Reduced Claudin-12 Expression Predicts Poor Prognosis in Cervical Cancer

Background: Within the claudin (CLDN) family, CLDN12 mRNA expression is altered in various types of cancer, but its clinicopathological relevance has yet to be established due to the absence of specific antibodies (Abs) with broad applications. Methods: We generated a monoclonal Ab (mAb) against human/mouse CLDN12 and verified its specificity. By performing immunohistochemical staining and semiquantification, we evaluated the relationship between CLDN12 expression and clinicopathological parameters in tissues from 138 cases of cervical cancer. Results: Western blot and immunohistochemical analyses revealed that the established mAb selectively recognized the CLDN12 protein. Twenty six of the 138 cases (18.8%) showed low CLDN12 expression, and the disease-specific survival (DSS) and recurrence-free survival rates were significantly decreased compared with those in the high CLDN12 expression group. We also demonstrated, via univariable and multivariable analyses, that the low CLDN12 expression represents a significant prognostic factor for the DSS of cervical cancer patients (HR 3.412, p = 0.002 and HR 2.615, p = 0.029, respectively). Conclusions: It can be concluded that a reduced CLDN12 expression predicts a poor outcome for cervical cancer. The novel anti-CLDN12 mAb could be a valuable tool to evaluate the biological relevance of the CLDN12 expression in diverse cancer types and other diseases.     

Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren’s Syndrome Model Mice

Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells infiltrated the salivary glands (SG) of aged mice. An analysis of isolated epithelial cells from SG revealed that the expression levels of the chemokine CXCL13 were elevated in aged mice. Senescence-associated T cells (SA-Ts), which secrete large amounts of atypical pro-inflammatory cytokines, are involved in the pathogenesis of metabolic disorders and autoimmune diseases. The present results showed that SA-Ts and B cells, which express the CXCL13 receptor CXCR5, accumulated in the SG of aged mice, particularly females. CD4⁺ T cells derived from aged mice exhibited stronger in vitro migratory activity toward CXCL13 than those from young mice. In a mouse model of Sjögren’s syndrome (SS), SA-Ts also accumulated in SG, presumably via CXCL12-CXCR4 signaling. Collectively, the present results indicate that SA-Ts accumulate in SG, contribute to the pathogenesis of age- and SS-related sialadenitis by up-regulating chemokines in epithelial cells, and have potential as therapeutic targets for the treatment of xerostomia caused by these types of sialadenitis.     

Cover Image,Volume 69, Issue 3

The cover image is based on the Mini‐Review Well‐defined, environment‐friendly synthesis of polypeptides based on phosgene‐free transformation of amino acids into urethane derivatives and their applications by Takeshi Endo et al., https://doi.org/10.1002/pi.5952 . Cover image © Takeshi Endo Images.

     

Effect of Electron Correlation on Phonon Spectra in Cuprates

We examine theoretically the phonon dynamics in the electron-phonon-coupled systems. The model Hamiltonian is a one-dimensional Hubbard model where the hopping of electrons induces the electron-phonon coupling. The numerically exact diagonalization of the Hamiltonian with truncation of the total number of phonons is performed. We calculate the phonon excitation spectra and find that the softening of phonons occurs in insulating case, and a diffusive character appears in the metallic case. We also calculate the charge and spin excitation spectra and find that the dynamics of the phonon coupled with the hopping of electrons is affected by the low energy charge and spin excitations.     

Markedly compressible behaviors of gellan hydrogels in a constrained geometry at ultraslow strain rates

The fracture behaviors of gellan hydrogels under compression remarkably depend on the strain rate as well as the boundary conditions for lateral expansion. In the geometry with no constraint for lateral expansion (conventional uniaxial compression), the gels rupture at relatively small strains independently of the compression rates. In contrast, when the gels are compressed extremely slowly (at a strain rate of ca. 10⁻⁵ s⁻¹) in the geometry prohibiting the lateral expansion at their top and bottom surfaces, they are remarkably compressible down to 2% of the initial height without macroscopic fracture and they are accompanied by a large amount of water release. In such markedly compressed gels, many microscopic cracks are formed around the central layer, where strain concentration occurs due to the nonuniform deformation arising from the constrained geometry. In the highly compressible case, the formation of macroscopic cracks is prevented by the localization of microscopic cracks as well as the enhancement in mechanical toughness by a significant increase in polymer concentration due to water release.     

Hydrothermal corrosion of magnesiapartially-stabilized zirconia

Changes in the phase compositions and microstructures of magnesia-partially-stabilized zirconia (Mg-PSZ) were studied in water at 80–300 °C, 1 m HCl solutions at 80–140 °C and 1 m CH₃COOH-CH₃COONa buffer solutions at pH 3 and 80–140 °C for 10–40 days. The tetragonal to monoclinic phase transformation and the degradation of the fracture strength occurred in water above 200 °C. On the other hand, although no noticeable tetragonal to monoclinic phase transformation proceeded in 1 m HCl solutions and 1 m CH₃COOH-CH₃-COONa buffer solutions at pH 3 below 140 °C, the fracture strength of Mg-PSZ greatly degraded. The dissolution of Mg²⁺ ion was observed in water above 200 °C and in 1 m HCl solutions above 80 °C.     

Application of gene gun for local-regional cancer

We studied the in vivo gene transfusion using a gene gun, formerly used in plants and culture cells. The hand-held type gene gun (Helios Gene Gun System) is simple and convenient for effective gene transfection in living animals. This method has some advantages in that there is no need for use of viral vector, independence on the cell cycle and local inducement of plural genes. There is a great possibility for application to local-regional cancer.     

Voltage-time characteristics for steep-front impulse voltages ofparticle-contaminated spacers in SF6 gas-insulated switchgear

The voltage-time characteristics of spacer surfaces for steep-front impulse waves are investigated under a particle-contaminated condition in SF₆ gas. The characteristics are measured as a function of particle length, particle position, and space shapes. Flashover voltages monotonically increase in the submicrosecond region as time to flashover is shorter, and are a minimum in the 1 μs region. Applicability of the equal voltage-time area criterion for estimating the voltage-time characteristics is discussed and the estimation is clarified. Moreover, it is demonstrated that an optimized spacer with ribs greatly improves flashover voltages in the submicrosecond region as well as in the 1 μs and power frequency region     

Involvement of brain serotonergic function in lidocaine-induced convulsions in mice

Influences of drug-induced manipulations of central serotonergic function on lidocaine- and pentylenetetrazol (PTZ)-induced convulsions were examined in mice. Agents that suppressed serotonergic transmission increased, whereas drugs that facilitated serotonin (5-HT) function decreased the incidence of lidocaine-induced convulsions. These treatments had similar influences on the incidence of PTZ-induced convulsions. Lidocaine (10(-5)-10(-3) M) reduced the stimulation evoked [3H]5-HT release from cortical slices, followed with an increased spontaneous [3H] overflow at higher concentrations. These results may suggest that brain 5-HT neurons are causally involved as inhibitory neurons in lidocaine-induced convulsions as in the case of PTZ-induced convulsions.