Pathophysiological Roles of Actin-Binding Scaffold Protein,Ezrin

Ezrin is one of the members of the ezrin/radixin/moesin (ERM) family of proteins. It was originally discovered as an actin-binding protein in the microvilli structure about forty years ago. Since then, it has been revealed as a key protein with functions in a variety of fields including cell migration, survival, and signal transduction, as well as functioning as a structural component. Ezrin acts as a cross-linker of membrane proteins or phospholipids in the plasma membrane and the actin cytoskeleton. It also functions as a platform for signaling molecules at the cell surface. Moreover, ezrin is regarded as an important target protein in cancer diagnosis and therapy because it is a key protein involved in cancer progression and metastasis, and its high expression is linked to poor survival in many cancers. Small molecule inhibitors of ezrin have been developed and investigated as candidate molecules that suppress cancer metastasis. Here, we wish to comprehensively review the roles of ezrin from the pathophysiological points of view.     

Therapeutic Targets and Emerging Treatments in Advanced Chondrosarcoma

Simple SummaryChondrosarcomas develop chemoresistance to standard anticancer drugs, making it difficult to control unresectable or metastatic chondrosarcomas. To improve the clinical outcomes of chondrosarcoma, new treatment approaches, such as molecule-targeting agents and immunotherapy, are needed. Recent research has revealed promising biomarkers and therapeutic targets for chondrosarcoma. In addition, several molecule-targeting agents have shown favorable antitumor activities in several clinical studies in patients with advanced sarcomas, including chondrosarcoma. This review summarizes recent basic studies on biomarkers and therapeutic targets and recent clinical studies on treating chondrosarcomas.AbstractDue to resistance to standard anticancer agents, it is difficult to control the disease progression in patients with metastatic or unresectable chondrosarcoma. Novel therapeutic approaches, such as molecule-targeting drugs and immunotherapy, are required to improve clinical outcomes in patients with advanced chondrosarcoma. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including IDH1/2 and COL2A1. Several molecule-targeting agents and immunotherapies have shown favorable antitumor activity in clinical studies in patients with advanced chondrosarcomas. This review summarizes recent basic studies on biomarkers and molecular targets and recent clinical studies on the treatment of chondrosarcomas.     

Analysis of Plasmalogen Species in Foodstuffs

Ethanolamine plasmalogen (PlsEtn), which is present at high levels in brains, is believed to be involved in neuronal protection. The present study was performed to search for PlsEtn resources in foodstuffs. The foodstuffs examined showed a wide range of PlsEtn contents from 5 to 549 μmol/100 g wet wt. The marine invertebrates, blue mussel, and ascidian had high PlsEtn contents (over 200 μmol/100 g wet wt). Profiling of the molecular species showed that the predominant fatty acids of PlsEtn species were 20:5 (EPA) and 22:6 (DHA) at the sn‐2 position of the glycerol moiety in marine foodstuffs, whereas major PlsEtn species in land foodstuffs were 20:4. Following quantitative analysis by multiple reaction monitoring, the ascidian viscera were shown to contain the highest levels of 18:0/20:5‐PlsEtn and 18:0/22:6‐PlsEtn (86 and 68 μmol/100 g wet wt, respectively). In order to evaluate a neuronal antiapoptotic effect of these PlsEtn species, human neuroblastoma SH‐SY5Y cells were treated with ethanolamine glycerophospholipid (EtnGpl), purified from the ascidian viscera, under serum starvation conditions. Extrinsic EtnGpl from ascidian viscera showed stronger suppression of cell death induced by serum starvation than with bovine brain EtnGpl. The EtnGpl from ascidian viscera strongly suppressed the activation of caspase 3. These results suggest that PlsEtn, especially that containing EPA and DHA, from marine foodstuffs is potentially useful for a therapeutic dietary supplement preventing neurodegenerative diseases, such as Alzheimer's disease (AD).     

Nondestructive determination of fatty acid composition of husked sunflower (Helianthus annua L.) seeds by near-infrared spectroscopy

Determination of the fatty acid composition of sunflower (Helianthus annua L.) seeds by near-infrared (NIR) spectroscopy was examined. Sunflower seeds were husked (removed from their hulls by a husking machine or manually with a knife). NIR spectra of these seeds were scanned from 1100 to 2500 nm at 2-nm intervals in a whole-grain cell with a wideangle moving drawer for machine-husked seeds or in a single-grain cup for a manually husked single-grain seed. The extracted oils from machine-husked seeds also were scanned by sandwiching them between a pair of slide glasses to create a thin layer and by placing them on a syrup cup. For extracted oil, the absorption band around 1720 nm filled out to the shorter wavelength region in the NIR second-derivative spectra as the percentage of the linoleic acid moiety increased, because linoleic acid absorbs in this region. On the other hand, for husked seeds and for a single-grain seed, as the percentage of linoleic acid increased, the trough at 1724 nm where oleic and saturated acids absorb decreased in the second-derivative NIR spectra. Determination of the fatty acid composition of sunflower seeds could be carried out successfully according to the NIR spectral pattern for both extracted oil (r=−0.989) and kernel seed (r=−0.993). This is important, especially for a manually husked single-grain seed (r=−0.971), because it can still be germinated after such nondestructive analysis.     

