Screening of Inhibitors Targeting Heat Shock Protein 47 Involved in the Development of Idiopathic Pulmonary Fibrosis

Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is causally related to fibrotic diseases, including idiopathic pulmonary fibrosis. The identification of Compounds that interfere with the HSP47-collagen interaction is essential for the development of relevant therapeutics. Herein, we prepared human HSP47 as a soluble fusion protein expressed in E. coli and established an assay system for HSP47 inhibitor screening. We screened a natural and synthetic Compound library established at Nagasaki University. Among 1023 Compounds, 13 exhibited inhibitory activity against human HSP47, of which three inhibited its function in a dose-dependent manner. Epigallocatechin-3-O-gallate, one of these three Compounds, is a typical polyphenol Compound derived from tea leaves. Structurally related Compounds were synthesized and examined for their activity, revealing a hydroxyl group at A-ring position 5 as important for its activity. The present findings provide valuable insight for the development of natural product-derived therapeutics for fibrotic diseases, including idiopathic pulmonary fibrosis.     

Links between Immune Cells from the Periphery and the Brain in the Pathogenesis of Epilepsy: A Narrative Review

Accumulating evidence has demonstrated that the pathogenesis of epilepsy is linked to neuroinflammation and cerebrovascular dysfunction. Peripheral immune cell invasion into the brain, along with these responses, is implicitly involved in epilepsy. This review explored the current literature on the association between the peripheral and central nervous systems in the pathogenesis of epilepsy, and highlights novel research directions for therapeutic interventions targeting these reactions. Previous experimental and human studies have demonstrated the activation of the innate and adaptive immune responses in the brain. The time required for monocytes (responsible for innate immunity) and T cells (involved in acquired immunity) to invade the central nervous system after a seizure varies. Moreover, the time between the leakage associated with blood–brain barrier (BBB) failure and the infiltration of these cells varies. This suggests that cell infiltration is not merely a secondary disruptive event associated with BBB failure, but also a non-disruptive event facilitated by various mediators produced by the neurovascular unit consisting of neurons, perivascular astrocytes, microglia, pericytes, and endothelial cells. Moreover, genetic manipulation has enabled the differentiation between peripheral monocytes and resident microglia, which was previously considered difficult. Thus, the evidence suggests that peripheral monocytes may contribute to the pathogenesis of seizures.     

Identification of Tumor Suppressive Genes Regulated by miR-31-5p and miR-31-3p in Head and Neck Squamous Cell Carcinoma

We identified the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC) tissues by RNA sequencing, in which 168 miRNAs were significantly upregulated, including both strands of the miR-31 duplex (miR-31-5p and miR-31-3p). The aims of this study were to identify networks of tumor suppressor genes regulated by miR-31-5p and miR-31-3p in HNSCC cells. Our functional assays showed that inhibition of miR-31-5p and miR-31-3p attenuated cancer cell malignant phenotypes (cell proliferation, migration, and invasion), suggesting that they had oncogenic potential in HNSCC cells. Our in silico analysis revealed 146 genes regulated by miR-31 in HNSCC cells. Among these targets, the low expression of seven genes (miR-31-5p targets: CACNB2 and IL34; miR-31-3p targets: CGNL1, CNTN3, GAS7, HOPX, and PBX1) was closely associated with poor prognosis in HNSCC. According to multivariate Cox regression analyses, the expression levels of five of those genes (CACNB2: p = 0.0189; IL34: p = 0.0425; CGNL1: p = 0.0014; CNTN3: p = 0.0304; and GAS7: p = 0.0412) were independent prognostic factors in patients with HNSCC. Our miRNA signature and miRNA-based approach will provide new insights into the molecular pathogenesis of HNSCC.     

Analysis of Reusability using ‘Marginal Reuse Rate’

While reuse is an effective lifecycle option in terms of reduction of environmental loads and value of reutilization, reuse has inherent difficulties. Our naive question is why component reuse of home appliances seems impossible while that of photocopiers succeeded. This paper clarifies an essential factor for successful reuse; that is, the balance between supply and demand of reusables, and proposes an index named ‘marginal reuse rate,’ which indicates upper limit of reusability. By using this index, reusability of several products is analyzed. The marginal reuse rate indicates that design of lifecycle, in addition to product design, is indispensable for successful reuse.     

