Synthesis and antihepatotoxic and antiproliferative activities of di- and tri-O-caffeoylquinic acid derivatives

Methyl di- and tri-O-caffeoylquinates were synthesized by esterification of methyl quinate with di-O-acetylcaffeoyl chloride, following deprotection of the acetyl groups. Moreover, 4,5-di-O-caffeoylquinic acid was synthesized by esterification of quinide with di-O-acetylcaffeoyl chloride, followed by a hydrolysis of product quinide. These synthetic compounds were tested for their hepatoprotective activity on _D-galactosamine (_D-GalN)/tumor necrosis factor-α (TNF- α)-induced cell death in primary cultured mouse hepatocytes, which possessed significant hepatoprotective activity concentration-dependently. The activity was enhanced by the presence of caffeoyl group. On the other hand, they showed only weak antiproliferative activities against murine colon 26-L5 carcinoma, human HT-1080 fibrosarcoma, murine B16-BL6 melanoma, and human lung carcinoma A-549 cells. メチルジおよびトリカフェオイルキネート化合物1-4は,メチルキネート6をジアセチルカフェオイルクロライド7でエステル化した後,アセチル基の脱保護によって合成した。さらに,4,5-ジカフェオイルキナ酸5は,キニド8を7とエステル化して生成したキニド8aの加水分解により合成した。これらの合成した化合物1-5を用いてマウス初代培養肝細胞の_D-GalN/TNF-α誘発肝細胞死における肝保護活性の試験を行ったところ,濃度依存的な肝保護活性が認められた。その活性はカフェオイル基の存在により増強された。一方,これらの化合物1-5はマウス26-L5大腸癌腫,ヒトHT-1080繊維芽肉腫,マウスB16-BL6黒色種,及びヒトA-549肺癌腫に対し弱い細胞増殖抑制活性を示した

Three-dimensional observation and analysis of remineralization in dentinal caries lesions

The remineralization mechanism in dental caries lesions is not completely understood. This study reports on ultrastructural and chemical changes observed within arrested caries lesions. Carious human teeth were observed using scanning electron microscopy (SEM) and focused-ion-beam (FIB)-SEM. The crystals detected in the caries lesions were characterized by transmission electron microscopy (TEM), along with chemical element mapping using energy-dispersive spectroscopy (EDS)-STEM. FIB-SEM 3D reconstructions revealed a severely damaged dentin surface abundantly covered by bacteria. Although the dentin tubules were clogged up to a depth of 100 mu m, bacterial invasion into dentin tubules was not observed. TEM crystal analysis and EDS-STEM revealed the presence of Ca and P, as well as of Mg within the HAp crystals deposited inside the dentin tubules. It was concluded that extensive remineralization with deposition of Mg-HAp crystals had occurred in dentin tubules of caries-arrested dentin. Understanding the natural remineralization process is thought to be helpful for developing clinical biomimetic remineralization protocols

Sandblasting may damage the surface of composite CAD-CAM blocks

　OBJECTIVE:　 CAD-CAM blocks to fabricate semi-direct and indirect restorations are available in different sorts of ceramics as well as composite. In order to bond restorations prepared out of composite blocks into tooth cavities, it is recommended to gently sandblast the surface prior to the application of a primer/adhesive. Today, the effect of sandblasting composite block surfaces has not thoroughly been investigated. In this study, the ultra-structure of composite CAD-CAM blocks was investigated with special attention to the effect of sandblasting on the surface topography and of silanization on the bonding performance. 　METHODS:　 Five different composite CAD-CAM blocks were involved. We correlatively investigated their structural and chemical composition using X-ray diffraction (XRD), energy dispersion spectroscopy (EDS), scanning electron microscopy (SEM) and (scanning) transmission electron microscopy ((S)TEM). The effect of sandblasting was also imaged in cross-section and at the interface with composite cement. Finally, we measured the shear bond strength to the sandblasted block surface with and without silanization. 　RESULTS:　 All composite blocks revealed a different ultra-structure. Sandblasting increased surface roughness and resulted in an irregular surface with some filler exposure. Sandblasting also damaged the surface. When the sandblasted composite blocks were silanized, superior bonding receptiveness in terms of higher bond strength was achieved except for Shofu Block HC. 　SIGNIFICANCE:　 Sandblasting followed by silanization improved the bond strength to composite CAD-CAM blocks. However, sandblasting may also damage the composite CAD-CAM block surface. For the composite CAD-CAM block Shofu Block HC, the damage was so severe that silanization did not improve bond strength

Striatal TRPV1 activation by acetaminophen ameliorates dopamine D2 receptor antagonists-induced orofacial dyskinesia

