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Chinese Journal of Experimental Traditional Medical Formulae ; (24): 226-238, 2023.
Article in Chinese | WPRIM | ID: wpr-975176


Pyroptosis, an atypical new cell death mode other than apoptosis and necrosis, has been discovered in recent years. Pyroptosis depends on the cleavage of gasdermins (GSDMs) by Caspases. The activated GSDMs act on the plasma membrane to form a perforation, which results in cell lysis and triggers inflammation and immune response. Pyroptosis can be induced by four distinct signaling pathways, including canonical and non-canonical inflammasome pathways, apoptosis-associated Caspases-mediated pathway, and granzyme pathway. In these signaling pathways, GSDMs are the executors of pyroptosis. Pyroptosis is associated with the death of tumor cells and the inflammatory damage of normal tissues. Recent studies have demonstrated that moderate pyroptosis can lead to tumor cell death to exert an anti-tumor effect, and meanwhile stimulate the tumor immune microenvironment, while it can promote tumor development. Despite the good performance, drug-based anti-tumor therapies such as tumor immunotherapy, chemotherapy, and targeted therapy have some shortcomings such as drug resistance, recurrence, and damage to normal tissues. The latest research shows that a variety of natural compounds have anti-tumor effects in the auxiliary treatment of tumors by mediating the pyroptosis pathways in a multi-target and multi-pathway manner, which provide new ideas for the study of anti-tumor therapy. We reviewed the molecular mechanism of pyroptosis and the regulatory role of pyroptosis in tumors and tumor immune microenvironment, and summarized the recent research progress in the natural medicinal components regulating pyroptosis in anti-tumor therapy, with a view to providing ideas for the research on the anti-tumor therapy based on pyroptosis.

Chinese Journal of Natural Medicines (English Ed.) ; (6): 423-435, 2023.
Article in English | WPRIM | ID: wpr-982713


Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.

Humans , NF-kappa B/metabolism , Lipopolysaccharides/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Acute Lung Injury/metabolism , Lung , Phosphate-Binding Proteins/therapeutic use , Pore Forming Cytotoxic Proteins/therapeutic use
The Journal of Practical Medicine ; (24): 535-539,547, 2018.
Article in Chinese | WPRIM | ID: wpr-697649


Objective To investigate the mRNA-based anticancer gene transfer in MSCs-mediated cytotox-icity of glioma cells. Methods TRAIL mRNA and PTEN mRNA were synthesized in vitro. Immunoblotting assay was used to detect the expression of TRAIL and PTEN in the transfected MSCs.Transwell co-culture was perform to detect the migration ability of MSCs after gene transfection. The bioluminescence,live/dead staining and real time cell analyzer were used to analyze the viability of DBTRG cells. Results Compared with non-transfected MSCs, an enhanced migration rate was observed in MSCs with two kind of mRNA transfection.TRAIL-and PTEN-mRNA-induced cytotoxicity in DBTRG glioma cell was correlated with the ratio of the conditioned medium of the transfect-ed MSCs. A synergistic action was observed in TRAIL and PTEN in the transwell co-culture model. Conclusion The present study reveals the effect of synthesized mRNA-based gene transfer on mesenchymal stem cell-mediated cytotoxicity of glioma cells(DBTRG).