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111.
R. Kato Y. Okuno C. Kaga M. Kunimatsu T. Kobayashi H. Honda 《Chemical biology & drug design》2005,66(Z1):146-153
Abstract: Despite their low molecular weight and simple structure, peptides regulate vital reactions of various cells. With higher standards of safety and purity required in clinical researches, chemically synthesized peptides are considered as an ideal alternative material for animal‐derived materials in the regulation of cellular events. However, effective high‐throughput assay for studying peptide‐cell interactions has not been established to design peptide with objective function. Here, we report the effectiveness of the utilization of peptide array combined with cell assay for the design of cell‐interactive peptides. As a model case, peptide that regulates tumor cell viability with support‐bound form was explored. By culturing cells on peptide array, we found a novel 5‐mer sequence CNNLP (Cys‐Asp‐Asp‐Leu‐Pro) that strongly inhibits viability of tumor cells (leukemia and adenocarcinoma) from human Fas antigen ligand. We here indicate the advantageous features of peptide array, which are ‘feasibility in examining combinatorial amino acid substitutions’ and ‘indicative data consist of effective and ineffective substitutions from an assay’, contributes greatly for studying peptide‐cell interaction. These features differentiate peptide array from other peptide library screening strategy. As a result, we succeeded in obtaining 29 novel tumor‐growth inhibitory peptides with it solid‐bound form, and structural rules that suggest ideal peptide design for acquiring objective peptide function. 相似文献
112.
细胞色素P450与药物代谢的研究现状 总被引:15,自引:8,他引:15
细胞色素P450(CYP)在众多中西药物代谢中起着非常重要的作用。本文综述了与药物代谢相关的CYP亚型、CYP与药物相互作用的关系及中药对CYP的影响,旨在合理解释和预测临床上药物间相互作用和药物不良反应等。同时选择适当的药物作为探针来评价CYP的活性,为实现临床个体化给药提供科学依据。 相似文献
113.
Stefan Lucian Popa Dinu Iuliu Dumitrascu Cristina Pop Teodora Surdea-Blaga Abdulrahman Ismaiel Giuseppe Chiarioni Dan Lucian Dumitrascu Vlad Dumitru Brata Simona Grad 《Nutrients》2022,14(10)
Functional dyspepsia represents one of the most common and prevalent disorders of the brain–gut interaction, with a large number of widespread risk factors being identified. With an intricate pathogenesis and symptomatology, it heavily impacts the quality of life and, due to the limited efficacy of traditional pharmacological agents, patients are likely to seek other medical and non-medical solutions to their problem. Over the last few years, significant research in this domain has emphasized the importance of various psychological therapies and nutritional recommendations. Nevertheless, a correlation has been established between functional dyspepsia and food intolerances, with more and more patients adopting different kinds of exclusion diets, leading to weight loss, restrictive eating behaviour and an imbalanced nutritional state, further negatively impacting their quality of life. Thus, in this systematic review, we aimed at analysing the impact and efficiency of certain exclusion diets undertook by patients, more precisely, the gluten-free diet and the low-FODMAP diet. 相似文献
114.
目的 探究不同的左前降支(left anterior descending, LAD)狭窄程度和分叉血管曲率对血流动力学的影响。方法 建立不同分叉血管曲率半径和 LAD 分支狭窄率的理想模型,使用流固耦合( fluid-structure interaction, FSI)方法评估不同曲率半径和不同狭窄率情况下对血流和壁面剪切力相关指标的影响。 结果 LAD 发生狭窄后,高震荡剪切指数(oscillatory shear index, OSI)和高相对滞留时间(relative residence time, RRT)区域主要分布于 LAD 分叉脊对侧、弯曲外侧狭窄位置下游近端和弯曲内侧下游远端,并且随着狭窄程度的增加会扩大其区域与程度;由于曲率半径减小,弯曲内侧中的高 OSI 和 RRT 会向 LAD 下游远端分布,高 RRT 区域面积相对整个血管面积平均降幅能够达到 35. 68% 。 结论 LAD 狭窄的存在会增加狭窄位置下游和 LAD 分叉脊对侧发生继发性狭窄的风险。 曲率降低会促进弯曲内侧斑块的形成与发展,但从整个血管来看,又会细微地降低斑块形成概率。 研究结果可为治疗 LAD 病变与预防继发性狭窄提供方案设计与优化的理论参考。 相似文献
115.
