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了解茵芋碱A治疗与U-937细胞相关的非霍奇金淋巴瘤的分子机制:生物信息学方法,第一部分。

Understanding the Molecular Mechanisms of Incomptine A in Treating Non-Hodgkin Lymphoma Associated with U-937 Cells: Bioinformatics Approaches, Part I.

作者信息

Calzada Fernando, García-Hernández Normand, Bautista Elihú, Sánchez-López José Manuel, Valdes Miguel, Velázquez Claudia, Barbosa Elizabeth

机构信息

Unidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades, 2° Piso CORSE, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City 06725, Mexico.

Unidad de Investigación Médica en Genética Humana, UMAE Hospital Pediatría 2º Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City 06725, Mexico.

出版信息

Pharmaceuticals (Basel). 2024 Dec 24;18(1):5. doi: 10.3390/ph18010005.

Abstract

: Incomptine A () has been reported to have cytotoxic activity in non-Hodgkin lymphoma cancer cell lines and have effects on U-937 cells, including the induction of apoptosis, the production of reactive oxygen species, and the inhibition of glycolytic enzymes. Also, has cytotoxic activity in the triple-negative subtypes, HER2+, and luminal A of breast cancer cells, with its properties being associated with an effect on the antiapoptotic function of Hexokinase II (HKII). : In this research, we reviewed the altered levels of proteins present in the lymph nodes of male Balb/c mice inoculated with U-937 cells and treated with or methotrexate, as well as mice only inoculated with cancer cells. : Five approaches, including Tandem Mass Tag (TMT), Gene ontology (GO), Reactome, KEGG pathway analysis, and molecular docking, were used. : TMT showed that 74 proteins were differentially expressed, out of which 12 presented overexpression (FC ≥ 1.5) and 62 were under expressed (FC ≤ 0.67). In general, the TMT approach showed that had a better effect on proteins than methotrexate. Gene ontology, Reactome, and KEGG pathway analysis showed that proteins with altered levels may be implicated in several processes, including gene silencing by RNA, oxidative phosphorylation, glycolysis/gluconeogenesis, cytoskeleton organization, and ATP metabolic and energetic processes. The molecular docking analysis, which used 23 altered proteins as targets, revealed that interacted with all the proteins used. : The results obtained using the five bioinformatic approaches provide information and show that could be used to treat non-Hodgkin lymphoma induced with the U-937 cell line. Also, it could provide a basis for future research and the development of clinical trials.

摘要

据报道,Incomptine A()在非霍奇金淋巴瘤癌细胞系中具有细胞毒性活性,并对U - 937细胞有影响,包括诱导细胞凋亡、产生活性氧物种以及抑制糖酵解酶。此外,其在乳腺癌细胞的三阴性亚型、HER2 +和管腔A型中具有细胞毒性活性,其特性与对己糖激酶II(HKII)抗凋亡功能的影响有关。:在本研究中,我们回顾了接种U - 937细胞并用或甲氨蝶呤处理的雄性Balb / c小鼠淋巴结中存在的蛋白质水平变化,以及仅接种癌细胞的小鼠。:使用了五种方法,包括串联质谱标签(TMT)、基因本体论(GO)、Reactome、KEGG通路分析和分子对接。:TMT显示有74种蛋白质差异表达,其中12种呈现过表达(FC≥1.5),62种表达下调(FC≤0.67)。总体而言,TMT方法表明,与甲氨蝶呤相比,对蛋白质的影响更好。基因本体论、Reactome和KEGG通路分析表明,水平改变的蛋白质可能参与多个过程,包括RNA介导的基因沉默、氧化磷酸化、糖酵解/糖异生、细胞骨架组织以及ATP代谢和能量过程。以23种改变的蛋白质为靶点的分子对接分析表明,与所有使用的蛋白质相互作用。:使用这五种生物信息学方法获得的结果提供了信息,并表明可用于治疗由U - 937细胞系诱导的非霍奇金淋巴瘤。此外,它可为未来的研究和临床试验的开展提供基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4563/11768224/62238f07cf01/pharmaceuticals-18-00005-g001.jpg

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