Gut microbial fatty acid metabolites (KetoA and KetoC) affect the progression of nonalcoholic steatohepatitis and reverse cholesterol transport metabolism in mouse model

Nonalcoholic steatohepatitis (NASH) is a common liver disease that occurs in both alcoholics and nonalcoholics. Oxidative stress is a possible causative factor for liver diseases including NASH. Gut microorganisms, especially lactic acid bacteria, can produce unique fatty acids, including hydroxy, oxo, conjugated, and partially saturated fatty acids. The oxo fatty acid 10-oxo-11(E)-octadecenoic acid (KetoC) provides potent cytoprotective effects against oxidative stress through activation of Nrf2-ARE pathway. The aim of this study was to explore the preventive and therapeutic effects of gut microbial fatty acid metabolites in a NASH mouse model. The mice were divided into 3 experimental groups and fed as follows: (1) high-fat diet (HFD) (2) HFD mixed with 0.1% KetoA (10-oxo-12(Z)-octadecenoic acid), and (3) HFD mixed with 0.1% KetoC. After 3 weeks of feeding, plasma parameters, liver histology, and mRNA expression of multiple genes were assessed. There was hardly any difference in fat accumulation in the histological study; however, no ballooning occurred in 2/5 mice of KetoC group. Bridging fibrosis was not observed in the KetoA group, although KetoA administration did not significantly suppress fibrosis score (p = 0.10). In addition, KetoC increased the expression level of HDL related genes and HDL cholesterol levels in the plasma. These results indicated that KetoA and KetoC may partly affect the progression of NASH in mice models.     

A Novel Method for Visualizing Melanosome and Melanin Distribution in Human Skin Tissues

Melanin incorporated into keratinocytes plays an important role in photoprotection; however, abnormal melanin accumulation causes hyperpigmentary disorders. To understand the mechanism behind the accumulation of excess melanin in the skin, it is essential to clarify the spatial distribution of melanosomes or melanin in the epidermis. Although several markers have been used to detect melanosomes or melanin, no suitable markers to determine the precise localization of melanin in the epidermis have been reported. In this study, we showed that melanocore-interacting Kif1c-tail (M-INK), a recently developed fluorescent probe for visualizing mature melanosomes, binds to purified melanin in vitro, and applied it for detecting melanin in human skin tissues. Frozen skin sections from different phototypes were co-stained for the hemagglutinin (HA)-tagged M-INK probe and markers of melanocytes or keratinocytes, and a wide distribution of melanin was observed in the epidermis. Analysis of the different skin phototypes indicated that the fluorescent signals of HA-M-INK correlated well with skin color. The reconstruction of three-dimensional images of epidermal sheets enabled us to observe the spatial distribution of melanin in the epidermis. Thus, the HA-M-INK probe is an ideal tool to individually visualize melanin (or melanosome) distribution in melanocytes and in keratinocytes in skin tissues.     

Autophagy and Autophagy-Related Diseases: A Review

Autophagy refers to the process involving the decomposition of intracellular components via lysosomes. Autophagy plays an important role in maintaining and regulating cell homeostasis by degrading intracellular components and providing degradation products to cells. In vivo, autophagy has been shown to be involved in the starvation response, intracellular quality control, early development, and cell differentiation. Recent studies have revealed that autophagy dysfunction is implicated in neurodegenerative diseases and tumorigenesis. In addition to the discovery of certain disease-causing autophagy-related mutations and elucidation of the pathogenesis of conditions resulting from the abnormal degradation of selective autophagy substrates, the activation of autophagy is essential for prolonging life and suppressing aging. This article provides a comprehensive review of the role of autophagy in health, physiological function, and autophagy-related disease.     

Platinum on Carbon‐Catalyzed H–D Exchange Reaction of Aromatic Nuclei due to Isopropyl Alcohol‐Mediated Self‐ Activation of Platinum Metal in Deuterium Oxide

An efficient and simple deuteration method of arenes using the platinum on carbon‐isopropyl alcohol‐cyclohexane‐deuterium oxide combination under hydrogen gas‐free conditions was accomplished. Since the hydrogen–deuterium exchange reaction cannot be promoted without isopropyl alcohol, zerovalent platinum metal (on carbon) is self‐activated by the in situ‐generated very low amount of hydrogen or hydrogen–deuterium gas derived from isopropyl alcohol or isopropyl alcohol‐d₁. Deuterium‐labeled compounds with high deuterium contents can be easily isolated by the filtration of platinum on carbon and simple extraction. The present hydrogen gas‐free method is safe from the viewpoint of process chemistry and various arenes possessing a variety of reducible functionalities within the molecule could be effectively and directly deuterium‐labeled without undesired reduction.     

