Pei Lu

Prostate cancer risk and aggressiveness associated with the CYP1B1 4326C/G (Leu432Val) polymorphism: a meta-analysis of 2788 cases and 2968 controls

To derive a precise estimation of the associations between the cytochrome P450 1B1 (CYP1B1) 4326C/G variants and prostate cancer (PCa) risk or aggressiveness, a meta-analysis was performed using all eligible published studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association in seven literature studies with 2788 cases and 2968 controls. In the overall analysis, no significant association was found between the CYP1B1 4326C/G polymorphism and PCa risk, but ethnicity subgroup analyses and a case-source analysis revealed significant associations. The 4326G allele showed a significant association with increased PCa risk in Asians (OR=1.52, 95% CI: 1.20-1.92), and significant associations were also observed in a heterozygote comparison (OR=1.40, 95% CI: 1.03-1.89), a homozygote comparison (OR=2.38, 95% CI: 1.31-4.33) and in a dominant genetic model (OR=1.52, 95% CI: 1.14-2.01). Moreover, the 4326G allele was also significantly correlated with an increased risk of sporadic PCa (OR=1.13, 95% CI: 1.04-1.24), and significant associations were observed in a heterozygote comparison (OR=1.16, 95% CI: 1.02-1.33), a homozygote comparison (OR=1.24, 95% CI: 1.03-1.49) and a dominant genetic model (OR=1.19, 95% CI: 1.05-1.34). The overall analyses and all subgroup analyses showed no significant association between the 4326C/G polymorphism and PCa aggressiveness. Our meta-analysis showed that CYP1B1 4326G allele is significantly associated with an increased PCa risk in Asians and in sporadic PCa cases.

Serum MicroRNA-99a Helps Detect Acute Rejection in Renal Transplantation.

BACKGROUND MicroRNAs (miRNAs) are short, single-stranded, non-coding RNAs, and they are becoming increasingly known as potential biomarkers for a variety of pathologies. However, the significance of circulating miRNAs in renal transplantation patients needs further studies. MATERIALS AND METHODS An miRNA array was used to profile the serum miRNAs of stable transplantation patients and transplantation patients with acute rejection (AR). We performed quantitative real-time polymerase chain reaction with the serum samples from 12 patients with AR, 11 control transplantation patients without rejection, and 15 transplantation patients with delayed graft function (DGF) for validation. Receiver operator characteristic analysis was used to assess the diagnostic capacity of serum miRNA. RESULTS The miR-99a, miR-100, miR-151a, let-7a, let-7c, and let-7f were deregulated in the serum of the patients with AR. In the validation set, only miR-99a and miR-100 were upregulated in the AR group. We further evaluated the expression levels of miR-99a and miR-100 in the DGF group. Only miR-99a was observed with the potent diagnostic value in discriminating AR patients from stable patients (area under the curve [AUC] = 0.750, 95% confidence interval [CI] = 0.529-0.971, P = .042) and DGF patients (AUC = 0.811, 95% CI = 0.600-1.000, P = .006). CONCLUSION Serum miR-99a may serve as a biomarker of AR in renal transplantation patients. Further studies are required to confirm the results.

Advanced glycation end products accelerate arteriosclerosis after renal transplantation through the AGE/RAGE/ILK pathway

BACKGROUND The effects of advanced glycation end products (AGEs) on arteriosclerosis (AS) after kidney transplantation and the molecular mechanisms involved remain unclear. METHODS Samples were collected from 30 healthy volunteers and 30 renal transplant recipients (RTRs) to determine the levels of AGEs and to observe both histological changes and α-smooth muscle actin (α-SMA) and osteopontin (OPN) expression. Furthermore, we analyzed α-SMA, OPN and integrin-linked kinase (ILK) in rat vascular smooth muscle cells (VSMCs) that were treated with AGEs and in ILK plasmid transfected rat VSMCs treated with AGEs. Finally, we measured the expression of ILK and the receptor for advanced glycation end (RAGE) products in rat VSMCs treated with AGEs and an anti-RAGE antibody. RESULTS Significant differences in the histological changes, serum AGEs, and expression of α-SMA and OPN in arterial walls were noted between healthy volunteers and RTRs. Significant OPN and ILK overexpression and reduced α-SMA expression were detected in a time-dependent manner in rat VSMCs after treatment with AGEs. Similar outcomes were observed regarding the overexpression of ILK, and these results could be prevented via RAGE inhibition. CONCLUSIONS AGEs may play a critical role in the formation and progression of AS after renal transplantation by inducing VSMCs-to-osteoblast trans-differentiation through the AGE/RAGE/ILK pathway.

