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1.
Lili Chen Nanami Fujisawa Masato Takanohashi Mazaya Najmina Koichiro Uto Mitsuhiro Ebara 《International journal of molecular sciences》2021,22(5)
This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can achieve mutual synergy of hyperthermia, chemotherapy, and thermo-molecularly targeted therapy for highly potent therapeutic effects. The nanofiber is composed of biodegradable poly(ε-caprolactone) with doxorubicin, magnetic nanoparticles, and 17-allylamino-17-demethoxygeldanamycin. The nanofiber exhibits distinct hyperthermia, owing to the presence of magnetic nanoparticles upon exposure of the mesh to an alternating magnetic field, which causes heat-induced cell killing as well as enhanced chemotherapeutic efficiency of doxorubicin. The effectiveness of hyperthermia is further enhanced through the inhibition of heat shock protein activity after hyperthermia by releasing the inhibitor 17-allylamino-17-demethoxygeldanamycin. These findings represent a smart nanofiber system for potent cancer therapy and may provide a new approach for the development of localized medication delivery. 相似文献
2.
Dr. Daniel Feder Dr. Siti H. Mohd-Pahmi Dr. Waleed M. Hussein Prof. Luke W. Guddat Prof. Ross P. McGeary Prof. Gerhard Schenk 《ChemMedChem》2021,16(21):3342-3359
Metallohydrolases form a large group of enzymes that have fundamental importance in a broad range of biological functions. Among them, the purple acid phosphatases (PAPs) have gained attention due to their crucial role in the acquisition and use of phosphate by plants and also as a promising target for novel treatments of bone-related disorders and cancer. To date, no crystal structure of a mammalian PAP with drug-like molecules bound near the active site is available. Herein, we used a fragment-based design approach using structures of a mammalian PAP in complex with the MaybridgeTM fragment CC063346, the amino acid L-glutamine and the buffer molecule HEPES, as well as various solvent molecules to guide the design of highly potent and efficient mammalian PAP inhibitors. These inhibitors have improved aqueous solubility when compared to the clinically most promising PAP inhibitors available to date. Furthermore, drug-like fragments bound in newly discovered binding sites mapped out additional scaffolds for further inhibitor discovery, as well as scaffolds for the design of inhibitors with novel modes of action. 相似文献
3.
Marta Baranowska-Kuczko Hanna Kozowska Monika Kloza Ewa Harasim-Symbor Micha Biernacki Irena Kasacka Barbara Malinowska 《International journal of molecular sciences》2021,22(9)
Our study aimed to examine the effects of hypertension and the chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on vascular function and the endocannabinoid system in spontaneously hypertensive rats (SHR). Functional studies were performed on small mesenteric G3 arteries (sMA) and aortas isolated from SHR and normotensive Wistar Kyoto rats (WKY) treated with URB597 (1 mg/kg; twice daily for 14 days). In the aortas and sMA of SHR, endocannabinoid levels and cannabinoid CB1 receptor (CB1R) expression were elevated. The CB1R antagonist AM251 diminished the methanandamide-evoked relaxation only in the sMA of SHR and enhanced the vasoconstriction induced by phenylephrine and the thromboxane analog U46619 in sMA in SHR and WKY. In the sMA of SHR, URB597 elevated anandamide levels, improved the endothelium-dependent vasorelaxation to acetylcholine, and in the presence of AM251 reduced the vasoconstriction to phenylephrine and enhanced the vasodilatation to methanandamide, and tended to reduce hypertrophy. In the aortas, URB597 elevated endocannabinoid levels improved the endothelium-dependent vasorelaxation to acetylcholine and decreased CB1R expression. Our study showed that hypertension and chronic administration of URB597 caused local, resistance artery-specific beneficial alterations in the vascular endocannabinoid system, which may bring further advantages for therapeutic application of pharmacological inhibition of FAAH. 相似文献
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为改善南海东部惠州25-8油田大斜度井因泥岩水化造浆而引起的井壁失稳和钻井液增稠影响携砂的问题,在现有成熟PLUS/KCl钻井液的基础上开展复合盐阳离子聚合物钻井液研究,对钻井液配方进行了优化,评价了优化后钻井液的流变性、抑制性、封堵性和润滑性,并在惠州油田进行了现场应用。结果表明,复合盐阳离子聚合物钻井液配方中,无机盐类抑制剂KCl和NaCl的适宜加量为3%和12%、有机阳离子聚合物抑制剂PF-CPI适宜的加量为2.0%。该钻井液抑制性强,防膨率高达93.32%,钻屑回收率87.56%;受到钻屑侵污后的钻井液流变性能波动小,仍具有较低的黏度和合适的切力,有利于大斜度井携砂;封堵性和润滑性均优于PLUS/KCl钻井液体系。现场应用2口井,钻井液流变性良好,平均起下钻速度提高,钻井过程顺利,无复杂情况发生。复合盐阳离子聚合物钻井液可改善南海大斜度井起下钻阻卡的问题。 相似文献
6.
