The significance of PD-1/PD-L1 imbalance in ulcerative colitis.

Objectives: To investigate the expression and significance of programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1) in the mucosal tissues and peripheral blood of patients with ulcerative colitis (UC). Methods: Eighty patients with UC were recruited from January 2021 to August 2022 from the Shanxi Province People's Hospital. PD-1 and PD-L1 expression was assessed by immunohistochemistry in mucosal tissues. An enzyme-linked immunosorbent assay was used to measure soluble PD-1 and PD-L1 levels in peripheral blood serum, and the membrane-bound forms of PD-1 (mPD-1), (T-helper cell) Th1 and Th17, in peripheral blood were determined by flow cytometry. Result: PD-1 expression was observed only in the monocytes of the mucosal lamina propria of UC patients, while PD-L1 was mainly located in both epithelial cells and monocytes on the cell membrane. The expression level of PD-1/PD-L1 in the monocytes and epithelial cells of mucosal lamina propria increased with disease activity (P < 0.05). The percentages of PD-1/T and PD-1/CD4+T in the peripheral blood of moderate UC patients (PD-1/T 12.83 ± 6.15% and PD-1/CD4+T 19.67 ± 9.95%) and severe UC patients (PD-1/T 14.29 ± 5.71% and PD-1/CD4+T 21.63 ± 11.44%) were higher than in mild UC patients (PD-1/T 8.17 ± 2.80% and PD-1/CD4+T 12.44 ± 4.73%; P < 0.05). There were no significant differences in PD-1/CD8+T cells between mild and severe UC patients (P > 0.05). There was a statistically significant difference in the expression level of sPD-L1 between the UC groups and healthy controls, and the expression level of sPD-L1 increased with disease severity (P < 0.05); however, there was no statistically significant difference in sPD-1 expression levels between the UC groups and healthy controls (P > 0.05). The correlation coefficients between Th1 and sPD-L1, PD-1/T, PD-1/CD4+T and PD-1/CD8+T were 0.427, 0.589, 0.486, and 0.329, respectively (P < 0.001). The correlation coefficients between Th17 and sPD-L1, PD-1/T, PD-1/CD4+T and PD-1/CD8+T were 0.323, 0.452, 0.320, and 0.250, respectively (P < 0.05). Conclusion: The expression level of PD-1/PD-L1 was correlated with UC disease activity, and two forms of PD-1 and PD-L1 may be used as a potential marker for predicting UC and assessing disease progression in UC patients. PD-1/PD-L1 imbalance was a significant phenomenon of UC immune dysfunction. Future research should focus on two forms of PD-1/PD-L1 signaling molecules to better understand the pathogenesis of UC and to identify potential drug therapies.

Determination of the Acute and Chronic Toxicity of Sulfate from the Sulfur Autotrophic Denitrification Process to Juvenile Zebrafish (Danio rerio).

Sulfur-based materials are widely used as electron donors for denitrification to enhance nitrogen removal from water. This leads to an increased sulfate concentration in the effluent or sulfate accumulation in recirculating aquaculture systems. This study explored acute and chronic toxicity of sulfate to juvenile zebrafish (Danio rerio) and investigated the histopathological changes in the gills of juvenile zebrafish exposed to sulfate. Results show that zebrafish had a high tolerance to sulfate, with no acute toxicity at sulfate concentrations from 250 to 3200 mg/L. For the chronic toxicity study, it was found that zebrafish mortality decreased with the increase in sulfate concentrations ranging from 250 to 1500 mg/L. In contrast, when the sulfate concentration was 1500-3000 mg/L, zebrafish mortality increased with the increasing sulfate concentration. In addition, in the ion balance test, KCl was added to balance the effects of Na+ from the Na2SO4 used to obtain the desired sulfate concentrations, showing that fish mortality correspondingly increased with increasing KCl addition. Furthermore, when living in an environment with elevated sulfate concentrations for a long period, changes were observed in the morphology, behavior, and gill tissue of the zebrafish, including slow and lateral swimming; bottom settling; and large opening and closing, lamellar fusion, and necrosis of gills. This research reveals the toxicity of sulfate to aquatic organisms, providing a scientific basis for the promotion and application of sulfur or sulfur-based materials in autotrophic reduction processes for wastewater treatment.