Glycyrrhizin improves the pathogenesis of psoriasis partially through IL-17A and the SIRT1-STAT3 axis.

BACKGROUND: The anti-inflammatory effect of glycyrrhizin has been widely recognized, while the specific mechanism of glycyrrhizin in psoriasis remains poorly understood. RESULTS: In the imiquimod-induced mouse model of psoriasis (IMD), we found that glycyrrhizin can substantially improve the adverse symptoms in mice. The hematoxylin-eosin staining results showed that glycyrrhizin can also improve the pathological state of skin cells in IMD mice. Using enzyme-linked immunosorbent assay (ELISA), we found that glycyrrhizin substantially inhibited the expression of IL-17A and IFN-γ in the serum of IMD mice. In order to simulate the effect of IL-17A on keratinocytes in psoriasis, we treated HaCaT cells with 100 ng/mL IL-17A (IL-17A-HaCaT cells) for 48 h. Then, using cell-counting kit-8 (CCK-8) and ELISA assays, we found that glycyrrhizin inhibited the proliferation of IL-17A-HaCaT cells and reversed the promotion of IL-6, CCL20, and TNF-α induced by IL-17A. Further, western blotting (WB) results indicated that glycyrrhizin promoted the expression of SIRT1 and inhibited the expression of STAT3 and phosphorylated STAT3 (p-STAT3). By treating IL-17A-HaCaT cells with EX-527 (a potent and selective inhibitor of SIRT1), combined with CCK-8 and WB experiments, we initially found that EX-527 inhibited the proliferation of IL-17A-HaCaT cells and promoted the expression of STAT3, p-STAT3, and acetylated STAT3 (a-STAT3). However, when glycyrrhizin was added at the same time, the proliferation of IL-17A-HaCaT cells increased, and the expression of STAT3, p-STAT3, and a-STAT3 reduced. We then knocked down the expression of SIRT1 via small interfering RNA in IL-17A-HaCaT cells, and the results were consistent with those of EX-527. CONCLUSIONS: Together, these results indicated that glycyrrhizin improved psoriasis by inhibiting the expression of IL-17A and IFN-γ in vivo and suppressed the proliferation of IL-17A-HaCaT cells and the expression of STAT3, p-STAT3, and a-STAT3 by upregulating SIRT1 in vitro.

Oral administration of Clostridium butyricum CGMCC0313-1 reduces ovalbumin-induced allergic airway inflammation in mice.

BACKGROUND AND OBJECTIVE: Probiotic bacteria can induce immune regulation or immune tolerance in patients with allergic diseases, but the underlying mechanisms are still unclear. There has been a growing interest in the use of beneficial bacteria for allergic diseases recently. This study aimed at exploring whether Clostridium butyricum CGMCC0313-1 (C. butyricum) can reduce ovalbumin (OVA)-induced allergic airway inflammation in a mouse model. METHODS: Mouse model of allergic airway inflammation induced via OVA was used in this study. C. butyricum was administered daily by the oral route during or after the sensitization. Airway function, pulmonary airway inflammation, mast cell degranulation, T helper (Th)-specific and anti-inflammatory cytokines, OVA-specific Ig, matrix metalloproteinase 9 (MMP-9) and histopathological alterations were examined. RESULTS: C. butyricum significantly reduced lung resistance in the asthmatic mice. Pulmonary airway inflammation, mast cell degranulation, airway remodelling and the expression of OVA-specific IgE/G1 were suppressed by oral C. butyricum. It also reversed the imbalance of Th1/Th2 and increased the anti-inflammatory cytokine IL-10. CONCLUSION: C. butyricum reduces OVA-induced allergic airway inflammation in mice and might be an additional or supplementary therapy for allergic asthma.

Enhanced EPR effects by tumour stromal cell mimicking nanoplatform on invasive pituitary adenoma.

Rapid advances in nanomedicine have enabled potential applications in cancer therapy. The enhanced permeability and retention (EPR) effect is the primary rationale for the passive targeting of nanoparticles in oncology. However, growing evidence indicates that the accumulation of nanomaterials via the EPR effect could be more efficient. Inspired by our clinical observation of the Gap Junction connecpion between folliculostellate cells and pituitary adenoma cells, we designed a novel drug delivery system that targets tumours by coating folliculostellate cell (FS) membranes onto PLGA nanoparticles (NPs). The resulting FSNPs, inheriting membrane proteins from the folliculostellate cell membrane, significantly enhanced the EPR effect compared to nanoparticles without cancer cell membranes. We further demonstrated that mitotane encapsulation improved the therapeutic efficacy of mitotane in both heterotopic and orthotopic pituitary adenoma models. Owing to its significant efficacy, our FS cell membrane-coated nanoplatforms has the potential to be translated into clinical applications for the treatment of invasive pituitary adenoma.