Keshun Liu 《Journal of the American Oil Chemists' Society》2019,96(6):635-645
For measuring trypsin inhibitor (TI) activities in soybean products, the current standard method, approved and reapproved by American Oil Chemists Society (Method Ba 12-75) and American Association of Cereal Chemists International (Method 22-40.01), features mixing trypsin with a series of inhibitor levels and then adding a substrate to start the colorimetric reaction. Yet, previous studies have shown flaws with the method, particularly with using several inhibitor levels and the sequence of adding the substrate last. The present study showed that with varying levels of dilution and volumes of a dilute sample extract, the pH of the premix (the mixture of a dilute sample extract and trypsin solution) ranged 3.30–3.60 for raw soy flour, and 3.20–6.70 for toasted soy. Within these premix pH ranges, the standard method of adding substrate last would give TI values equal to or less than those measured by the same method except for adding the enzyme last. The standard method was subsequently improved by using a single sample extract level and the enzyme-last sequence. Other modifications included making stock solutions for reagents, adding Ca2+ to the trypsin solution, diluting sample extracts to a level that causes 30–70% of inhibition, and running both reference and sample blanks for better controls. Alternatively, the full volume assay (10 mL total, as in the standard method) was further modified by using half the volume of each reagent with the same concentration. Compared to the standard method, the improved methods gave more consistent results when assaying 11 selected soy products. The half volume (5 mL) and full volume methods gave the same results, but the former could increase assay sensitivity and reduce amounts of reagents used. 相似文献
7.
布鲁顿式酪氨酸激酶(Btk)和两面神激酶3(JAK3)均是自身免疫性疾病和血液系统恶性肿瘤的潜力靶标。以4-氯吡咯并嘧啶为原料,经7步反应合成了一系列7H-吡咯并[2,3-d]嘧啶-4-胺衍生物,其结构经1HNMR、13CNMR和MS(ESI)分析证实。体外依次考察了所得化合物分别对Btk和JAK3激酶的活性、以及对部分B淋巴细胞瘤细胞系的抗增殖活性。结果表明,四氢吡咯烷基取代的衍生物NB1~4对Btk(IC50<3 nmol/L)和JAK3(IC50<165 nmol/L)均能有效抑制,其余化合物只对Btk显示抑制效果;而且NB2和NB4对所测试的多种B细胞淋巴瘤细胞系的抗增殖活性均优于阳性对照泛激酶抑制剂依鲁替尼及Btk单靶点抑制剂。其中,对Jeko-1细胞的抑制能力最佳(IC50<3μmol/L),其次是OCI-LYI(IC50<4μmol/L)、SUDHL-6(IC50<6μmol/L)和HBL-1*(IC50<6.5μmol/L),最差为SUDHL-4细胞(IC50<11μmol/L)。这些发现可为开发B细胞淋巴瘤的多靶点药物提供新的思路。 相似文献
8.
9.
Mohammad Ali Karambeigi Narges Fallah Manouchehr Nikazar Riyaz Kharrat 《Petroleum Science and Technology》2019,37(20):2146-2149
Asphaltene deposition has a significant detrimental effect on oilfield production. The key to effective treatment of asphaltene deposition is recognition of the problem. Asphaltene and effective treatment can be identified and quantified using laboratory methods. The most commonly way to asphaltene precipitation reduction is applying an asphaltene inhibitor. Most researchers investigate the effect of asphaltene inhibitors on fluid and precipitation reduction in static tests. This study is a coherent approach to measure effect of asphaltene precipitation on reservoir permeability and survey effect of asphaltene inhibitors on damage permeability. 相似文献
10.
研究对N-亚硝胺具有阻断作用的复合香辛料亚硝化抑制剂(composite spice nitrosation inhibitor,CSNI) 在西式培根中的应用效果。设计4 组实验:1)阴性对照(negative control,NC)组:以原料肉质量计,配 制由0.06%亚硝酸钠、9%食盐、1.5%复合磷酸盐、5%白糖等组成的腌制液,注射量为20%;2)阳性对照 (positive control,PC)组:在NC组基础上添加0.055%异抗坏血酸钠;3)CSNI组:在NC组中添加CSNI; 4)PC+CSNI组:在PC组中添加CSNI。制成西式培根,分别对西式培根成品和烧烤(200 ℃,5 min)西式培根进 行感官评定、pH值、红度值(a*)、硫代巴比妥酸反应物(thiobarbituric acid reactive substances,TBARs)值、亚 硝酸盐残留量、生物胺含量及N-亚硝胺含量测定。结果表明:相比NC、PC组,PC+CSNI组西式培根成品的感官 评分最高,TBARs值(0.24 mg/kg)、亚硝酸盐残留量(20.48 mg/kg)和生物胺总量(184.68 mg/kg)均处于较低 水平,CSNI对N-亚硝胺的形成(总量为9.29 μg/kg),特别是N-二甲基亚硝胺的形成有显著的阻断效果,且CSNI的 添加对产品的pH值和a*均未造成显著影响;西式培根烧烤后,由于水分和脂肪溶出,致使烧烤西式培根的亚硝酸 盐残留量、生物胺含量和N-亚硝胺含量总体呈升高趋势,但均未超过相关规定的限量值。 相似文献