Crack-Healing Behavior of Si3N4/SiC Ceramics under Cyclic Stress and Resultant Fatigue Strength at the Healing Temperature

Si₃N₄/SiC composite ceramics were sintered and subjected to three-point bending. A semi-elliptical surface crack of 100 μm surface length was made on each specimen. The crack-healing behavior under cyclic stress of 5 Hz, and resultant cyclic fatigue strengths at healing temperatures of 1100° and 1200°C, were systematically investigated. The main conclusions are as follows: (1) Si₃N₄/SiC composite ceramics have an excellent ability to heal a crack at 1100° and 1200°C. (2) This sample could heal a crack even under cyclic stress at a frequency of 5 Hz. (3) The crack-healed sample exhibited quite high cyclic fatigue strength at each crack-healing temperature, 1100° and 1200°C.     

Fabrication of porous magnesium spinel with directional pores by unidirectional solidification

A porous magnesium spinel (MgAl₂O₄) with directional pores was fabricated by unidirectional solidification in pressurized argon and hydrogen mixed gases. Two different kinds of pores with large directional and small facet shape were formed in the solidified samples. The former pores were dominant in the porous structure. A small amount of free corundum phase was formed in the solidified porous spinel as a secondary phase by vaporization of MgO component during the solidification process. With increasing total gas pressure, the pore size of the solidified samples decreased while no change in the porosity. The porosity and pore size of the samples increased with increasing hydrogen partial pressure. The porosities of the samples fabricated under 10%H₂–90%Ar and 1%H₂–99%Ar mixed gases were 30 and 10%, respectively, and that under Ar atmosphere was very low, non-porous.     

Mechanical properties of silicon-doped diamond-like carbon films prepared by pulse-plasma chemical vapor deposition

Silicon-doped diamond-like carbon (Si-DLC) films were prepared by dc pulse-plasma chemical vapor deposition (CVD), using a mixture of acetylene (C₂H₂) and tetramethylsilane (TMS) as the material gas. The pulse voltage was varied from − 2 to − 5 kV, and the TMS flow ratio (TMS/(C₂H₂ + TMS)) was varied from 0 to 40%. At a pulse voltage of − 2 kV, an increase in TMS flow ratio leads to a decrease in hardness. In contrast, at a pulse voltage of − 5 kV, an increase in TMS flow ratio leads to a slight increase in hardness. The high hydrogen concentration in the films due to an increase in TMS flow ratio promotes the formation of polymeric sp³ C―H bonds, resulting in the fabrication of soft films at a low pulse voltage of − 2 kV. However, an increase in the effect of ion peening on the growth face results in the formation of hard films at a high pulse voltage of − 5 kV. Then, at a pulse voltage of − 5 kV fabricating hard Si-DLC films, an increase in TMS flow ratio leads to an increase in the silicon content in the films, resulting in a decrease in the friction coefficient. Therefore, it is clarified that Si-DLC films fabricated by dc pulse-plasma CVD under a high pulse voltage and high TMS flow ratio exhibit high hardness and a low friction coefficient. Moreover, to investigate the friction coefficient of Si-DLC films fabricated by dc pulse-plasma CVD, films deposited by dc plasma CVD were also evaluated. To obtain the same low friction coefficient, dc pulse-plasma CVD requires less TMS than dc plasma CVD. Hence, it is also clarified that Si-DLC films can be fabricated at a low cost by dc pulse-plasma CVD.     

Synthesis of CeO2-ZrO2 solid solution by glycothermal method and its oxygen release capacity

The glycothermal (GT) reaction of Ce acetate and Zr alkoxide directly yielded CeO₂-ZrO₂ solid solutions in a region of low Ce content ≤40 mol%. Of the CeO₂-ZrO₂ solid solutions obtained by the GT method and subsequent calcination at 500 or 800 °C, the sample with 20 mol% Ce content had the largest BET surface area. This sample exhibited the highest Ce-based oxygen release capacity in the whole Ce/Zr composition range. The oxygen release capacities of CeO₂-ZrO₂ solid solutions synthesized by the GT method were much larger than those of the samples prepared by a coprecipitation (CP) method. The Reitveld analysis and the repetitive reduction-oxidation experiment indicated that the CeO₂-ZrO₂ solid solution synthesized by the GT method has a homogeneous structure as compared with that prepared by the CP method.     

Surface and pore structure of alumina derived from xerogel/aerogel

The alkyl derivatives of boehmite were prepared by solvothermal reaction of aluminum isopropoxide in n-alcohols (ethanol, 1-butanol, 1-hexanol, 1-octanol and 1-dodecanol) and the products were recovered as aerogel/xerogel by the removal of the solvent at the end of reaction. Aerogel or xerogel can be obtained simply by using only a reaction vessel (autoclave) and the obtained products were composed of plate-like particles having a well-developed boehmite structure. The alumina powders obtained by calcination of these products had relatively large pore-volumes ranging from 1.35 to 2.56 cm³/g. Transformation into α-Al₂O₃ was retarded even after calcination at 1200 °C. The effect of n-alcohols used in the solvothermal reaction on the phase, morphology and pore-texture of the alumina samples are discussed.