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尿苷和丙酮酸可保护 T 细胞的增殖能力免受线粒体毒性抗生素的影响:一项临床初步研究。

Uridine and pyruvate protect T cells' proliferative capacity from mitochondrial toxic antibiotics: a clinical pilot study.

机构信息

Department of Interdisciplinary Medicine, "Aldo Moro" University of Bari, 70124, Bari, Italy.

Department of Emergency and Organ Transplants, "Aldo Moro" University of Bari, 70124, Bari, Italy.

出版信息

Sci Rep. 2021 Jun 18;11(1):12841. doi: 10.1038/s41598-021-91559-8.

Abstract

Antibiotics that inhibit bacterial protein or nucleic acid synthesis and function can exert an off-target action on mitochondria (mitotoxic antibiotics), making actively dividing mammalian cells dependent on uridine and pyruvate supplementation. Based on this rationale, we carried out, for the first time, a randomized pilot study in 55 patients with asymptomatic bacteriuria or positive sperm culture, each treated with a single mitotoxic antibiotic with or without oral supplementation of uridine + pyruvate (Uripyr, Mitobiotix, Italy). The in vivo and ex vivo data show a a 3.4-fold higher value in the differential (before and after the antibiotic treatment) lymphocytes count and a 3.7-fold increase in the percentage of dividing T cells, respectively, in the Uripyr vs the control group. Our findings lay the groundwork to enhance the synergy between antibiotics and the immune system in order to optimize the administration protocols and widen the application potentials of antibiotic therapies as well as to re-evaluate old "forgotten" molecules to fight bacterial infections in the antibiotics resistance era.

摘要

能够抑制细菌蛋白质或核酸合成和功能的抗生素可以对线粒体产生非靶向作用(线粒体毒性抗生素),从而使活跃分裂的哺乳动物细胞依赖于尿苷和丙酮酸的补充。基于这一原理,我们首次在 55 名无症状菌尿或阳性精液培养的患者中进行了一项随机试点研究,每位患者均接受一种单一的线粒体毒性抗生素治疗,并辅以口服尿苷+丙酮酸(Uripyr,Mitobiotix,意大利)。体内和体外数据分别显示,在 Uripyr 组与对照组相比,淋巴细胞计数的差异(抗生素治疗前后)增加了 3.4 倍,分裂 T 细胞的百分比增加了 3.7 倍。我们的研究结果为增强抗生素和免疫系统之间的协同作用奠定了基础,以便优化抗生素治疗方案,并扩大抗生素治疗的应用潜力,同时重新评估在抗生素耐药时代用于对抗细菌感染的旧“被遗忘”分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb43/8213784/d03a8fb842c9/41598_2021_91559_Fig1_HTML.jpg

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