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1.
Mastocytosis is a type of myeloid neoplasm characterized by the clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells that infiltrate one or more organ systems. Systemic mastocytosis (SM) is a more aggressive variant of mastocytosis with extracutaneous involvement, which might be associated with multi-organ dysfunction or failure and shortened survival. Over 80% of patients with SM carry the KIT D816V mutation. However, the KIT D816V mutation serves as a weak oncogene and appears to be a late event in the pathogenesis of mastocytosis. The management of SM is highly individualized and was largely palliative for patients without a targeted form of therapy in past decades. Targeted therapy with midostaurin, a multiple kinase inhibitor that inhibits KIT, has demonstrated efficacy in patients with advanced SM. This led to the recent approval of midostaurin by the United States Food and Drug Administration and European Medicines Agency. However, the overall survival of patients treated with midostaurin remains unsatisfactory. The identification of genetic and epigenetic alterations and understanding their interactions and the molecular mechanisms involved in mastocytosis is necessary to develop rationally targeted therapeutic strategies. This review briefly summarizes recent developments in the understanding of SM pathogenesis and potential treatment strategies for patients with SM. 相似文献
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Margarita A. Sazonova Vasily V. Sinyov Anastasia I. Ryzhkova Marina D. Sazonova Tatiana V. Kirichenko Victoria A. Khotina Zukhra B. Khasanova Natalya A. Doroschuk Vasily P. Karagodin Alexander N. Orekhov Igor A. Sobenin 《International journal of molecular sciences》2021,22(2)
Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress. 相似文献
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Quantitative UPLC‐MS/MS analysis of chlorogenic acid derivatives in antioxidant fractionates from dandelion (Taraxacum officinale) root
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Owen Kenny Thomas J. Smyth Chandralal M. Hewage Nigel P. Brunton 《International Journal of Food Science & Technology》2015,50(3):766-773
While qualitative studies have identified chlorogenic acids in antioxidant extracts, particularly ethyl acetate‐derived extracts, of Taraxacum officinale, quantitative analysis of these phenolic compounds remains largely unreported for this species. In this study, bioactivity‐guided fractionation of an antioxidant crude ethyl acetate extract (DPPH = 295.481 ± 0.955 mg TE g?1 extract) from T. officinale root resulted in a number of reverse‐phase fractions that demonstrated high antioxidant activity (DPPH = 1058.733–1312.136 mg TE g?1 extract), stronger than that of the synthetic antioxidant Trolox®. UPLC‐MS/MS screening of these fractions for the presence of selected mono‐ and di‐caffeoylquinic acids revealed large quantities of 1,5‐dicaffeoylquinic acid present in several fractions (853.052–907.324 μg mg?1), respectively. Due to the antioxidant potency and high levels of 1,5‐dicaffeoylquinic acid observed in these fractions, it was concluded that specifically this chlorogenic acid derivative is a major contributor to the antioxidant efficacy of dandelion root. 相似文献
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在制导炸弹半实物仿真试验中经常发现,同一发制导炸弹多次仿真的俯仰角差别较大,同一批次制导炸弹投弹试验的遥测俯仰角与仿真俯仰角差别也较大,但是俯仰角的收敛趋势均一致,实测脱靶量与仿真脱靶量都合格,且具有一致性。为了分析出现上述现象的原因,基于协方差分析描述函数法(CADFT),建立了制导炸弹半实物仿真系统的误差传播理论,计算了仿真姿态角和姿态角速度的误差。分析了仿真姿态角和姿态角速度的误差对仿真结果的影响。结果表明,在仿真系统各种误差中,气动力和气动力矩误差是主要误差,是引起仿真俯仰角差别的重要原因; 姿态角的动态验模方法不适用于制导炸弹仿真模型,而脱靶量的静态验模方法适用于制导炸弹仿真模型。 相似文献
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An Improved Immune Genetic Algorithm for Solving the Optimization Problems of Computer Communication Networks 总被引:4,自引:0,他引:4
1 IntroductionIndesigningacomputercommunicationnet work ,thenetworkaveragedelayisanimportantpa rameterinthenetworkperformance .Inthispaper,weonlyconsiderM /M/1networks,whichmeansthatthemessageprocessingtimeisaprobabilisticdensityfunctionwithnegativepower,thegroupar rivalandsendingisofPoissiondistributionwithasinglequeue .Supposethatthenetworktopologicalstructureandtheestimatesoftheexternaltrafficrequirementsaregiven ,howtoselecttheoptimalroutestobeusedbythecommunicatingnodesinthenetworksoast… 相似文献
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27例乙型血友病患者Ⅸ因子基因突变研究 总被引:1,自引:0,他引:1
采用PCR(聚合酶链反应)及GAWTS(GenomicAmplificationwithTranscriptsSequencing)技术,研究了江苏、湖北、山东、广东、福建、宁夏六省区27例乙型血友病患者及其家系成员FⅨ(九因子)基因各2.2Kb DNA序列。在2l例中发现20种不同类型的突变。其中12种是未曾报道的新突变。38%的突变发生在CpG二核苷致序列上,进一步证实了CpG确系突变热点。同时检出6例女性为致病基因携带者。对开展基因产前诊断及优生优育等,具有重要意义。 相似文献
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