Studies on the Dehydrogenative Polymerizations of Monolignol β-glycosides. Part 3: Horseradish Peroxidase–Catalyzed Polymerizations of Triandrin and Isosyringin

Abstract

Horseradish peroxidase–catalyzed dehydrogenative polymerizations of the p-hydroxyphenyl monolignol glucoside (triandrin (1P)) and the syringyl monolignol glucoside (isosyringin (1S)) resulted in the formation of water-soluble lignin-like polymers (DHPs). The polymerization of 1P gave highly polymerized DHPs in high yields as did previously reported polymerization of the guaiacyl monolignol glucoside (isoconiferin (1G)). It was shown that the hydrophilic D-glucose units of 1G and 1P contribute to a marked increase in the molecular weights of the resulting DHPs. On the other hand, the homogeneous phase polymerization of 1S, similar to the polymerization of sinapyl alcohol, gave DHPs with extremely low molecular masses in poor yields. Structural characterization indicated that the DHPs from 1P and 1S were lignin-like polymers containing glucosidic units on their sidechains. It was also confirmed that D-glucosyl units introduced onto the γ-position of monolignols do not significantly affect the electrochemical oxidizability and the kinetics of the HRP-catalyzed initial monomer consumption.     

Development of Sustained-Release Tablets Containing Sodium Valproate: In Vitro and In Vivo Correlation

ABSTRACT

We have developed a 200 mg and 400 mg sustained-release sodium valproate tablet that allows effective blood concentration of the active drug with once-a-day dosing. The controlled dissolution or sustained release of the drug was attained by a membrane-controlled system. A single-coating system did not adequately control the dissolution rate, and therefore double-coated tablets were prepared and a human pharmacokinetic study was conducted. With the 200 mg VPA-Na tablets, the nonfasting C_max was only 20% higher than the fasting C_max. An in vitro dissolution test was conducted to predict the effects of food on drug dissolution after administration of this tablet. A relatively good correlation was observed between the absorption profiles and the dissolution profiles of the drug.     

A new glass GEM with a single-sided guard-ring structure

The gas electron multiplier (GEM) is a gaseous detector that is widely used in many applications. Our glass GEM (G-GEM) comprises a photo-etchable glass (PEG3, HOYA Corporation, Japan). Our research indicated that it shows superior performance compared with other gas detectors. In this article, a new type of G-GEM is introduced. It has a guard-ring structure around the holes in order to improve the spark tolerance by reducing the total capacitance of each hole structure. A measured gas gain of approximately 7500 is attained for this new G-GEM with a single-sided guard-ring structure using a gas mixture of Ar (90%) and CH₄ (10%) in the gas flow mode. An energy resolution of 17.3% (FWHM) is also achieved with a collimated 6 keV X-ray beam. The results of a 10 to 12 hour gas gain stability measurements are also shown.     

Fluoroscopic bone fragment tracking for surgical navigation in femur fracture reduction by incorporating optical tracking of hip joint rotation center

A new method for fluoroscopic tracking of a proximal bone fragment in femoral fracture reduction is presented. The proposed method combines 2-D and 3-D image registration from single-view fluoroscopy with tracking of the head center position of the proximal femoral fragment to improve the accuracy of fluoroscopic registration without the need for repeated manual adjustment of the C-arm as required in stereo-view registrations. Kinematic knowledge of the hip joint, which has a positional correspondence with the femoral head center and the pelvis acetabular center, allows the position of the femoral fragment to be determined from pelvis tracking. The stability of the proposed method with respect to fluoroscopic image noise and the desired continuity of the fracture reduction operation is demonstrated, and the accuracy of tracking is shown to be superior to that achievable by single-view image registration, particularly in depth translation.     

Giant thermoelectric Seebeck coefficient of a two-dimensional electron gas in SrTiO3

Enhancement of the Seebeck coefficient (S ) without reducing the electrical conductivity (sigma) is essential to realize practical thermoelectric materials exhibiting a dimensionless figure of merit (ZT=S2 x sigma x T x kappa-1) exceeding 2, where T is the absolute temperature and kappa is the thermal conductivity. Here, we demonstrate that a high-density two-dimensional electron gas (2DEG) confined within a unit cell layer thickness in SrTiO(3) yields unusually large |S|, approximately five times larger than that of SrTiO(3) bulks, while maintaining a high sigma2DEG. In the best case, we observe |S|=850 microV K-1 and sigma2DEG=1.4 x 10(3) S cm-1. In addition, by using the kappa of bulk single-crystal SrTiO(3) at room temperature, we estimate ZT approximately 2.4 for the 2DEG, corresponding to ZT approximately 0.24 for a complete device having the 2DEG as the active region. The present approach using a 2DEG provides a new route to realize practical thermoelectric materials without the use of toxic heavy elements.