An herbal drug combination identified by knowledge graph alleviates the clinical symptoms of plasma cell mastitis patients: a nonrandomized controlled trial
- Shengjing Hospital of China Medical University, China
- Dalian University of Technology, China
- China Resources Sanjiu Medical and Pharmaceutical Co, Ltd, China
- Peking University, China
- Shanghai BeautMed Corporation, China
- University of Copenhagen, Denmark
Abstract
Background: 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 evidences suggest 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 through hitting multiple discrete cellular targets.
Methods: We have developed a knowledge graph architecture towards 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.
Results: 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 of general health status.
Conclusions: In summary, we reported that an herbal drug combination identified by knowledge graph can alleviate the clinical symptoms of plasma cell mastitis 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 for PCM treatment. Our data suggests that the herbal drug combination is expected to feature prominently in future PCM treatment.
Funding: 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).
Clinical trial number: ClinicalTrials.gov: NCT05530226.
Data availability
Figure 1-3 are computational study and therefore no data have been generated for the manuscript. In addition, Figure 4 - Source Data, Figure 5 - Source Data, Figure 6 - Source Data 1, Figure 6 - Source Data 2 and Figure 6 - Source Data 3 contain the numerical data used to generate the figures have been included in the manuscript.
Article and author information
Author details
Funding
National Natural Science Foundation of China (81874301)
- Yongliang Yang
National Natural Science Foundation of China (81572609)
- Caigang Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The protocol was approved by the Institutional Review Board (IRB) of the China Medical University (approval number: 2021PS024T). This study was registered with ClinicalTrials.gov: NCT05530226. All patients provided written informed consent.
Copyright
© 2023, Liu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 616
- views
-
- 134
- downloads
-
- 4
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
An herbal drug combination identified by knowledge graph alleviates the clinical symptoms of plasma cell mastitis patients: a nonrandomized controlled trial
eLife 12:e84414.
https://doi.org/10.7554/eLife.84414
Further reading
-
- Medicine
- Neuroscience
Background:
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious therapy-limiting side effect of commonly used anticancer drugs. Previous studies suggest that lipids may play a role in CIPN. Therefore, the present study aimed to identify the particular types of lipids that are regulated as a consequence of paclitaxel administration and may be associated with the occurrence of post-therapeutic neuropathy.
Methods:
High-resolution mass spectrometry lipidomics was applied to quantify d=255 different lipid mediators in the blood of n=31 patients drawn before and after paclitaxel therapy for breast cancer treatment. A variety of supervised statistical and machine-learning methods was applied to identify lipids that were regulated during paclitaxel therapy or differed among patients with and without post-therapeutic neuropathy.
Results:
Twenty-seven lipids were identified that carried relevant information to train machine learning algorithms to identify, in new cases, whether a blood sample was drawn before or after paclitaxel therapy with a median balanced accuracy of up to 90%. One of the top hits, sphinganine-1-phosphate (SA1P), was found to induce calcium transients in sensory neurons via the transient receptor potential vanilloid 1 (TRPV1) channel and sphingosine-1-phosphate receptors.SA1P also showed different blood concentrations between patients with and without neuropathy.
Conclusions:
Present findings suggest a role for sphinganine-1-phosphate in paclitaxel-induced biological changes associated with neuropathic side effects. The identified SA1P, through its receptors, may provide a potential drug target for co-therapy with paclitaxel to reduce one of its major and therapy-limiting side effects.
Funding:
This work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG, Grants SFB1039 A09 and Z01) and by the Fraunhofer Foundation Project: Neuropathic Pain as well as the Fraunhofer Cluster of Excellence for Immune-Mediated Diseases (CIMD). This work was also supported by the Leistungszentrum Innovative Therapeutics (TheraNova) funded by the Fraunhofer Society and the Hessian Ministry of Science and Arts. Jörn Lötsch was supported by the Deutsche Forschungsgemeinschaft (DFG LO 612/16-1).
-
- Medicine
- Neuroscience
A complex extracted from the amniotic membrane in humans reduces post-surgical pain in mice by directly inhibiting pain-sensing neurons.
