Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes

Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH.     

Implication of phosphorylation of the myosin II regulatory light chain in insulin-stimulated GLUT4 translocation in 3T3-F442A adipocytes

In adipocytes, insulin stimulates glucose transport primarily by promoting the translocation of GLUT4 to the plasma membrane. Requirements for Ca(2+)/calmodulin during insulin-stimulated GLUT4 translocation have been demonstrated; however, the mechanism of action of Ca(2+) in this process is unknown. Recently, myosin II, whose function in non-muscle cells is primarily regulated by phosphorylation of its regulatory light chain by the Ca(2+)/calmodulin-dependent myosin light chain kinase (MLCK), was implicated in insulin-stimulated GLUT4 translocation. The present studies in 3T3-F442A adipocytes demonstrate the novel finding that insulin significantly increases phosphorylation of the myosin II RLC in a Ca(2+)-dependent manner. In addition, ML-7, a selective inhibitor of MLCK, as well as inhibitors of myosin II, such as blebbistatin and 2,3-butanedione monoxime, block insulin-stimulated GLUT4 translocation and subsequent glucose transport. Our studies suggest that MLCK may be a regulatory target of Ca(2+)/calmodulin and may play an important role in insulin-stimulated glucose transport in adipocytes.     

Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury

Reactive oxygen species (ROS) play a crucial role in acute lung injury. Tissue inflammation, the increased vascular permeability, and plasma exudation are cardinal features of acute lung injury. Angiopoietin-1 (Ang1) has potential therapeutic applications in preventing vascular leakage and also has beneficial effects in several inflammatory disorders. Recently developed COMP-Ang1 is more potent than native Ang1 in phosphorylating tyrosine kinase with immunoglobulin and EGF homology domain 2 receptor in endothelial cells. However, there are no data on effects and related molecular mechanisms of COMP- Ang1 on ROS-induced acute lung injury. We used hydrogen peroxide (H2O2)-inhaled mice to evaluate the effect of COMP-Ang1 on pulmonary inflammation, bronchial hyper-responsiveness, and vascular leakage in acute lung injury. The results have revealed that VEGF expression, the levels of IL-4, TNF-alpha, IL-1beta, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in lungs, the levels of hypoxia-inducible factor-1alpha (HIF-1alpha) and NF-kappaB in nuclear protein extracts, phosphorylation of Akt, and vascular permeability were increased after inhalation of H2O2 and that the administration of COMP-Ang1 markedly reduced airway hyper-responsiveness, pulmonary inflammation, plasma extravasation, and the increases of cytokines, adhesion molecules, and VEGF in lungs treated with H2O2. We have also found that the activation of HIF-1a and NF-kB and the increase of phosphoinositide 3-kinase activity in lung tissues after H2O2 inhalation were decreased by the administration of COMP-Ang1. These results suggest that COMP-Ang1 ameliorates ROS-induced acute lung injury through attenuating vascular leakage and modulating inflammatory mediators.     

Solid-state relaxations in linear low-density (1-octene comonomer), low-density,and high-density polyethylene blends

Extensive thermal and relaxational behavior in the blends of linear low-density polyethylene (LLDPE) (1-octene comonomer) with low-density polyethylene (LDPE) and high-density polyethylene (HDPE) have been investigated to elucidate miscibility and molecular relaxations in the crystalline and amorphous phases by using a differential scanning calorimeter (DSC) and a dynamic mechanical thermal analyzer (DMTA). In the LLDPE/LDPE blends, two distinct endotherms during melting and crystallization by DSC were observed supporting the belief that LLDPE and LDPE exclude one another during crystallization. However, the dynamic mechanical β and γ relaxations of the blends indicate that the two constituents are miscible in the amorphous phase, while LLDPE dominates α relaxation. In the LLDPE/HDPE system, there was a single composition-dependent peak during melting and crystallization, and the heat of fusion varied linearly with composition supporting the incorporation of HDPE into the LLDPE crystals. The dynamic mechanical α, β, and γ relaxations of the blends display an intermediate behavior that indicates miscibility in both the crystalline and amorphous phases. In the LDPE/HDPE blend, the melting or crystallization peaks of LDPE were strongly influenced by HDPE. The behavior of the α relaxation was dominated by HDPE, while those of β and γ relaxations were intermediate of the constituents, which were similar to those of the LLDPE/HDPE blends. © 1997 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 35 : 1633–1642, 1997     

Anti-Melanogenic Properties of Velutin and Its Analogs

Velutin, one of the flavones contained in natural plants, has various beneficial activities, such as skin whitening, as well as anti-inflammatory, anti-allergic, antioxidant, and antimicrobial activities. However, the relationship between the structure of velutin and its anti-melanogenesis activity is not yet investigated. In this study, we obtained 12 velutin derivatives substituted at C5, C7, C3′, and C4′ of the flavone backbone with hydrogen, hydroxyl, and methoxy functionalities by chemical synthesis, to perform SAR analysis of velutin structural analogues. The SAR study revealed that the substitution of functional groups at C5, C7, C3′, and C4′ of the flavone backbone affects biological activities related to melanin synthesis. The coexistence of hydroxyl and methoxy at the C5 and C7 position is essential for inhibiting tyrosinase activity. However, 1,2-diol compounds substituted at C3′ and C4′ of flavone backbone induce apoptosis of melanoma cells. Further, substitution at C3′ and C4′ with methoxy or hydrogen is essential for inhibiting melanogenesis. Thus, this study would be helpful for the development of natural-derived functional materials to regulate melanin synthesis.     

