Ischemia/reperfusion injury (IRI) is a major cause of acute kidney damage, which often occurs in deceased donor kidney transplants. Cathelicidin PR-39 peptide possesses anti-inflammatory and wound repair effects through tissue angiogenesis and anti-apoptosis. This study assessed the role of PR-39 in anti-apoptosis in vitro using a lentiviral vector with a kidney specific promoter (KSP) to drive PR-39 expression. Our data revealed that PR-39 peptide was specifically over-expressed in kidney-derived HK-2 cells, but was scarcely detected in non-kidney tissue-derived cells. PR-39 over-expression had a protective role in the hypoxia/re-oxygenation (H/R) treated cells. The antiapoptotic activity of PR-39 peptide was mediated by the inhibition of caspase-2, caspase-12 and caspase-3 activity in the endoplasmic reticulum (ER) stress-induced apoptotic pathway. It was also revealed that the anti-apoptotic effect of PR-39 peptide was mediated by an apoptosis-related protein, cellular inhibitor apoptosis protein-2 (c-IAP-2). Taken together, the current data demonstrate that PR-39 expression driven by KSP could prevent kidney damage (apoptosis) from IRI via the ER stress-induced apoptotic pathway.
Background:Immunosuppressive agents are still inefficient in preventing biopsy-proven acute rejection (BPAR) after expanded criteria donor (ECD) kidney transplantation. The aim of this study was to investigate the relationships between early immunosuppressive exposure and the development of BPAR.Methods:We performed a retrospective study of 58 recipients of ECD kidney transplantation treated with enteric-coated-mycophenolate sodium, tacrolimus (Tac), and prednisone. The levels of mycophenolic acid-area under the curve (MPA-AUC)0-12h and Tac C0 were measured at the 1st week and the 1st month posttransplant, respectively. The correlation was assessed by multivariate logistic regression.Results:The occurrence rates of BPAR and antibody-mediated rejection were 24.1% and 10.3%, respectively. A low level of MPA-AUC0-12h at the 1st week posttransplant was found in BPAR recipients (38.42 ± 8.37 vs. 50.64 ± 13.22, P < 0.01). In addition, the incidence of BPAR was significantly high (P < 0.05) when the MPA-AUC0-12h level was <30 mg·h-1·L-1 at the 1st week (15.0% vs. 44.4%) or the Tac C0 was <4 ng/ml at the 1st month posttransplant (33.3% vs. 21.6%). Multivariable logistic regression analysis showed that the MPA-AUC0-12h at the 1st week (OR: 0.842, 95% CI: 0.784-0.903) and the Tac C0 at the 1st month (OR: 0.904, 95% CI: 0.822–0.986) had significant inverse correlation with BPAR (P < 0.05).Conclusions:Low-level exposure of MPA and Tac C0 in the early weeks posttransplant reflects an increased acute rejection risk, which suggested that MPA-AUC0-12h <30 mg·h-1·L-1 and Tac C0 <4 ng/ml should be avoided in the first few weeks after transplantation.
Previous studies showed that EGR3 gene located in chromosome 8p21.3 was involved in the etiology of schizophrenia. However, the finding failed to be replicated in several case-control studies. To investigate the genetic role of the EGR3 gene in Chinese psychiatric patients, we genotyped five single nucleotide polymorphisms (SNPs) in EGR3 gene locus using 93 nuclear families in Han Chinese, and performed transmission disequilibrium test (TDT). In this study, two SNPs (rs1996147 and rs3750192) showed significant association with schizophrenia (c2>4.40, P<0.05). In the linkage disequilibrium analysis, the significant association was also found in two- (rs3750192-rs35201266), three- (rs1877670- rs3750192-rs7009708) and four-SNP (rs1996147-rs1877670-rs3750192-rs7009708) tests of haplotype analyses (c2>7.10, global P<0.05). Overall, the results suggested that EGR3 gene may play an important role in schizophrenia susceptibility in the Han Chinese population, and further functional exploration of the EGR3 gene will contribute to the underlying molecular mechanism for schizophrenia pathogenesis.
Effective use of immunosuppressive agents to avoid the occurrence of nephrotoxicity and rejection in recipients with delayed graft function (DGF) is a concern for physicians. We investigated the outcomes of treatment with enteric-coated mycophenolate sodium (EC-MPS) in combination with a low-dose of tacrolimus (Tac) in renal transplantation for recipients with a high risk of DGF. We conducted a retrospective study of 61 recipients with a high risk of DGF who were treated with EC-MPS and low-dose Tac. The recipients were separated into a no-DGF group and a DGF group, based on whether DGF actually occurred. The results showed that although EC-MPS and Tac doses were similar in both groups, the percentage of recipients whose mycophenolic acid area under the curve 0-12 h (MPA-AUC 0-12 h ) was below 30 (mg•h)/L was significantly higher and the Tac trough concentration significantly lower in the DGF group one week after transplantation. Notably, a higher incidence of biopsy-proven acute rejection (BPAR) was found in the DGF group and among all recipients whose MPA-AUC 0-12 h was less than 30 (mg•h)/L at one week after transplantation. One-year graft survival, patient survival, allograft function, and the incidence of the most common adverse events were similar in the two groups. In conclusion, the immunosuppressive regime is applicable to Chinese kidney transplant recipients, and early low exposure to EC-MPS was related to acute rejection in the recipients at a high risk of DGF.
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