Clinical Efficacy and Safety of Pamidronate Therapy on Bone Mass Density in Early Post-Renal Transplant Period: A Meta-Analysis of Randomized Controlled Trials

Introduction The overall effect of pamidronate on bone mass density (BMD) in the early renal transplant period varies considerably among studies. The effects of pamidronate on graft function have not been determined. Materials and Methods A comprehensive search was conducted in PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase independently by two authors. Randomized controlled trials of pamidronate evaluating bone loss in the first year of renal transplantation were included. Methods reported in the “Cochrane Handbook for Systematic Reviews of Interventions 5.0.2” were used to evaluate changes of lumbar spine and femoral neck BMD, and serum creatinine, calcium and intact parathyroid hormone (iPTH) levels. Fixed or random effect models were used as appropriate. Results Six randomized trials evaluating 281 patients were identified. One hundred forty-four were treated with pamidronate and 137 were control patients. Administration of pamidronate was associated with significant reduction of bone loss in the lumbar spine, compared to the control group (standardized mean difference (SMD)  = 24.62 [16.25, 32.99]). There was no difference between the pamidronate treated and control femoral neck BMD (SMD  = 3.53 [−1.84, 8.90]). A significant increase in the serum creatinine level of the intervention group was seen, compared to the control group. The serum calcium and iPTH of the pamidronate and control groups were not different after 1 year (serum creatinine: SMD  = −3.101 [−5.33, −0.89]; serum calcium: SMD  = 2.18 [−0.8, 5.16]; serum iPTH: SMD  = 0.06 [−0.19, 0.31]). Heterogeneity was low for serum calcium and iPTH and high for serum creatinine. Conclusions This meta-analysis demonstrated the beneficial clinical efficacy of pamidronate on BMD with no association with any alteration in graft function during the first year of renal transplantation. Significant heterogeneity precludes the conclusion of the relationship between serum creatinine and pamidronate.

The risks, degree of malignancy and clinical progression of prostate cancer associated with the MDM2 T309G polymorphism: a meta-analysis.

To determine the risk, malignant degree and clinical progression of prostate cancer (PCa) associated with mouse double-minute 2 protein (MDM2) T309G variants, a meta-analysis was performed on all eligible published studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess these associations in seven studies that included 5151 cases and 1003 controls. In the overall analysis, the 309G allele was significantly associated with a decreased PCa risk (OR=0.85, 95% CI: 0.74-0.97); this was also the case for the homozygous comparison (OR=0.72, 95% CI: 0.55-0.95) and the dominant genetic model (OR=0.79, 95% CI: 0.65-0.96). The 309G allele was also found to be significantly associated with lower degrees of PCa malignancy (OR=0.85, 95% CI: 0.75-0.96) in the overall analysis, as well as in the heterozygous comparison (OR=0.79, 95% CI: 0.65-0.96), homozygous comparison (OR=0.76, 95% CI: 0.58-0.98) and dominant genetic model (OR=0.81, 95% CI: 0.68-0.96). Furthermore, grouping analysis showed that the 309G allele in Caucasians was significantly correlated with a decreased PCa risk (OR=0.77, 95% CI: 0.61-0.96); this was also the case in the homozygous comparison (OR=0.51, 95% CI: 0.31-0.86). The grouping analysis also showed that the 309G variant in Caucasians was significantly associated with a lower degree of PCa malignancy in all of the genetic models. In addition, we found that the 309G variant in Caucasians was significantly associated with a slower PCa clinical progression in all of the genetic models. In summary, our meta-analysis showed that the MDM2 309G variant was significantly associated with a decreased PCa risk, lower malignant degree and slower clinical progression in Caucasians, but there was no obvious association in the Asian population.

Direct-acting antiviral agent efficacy and safety in renal transplant recipients with chronic hepatitis C virus infection: A Prisma-compliant study

Background: The efficacy and safety of direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV)-infected renal transplant recipients (RTRs) has not been determined. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and assessed the quality of eligible studies using the Joanna Briggs Institute scale. DAA efficacy and safety were assessed using standard mean difference (SMD) with 95% confidence intervals (95%CIs). Results: Six studies (360 RTRs) were included. Two hundred thirty six RTRs (98.3%) achieved sustained virological response within 12 weeks; HCV infection was cleared in 239 RTRs after 24-week treatment. Liver function differed significantly pre- and posttreatment (alanine aminotransferase, SMD: 0.96, 95%CIs: 0.65, 1.26; aspartate aminotransferase, SMD: 0.89, 95%CIs: 0.60, 1.18); allograft function pre- and posttreatment was not statistically different (serum creatinine, SMD: −0.13, 95%CIs: −0.38, 0.12; estimated glomerular filtration rate, SMD: 0.20, 95%CIs: −0.11, 0.51). General symptoms (fatigue nausea dizziness or headache) were the most common adverse events (AEs) (39.3%). Severe AEs, that is, anemia, portal vein thrombosis, and streptococcus bacteraemia and pneumonia, were present in 1.1%, 0.6%, and 1.1% of RTRs, respectively. Conclusion: Our findings suggest that DAAs are highly efficacious and safe for treating HCV-infected RTRs and without significant AE.

