Cancer Stem Cell and Translation Medicine Lab, Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China.
School of Bioengineering, Dalian University of Technology, Dalian, China.
Elife. 2023 Mar 14;12:e84414. doi: 10.7554/eLife.84414.
Plasma cell mastitis (PCM) is a nonbacterial breast inflammation with severe and intense clinical manifestation, yet treatment methods for PCM are still rather limited. Although the mechanism of PCM remains unclear, mounting evidence suggests that the dysregulation of immune system is closely associated with the pathogenesis of PCM. Drug combinations or combination therapy could exert improved efficacy and reduced toxicity by hitting multiple discrete cellular targets.
We have developed a knowledge graph architecture toward immunotherapy and systematic immunity that consists of herbal drug-target interactions with a novel scoring system to select drug combinations based on target-hitting rates and phenotype relativeness. To this end, we employed this knowledge graph to identify an herbal drug combination for PCM and we subsequently evaluated the efficacy of the herbal drug combination in clinical trial.
Our clinical data suggests that the herbal drug combination could significantly reduce the serum level of various inflammatory cytokines, downregulate serum IgA and IgG level, reduce the recurrence rate, and reverse the clinical symptoms of PCM patients with improvements in general health status.
In summary, we reported that an herbal drug combination identified by knowledge graph can alleviate the clinical symptoms of PCM patients. We demonstrated that the herbal drug combination holds great promise as an effective remedy for PCM, acting through the regulation of immunoinflammatory pathways and improvement of systematic immune level. In particular, the herbal drug combination could significantly reduce the recurrence rate of PCM, a major obstacle to PCM treatment. Our data suggests that the herbal drug combination is expected to feature prominently in future PCM treatment.
C. Liu's lab was supported by grants from the Public Health Science and Technology Project of Shenyang (grant: 22-321-32-18); Y. Yang's laboratory was supported by the National Natural Science Foundation of China (grant: 81874301), the Fundamental Research Funds for Central University (grant: DUT22YG122), and the Key Research project of 'be Recruited and be in Command' in Liaoning Province (2021JH1/10400050).
NCT05530226.
浆细胞性乳腺炎（PCM）是一种非细菌性乳腺炎，临床表现严重且剧烈，但 PCM 的治疗方法仍然相当有限。虽然 PCM 的发病机制尚不清楚，但越来越多的证据表明免疫系统失调与 PCM 的发病机制密切相关。药物联合或联合治疗可以通过打击多个离散的细胞靶点来发挥改善疗效和降低毒性的作用。
我们开发了一个免疫治疗和系统免疫的知识图谱架构，该架构包含草药药物靶点相互作用和一个新的评分系统，以根据靶点命中率和表型相关性选择药物组合。为此，我们利用这个知识图谱来确定一种用于 PCM 的草药药物组合，然后我们在临床试验中评估了该草药药物组合的疗效。
我们的临床数据表明，该草药药物组合可以显著降低各种炎症细胞因子的血清水平，下调血清 IgA 和 IgG 水平，降低复发率，并逆转 PCM 患者的临床症状，改善整体健康状况。
总之，我们报告说，通过知识图谱确定的草药药物组合可以缓解 PCM 患者的临床症状。我们证明，该草药药物组合具有很大的潜力作为 PCM 的有效治疗方法，通过调节免疫炎症途径和改善系统免疫水平发挥作用。特别是，该草药药物组合可以显著降低 PCM 的复发率，这是 PCM 治疗的一个主要障碍。我们的数据表明，该草药药物组合有望在未来的 PCM 治疗中发挥重要作用。
刘 C 的实验室得到了沈阳市公共卫生科学技术项目（资助：22-321-32-18）的支持；杨 Y 的实验室得到了国家自然科学基金（资助：81874301）、中央高校基本科研业务费（资助：DUT22YG122）和辽宁省“特聘教授”支持计划重点项目（2021JH1/10400050）的支持。
NCT05530226。
