Epigenetic Targets for Oligonucleotide Therapies of Pulmonary Arterial Hypertension

Arterial wall remodeling underlies increased pulmonary vascular resistance and right heart failure in pulmonary arterial hypertension (PAH). None of the established vasodilator drug therapies for PAH prevents or reverse established arterial wall thickening, stiffening, and hypercontractility. Therefore, new approaches are needed to achieve long-acting prevention and reversal of occlusive pulmonary vascular remodeling. Several promising new drug classes are emerging from a better understanding of pulmonary vascular gene expression programs. In this review, potential epigenetic targets for small molecules and oligonucleotides will be described. Most are in preclinical studies aimed at modifying the growth of vascular wall cells in vitro or normalizing vascular remodeling in PAH animal models. Initial success with lung-directed delivery of oligonucleotides targeting microRNAs suggests other epigenetic mechanisms might also be suitable drug targets. Those targets include DNA methylation, proteins of the chromatin remodeling machinery, and long noncoding RNAs, all of which act as epigenetic regulators of vascular wall structure and function. The progress in testing small molecules and oligonucleotide-based drugs in PAH models is summarized.     

Contributions of higher order terms to nonlinear waves in fluid-filled elastic tubes: strongly dispersive case

In the present work, employing the nonlinear equations of an incompressible, isotropic and elastic thin tube and the approximate equations of an incompressible inviscid fluid, and then utilizing the modified reductive perturbation technique presented by us [15] the amplitude modulation of weakly nonlinear waves is examined. It is shown that the first order term in the perturbation expansion is governed by a nonlinear Schrödinger equation and the second order term is governed by the linearized Schrödinger equation with a nonhomogeneous term. In the longwave limit a travelling wave type of solution to these equations are also given.     

吲哚美辛对荷瘤小鼠抗肿瘤作用机制的实验研究

用微观放射自显影技术及免疫组化法探讨了非甾体类抗炎药吲哚美辛(IN)对Lewis肺癌的生长抑制作用机制。结果显示:与对照组相比,实验组IN的抑瘤率为55.05%;IN可显著下调Bcl-2蛋白的表达(t=6.154,P<0.001),对Bax蛋白的表达没有明显影响(t=2.101,P>0.05)。放射自显影结果显示,在肿瘤细胞的细胞膜、细胞浆及细胞核中均有黑色银颗粒分布,且在用药后12 h时肿瘤组织中的平均银颗粒数高于4、7、243、6 h时。以上结果表明,IN可抑制Lewis肺癌的生长,其机制与下调抗凋亡蛋白Bcl-2的表达及降低Bcl-2/Bax的比值有关;IN可进入到肿瘤细胞内发挥抗肿瘤作用。     

An automated tanh-function method for finding solitary wave solutions to non-linear evolution equations

The tanh-function method for finding explicit travelling solitary wave solutions to non-linear evolution equations is described. The method is usually extremely tedious to use by hand. We present a Mathematica package ATFM that deals with the tedious algebra and outputs directly the required solutions. The use of the package is illustrated by applying it to a variety of equations; not only are previously known solutions recovered but in some cases more general forms of solution are obtained.     

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.     

Dynamics of Bacterial Community Structure in the Rhizosphere and Root Nodule of Soybean: Impacts of Growth Stages and Varieties

Bacterial communities in rhizosphere and root nodules have significant contributions to the growth and productivity of the soybean (Glycine max (L.) Merr.). In this report, we analyzed the physiological properties and dynamics of bacterial community structure in rhizosphere and root nodules at different growth stages using BioLog EcoPlate and high-throughput sequencing technology, respectively. The BioLog assay found that the metabolic capability of rhizosphere is in increasing trend in the growth of soybeans as compared to the bulk soil. As a result of the Illumina sequencing analysis, the microbial community structure of rhizosphere and root nodules was found to be influenced by the variety and growth stage of the soybean. At the phylum level, Actinobacteria were the most abundant in rhizosphere at all growth stages, followed by Alphaproteobacteria and Acidobacteria, and the phylum Bacteroidetes showed the greatest change. But, in the root nodules Alphaproteobacteria were dominant. The results of the OTU analysis exhibited the dominance of Bradyrhizobium during the entire stage of growth, but the ratio of non-rhizobial bacteria showed an increasing trend as the soybean growth progressed. These findings revealed that bacterial community in the rhizosphere and root nodules changed according to both the variety and growth stages of soybean in the field.     

稀盐酸中锰结核还原浸出溶液净化除铁

针对酸性氯化物中黄铁矿还原浸出锰结核的溶液成分特点，选择黄钠铁矾法进行了沉淀分离铁的研究。结果表明温度和晶种以及溶液ｐＨ值是影响铁矾沉淀的重要因素。在ｐＨ２．０左右，溶液温度高于９０℃，足量晶种加入的情形下，１５０ｍｉｎ后可将溶液中的铁含量降至０．１ｇ／Ｌ。沉矾过程的表观活化能为９４．６６ｋＪ／ｍｏｌ。黄铁矿氧化生成的硫酸根随铁一同沉淀，从而消除了ＳＯ２－４在氯化物体系中的积累。     

用闪锌矿(方铅矿)精矿催化还原软锰矿(大洋锰结核矿)制取硫酸锰

在稀硫酸(或稀盐酸)溶液中，用闪锌矿(或方铅矿)精矿作还原剂，用可溶性铁盐作催化剂，分解软锰矿(或大洋锰结核矿)，同时制取锰盐和锌盐。该工艺具有反应快速、彻底，工艺流程简单等特点，同时省去了软锰矿的还原焙烧和锌(铅)精矿的氧化焙烧，能够大幅度提高锰、锌(铅)矿的浸出率，对原料矿的品级没有严格要求。