UMI-77 Modulates the Complement Cascade Pathway and Inhibits Inflammatory Factor Storm in Sepsis Based on TMT Proteomics and Inflammation Array Glass Chip

Sepsis is a systemic inflammatory response syndrome caused by infection, which has no specific drug at present. UMI-77 can significantly improve the survival rate of septic mice; the detailed role of UMI-77 and its underlying mechanisms in sepsis are not clear. Inflammation array glass chip and proteomic analyses were performed to elucidate the latent mechanism of UMI-77 in the treatment of sepsis. The results showed that 7.0 mg/kg UMI-77 improved the 5 day survival rate in septic mice compared to the LPS group (60.964 vs 9.779%) and ameliorated the pathological conditions. Inflammation array glass chip analysis showed that sepsis treatment with UMI-77 may eventually through the suppression of the characteristic inflammatory storm-related cytokines such as KC, RANTES, LIX, IL-6, eotaxin, TARC, IL-1β, and so on. Proteomics analysis showed that 213 differential expression proteins and complement and coagulation cascades were significantly associated with the process for the UMI-77 treatment of sepsis. The top 10 proteins including Apoa2, Tgfb1, Serpinc1, Vtn, Apoa4, Cat, Hp, Serpinf2, Fgb, and Serpine1 were identified and verified, which play important roles in the mechanism of UMI-77 in the treatment of sepsis. Our findings indicate that UMI-77 exerts an antisepsis effect by modulating the complement cascade pathway and inhibiting inflammatory storm factors.

 

Comments:

Thank you for sharing this information about the potential treatment of sepsis using UMI-77. Based on the data you provided, it appears that UMI-77 demonstrates a significant therapeutic effect in septic mice. The key findings from your study include:

1. **Survival Rate Improvement:** UMI-77, at a dosage of 7.0 mg/kg, significantly improved the 5-day survival rate in septic mice compared to the group treated with lipopolysaccharide (LPS). The survival rate increased from 9.779% in the LPS group to 60.964% in the UMI-77-treated group.

2. **Pathological Improvement:** UMI-77 ameliorated the pathological conditions associated with sepsis in mice.

3. **Inflammatory Storm Suppression:** Inflammation array glass chip analysis revealed that UMI-77 treatment suppressed characteristic inflammatory storm-related cytokines such as KC, RANTES, LIX, IL-6, eotaxin, TARC, and IL-1β. This suppression of inflammatory cytokines is crucial in mitigating the damaging effects of sepsis.

4. **Proteomic Analysis:** Proteomic analysis identified 213 differential expression proteins. The complement and coagulation cascades, as well as specific proteins including Apoa2, Tgfb1, Serpinc1, Vtn, Apoa4, Cat, Hp, Serpinf2, Fgb, and Serpine1, were significantly associated with the process of UMI-77 treatment in sepsis. These proteins are implicated in the mechanism of UMI-77's effectiveness against sepsis.

5. **Mechanism Insights:** UMI-77 exerts its antisepsis effect by modulating the complement cascade pathway and inhibiting inflammatory storm factors. Modulation of the complement cascade is particularly important, as it plays a significant role in the immune response and can contribute to the pathogenesis of sepsis.

These findings provide valuable insights into the potential mechanisms through which UMI-77 acts to alleviate sepsis in mice. Further research and clinical studies will be essential to validate these results and explore the translational potential of UMI-77 in human sepsis cases.