Morphology and preferred orientation of Y2O3 film prepared by high-speed laser CVD

Yttria (Y₂O₃) films were prepared at high deposition rates of up to 83 nm/s (300 μm/h) by laser chemical vapor deposition (LCVD) using an Y(dpm)₃ precursor. The effects of deposition conditions, mainly total gas pressure and laser power, on morphology, deposition rate and preferred orientation were studied. Plasma was produced around the substrate over a critical laser power resulting in significant increases in deposition temperature and deposition rate. The high deposition rate (300 μm/h) by LCVD was about 100 to 1000 times as high as those by conventional CVD. The morphology of Y₂O₃ films changed from faceted and columnar structures with high (400) orientation to a columnar structure with high (440) orientation, and finally to a cone-like structure with moderate (440) orientation with increasing total gas pressure (P_tot).     

A New Process to Make a Porous PTFE Structure from Aqueous PTFE Dispersion with the Help of Hydrogel

A novel method to make a porous material having relatively large cell diameter (200–300 m), which consisted of mainly poly(tetrafluoroethylene) (PTFE), was developed from aqueous PTFE dispersion by using the characteristics of hydrogel with the addition of carbon nanofiber (CNF). The porous material was produced as follows: firstly, an aqueous agar gel containing PTFE and CNF was prepared; secondly, the gel was freeze-dried; thirdly, the dried gel was heat-treated at 400°C where the agar was almost decomposed and PTFE became molten. The porous material showed electric conductivity (about 50 ), high porosity (about 96 vol%), and relatively uniform cell structures without shrinkage during freeze drying and heat treatment. While the method without CNF resulted in large shrinkage during heat treatment, meaning that CNF prevented the shrinkage. It was explained by the idea that the existence of rigid CNF, which was dispersed in the cell wall, prohibited the shrinkage of PTFE during heat treatment. It was unexpectedly found by SEM analysis that the porous materials had another macro-porous structure inside the cell wall, suggesting that the developed materials had a double porous structure.     

Durability of radiation-sterilized polymers III. Oxidation layer determined by chemiluminescence

Chemiluminescence (CL) analysis was used for determining the oxidation layer formed by the irradiation of polypropylene for medical supplies. The depth of the oxidation layer from the surface depended on dose rate and increased with decreasing dose rate. The oxidation occurred remarkably at a region near the surface area of the film where the diffusion of oxygen is more sufficient. On the contrary, there was very little oxidation in the interior portion. The oxidation layers of polypropylene samples irradiated with electron beam showed U-shaped profiles in the cross-section of film as did as a sample irradiated with γ-rays. However, the degree of oxidation by irradiation with electron beam was very small; CL intensity at the surface area was only one-third that for the γ-irradiated samples.     

Radiation grafting of α,β,β-trifluoroethylenesulfonyl fluoride onto low-density polyethylene film by simultaneous irradiation method. I. Kinetic study of simultaneous-irradiation grafting

α,β,β-Trifluoroethylenesulfonyl fluoride (TFESF) was grafted onto polyethylene (PE) film by a simultaneous-irradiation method. The influences of the grafting conditions were analyzed kinetically. The dependencies of the grafting rate on the dose rates and monomer concentrations ranging from 10 to 75% were found to be of 1 and 0 order, respectively. The overall activation energy for the graft polymerization was 2.05 × 10⁴ J/mol. The grafting rate was found to be independent of the film thicknesses ranging from 25 to 100 μm.     

Effect of green compact structure on the sintering of alumina

The effect of particle agglomeration on sintering has been studied by slipcasting suspensions with pH values ranging from 2 to 11. The rate of densification has been found to depend on the degree of agglomeration. Complete dispersion of alumina primary particles has not been attained through adjustment of pH of suspensions, and agglomerates also remained in the best-dispersed suspension. Elimination of the agglomerates by sedimentation lowered the densification temperature of slip-cast compacts. The grain size-density curve is a function of temperature. High-density and small-grained sintered bodies were obtained by low-temperature long-time firing.     

Fast computation of computer-generated hologram using Xeon Phi coprocessor

We report fast computation of computer-generated holograms (CGHs) using Xeon Phi coprocessors, which have massively x86-based processors on one chip, recently released by Intel. CGHs can generate arbitrary light wavefronts, and therefore, are promising technology for many applications: for example, three-dimensional displays, diffractive optical elements, and the generation of arbitrary beams. CGHs incur enormous computational cost. In this paper, we describe the implementations of several CGH generating algorithms on the Xeon Phi, and the comparisons in terms of the performance and the ease of programming between the Xeon Phi, a CPU and graphics processing unit (GPU).