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We demonstrate second-harmonic generation (SHG) in a silicon-carbide (SiC)-based heterostructure photonic crystal nanocavity by using a pulsed laser. We observe SHG light radiated from the SiC nanocavity and estimate the conversion efficiency in the cavity to be 2.59×10(-5) (=0.15  W(-1)) at an average input power of 0.17 mW. The near-field patterns and polarization characteristics of the SHG light are investigated experimentally and theoretically, and the results are in qualitatively good agreement.

Acupuncture is frequently used as an alternative therapy for Parkinson's disease (PD), and it attenuates dopaminergic (DA) neurodegeneration in the substantia nigra (SN) in PD animal models. Using proteomic analysis, we investigated whether acupuncture alters protein expression in the SN to favor attenuation of neuronal degeneration. In C57BL/6 mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg/day), intraperitoneal (i.p.) for 5 days, 2 or 100 Hz electroacupuncture (EA) was applied at the effective and specific acupoint, GB34, once a day for 12 consecutive days from the first MPTP treatment. Both treatments in MPTP mice led to restoration of behavioral impairment and rescued tyrosine hydroxylase (TH)-positive DA neurodegeneration. Using peptide fingerprinting MS, we identified changes in 22 proteins in the SN following MPTP treatment, and nine of these proteins were normalized by EA. They were involved in cell death regulation, inflammation, or restoration from damage. The levels of cyclophilin A (CypA), which is a neuroprotective agent, were unchanged by MPTP treatment but were increased in MPTP-EA mice. These results suggest that acupoint GB34-specific EA changes protein expression profiles in the SN in favor of DA neuronal survival in MPTP-treated mice, and that EA treatment may be an effective therapy for PD patients.

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When we were studying phosphorylated proteins in the rat brain after electroconvulsive shock (ECS), we observed the rapid phosphorylation of a 75-kDa protein, which cross-reacted with the anti-phospho-p70 S6 kinase antibody. The phosphorylated protein was purified and identified as moesin, a member of the ezrin/radixin/ moesin (ERM) family and a general cross-linker between cortical actin filaments and plasma membranes. The purified moesin from rat brain was phosphorylated at serine and threonine residues. Moesin was rapidly phosphorylated at the threonine 558 residue after ECS in the rat hippocampus, peaked at 1 min, and returned to the basal level by 2 min after ECS. To investigate the mechanism of moesin phosphorylation in neuronal cells, we stimulated a rat hippocampal progenitor cell, H19 -7/ IGF-IR, with glutamate, and observed the increased phosphorylation of moesin at Thr-558. Glutamate transiently activated RhoA, and constitutively active RhoA increased the basal level phosphorylation of moesin. The inhibition of RhoA and its effector, Rho kinase, abolished increased Thr-558 phosphorylation by glutamate in H19 -7/IGF-IR cells, suggesting that the phosphorylation of moesin at Thr-558 in H19 -7/IGF-IR cells by glutamate is mediated by RhoA and Rho kinase activation. Electroconvulsive shock (ECS)1 has been used for the treatments of psychiatric disorders such as depression, schizophrenia, and manic-depressive illness. Although the mechanism of the treatment has not been elucidated, recent progress in the cellular and molecular biology of neuronal tissues has enabled neuronal functions to be linked to the regulation of gene expression and intracellular signal transduction (1). Previously, we reported (4) that ECS induces the expressions of various immediate early genes such as c-fos, junB, and TiS-8 and that it suppresses the expression of inositol 1,4,5-triphosphate kinase and inositol 1,4,5-triphosphate receptor genes. We also observed (2-5, 7) that ECS caused the phosphorylation of many signaling molecules, including those in the Pyk2-Ras-Raf-MEK-ERK pathway, and of stress-signaling pathways in various rat brain regions.Earlier we reported that ECS induces the phosphorylation of CREB in the rat hippocampus (6). Several protein kinases have been suggested to be CREB kinases in neuronal tissues, and we looked for protein kinases potentially responsible for CREB phosphorylation. When we were studying the phosphorylation of one of the suggested CREB kinases, ribosomal S6 kinase (S6K), we observed that a 75-kDa protein in the rat hippocampus was rapidly phosphorylated after ECS. This was detected by an antibody specific to phospho-p70 S6K. The protein was not detected by the anti-p70 S6K antibody, suggesting that this protein was detected nonspecifically by an anti-phospho-p70-S6K antibody. So we purified and identified this protein as moesin (membrane-organizing extension spike protein), a member of the ezrin/radixin/moesin (ERM) family of proteins.

Levels of the cytokines IL-6, IL-1alpha, and tumor necrosis factor-alpha (TNF-alpha) are significantly higher in lesional than in non-lesional skin of patients with vitiligo. However, how cytokines affect pigmentation is not fully understood. To examine the mechanism, Western blot analysis with TNF-alpha, Fas ligand (FasL), and downstream signaling molecules such as I-kappaB, NF-kappaB, TNF-R1-associated factor 2, Akt, and PTEN (phosphatase and tension homologue) were performed for the suction-blistered depigmented and normally pigmented epidermis from 10 patients. Levels of TNF-alpha and FasL were significantly higher in the depigmented epidermis. Interestingly, phosphorylation levels of I-kappaB, NF-kappaB, and Akt were lower in the depigmented epidermis. Moreover, PTEN, which could inhibit the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, was significantly higher in depigmented epidermis, implying that vitiliginous keratinocytes may be more susceptible to TNF-alpha-mediated apoptosis through impaired Akt and NF-kappaB activation. To test this hypothesis, cultured normal human keratinocytes were treated with TNF-alpha in the presence of a PI3K inhibitor to suppress Akt activation. Keratinocytes showing impaired Akt activation demonstrated increased apoptosis with less activation of NF-kappaB. Thus, reduced activation of NF-kappaB via impaired PI3K/Akt activation under increased TNF-alpha levels could result in increased apoptosis of vitiliginous keratinocytes.

Despite accumulating evidence of the clinical effectiveness of acupuncture, its mechanism remains largely unclear. We assume that molecular signaling around the acupuncture needled area is essential for initiating the effect of acupuncture. To determine possible bio-candidates involved in the mechanisms of acupuncture and investigate the role of such bio-candidates in the analgesic effects of acupuncture, we conducted 2 stepwise experiments. First, a genome-wide microarray of the isolated skin layer at the GB34-equivalent acupoint of C57BL/6 mice 1 hour after acupuncture found that a total of 236 genes had changed and that extracellular signal–regulated kinase (ERK) activation was the most prominent bio-candidate. Second, in mouse pain models using formalin and complete Freund adjuvant, we found that acupuncture attenuated the nociceptive behavior and the mechanical allodynia; these effects were blocked when ERK cascade was interrupted by the mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) inhibitor U0126 (.8 μg/μL). Based on these results, we suggest that ERK phosphorylation following acupuncture needling is a biochemical hallmark initiating the effect of acupuncture including analgesia. Perspective This article presents the novel evidence of the local molecular signaling in acupuncture analgesia by demonstrating that ERK activation in the skin layer contributes to the analgesic effect of acupuncture in a mouse pain model. This work improves our understanding of the scientific basis underlying acupuncture analgesia.