigonal (space group P 3 m 1, Z =2) with lattice dimensions a =0.332471(3) nm, c =2.19717(2) nm, and V =0.210330(3) nm³. The final reliability indices calculated from the Rietveld refinement were R _wp=6.56% ( S =1.58), R _p=4.92%, R _B=1.90%, and R _F=0.98%. The compound shows an intergrowth structure with NaCl-type [Zr₂C₃] thin slabs separated by Al₄C₃-type [Al₈C₇] layers.     

Decomposition of methane in the presence of carbon dioxide over Ni catalysts

Methane decomposition was carried out in the presence of CO₂ over the nickel catalysts. Spherical alumina and glycothermally synthesized zirconia were used as the catalyst supports. In the presence of CO₂, CH₄ was decomposed in the same fashion as pure methane decomposition, and fibrous carbons were formed. However, the formation of hydrogen, carbon monoxide, and water continued even after the apparent carbon formation ceased, and this phenomenon was observed irrespective of the support materials. These results showed a sharp contrast against the results for the pure methane decomposition where the catalyst was completely deactivated when the carbon formation ceased. Further carbon formation was observed when the feed gas containing CO₂ was replaced with pure CH₄. Mechanisms for these phenomena are discussed from the thermodynamical point of view.     

Role of ERK Pathway in the Pathogenesis of Atopic Dermatitis and Its Potential as a Therapeutic Target

Atopic dermatitis (AD) is an eczematous skin disorder characterized by type 2 inflammation, barrier disruption, and intense itch. In addition to type 2 cytokines, many other cytokines, such as interferon gamma (IFN-γ), interleukin 17 (IL-17), and interleukin 22 (IL-22), play roles in the pathogenesis of AD. It has been reported that the extracellular signal-regulated kinase (ERK) is downstream of such cytokines. However, the involvement of the ERK pathway in the pathogenesis of AD has not yet been investigated. We examined the expression of p-ERK in mouse and human AD skin. We also investigated the effects of the topical application of an ERK inhibitor on the dermatitis score, transepidermal water loss (TEWL), histological change, and expression of filaggrin, using an AD-like NC/Nga murine model. The effects of an ERK inhibitor on filaggrin expression in normal human epidermal keratinocytes (NHEKs) and on chemokine production from bone marrow-derived dendritic cells (BMDCs) were also evaluated. p-ERK was highly expressed in mouse and human AD skin. Topical application of an ERK inhibitor alleviated the clinical symptoms, histological changes, TEWL, and decrease in expression of filaggrin in the AD-like NC/Nga murine model. The ERK inhibitor also restored the IL-4 induced reduction in the expression of filaggrin in NHEK, and inhibited chemokine production from BMDC induced by IL-4. These results indicate that the ERK pathway is involved in the pathogenesis of AD, and suggest that the ERK pathway has potential as a therapeutic target for AD in the future.     

Analog Computation Using Single-Electron Circuits

Analog computation is a processing method that solves a given problem by utilizing an analogy of a physical system to the problem. An idea is presented here for relating the behavior of single-electron circuits to analog computation. As an instance, a method is proposed for solving a combinatorial problem, the three-colorability problem, by using the properties of single-electron circuits. In problem solving, a single-electron circuit is constructed that is analogous to a given problem; then, through an annealing procedure, the circuit is made to settle down to its minimun energy state. The correct solution to the problem can be obtained by checking the final arrangement of electrons in the circuit. Analog computation is a promising architecture for single-electron computing systems.     

TLR4-Mediated Inflammatory Responses Regulate Exercise-Induced Molecular Adaptations in Mouse Skeletal Muscle

Endurance exercise induces various adaptations that yield health benefits; however, the underlying molecular mechanism has not been fully elucidated. Given that it has recently been accepted that inflammatory responses are required for a specific muscle adaptation after exercise, this study investigated whether toll-like receptor (TLR) 4, a pattern recognition receptor that induces proinflammatory cytokines, is responsible for exercise-induced adaptations in mouse skeletal muscle. The TLR4 mutant (TLR4m) and intact TLR4 control mice were each divided into 2 groups (sedentary and voluntary wheel running) and were housed for six weeks. Next, we removed the plantaris muscle and evaluated the expression of cytokines and muscle regulators. Exercise increased cytokine expression in the controls, whereas a smaller increase was observed in the TLR4m mice. Mitochondrial markers and mitochondrial biogenesis inducers, including peroxisome proliferator-activated receptor beta and heat shock protein 72, were increased in the exercised controls, whereas this upregulation was attenuated in the TLR4m mice. In contrast, exercise increased the expression of molecules such as peroxisome proliferator-activated receptor-gamma coactivator 1-alpha and glucose transporter 4 in both the controls and TLR4m mice. Our findings indicate that exercise adaptations such as mitochondrial biogenesis are mediated via TLR4, and that TLR4-mediated inflammatory responses could be involved in the mechanism of adaptation.     

Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial Inflammation

Connexin 30 (Cx30), which forms gap junctions between astrocytes, regulates cell adhesion and migration, and modulates glutamate transport. Cx30 is upregulated on activated astroglia in central nervous system inflammatory lesions, including spinal cord lesions in mutant superoxide dismutase 1 (mSOD1) transgenic amyotrophic lateral sclerosis (ALS) model mice. Here, we investigated the role of Cx30 in mSOD1 mice. Cx30 was highly expressed in the pre-onset stage in mSOD1 mice. mSOD1 mice with knockout (KO) of the Cx30 gene (Cx30KO-mSOD1 mice) showed delayed disease onset and tended to have an extended survival period (log-rank, p = 0.09). At the progressive and end stages of the disease, anterior horn cells were significantly preserved in Cx30KO-mSOD1 mice. In lesions of these mice, glial fibrillary acidic protein/C3-positive inflammatory astroglia were decreased. Additionally, the activation of astrocytes in Cx30KO-mSOD1 mice was reduced compared with mSOD1 mice by gene expression microarray. Furthermore, expression of connexin 43 at the pre-onset stage was downregulated in Cx30KO-mSOD1 mice. These findings suggest that reduced expression of astroglial Cx30 at the early disease stage in ALS model mice protects neurons by attenuating astroglial inflammation.     

No. 6Vol. 42, No. 2, pp. 121–127, 2008Makeup inhibits reduction of reactive oxygen scavenging enzyme activity induced by mental stress

Recent studies showed that makeup reduces mental stress, indicated by not only psychological but also physiological values. In this study, we examined the relationship between mental stress and the activity of reactive oxygen scavenging enzymes such as superoxide dismutase (SOD) and catalase (CAT), and the effect of the mental stress reduction by makeup on the activity of reactive oxygen scavenging enzymes. In experiment 1, we measured the concentration of cortisol and activity of SOD in saliva after the addition of mental stress. In this result, the concentration of cortisol increased and the activity of SOD decreased significantly. As we examined the effect of makeup following the mental stress addition in experiment 2, the concentration of cortisol decreased and the activity of SOD and CAT increased. Moreover, we showed a decrease in the anxiety state and increase in spiritual health as the psychological effects. Those results suggest that makeup psychologically canceled anxiety and physiologically inhibited the reduction of reactive oxygen scavenging enzyme activity induced by the mental stress.