ジスキネジア新治療法の発見 --副作用を減らす併用薬から新しい創薬標的へ--. 京都大学プレスリリース. 2021-04-16.Antipsychotics often cause tardive dyskinesia, an adverse symptom of involuntary hyperkinetic movements. Analysis of the U.S. Food and Drug Administration Adverse Event Reporting System and JMDC insurance claims revealed that acetaminophen prevents the dyskinesia induced by dopamine D₂ receptor antagonists. In vivo experiments further showed that a 21-day treatment with haloperidol increased the number of vacuous chewing movements (VCMs) in rats, an effect that was inhibited by oral acetaminophen treatment or intracerebroventricular injection of N-(4-hydroxyphenyl)-arachidonylamide (AM404), an acetaminophen metabolite that acts as an activator of the transient receptor potential vanilloid 1 (TRPV1). In mice, haloperidol-induced VCMs were also mitigated by treatment with AM404 applied to the dorsal striatum, but not in TRPV1-deficient mice. Acetaminophen prevented the haloperidol-induced decrease in the number of c-Fos⁺/preproenkephalin⁺ striatal neurons in wild-type mice but not in TRPV1-deficient mice. Finally, chemogenetic stimulation of indirect-pathway medium spiny neurons in the dorsal striatum decreased haloperidol-induced VCMs. These results suggest that acetaminophen activates the indirect pathway neurons by activating TRPV1 channels via AM404

Prediction Models for BMI and NAFLD

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. Disulfide bond‐forming oxidoreductase A‐like protein (DsbA‐L) is known to be a key molecule in protection against obesity and obesity‐induced inflammation. In the present study, we used a modeling and simulation approach in an attempt to develop body mass index (BMI) and BMI‐based NAFLD prediction models incorporating the DsbA‐L polymorphism to predict the BMI and NAFLD in 341 elderly subjects. A nonlinear mixed‐effect model best represented the sigmoidal relationship between the BMI and the logit function of the probability of NAFLD prevalence. The final models for BMI and NAFLD showed that DsbA‐L rs1917760 polymorphism, age, and gender were associated with the BMI, whereas gender, patatin‐like phospholipase 3 rs738409 polymorphism, HbA1c, and high‐density and low‐density lipoprotein cholesterol levels were associated with the risk of NAFLD. This information may aid in the genetic‐based prevention of obesity and NAFLD in the general elderly population

Real time assessment of surface interactions with a titanium passivation layer by surface plasmon resonance

Due to the high corrosion resistance and strength to density ratio titanium is widely used in industry, and also in a gamut of medical applications. Here we report for the first time on our development of a titanium passivation layer sensor that makes use of surface plasmon resonance (SPR). The deposited titanium metal layer on the sensor was passivated in air, similarly to titanium medical devices. Our "Ti-SPR sensor" enables analysis of biomolecule interactions with the passivated surface of titanium in real time. As a proof of concept, corrosion of a titanium passivation layer exposed to acid was monitored in real time. The Ti-SPR sensor can also accurately measure the time-dependence of protein adsorption onto the titanium passivation layer at sub-nanogram per square millimeter accuracy. Besides such SPR analyses, SPR imaging (SPRI) enables real time assessment of chemical surface processes that occur simultaneously at "multiple independent spots" on the Ti-SPR sensor, such as acid corrosion or adhesion of cells. Our Ti-SPR sensor will therefore be very useful to study titanium corrosion phenomena and biomolecular titanium-surface interactions with application in a broad range of industrial and biomedical fields

Excitation of helically-trapped-energetic-ion driven resistive interchange modes with intense deuterium beam injection and enhanced effect on beam ions/bulk plasmas of LHD

Energetic ion driven resistive InterChange modes (EICs) accompanying repeated bursts of the magnetic fluctuations were found in hydrogen campaign of large helical device. The pressure gradient of helically trapped energetic particles, which are mainly produced by perpendicularly injected beams, drives this mode. Recently, perpendicular neutral beam injection (PERP-NBI) systems are upgraded for deuterium plasma campaign. The beam energies of the two PERP-NBIs are increased from 40/40 keV to 60/80 keV, respectively. And the injection powers increase from 6/6 MW to 9/9 MW, as well. As results of these upgrades of NBIs, the β value of helically trapped energetic ions, , has increased up to  ∼0.35% and induced EICs with larger bursts and smaller repetition frequencies. It is found that the threshold of to excite EICs increases with deuterium PERP-NBIs. The amplitude of each burst and effect on energetic beam ions become larger when is larger. In addition, a large electrostatic potential about  −25 kV is observed when EICs are excited, which is about two times larger than the potential observed in hydrogen campaign. The transient increases of the electron density and temperature in edge regions are clearly observed when the electrostatic potential is formed