Ulinastatin reduces myocardial injury induced by doxorubicin in SD rats.

OBJECTIVE: The aim of this study was to observe the protective effect of Ulinastatin on myocardial injury induced by doxorubicin (DOX) in rats. MATERIALS AND METHODS: 30 male Sprague Dawley (SD) rats were divided into control group, DOX group, and Ulinastatin group by random number table method. The control group was intraperitoneally injected with saline, while the DOX group and the Ulinastatin group were injected intraperitoneally with DOX (2 mg/kg) once every other day to establish an acute myocardial injury (AMI) model. In the Ulinastatin group, Ulinastatin (1500 IU/100 mg) was injected intraperitoneally once a day for 2 weeks after the model was established. The changes in cardiac structure were observed with a light microscope, the changes in cardiac function in rats were detected with biochemical kits, and expression of oxidative stress and inflammatory response-related factors were detected by Western blotting, enzyme-linked immunosorbent assay (ELISA), and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). RESULTS: Myocardial tissues in the control group were neatly arranged and dense, with complete and clear structure. The myocardial tissues in the DOX group were disorderly arranged, the interstitial fibrosis was evident, and the myocardial transverse striations broke and disappeared. The structure of tissues in Ulinastatin group was dramatically relieved compared with DOX group. The serum SOD and GSH-Px levels of the DOX groups were significantly lower than those of the control group, while the levels of MDA and ROS were dramatically higher than those of the control group. The serum SOD and GSH-Px level of Ulinastatin group were higher than that of DOX group, and the levels of MDA and ROS were lower than those of DOX group. LDH, AST, ALT, and CK levels were dramatically higher than those in the control group, while the above-mentioned serum myocardial zymogram levels in the Ulinastatin group were decreased. The expressions of IL-1ß, IL-6, TNF-α, and iNOS in the DOX and Ulinastatin groups were dramatically higher than those in the control group, while the expressions of the above inflammatory factors in the Ulinastatin group were all inhibited. CONCLUSIONS: Ulinastatin intervention can reduce myocardial injury in rats with DOX. The protective effect may be due to the elimination of oxygen free radicals, enhanced antioxidant enzyme activity, reduced lipid peroxidation and inflammatory responses, and thus repaired myocardial injury.

Prognostic value of ZFP36 and SOCS3 expressions in human prostate cancer

Purpose: ZFP36 ring finger protein (ZFP36) and the suppressor of cytokine signaling 3 (SOCS3) have been reported to, respectively, regulate NF-jB and STAT3 signaling pathways. To better understand the correlation of NF-jB and STAT3 negative regulates pathway, we have investigated the involvement of ZFP36 and SOCS3 expressions in human prostate cancer (PCa). Methods: In the present study, paired patient tissue microarrays were analyzed by immunohistochemistry, and the ZFP36 protein expression was quantitated as immunoreactive scores in patients with PCa. Associations between ZFP36/SOCS3 expression and various clinicopathological features and prognosis of PCa patients were statistically analyzed based on the Taylor database. Then, the functions of ZFP36 and SOCS3 in cancerous inflammation were determined using qPCR and immunohistochemistry in vitro and in vivo. Results: ZFP36 protein expression in PCa tissues was significantly lower than those in non-cancerous prostate tissues (P < 0.05). In mRNA level, ZFP36 and SOCS3 had a close correlation with each other (P < 0.01, Pearson r = 0.848), and its upregulation was both significantly associated with low Gleason score (P < 0.001 and P < 0.001, respectively), negative metastasis (P < 0.001 and P < 0.001, respectively), favorable overall survival (P < 0.001 and P < 0.05, respectively), and negative biochemical recurrence (P < 0.001 and P < 0.001, respectively). Functionally, LPS treatment could lead to the overexpression of ZFP36 and SOCS3 in vitro and vivo. Conclusions: Our data offer the convincing evidence for the first time that the aberrant expressions of ZFP36 and SOCS3 may be involved into the progression and patients’ prognosis of PCa, implying their potentials as candidate markers of this cancer

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Prognostic value of ZFP36 and SOCS3 expressions in human prostate cancer.

