α2,6‐sialylation, catalyzed by α2,6‐sialyltransferase (ST6GAL1), plays a pivotal role in immune responses. However, the role of ST6GAL1 in the pathogenesis of ulcerative colitis (UC) remains unknown. ST6GAL1 mRNA is highly expressed in UC tissues compared with the corresponding adjacent normal tissues, and α2,6‐sialylation is significantly increased in the colon tissues of patients with UC. The expression of ST6GAL1 and proinflammatory cytokines, such as interleukin (IL)‐2, IL‐6, IL‐17, and interferon‐gamma, is also increased. The number of CD4⁺ T cells increases in UC patients. St6gal1 gene knockout (St6gal1^−/‐) rats are established by clustered regularly interspaced short palindromic repeats (CRISPR)‐associated gene knockout system. St6gal1 deficiency reduces the levels of pro‐inflammatory cytokines and alleviates colitis symptoms in UC model rats. Ablation of α2,6‐sialylation inhibits the transport of the TCR to lipid rafts and suppresses CD4⁺ T‐cell activation. The attenuation of TCR signaling downregulates the expression of NF‐κB in ST6GAL^1‐/‐ CD4⁺ T‐cells. Moreover, NF‐κB could bind to the ST6GAL1 promoter to increase its transcription. Ablation of ST6GAL1 downregulates the expression of NF‐κB and reduces the production of proinflammatory cytokines to relieve UC pathogenesis, which is a potential novel target for the clinical treatment of UC.

The purpose of the present study was to investigate the effects and underlying mechanisms of diallyl sulfide (DAS), an organosulfur compound extracted from garlic, on drug-induced or chemical-induced liver injury caused by acetaminophen (APAP) or carbon tetrachloride (CCl₄) in mice.

The treatment of ulcerative colitis (UC) is still an intractable medical problem. Polysaccharides are promising candidates for the treatment of UC and have received widespread attention in recent years. The objective of this study was to explore the protective effect and underlying mechanism of dandelion polysaccharide (DP) on dextran sulfate sodium (DSS)‐induced colitis in mice. Our results showed that oral administration of DP could dramatically alleviate colonic lesions, as evidenced by reduced DAI scores, shortening of colon length, and ameliorating pathologic abnormalities in colons. Additionally, the expressions of pro‐inflammatory factors (TNF‐α, IL‐1β, and IL‐6) and the infiltration of inflammation‐regulation cells, marked by myeloperoxidase and F4/80, were also inhibited after DP treatment. Moreover, DP treatment also markedly suppressed the nuclear translocation of NF‐κB‐p65 and the activation of the NLRP3 inflammasome. Furthermore, DP also activated the Nrf2/HO‐1 pathway and reduced the oxidative stress induced by DSS. Overall, these results suggest that DP could be a promising novel therapeutic approach for the treatment of UC.

Carbon tetrachloride (CCl₄)-mediated liver damage has been well recognized, but the sources and mechanisms of mitochondrial damage during this progress still remain poorly understood. Accumulating evidence has revealed that LonP1-TDP-43 pathway affect proper mitochondrial integrity and function in neurodegenerative diseases. The current study aims to investigate whether mitochondrial oxidative stress regulate LonP1-TDP-43 pathway and the possible roles of this pathway in CCl₄-driven liver fibrosis. We found that TDP-43 interacted with LonP1 in chronic CCl₄ exposure-induced hepatic fibrogenesis. Moreover, CCl₄ led to deficiency of LonP1 and excessive accumulation of TDP-43 on mitochondria. Particularly, the gene correlation analysis for liver fibrosis patients RNA sequencing (RNA-seq) results (GSE159676) showed an obvious negative correlation between LonP1 and TDP-43. By contrast, MitoQ enhanced the occurrence of mitochondrial unfolded protein response (mtUPR), especially the activation of LonP1 after CCl₄ treatment. Importantly, mitochondrial antioxidant also promoted the degradation of TDP-43 and alleviated mitochondrial damage. In addition, our results showed that CCl₄ induced the release of mitochondrial DNA (mtDNA) and effectively elevated cGAS-STING-mediated immune response, which can be inhibited by MitoQ. Finally, MitoQ prevented CCl₄-induced liver fibrosis. Together, our study revealed that LonP1-TDP-43 pathway mediated by mitochondrial oxidative stress participated in the progress of CCl₄-drived liver fibrosis. Therefore, mitigating or reversing mitochondrial damage through targeting LonP1-TDP-43 pathway may serve as a promising therapeutic strategy for CCl₄ exposure-induced liver diseases.