PADI1 and Its Co-Expressed Gene Signature Unveil Colorectal Cancer Prognosis and Immunotherapy Efficacy.

Peptidyl arginine deiminase 1 (PADI1) catalyzes protein citrullination and has a role in regulating immune responses. The tumor immune microenvironment has been reported to be important in colorectal cancer (CRC), which was correlated with the ability of CRC patients to benefit from immunotherapy. However, there is a lack of molecular markers for matching CRC immunotherapy. Previously, single-gene risk models have only considered the effect of individual genes on intrinsic tumor properties, ignoring the role of genes and their co-expressed genes as a whole. In this study, we analyzed the differential expression of PADI1 in colorectal cancer (CRC). We found that PADI1 was highly expressed in CRC. Subgroup survival analysis revealed a prognostic survival difference for PADI1 in CRC patients aged less than 65 years, male, T stage, N0, M0, and stage I-II (p < 0.05). In addition, we analyzed the functions and signaling pathways associated with PADI1 in CRC and found that it was highly enriched in several immune-related functions and pathways. Then, a set of PADI1 co-expressed genes (PCGs) risk-prognosis scores was developed with PADI1 as the core, which could accurately predict the prognosis of CRC (p < 0.05). PCGs risk score can be an independent prognostic factor for CRC. A new set of Norman plot models were developed for clinical characteristics with age, sex, and TNM stage, which can accurately predict CRC 1, 3, and 5 years survival, and calibration curves and decision curve analysis (DCA) validated the accuracy of the models. The risk score assessed the immune microenvironment of CRC and found that the immune score was higher in the low-risk group, and CD4+ T cells, helper T cells, and eosinophils were more infiltrated in the low-risk group (p < 0.05). Immunotherapy efficacy was better in the low-risk group (p < 0.05). The underlying mechanism may be that the high-risk group of PCGs was enriched in some pathways that promote immune escape and immune dysfunction. In conclusion, PCGs may better predict CRC prognosis and immunotherapeutic response.

Effects of ulinastatin on renal ischemia-reperfusion injury in rats.

AIM: To investigate the effect and possible mechanism of ulinastatin on renal ischemia-reperfusion injury in rats. METHODS: Male Sprague-Dawley rats were subjected to 45-min bilateral renal ischemia, treated with intravenously 12,500 U ulinastatin at 30 min prior to ischemia and at the beginning of reperfusion, compared with a nontreated group without ulinastatin and a sham-operation group without bilateral renal ischemia. After 0 h, 2 h, 6 h, 12 h, and 24 h of reperfusion, serum creatinine and blood urea nitrogen were measured for the assessment of renal function, renal sections were used for histologic grading of renal injury, for immunohistochemical localization of Bcl-2 and heat shock protein 70. Renal ultrastructure was observed through a transmission electron microscope. RESULTS: Ulinastatin significantly reduced the increase in blood urea nitrogen and creatinine produced by renal ischemia-reperfusion, suggesting an improvement in renal function. Ulinastatin reduced the histologic evidence of renal damage associated with ischemia-reperfusion and accompanied with an up-regulation in the expression of Bcl-2 protein, but it had no significant effect on the expression of HSP 70. Ulinastatin also significantly reduced kidney ultrastructure damage caused by renal ischemia-reperfusion. CONCLUSION: The protease inhibitor, ulinastatin, reduced the renal dysfunction and injury associated with ischemia-reperfusion of the kidney. The protective effect of ulinastatin might be associated with the up-regulation of Bcl-2 expression and the effect on membrane fragility.

[Effects of ulinastatin on renal ultrastructure after ischemia-reperfusion in rats].

OBJECTIVE: To investigate the effect of ulinastatin on renal function and ultrastructure changes after renal ischemia-reperfusion in rats. METHODS: Acute ischemic renal injury model was established (45 min of bilateral renal ischemia and reperfusion for 24 h). Thirty Male SD rats were randomly divided into 3 groups: sham operation group (control group or group C, without renal ischemia), renal ischemia-reperfusion group (ischemia-reperfusion group or group I, without ulinastatin), renal ischemia-reperfusion and ulinastatin intravenous injection group (ulinastatin group or group U). BUN level, serum creatinine values and renal ultrastructure were measured. RESULTS: Serum creatinine (167 +/- 39) micromol/L and BUN concentration (21 +/- 7) mmol/L in group I were significantly higher than those in group U: serum creatinine (116 +/- 13) micromol/L and BUN concentration (14.1 +/- 2.6) mmol/L (P < 0.05). The renal ultrastructure was greatly injured in group I, meanwhile, it was obviously ameliorated in group U. CONCLUSION: Ulinastatin greatly improved renal function and provides remarkable protection on renal ultrastructure after ischemia-reperfusion of kidney in rats.