Performance of the ImmuKnow Assay in Differentiating Infection and Acute Rejection After Kidney Transplantation: A Meta-Analysis

BACKGROUND The ImmuKnow test is an assay for determining the functional activity of immunocytes, which reflects cell-mediated immune responses in populations undergoing organ transplantation. METHODS Electronic and manual searches were conducted to identify studies of the ImmuKnow test. After methodological quality assessment and data extraction, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were assessed, and summary receiver operating characteristic analysis was performed systematically. The extent of heterogeneity was explored. RESULTS Six studies were identified for analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR of ImmuKnow for predicting the risk of infection were 0.51 (95% confidence interval [CI], 0.45-0.57), 0.75 (95% CI, 0.71-0.78), 1.97 (95% CI, 0.91-4.26), 0.67 (95% CI, 0.38-1.19), and 3.56 (95% CI, 0.80-15.89), respectively. A DOR of 13.81 (95% CI, 0.79-240.44), with a sensitivity of 0.51 (95% CI, 0.40-0.61), a specificity of 0.90 (95% CI, 0.87-0.93), a PLR of 4.45 (95% CI, 0.91-21.74), and an NLR of 0.35 (95% CI, 0.08-1.45), was found in the analysis of the predictive value for acute rejection. The summary receiver operating characteristic curve values for ImmuKnow in distinguishing patients with infections from those with acute rejections were 0.631 ± 0.215 and 0.986 ± 0.015, respectively. CONCLUSIONS Our analysis did not support the use of the ImmuKnow assay to predict or monitor the risks of infection and acute rejection in renal transplant recipients. Further studies are needed to confirm the relationships between the ImmuKnow assay and infection and acute rejection in kidney transplantation.

Co-Incubation of Human Spermatozoa with Anti-VDAC Antibody Reduced Sperm Motility

Background: Voltage-dependent anion channel (VDAC), a channel protein, exists in the outer mitochondrial membrane of somatic cells and is involved in multiple physiological and pathophysiological processes. Up until now, little has been known about VDAC in male germ cells. In the present study, the relationship between VDAC and human sperm motility was explored. Methods: Highly motile human spermatozoa were incubated in vitro with anti-VDAC antibody. Total sperm motility, straight line velocity (VSL), curvilinear velocity (VCL), and average path velocity (VAP) were recorded. Intracellular free calcium concentration ([Ca2+]i), pH value (pHi), and ATP content were determined. Results: Co-incubation with anti-VDAC antibody reduced VSL, VCL, and VAP of spermatozoa. Co-incubation further reduced [Ca2+]i. Anti-VDAC antibody did not significantly alter total sperm motility, pHi and intracellular ATP content. Conclusion: The data suggest that co-incubation with anti-VDAC antibody reduces sperm motility through inhibition of Ca2+ transmembrane flow. In this way, VDAC participates in the modulation of human sperm motility through mediating Ca2+ transmembrane transport and exchange.

Alternations of galectin levels after renal transplantation

OBJECTIVES Galectins (gals), a growing family of β-galactoside-binding animal lectins, have been implicated in a variety of biological processes including fibrosis, angiogenesis, and immune activation, all of which are involved in hemodialysis (HD) and renal transplantation (RTx). In this study, we aimed to investigate serum gal levels in HD and RTx recipients. DESIGN AND METHODS 41 normal subjects, 41 RTx recipients and 32 HD patients were recruited for this study. RTx recipients were evaluated before transplantation as well as 3 months afterwards. Serum gals-1, 2, 3, 4, 8, and 9 were measured both at baseline and 3 months later in each group. RESULTS At baseline, there were no differences in gals-1, 2, 3, 4, 8, and 9 between the RTx and HD groups. However, the levels of gals-1, 2, 3, 8, and 9 in the RTx and HD groups were higher than that of normal subjects. In paired analyses, gals-1, 2, and 3 were significantly decreased in RTx patients (P<0.0001) at 3 months, while there was no change in the HD group. However, levels of gals-4, 8, and 9 did not significantly change in either the HD or RTx group. CONCLUSION Gal-1, 2, and 3 levels were high in maintenance HD patients. Kidney transplantation improved gal-1, 2, and 3 levels.

Osteopontin mediating cyclosporine A induced epithelial-to-mesenchymal transition on rat renal tubular epithelial cells.

Osteopontin (OPN) is highly correlated with cyclosporine A (CsA) nephrotoxicity. As epithelial‐to‐mesenchymal transition (EMT) of renal tubular epithelial cells plays an important role in CsA nephropathy, we investigated whether OPN mediated EMT of renal tubular epithelial cells upon CsA stimulation. OPN knockdown suppresses CsA induced EMT on NRK52E cells, and it also attenuates downregulation of E‐cadherin and upregulation of α‐smooth muscle actin (α‐SMA) and fibronectin (FN) that are induced by CsA. OPN alone can induce EMT on NRK52E cells, which also results in upregulation of TGF‐β1. Thus, OPN is a causative factor in mediating CsA induced EMT on NRK52E cells.