分类： 药物科学 >> 生物化学 提交时间： 2024-06-14
Yue Jiang
Xuelian Ren
Jing Zhao
Guobin Liu
Fangfang Liu
Xinlong Guo
Ming Hao
Hong Liu
Kun Liu
He Huang
摘要： Gemcitabine (GEM) is a potent chemotherapeutic agent widely employed in the treatment of various cancers, notably pancreatic cancer. Despite its clinical success, challenges related to GEM resistance and toxicity persist. Therefore, there is a pressing need for a deeper understanding of its intracellular mechanisms and potential targets. In this study, we utilized quantitative proteomics and thermal proteome profiling (TPP) to elucidate the effects of GEM. Our proteomic analysis revealed that GEM primarily affected DNA synthesis, leading to the upregulation of cell cycle and DNA replication proteins. Additionally, enrichment analysis highlighted the activation of the p53 pathway, shedding light on GEM-induced apoptosis mechanisms. Notably, we observed the upregulation S-phase kinase-associated protein 2 (SKP2), a cell cycle and chemoresistance regulator, in response to GEM treatment. Combining SKP2 inhibition with GEM showed synergistic effects in both cellular and animal models, suggesting SKP2 as a potential target for enhancing GEM sensitivity and overcoming chemoresistance. Furthermore, through TPP, we explored potential binding targets of GEM, which implies GEM’s broad anticancer effects. Together, these findings provide valuable insights into GEM’s molecular mechanisms and offer potential targets for improving treatment efficacy. This research holds the promise of advancing personalized treatment strategies and opening avenues for novel combination therapies to enhance outcomes in pancreatic cancer.
分类： 管理学 >> 管理学其他学科 提交时间： 2022-11-25 合作期刊: 《Economics & Management Review》
摘要： Agricultural green sustainable development has become an important strategy in every country, and whether this strategy can be realized depends on the development and popularization of the model of planting and breeding combined circular agriculture. Based on the related theories, a three-dimensional structure analysis model including the types of participants, project operation mode, planting and breeding structure and benefit is established in this paper. And by examining the typical case of green agriculture in China, in this study, three green farming models, namely, the animal-plant cycle model dominated by two agents, the three-dimensional cycle model with multi agents, and the three-stage cycle model dominated by individual investors, were summarized. Finally, through the comparison and induction of the models, the existing problems and optimization direction of the current basic models of planting and breeding cycle agriculture were put forward.
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