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41.
Peter Kubatka Martin Kello Karol Kajo Marek Samec Alena Liskova Karin Jasek Lenka Koklesova Tomas Kuruc Marian Adamkov Karel Smejkal Emil Svajdlenka Peter Solar Martin Pec Dietrich Büsselberg Vladimira Sadlonova Jan Mojzis 《International journal of molecular sciences》2021,22(1)
Comprehensive scientific data provide evidence that isolated phytochemicals or whole plant foods may beneficially modify carcinogenesis. The aim of this study was to evaluate the oncostatic activities of Rhus coriaria L. (sumac) using animal models (rat and mouse), and cell lines of breast carcinoma. R. coriaria (as a powder) was administered through the diet at two concentrations (low dose: 0.1% (w/w) and high dose: 1 % (w/w)) for the duration of the experiment in a syngeneic 4T1 mouse and chemically-induced rat mammary carcinoma models. After autopsy, histopathological and molecular analyses of tumor samples in rodents were performed. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were conducted. The dominant metabolites present in tested R. coriaria methanolic extract were glycosides of gallic acid (possible gallotannins). In the mouse model, R. coriaria at a higher dose (1%) significantly decreased tumor volume by 27% when compared to controls. In addition, treated tumors showed significant dose-dependent decrease in mitotic activity index by 36.5% and 51% in comparison with the control group. In the chemoprevention study using rats, R. coriaria at a higher dose significantly reduced the tumor incidence by 20% and in lower dose non-significantly reduced tumor frequency by 29% when compared to controls. Evaluations of the mechanism of oncostatic action using valid clinical markers demonstrated several positive alterations in rat tumor cells after the treatment with R. coriaria. In this regard, histopathological analysis of treated tumor specimens showed robust dose-dependent decrease in the ratio of high-/low-grade carcinomas by 66% and 73% compared to controls. In treated rat carcinomas, we found significant caspase-3, Bax, and Bax/Bcl-2 expression increases; on the other side, a significant down-regulation of Bcl-2, Ki67, CD24, ALDH1, and EpCam expressions and MDA levels. When compared to control specimens, evaluation of epigenetic alterations in rat tumor cells in vivo showed significant dose-dependent decrease in lysine methylation status of H3K4m3 and H3K9m3 and dose-dependent increase in lysine acetylation in H4K16ac levels (H4K20m3 was not changed) in treated groups. However, only in lower dose of sumac were significant decreases in the expression of oncogenic miR210 and increase of tumor-suppressive miR145 (miR21, miR22, and miR155 were not changed) observed. Finally, only in lower sumac dose, significant decreases in methylation status of three out of five gene promoters–ATM, PTEN, and TIMP3 (PITX2 and RASSF1 promoters were not changed). In vitro evaluations using methanolic extract of R. coriaria showed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). In conclusion, sumac demonstrated significant oncostatic activities in rodent models of breast carcinoma that were validated by mechanistic studies in vivo and in vitro. 相似文献
42.
Fernanda Rodríguez-Enríquez Dr. Dolores Viña Dr. Eugenio Uriarte Dr. Reyes Laguna Dr. Maria J. Matos 《ChemMedChem》2021,16(1):179-186
This study explores the potential of 7-amidocoumarins as multitarget agents against Parkinson's and Alzheimer's diseases, by modulating the substitution patterns within the scaffold. Sixteen compounds were synthesized via 7-amino-4-methylcoumarin acylation, and in vitro evaluation of the molecules against hMAO-A, hMAO-B, hAChE, hBuChE and hBACE1 was performed. Five compounds turned out to be potent and selective hMAO-B inhibitors in the nanomolar range, six displayed inhibitory activity of hMAO-A in the low micromolar range, one showed hAChE inhibitory activity and another one hBACE1 inhibitory activity. MAO-B reversibility profile of 7-(4’-chlorobenzamido)-4-methylcoumarin ( 10 ) was investigated, with this compound being a reversible inhibitor. Neurotoxicity on motor cortex neurons and neuroprotection against H2O2 were also studied, corroborating the safety profile of these molecules. Finally, theoretical ADME properties were also calculated, showing these molecules as good candidates for the optimization of a lead compound. Results suggest that by modulating the substitution pattern at position 7 of the scaffold, selective or multitarget molecules can be achieved. 相似文献
43.
44.
