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51.
Dr. Daisuke Okuno Dr. Noriho Sakamoto Dr. Mohammed S. O. Tagod Yoshiko Akiyama Dr. Sakiko Moriyama Dr. Takuto Miyamura Dr. Atsuko Hara Dr. Takashi Kido Dr. Hiroshi Ishimoto Prof. Yuji Ishimatsu Prof. Takashi Tanaka Prof. Jun Ishihara Prof. Kohsuke Takeda Prof. Yoshimasa Tanaka Prof. Hiroshi Mukae 《ChemMedChem》2021,16(16):2515-2523
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. 相似文献
52.
以Fe3O4纳米颗粒为核,正硅酸乙酯(TEOS)为前驱体,通过St?ber法合成了Fe3O4-SiO2核壳纳米颗粒。以γ-缩水甘油醚氧丙基三甲氧基硅烷(GPTMS)为改性剂对纳米颗粒进行改性,得到了环氧基功能化的Fe3O4-SiO2核壳纳米颗粒,随后将碳酸酐酶(carbonic anhydrase,CA)共价固定到纳米颗粒上,以实现CA固定化。采用傅立叶红外(FTIR)、透射电镜(TEM)等手段对载体材料进行表征;以对硝基苯酚乙酸酯(p-NPA)为底物,采用紫外分光光度仪测试酶活力,并对固定化酶进行了性能表征。试验结果表明,固定化酶的热稳定性、贮藏稳定性和循环使用性均优于同等条件下的游离酶,其在循环使用10次后仍保持84.2%的相对酶活力。 相似文献
53.
Svetlana V. Klinova Boris A. Katsnelson Ilzira A. Minigalieva Oksana P. Gerzen Alexander A. Balakin Ruslan V. Lisin Ksenia A. Butova Salavat R. Nabiev Oleg N. Lookin Leonid B. Katsnelson Larisa I. Privalova Daniil A. Kuznetsov Vladimir Ya. Shur Ekaterina V. Shishkina Oleg H. Makeev Irene E. Valamina Vladimir G. Panov Marina P. Sutunkova Larisa V. Nikitina Yuri L. Protsenko 《International journal of molecular sciences》2021,22(7)
Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO–NP and PbO–NP. These results correlate with a shift in the expression of myosin heavy chain (MHC) isoforms towards slowly cycling β–MHC. The type of CdO–NP + PbO–NP combined cardiotoxicity depends on the effect of the toxic impact, the extent of this effect, the ratio of toxicant doses, and the degree of stretching of cardiomyocytes and muscle type studied. Some indices of combined Pb–NP and CdO–NP cardiotoxicity and general toxicity (genotoxicity included) became fully or partly normalized if intoxication developed against background administration of a bioprotective complex. 相似文献
54.
Olga Azevedo Filipa Cordeiro Miguel Fernandes Gago Gabriel Miltenberger-Miltenyi Catarina Ferreira Nuno Sousa Damio Cunha 《International journal of molecular sciences》2021,22(9)
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat. 相似文献
55.
Aleksandra A. Ageeva Ilya M. Magin Alexander B. Doktorov Victor F. Plyusnin Polina S. Kuznetsova Alexander A. Stepanov Alexander A. Alekseev Nikolay E. Polyakov Tatyana V. Leshina 《International journal of molecular sciences》2021,22(12)
The study of the L- and D-amino acid properties in proteins and peptides has attracted considerable attention in recent years, as the replacement of even one L-amino acid by its D-analogue due to aging of the body is resulted in a number of pathological conditions, including Alzheimer’s and Parkinson’s diseases. A recent trend is using short model systems to study the peculiarities of proteins with D-amino acids. In this report, the comparison of the excited states quenching of L- and D-tryptophan (Trp) in a model donor–acceptor dyad with (R)- and (S)-ketoprofen (KP-Trp) was carried out by photochemically induced dynamic nuclear polarization (CIDNP) and fluorescence spectroscopy. Quenching of the Trp excited states, which occurs via two mechanisms: prevailing resonance energy transfer (RET) and electron transfer (ET), indeed demonstrates some peculiarities for all three studied configurations of the dyad: (R,S)-, (S,R)-, and (S,S)-. Thus, the ET efficiency is identical for (S,R)- and (R,S)-enantiomers, while RET differs by 1.6 times. For (S,S)-, the CIDNP coefficient is almost an order of magnitude greater than for (R,S)- and (S,R)-. To understand the source of this difference, hyperpolarization of (S,S)-and (R,S)- has been calculated using theory involving the electron dipole–dipole interaction in the secular equation. 相似文献
56.
Dr. Eric J. Strobel 《Chembiochem : a European journal of chemical biology》2021,22(22):3214-3224
Site-specific strategies for exchanging segments of dsDNA are important for DNA library construction and molecular tagging. Deoxyuridine (dU) excision is an approach for generating 3’ ssDNA overhangs in gene assembly and molecular cloning procedures. Unlike approaches that use a multi-base pair motif to specify a DNA cut site, dU excision requires only a dT→dU substitution. Consequently, excision sites can be embedded in biologically active DNA sequences by placing dU substitutions at non-perturbative positions. In this work, I describe a molecular tagging method that uses dU excision to exchange a segment of a dsDNA strand with a long synthetic oligonucleotide. The core workflow of this method, called deoxyUridine eXcision-tagging (dUX-tagging), is an efficient one-pot reaction: strategically positioned dU nucleotides are excised from dsDNA to generate a 3’ overhang so that additional sequence can be appended by annealing and ligating a tagging oligonucleotide. The tagged DNA is then processed by one of two procedures to fill the 5’ overhang and remove excess tagging oligo. To facilitate its widespread use, all dUX-tagging procedures exclusively use commercially available reagents. As a result, dUX-tagging is a concise and easily implemented approach for high-efficiency linear dsDNA tagging. 相似文献
57.
58.
为解决德兴铜矿采区运输道路雨季严重翻浆、旱季尘土飞扬的难题,通过一年多的考察调研,充分了解了浆土路的应用案例和推广动态,并全方位地了解其施工、运行和维护的整体过程,以及带来的成效。同时,对比分析浆土路应用过程中的道路参数、运输设备运行参数和黏土属性,类比分析云南集团鹤庆北衙矿业有限公司(简称“北衙金矿”)浆土路试验道路和锡林浩特国家能源胜利露天煤矿(简称“胜利露天煤矿”)FRT生物酶道路的运行效益。结果表明,德兴铜矿采用浆土路修筑技术是可行的,能大幅度降低采区道路运行和维护成本。 相似文献
59.
斜坡道是地下金属矿山的主要运输通道,其道路质量直接影响着矿山的安全运输和经济效益。针对斜坡道混凝土浇筑路面存在的筑路成本高、养护时间长、使用寿命短及维护困难等不足,引入浆土路修筑技术,开展了地下金属矿山斜坡道浆土路筑路材料配比试验、黏土搓条和崩解试验、水洗筛分试验,并在云南卡房分公司完成了浆土路试验路段的修筑。结果表明:浆土路筑路技术能够很好地应用于地下矿山道路修筑,具有施工工艺简单、筑路成本低、施工周期短、承载能力强、抑尘防滑和低碳环保等诸多优点,为地下金属矿山道路修筑提供了工程借鉴,对于矿山降本增效、节能减排及安全高效具有重要的意义。 相似文献
60.