The etiology and pathogenesis of ulcerative colitis (UC) remain unclear. Therefore, we observed the activation and transduction of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)–eukaryotic initiation factor 2α (eIF2α)–C/EBP homologous protein (CHOP) signaling axis from the perspective of endoplasmic reticulum stress (ERS) and explored the pathogenesis of UC. Cell survival rate, apoptosis rate, cycle distribution, cell permeability, ultrastructural changes in the ER, and the expression and transcription of key genes and proteins were detected. A UC mouse model was induced using dextran sulfate sodium. The disease activity index, tissue damage index, intestinal epithelial cell apoptosis, serum D-lactate, and diamine oxidase contents were determined. Blocking the PERK and CHOP nodes in the PERK–eIF2α–CHOP signaling axis increased stressed cell survival rate, G2 cell proportion, and monolayer cell transmembrane electrical impedance, but decreased the apoptosis rate and fluorescein isothiocyanate dextran content, so the ER structure could be alleviated. Treatment with 5-aminosalicylic acid significantly improved intestinal and systemic symptoms, and colonic mucosal damage was relieved. p-PERK, p-eIF2α, activating transcription factor 4, and CHOP gene transcription levels were higher in stressed cells than in normal cells, and 5-aminosalicylic acid reduced the expression of these proteins. Intestinal epithelial cells experience excessive ERS during UC, and the stress signal is successively transmitted to the apoptosis marker protein CHOP along the signal axis. Targeted blockage of the PERK–eIF2α–CHOP signaling axis may be an effective treatment strategy for UC.

Objective: To investigate the active components and functional mechanisms of FJSF in treating lung cancer using a network pharmacology approach and molecular docking combined with vitro experiments. Methods: Based on the TCMSP and related literature, the chemical components of related herbs in FJSF were collected. The active components of FJSF were screened by ADME parameters, and the targets were predicted by the Swiss Target Prediction database. The "drug-active ingredient-target" network was constructed by Cytoscape. Disease-related targets of lung cancer were acquired from GeneCards, OMIM, and TTD databases. Then drug-disease intersection target genes were obtained through the Venn tool. GO analysis and KEGG pathway enrichment analysis were performed via the Metascape database. Cytoscape was used to construct a PPI network and perform topological analysis. Kaplan-Meier Plotter was used to analyze the relationship between DVL2 and the prognosis of lung cancer patients. xCell method was used to estimate the relationship between DVL2 and immune cell infiltration in lung cancer. Molecular docking was performed by AutoDockTools-1.5.6. The results were verified by experiments in vitro. Results: FJSF contained 272 active ingredients and 52 potential targets for lung cancer. GO enrichment analysis is mainly related to cell migration and movement, lipid metabolism, and protein kinase activity. KEGG pathway enrichment analysis mainly involves PI3K-Akt, TNF, HIF-1, and other pathways. Molecular docking shows that the compound Xambioona、quercetin and methyl palmitate in FJSF has a strong binding ability with NTRK1, APC, and DVL2. Analysis of the data in UCSC to analyze the expression of DVL2 in lung cancer shows that DVL2 was overexpressed in lung adenocarcinoma tissues. Kaplan-Meier analysis shows that the higher DVL2 expression in lung cancer patients was associated with poorer overall survival and poorer survival in stage Ⅰ patients. It was negatively correlated with the infiltration of various immune cells in the lung cancer microenvironment. Vitro Experiment showed that Methyl Palmitate(MP) can inhibit the proliferation, migration, and invasion of lung cancer cells, and its mechanism of action may be to downregulate the expression of DVL2. Conclusion: FJSF may play a role in inhibiting the occurrence and development of lung cancer by downregulating the expression of DVL2 in A549 cells through its active ingredient Methyl Palmitate. These results provide scientific evidence for further investigations into the role of FJSF and Methyl Palmitate in the treatment of lung cancer.

Ulcerative colitis (UC) is a inflammatory disease. Herein we explored the impact of diammonium glycyrrhizinate (DG)-nanoliposomes on inflammation and oxidative stress in rats. DG-nanoliposomes were prepared, and the rats with UC were grouped into nanoliposome group, DG group, DG-nanoliposome group and blank group. Then we quantified the levels of IL-8, IL-6, IL-1β, TNF-α and Lactoperoxidase (LPO) in rats from each group by tissue biochemistry staining, and the protein levels of NF-κB p65 were detected by Western Blot (WB). The drug-loading capacity and efficiency of DG-nanoliposomes were 27.0% and 52.0%, respectively. A significantly increased Zeta potential was recorded in the DG-nanoliposomes compared to the unloaded nanoliposomes (P <0.05). The expression of IL-8, IL-6, IL-1β, TNF-α and LPO in rats receiving DG-nanoliposome s were remarkably lower than those receiving other treatments (P <0.05). A significant reduction of NF-κB p65 was detected in the samples from the DG-nanoliposome group compared to those receiving other treatments (P <0.05). In this study, DG-nanoliposomes were prepared and used for UC treatment in rats. The results proved that DG-nanoliposomes can regulate oxidative stress by inhibiting the TNF-α signaling pathway. Eventually, TNF-α, IL-8, IL-6, IL-1β, LPO and NF-κB p65 in UC rats were reduced, thereby improving the curative effect of DG-nanoliposomes on UC rats. However, some potential limitations still exist in this study, including the insufficient sample size and the limitation of the animal experiment. Despite limitations, DG-nanoliposomes are still a promising strategy in the field of UC therapy with great potential for clinical translation.