PURPOSE: ZFP36 ring finger protein (ZFP36) and the suppressor of cytokine signaling 3 (SOCS3) have been reported to, respectively, regulate NF-κB and STAT3 signaling pathways. To better understand the correlation of NF-κB and STAT3 negative regulates pathway, we have investigated the involvement of ZFP36 and SOCS3 expressions in human prostate cancer (PCa). METHODS: In the present study, paired patient tissue microarrays were analyzed by immunohistochemistry, and the ZFP36 protein expression was quantitated as immunoreactive scores in patients with PCa. Associations between ZFP36/SOCS3 expression and various clinicopathological features and prognosis of PCa patients were statistically analyzed based on the Taylor database. Then, the functions of ZFP36 and SOCS3 in cancerous inflammation were determined using qPCR and immunohistochemistry in vitro and in vivo. RESULTS: ZFP36 protein expression in PCa tissues was significantly lower than those in non-cancerous prostate tissues (P < 0.05). In mRNA level, ZFP36 and SOCS3 had a close correlation with each other (P < 0.01, Pearson r = 0.848), and its upregulation was both significantly associated with low Gleason score (P < 0.001 and P < 0.001, respectively), negative metastasis (P < 0.001 and P < 0.001, respectively), favorable overall survival (P < 0.001 and P < 0.05, respectively), and negative biochemical recurrence (P < 0.001 and P < 0.001, respectively). Functionally, LPS treatment could lead to the overexpression of ZFP36 and SOCS3 in vitro and vivo. CONCLUSIONS: Our data offer the convincing evidence for the first time that the aberrant expressions of ZFP36 and SOCS3 may be involved into the progression and patients' prognosis of PCa, implying their potentials as candidate markers of this cancer.

Effects of ischemic preconditioning in the late phase on homing of endothelial progenitor cells in renal ischemia/reperfusion injury.

OBJECTIVE: The aim of this study was to determine whether the mobilization and recruitment of endothelial progenitor cells (EPCs) contribute to the protection of kidneys from ischemia/reperfusion (I/R) injury after ischemic preconditioning (IPC) during the late phase. METHODS: Seventy-five male Sprague-Dawley rats were divided into the following groups: sham-operated (group A; n = 25), ischemia/reperfusion hosts that underwent 45 minutes of left renal artery ischemia (group B; n = 25), and ischemic preconditioning-treated group (group C; n = 25). Group C underwent 3 cycles of 5 minutes of occlusion and 5 minutes of reperfusion followed by 24 hours of reperfusion before the following 45 minutes of occlusion. Serum samples were collected and renal tissues harvested for histological examination terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemical staining, and Western blot analysis to determine the expression levels of CD34, VEGFR-2 (Vascular Endothelial Growth Factor Receptor 2)/flk-1, vascular endothelial growth factor (VEGF), and stromal cell-derived factor-1α (SDF-1α). RESULTS: Compared with group B, the levels of blood urea nitrogen (BUN), serum creatinine (Scr) and acute tubulointerstitial injury at 24 hours after operation were significantly reduced in group C. At 72 hours, tubular epithelial cell apoptosis was also decreased (17.6 ± 4.45 vs 63.8 ± 6.10; P < .01). CD34+ and flk-1+ cells that mostly accumulated in the medullopapillary parenchyma were significantly increased at 72 hours (P < .05). Expression levels of VEGF and SDF-1α were also significantly higher in group C (P < .05). CONCLUSION: The present work suggested that IPC protected kidneys from IR injury in the later phase through enhanced mobilization and recruitment of EPCs. VEGF and SDF-1α may play important roles in this protective effect.

Transplantation of both kidneys from one donor rat using end-to-end vascular anastomosis in normal saline.

BACKGROUND: End-to-end vascular anastomosis in the 0.9% NaCl solution was compared with conventional end-to-end vascular anastomosis in the model rat, with two kidneys from one donor rat harvested and transplanted to two recipient rats. METHODS: Two methods of suturing renal walls were used. In group A, the conventional end-to-end anastomosis was performed, where one person stitched veinous walls while the other washed them using the normal saline (n = 20). In group B, end-to-end anastomosis of renal vein walls was performed in 0.9% NaCl solution (n = 20). RESULTS: In the normal saline, the renal vein walls naturally extended and separated and the edges of the renal veins were revealed. In group B, the operation time and overall complication rate of suturing were reduced (P < .001). CONCLUSION: This is the first report of end-to-end vascular anastomosis in the normal saline in the model of rat kidney transplantation. This method, which does not require any special instruments, is fast, safe, and needs only one surgeon to perform the renal vascular suturing, and may be applied to other transplantation models.