通过金相试验方法测定42CrMo钢在890~930 ℃下保温10~240 min后的晶粒尺寸。结果表明,42CrMo钢在加热到试验温度890~930 ℃时已经完全奥氏体化,保温过程中的晶粒生长属于正常生长;加热温度对晶粒尺寸的影响较大,保温时间对晶粒尺寸的影响较小;随保温时间的延长晶粒生长缓慢,晶粒尺寸与保温时间满足指数小于1的函数关系。基于试验数据,通过线性回归得到晶粒长大的Beck模型参数,通过非线性回归得到Sellars和Anelli模型参数,3个模型的预测精度都较好,而Anelli模型的适用性要高于Beck模型和Sellars模型,故在预测42CrMo钢的奥氏体晶粒长大规律时宜使用Anelli模型。 相似文献
45.
Constantin Tnase Lucia Pintilie Raluca Elena Tnase 《International journal of molecular sciences》2021,22(4)
In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF2α and 1,15-PGF2α lactones, many 1,15-lactones of E2, E3, F2, F3, A2, and A3 were found in the marine mollusc Tethys fimbria and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of the compounds in different steps of the sequences. The many uses of δ-lactones not only for the synthesis of γ-lactones, but also for obtaining 9β-halogen-PGs and halogen-substituted cyclopentane intermediates, as synthons for new 9β-PG analogs and future applications, are also discussed. 相似文献
46.
详细计算了PVC生产精馏系统换热设备的热负荷、循环水量及运行成本,认为通过调整系统的运行温度和压力,精馏装置使用循环水替代7℃水具有可行性,这将有利于突破能耗高的技术瓶颈,最大程度地发挥节能降耗、减污增效的潜能。 相似文献
47.
通过对42CrMo4风机主轴结构尺寸、性能要求、材质特点等方面进行分析,对原有锻后热处理工艺进行优化,制定出既能达到锻后热处理效果又经济节能的工艺参数。 相似文献
48.
Christian Gentzsch Dr. Matthias Hoffmann Dr. Yasuhiro Ohshima Naoko Nose Dr. Xinyu Chen Prof. Dr. Takahiro Higuchi Prof. Dr. Michael Decker 《ChemMedChem》2021,16(9):1427-1437
The enzyme butyrylcholinesterase (BChE) represents a promising target for imaging probes to potentially enable early diagnosis of neurodegenerative diseases like Alzheimer's disease (AD) and to monitor disease progression in some forms of cancer. In this study, we present the design, facile synthesis, in vitro and preliminary ex vivo and in vivo evaluation of a morpholine-based, selective inhibitor of human BChE as a positron emission tomography (PET) tracer with a pseudo-irreversible binding mode. We demonstrate a novel protecting group strategy for 18F radiolabeling of carbamate precursors and show that the inhibitory potency as well as kinetic properties of our unlabeled reference compound were retained in comparison to the parent compound. In particular, the prolonged duration of enzyme inhibition of such a morpholinocarbamate motivated us to design a PET tracer, possibly enabling a precise mapping of BChE distribution. 相似文献
49.
50.
J. Thomas BRENNA 《粮油食品科技》2022,30(3):7-15
人体大脑和身体的发育,需要从食物中摄取均衡的营养物质。人类大脑是区分人类和其他动物的特征。食物中的必需脂肪酸是机体组织结构和功能的必要组成部分。Omega-6(O6)亚油酸(LA6)是皮肤组织的组成成分,且是炎症、血栓形成、免疫和其他信号分子的前体;Omega-3(O3)α-亚麻酸(ALA3),特别是其长链代谢产物——二十二碳六烯酸(DHA3),是大脑、视网膜和部分神经组织中的关键组分。从富含LA6脂肪酸(缺乏O3脂肪酸)的植物籽中提取出的廉价而优质油脂,是20世纪的西方国家食品工业生产的主要脂肪来源。在代谢通路中,高浓度的LA6脂肪酸可拮抗O3脂肪酸代谢,造成O3脂肪酸不足,因此,在给怀孕动物的饲料中,只提供富含LA6但缺乏O3脂肪酸的油脂作为唯一的脂肪来源,会导致幼崽大脑发育不良。过去20~30年的研究表明,低含量LA6且含DHA3的油脂可改善大脑的功能。近年来的研究较多集中在营养因素对大脑发育的影响,最新研究数据表明,脂肪酸平衡对营养不良儿童的大脑发育尤为重要。世界卫生组织(WHO)越来越重视大脑的营养健康,通过其下属的食品法典委员会,建议用于治疗严重急性营养不良儿童的即食治疗食品中,使用含有均衡脂肪酸组成/构成的脂肪。同样,脂肪酸均衡对老年人可能也很重要。目前,业界已经有了调整油脂成分的方法,以确保脂肪酸均衡,从而维持人体整个生命周期的大脑健康。 相似文献