Maria Cherba Boris H. J. M. Brummans Michael P. Hier Lauriane Gigure Gabrielle Chartier Hannah Jacobs Vronique-Isabelle Forest Alex Mlynarek Khalil Sultanem Melissa Henry 《Current oncology (Toronto, Ont.)》2022,29(5):3341
Patients with head and neck cancer report high unmet psychosocial needs as they undergo lifesaving treatments that can significantly alter their appearance and cause functional impairments. This qualitative analysis of recordings of 88 pre- and post-surgical consultations involving 20 patients respond to the need for empirical studies of patient–provider conversations about body image concerns. It indicates that the emphasis on concerns about survival, cure, and physical recovery during clinical consultations may leave concerns about the impacts of surgery on appearance and function unexplored and even silenced. The interviews with patients and medical team members that complement the analysis of the recordings suggest that an emphasis on survival, cure, and physical recovery can respond to the need for reassurance in the context of serious illness. However, it can also be problematic as it contributes to the silencing of patients’ concerns and to a potential lack of preparedness for the consequences of surgery. The results of this study can contribute to raising surgeons’ awareness of the interactional dynamics during clinical consultations. Moreover, the results highlight the unique role that surgeons can play in validating patients’ psychosocial concerns to support patients’ rehabilitation in both physical and psychosocial domains. 相似文献
116.
Identification
of RAD51–BRCA2 Inhibitors Using N-Acylhydrazone-Based
Dynamic Combinatorial Chemistry
Greta Bagnolini Beatrice Balboni Fabrizio Schipani Dario Gioia Marina Veronesi Francesca De Franco Cansu Kaya Ravindra P. Jumde Jose Antonio Ortega Stefania Girotto Anna K. H. Hirsch Marinella Roberti Andrea Cavalli 《ACS medicinal chemistry letters》2022,13(8):1262
RAD51 is an ATP-dependent recombinase, recruited by BRCA2 to mediate DNA double-strand breaks repair through homologous recombination and represents an attractive cancer drug target. Herein, we applied for the first-time protein-templated dynamic combinatorial chemistry on RAD51 as a hit identification strategy. Upon design of N-acylhydrazone-based dynamic combinatorial libraries, RAD51 showed a clear templating effect, amplifying 19 N-acylhydrazones. Screening against the RAD51–BRCA2 protein–protein interaction via ELISA assay afforded 10 inhibitors in the micromolar range. Further 19F NMR experiments revealed that 7 could bind RAD51 and be displaced by BRC4, suggesting an interaction in the same binding pocket of BRCA2. These results proved not only that ptDCC could be successfully applied on full-length oligomeric RAD51, but also that it could address the need of alternative strategies toward the identification of small-molecule PPI inhibitors. 相似文献
117.
118.
目的:研究2种不同的5-HT3拮抗剂止吐药格拉司琼和昂丹司琼对大鼠体内多西他赛药动学的影响。方法:Wistar♂大鼠随机分为3组(n=8),给药剂量为5 mg.kg-1。第1组只给多西他赛,第2组给予多西他赛15 min前给予格拉司琼0.4mg.kg-1,第3组给予多西他赛15 min前给予昂丹司琼1 mg.kg-1。3组大鼠分别于给药前和给药后2,15,30,90,240,480,720,1440 min取血用于测定药代动力学。结果:3组的平均消除半衰期分别为(236.4±53.5),(363.1±301.1),(328.2±206.1)min;平均药时曲线下面积(AUC0~t)范围分别为54597.0~88141.9,46932.8~72004.6,51585.6~70958.0μg.min.L-1[平均值±SD:(66664.8±11389.4),(60700.2±7666.6),(60018.4±7545.3)μg.min.L-1];清除率分别为(0.076±0.012),(0.08±0.013),(0.081±0.011)L.min.kg-1。第1组和第2组平均滞留时间没有显著性差异,第1组和第2组... 相似文献
119.
120.