[show abstract][hide abstract] ABSTRACT: We determined the protective effects of a high dose of ulinastatin on myocardial and renal function in patients undergoing aortic valve replacement with cardiopulmonary bypass (CPB).
Sixty patients were assigned randomly to either the ulinastatin group (n = 30) or the control group (n = 30). In the ulinastatin group, ulinastatin (300,000 U) was given after the induction of anesthesia, ulinastatin (400,000 U) was added to the CPB pump prime, and then ulinastatin (300,000 U) was administered after weaning from CPB. In the control group, the same volume of saline was administered at the same time points. Creatine kinase-MB levels were assessed 1 day before surgery, and on the first and second postoperative day (POD 1 and 2). Serum creatinine and cystatin C levels were assessed 1 day before surgery, upon intensive care unit arrival, and on POD 1 and 2. The level of plasma neutrophil gelatinase-associated lipocalin was assessed before induction of anesthesia, upon ICU arrival, and on POD 1.
No significant differences were observed in serum levels of creatine kinase-MB and biomarkers of renal injury between the two groups at any point during the study period.
Ulinastatin showed no cardiac or renal protective effects after CPB in patients undergoing aortic valve replacement.
Korean journal of anesthesiology 02/2012; 62(2):148-53.
[show abstract][hide abstract] ABSTRACT: Glioma stem cells (GSC) possess tumor-initiating potential and are relatively resistant to conventional chemotherapy and irradiation. Thus, they are considered to be major drivers for glioma initiation, progression, and recurrence. However, the precise mechanism governing acquisition of their drug resistance remains to be elucidated. Our previous study has shown that inhibitor of differentiation 4 (ID4) dedifferentiates Ink4a/Arf(-/-) mouse astrocytes and human glioma cells to glioma stem-like cells (induced GSCs or iGSCs). In this article, we report that ID4-driven iGSCs exhibit chemoresistant behavior to anticancer drugs through activation of ATP-binding cassette (ABC) transporters. We found that ID4 enhanced SOX2 protein expression by suppressing microRNA-9* (miR-9*), which can repress SOX2 by targeting its 3'-untranslated region. Consequently, ID4-mediated SOX2 induction enhanced ABCC3 and ABCC6 expression through direct transcriptional regulation, indicating that ID4 regulates the chemoresistance of iGSCs by promoting SOX2-mediated induction of ABC transporters. Furthermore, we found that short hairpin RNA-mediated knockdown of SOX2 in ID4-driven iGSCs resulted in loss of cancer stemness. Moreover, ectopic expression of SOX2 could dedifferentiate Ink4a/Arf(-/-) astrocytes and glioma cells to iGSCs, indicating a crucial role of SOX2 in genesis and maintenance of GSCs. Finally, we found that the significance of the ID4-miR-9*-SOX2-ABCC3/ABCC6 regulatory pathway is recapitulated in GSCs derived from patients with glioma. Together, our results reveal a novel regulatory mechanism by which ID4-driven suppression of miR-9* induces SOX2, which imparts stemness potential and chemoresistance to glioma cells and GSCs.
Cancer Research 05/2011; 71(9):3410-21. · 8.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: The mitochondrial pathway of swine influenza virus (SIV)-induced apoptosis was investigated using porcine kidney (PK-15) cells, swine testicle (ST) cells, and HeLa cervical carcinoma cells which are known not to support viral replication. As judged by cell morphology, annexin V staining, and DNA fragmentation, PK-15 and ST cells infected with three different subtypes of SIV (H1N1, H3N2, and H1N2) were obviously killed by apoptosis, not necrosis. SIV infection in PK-15 and HeLa cells was shown to decrease the cellular levels of Bcl-2 protein compared to that of mock-infected control cells at 24 h post-infection, whereas expression levels of Bax protein increased in the PK-15 cells, but did not increase in HeLa cells by SIV infection. Cytochrome c upregulation was also observed in cytosolic fractions of the PK-15 and HeLa cells infected with SIV. Apoptosome (a multi-protein complex consisting of cytochrome c, Apaf-1, caspase-9, and ATP) formation was confirmed by immunoprecipitation using cytochrome c antibody. Furthermore, SIV infection increased the cellular levels of TAJ, an activator of the JNK- stressing pathway, and the c-Jun protein in the PK-15 and HeLa cells. Taken together, these results suggest that the mitochondrial pathway should be implicated in the apoptosis of PK-15 cells induced by SIV infection.
Experimental and Molecular Medicine 03/2006; 38(1):11-7. · 2.57 Impact Factor