TNF-α-308G/A polymorphism associated with TNF-α protein expression in patients with diabetic nephropathy.

AIMS: This study was to clarify the regulated effects of TNF-α -308G/A polymorphism on TNF-α and investigate the relationship of -308G/A polymorphisms with diabetic nephropathy (DN) susceptibility. METHODS: 86 DN patients and 94 healthy individuals were enrolled in our study. Polymerase chain reaction-sequence specific primer (PCR-SSP) detection technology was used to testify single nucleotide polymorphism (SNP) of TNF-α gene. Enzyme-linked immunosorbent assay (ELISA) was used to measure the content of TNF-α protein. Odds ratio (OR) with 95% CI were used to evaluate the association of TNF-α -308G/A polymorphism and DN susceptibility. RESULTS: The level of TNF-α protein was much higher in DN patients compared to that of controls (P<0.05). For TNF-α -308G/A, G/A genotype could increase the risk for DN (OR=2.15, 95% CI=1.08-4.30). Moreover, a allele frequency was found higher in cases compared with controls, which suggested that A allele served as an genetic-susceptibility factor for DN (OR=1.89, 95% CI=1.10-3.26). Further analysis indicated that level of TNF-α for individuals with mutant genotype (GA and AA) were higher than that of individuals with wild genotype (P<0.05). However, AA genotype showed no effects on DN susceptibility (OR=2.08, 95% CI=0.56-7.33). CONCLUSION: TNF-α-308G/A polymorphism was associated with expression level of TNF-α and served as an genetic-susceptibility factor for DN.

EBP1 suppresses growth, migration, and invasion of thyroid cancer cells through upregulating RASAL expression.

Ebp1, a protein identified by its interactions with the ErbB3 receptor, has been characterized as a negative regulator of cancers. RAS GTPase-activating protein (RasGAP), RASAL1, was recently identified as a major tumor suppressor in thyroid cancer. In this study, we examined EBP1 expression in papillary and follicular thyroid cancer cells. We found that compared with normal thyroid cells, TPC1, WRO, and FTC133 thyroid tumor cells exhibited lower EBP1 expression at messenger RNA (mRNA) and protein levels. We then investigated the effects of forced EBP1 expression on growth, migration, and invasiveness of thyroid tumor cells. By using MTT and Boyden chamber assays, we showed that EBP1 overexpression dramatically reduced growth rate, migration, and invasiveness of K1 and FTC133 thyroid tumor cells. Furthermore, we explored the molecular mechanism underlying the effects of EBP1 on the cells by disclosing the correlation of EBP1 and RASAL1 expression. RASAL expression was elevated in thyroid tumor cells overexpressing EBP1. Knockdown RASAL by transduction of RASAL1 shRNA lentiviral particles markedly reduced RASAL levels with restoration of EBP1, and RASAL1 knockdown abrogated the effects of forced EBP1 expression on cell growth, migration, and invasiveness of thyroid tumor cells. These findings suggest that Ebp1 suppressed thyroid cancer cell lines by upregulating RASRAL expression.

Serum 25-hydroxyvitamin D level and diabetic nephropathy in patients with type 2 diabetes mellitus.

OBJECTIVE: Patients with chronic kidney disease have a very high prevalence of deficiency of 25-hydroxyvitamin D [25(OH)D]. We evaluate the association between 25(OH)D and diabetic nephropathy (DN) in a Chinese sample with type 2 diabetes mellitus. METHOD: The subjects were patients with diabetes mellitus who were hospitalized at our hospital during the period from June 2012 to July 2014. Serum levels of 25(OH)D were tested at admission. DN was defined as a urinary albumin-to-creatinine ratio ≥30 mg/g in a random spot urine sample. Multivariate analyses were performed using logistic regression models. RESULTS: We found that serum 25(OH)D levels were significantly lower in diabetes with DN as compared to without DN [8.5 (IQR 6.8-11.3) vs. 13.9 (IQR 11.2-18.2) ng/ml, P < 0.0001]. Based on the ROC curve, the optimal cutoff value of serum 25(OH)D levels as an indicator for diagnosis of DN was projected to be 10.5 ng/ml, which yielded a sensitivity of 82.6 % and a specificity of 72.7 %, with the area under the curve at 0.807 [95 % confidence interval (CI) 0.764-0.849]. Multivariate logistic regression analysis adjusted for common risk factors showed that with serum 25(OH)D level ≤10.5 ng/ml was an independent indicator of DN [odds ratio (OR) = 6.559; 95 % CI 2.864-11.368]. CONCLUSIONS: Our findings suggested that diabetes with DN had lower serum 25(OH)D levels and that determination of 25(OH)D statuses might be used to identify patients at increased risk of developing nephropathy complications.