An herbal drug combination identified by knowledge graph alleviates the clinical symptoms of plasma cell mastitis patients: A nonrandomized controlled trial.

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 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. Methods: 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. 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 in general health status. Conclusions: 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. Funding: 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). Clinical trial number: NCT05530226.

In vitro protective effects of pyrroloquinoline quinone on methylmercury-induced neurotoxicity.

Methylmercury (MeHg), as a well-known neurotoxicant, has been implicated to induce massive neurodegeneration. Pyrroloquinoline quinone (PQQ) is a novel redox cofactor and also exists in various plants and animal tissues. In vivo as well as in vitro experimental studies have shown that PQQ functions as an essential nutrient or antioxidant. In this study, we demonstrated the protective effects of PQQ on MeHg-induced neurotoxicity in PC12 cells. The results showed that after pretreatment of PC12 cells with PQQ prior to MeHg exposure, the MeHg-induced cytotoxicity was significantly attenuated, and then DNA fragmentation was correspondingly reduced. PQQ prevented the disruption of mitochondrial membrane potential, up-regulated the level of Bcl-2, and consequently inhibited the activation of caspase-3. Moreover, PQQ also decreased the production of ROS and maintained the GSH levels in PC12 cells exposed to MeHg. Thus, these data indicate that PQQ can protect neurons against MeHg-induced apoptosis and oxidative stress via ameliorating the mitochondrial dysfunction. Data from this study provide a new useful strategy for the treatment of neuronal toxicity induced by mercury toxins.