Cu/Zn Incorporation During Purification of Soluble Human EC-SOD from E. coli Stabilizes Proper Disulfide Bond Formation

Extracellular superoxide dismutase (EC-SOD) is the only enzyme that removes superoxide radical in the extracellular space. The reduction of EC-SOD is linked to many diseases, suggesting that the protein may have therapeutic value. EC-SOD is reported to be insoluble and to make inclusion bodies when overexpressed in the cytoplasm of Escherichia coli. The refolding process has the advantage of high yield, but has the disadvantage of frequent aggregation or misfolding during purification. For the first time, this study shows that fusion with maltose-binding protein (MBP), N-utilization substance protein A, and protein disulfide isomerase enabled the soluble overexpression of EC-SOD in the cytoplasm of E. coli. MBP-tagged human EC-SOD (hEC-SOD) was purified by MBP affinity and anion exchange chromatography, and its identity was confirmed by MALDI-TOF MS analysis. The purified protein showed good enzyme activity in vitro; however, there was a difference in metal binding. When copper and zinc were incorporated into hEC-SOD before MBP tag cleavage, the enzymatic activity was higher than when the metal ions were bound to the purified protein after MBP tag cleavage. Therefore, the enzymatic activity of hEC-SOD is associated with metal incorporation and protein folding via disulfide bond.     

Gd2AlGe2: An “Almost‐Zintl Phase” and a New Stacking Variant of the W2CoB2 Type

The synthesis, structure determination and calculated electronic structure of the new phase, Gd₂AlGe₂, are reported. The compound crystallizes in a new structure type with space group C2/c, a = 10.126(2) Å, b = 5.6837(12) Å, c = 7.7683(16) Å, and β = 104.729(3)s. Tight‐binding linear‐muffin‐tin orbital (TB‐LMTO‐ASA) calculations show a distinct minimum in the total density of states for this structure at 18 valence electrons per formula unit (Gd₂AlGe₂ has 17 valence electrons in its formula unit), which arises from polar covalent bonding within the three‐dimensional [AlGe₂] net, Gd‐Ge interactions and three‐center, two‐electron bonding between Al and Gd. The structure is a new stacking variant of the W₂CoB₂ structure type, which is observed for numerous ternary rare‐earth silicides and germanides.     

Iron Oxide Photoelectrode with Multidimensional Architecture for Highly Efficient Photoelectrochemical Water Splitting

Nanostructured metal oxide semiconductors have shown outstanding performances in photoelectrochemical (PEC) water splitting, but limitations in light harvesting and charge collection have necessitated further advances in photoelectrode design. Herein, we propose anodized Fe foams (AFFs) with multidimensional nano/micro-architectures as a highly efficient photoelectrode for PEC water splitting. Fe foams fabricated by freeze-casting and sintering were electrochemically anodized and directly used as photoanodes. We verified the superiority of our design concept by achieving an unprecedented photocurrent density in PEC water splitting over 5 mA cm⁻² before the dark current onset, which originated from the large surface area and low electrical resistance of the AFFs. A photocurrent of over 6.8 mA cm⁻² and an accordingly high incident photon-to-current efficiency of over 50 % at 400 nm were achieved with incorporation of Co oxygen evolution catalysts. In addition, research opportunities for further advances by structual and compositional modifications are discussed, which can resolve the low fill factoring behavior and improve the overall performance.     

Resonance Fluorescence of Gaseous Chlorine Excited by Laser Light

A powerful argon ion laser was used to excite gaseous chlorine molecules resonantly from the X¹Σ ground electronic state to the excited electronic state. Three progressions of P, R doublets which correspond to the excitation from J=37, 13 and 39 of v=0 of the X¹Σ state to v′=22, J′=38; v′=18, J′=12 and v′=16, J′=38 of the state, respectively, and then decaying to various vibrational levels of the X¹Σ state were observed. Of those, only the excitation from v=0, J=38 to v′=22, J′=38 transition has been reported before. Due to the extremely small transition probabilities, the spectral lines are much weaker than those of iodine and bromine. Their positions and their relative intensities were analyzed and compared with the result calculated from the known molecular constants and with the known Franck-Condon factors. Our data are consistent with the calculated results within the range of experimental error.