Background: Ulcerative colitis is an inflammatory bowel disease (IBD) that involves inflammation of the colon lining and rectum. Although a definitive cure for IBD has not been identified, various therapeutic approaches have been proposed to mitigate the symptomatic presentation of this disease, primarily focusing on reducing inflammation. The aim of the present study was to evaluate the therapeutic potential of combining dental pulp stem cells (DPSCs) with sulfasalazine in an acetic acid-induced ulcerative colitis rat model and to assess the impact of this combination on the suppression of inflammatory cytokines and the regulation of oxidative stress in vivo. Methods: Ulcerative colitis was induced in rats through transrectal administration of 3% acetic acid. The therapeutic effect of combining DPSCs and sulfasalazine on UC was evaluated by measuring the colonic weight/length ratio and edema markers; performing histopathological investigations of colon tissue; performing immunohistochemical staining for NF-κB-P65 and IL-1β; and evaluating oxidative stress and antioxidant indices via ELISA. Moreover, the proinflammatory markers NF-κB-P65, TNF-α and TLR-4 were assessed in colon tissue via ELISA. Furthermore, qRT‒PCR was used to estimate the expression levels of the TLR-4, NF-κB-P65, and MYD88 genes in colon tissue. Results: The investigated macroscopic and microscopic signs of inflammation were markedly improved after the combined administration of sulfasalazine and DPSCs, where a noticeable improvement in histological structure, with an intact mucosal epithelium and mild inflammatory infiltration in the mucosa and submucosa, with slight hemorrhage. The administration of either DPSCs or sulfasalazine, either individually or in combination, significantly reduced ROS levels and significantly increased XOD activity. The immunohistochemical results demonstrated that the combined administration of DPSCs and sulfasalazine attenuated NFκB-p65 and IL-1β expression. Finally, the combined administration of DPSCs and sulfasalazine significantly downregulated MyD88, NF-κB and TLR4 gene expression. Conclusions: Cotreatment with DPSCs and sulfasalazine had synergistic effects on ulcerative colitis, and these effects were relieved.

Liver fibrosis, a severe health issue linked to liver injury, inflammation, and cell death, often progresses to liver cancer without effective treatments. In this study, an exosome-nanoliposome hybrid loaded with caffeine (Caff) was developed for the management of liver fibrosis. The role of superparamagnetic iron oxide nanoparticles (SPION) in promoting targeted delivery to the liver was also investigated. Caff-loaded liposomes with variable phospholipid and stearylamine molar ratios were prepared and characterized. The formula with optimized characteristics (Caff/liposomes) selected by Design Expert exhibited a particle size of 179.73 ± 3.1 nm, a polydispersity index of 0.19 ± 0.02, an entrapment efficiency of 89.79 ± 21%, and a zeta potential of -35.50 ± 1.1 mV, and was used to encapsulate SPION. Caff/SPION liposomes were further loaded into exosomes, isolated from bone marrow-mesenchymal stem cells, and visualized by TEM. The biological experiment was conducted on rats with thioacetamide-induced liver injury to reveal the efficacy of exosome-Caff/SPION liposome hybrid (F1) in comparison to exosome-Caff/liposomes (F2) and exosome-SPION/liposomes (F3). Among all the tested formulations, F1 demonstrated the most promising results regarding liver function markers (ALT and AST), inflammatory molecules (IL-6, IL-10, TLR-4, Myd88, NF-κB), fibrotic protein (α-SMA), hepatocyte proliferative capacity (PCNA), as well as liver histoarchitecture. This finding suggests that the engineered Caff/SPION liposome-exosome hybrid can effectively enhance the targeting of the drug and the homing of exosomes to the injured liver, thereby representing a novel strategy for treating liver fibrosis.