Cardioprotective Effect of Sodium Ferulate in Diabetic Rats

Reactive oxygen species (ROS) play important roles in the occurrence and development in diabetic cardiomyopathy (DC). Ferulic acid is one of the ubiquitous compounds in diet. Sodium ferulate (SF) is its sodium salt. SF has potent free radical scavenging activity and can effectively scavenge ROS. The study investigated the effect of SF on cardioprotection in diabetic rats. The diabetic rats induced by streptozotocin (STZ) were treated with SF (110mg/kg) by gavage per day for 12 weeks. Results showed that the levels of nitric oxide (NO) and superoxide dismutase (SOD) activity in plasma and myocardium in SF-treated group were significantly higher than those in diabetic control group. The levels of malondialdehyde (MDA) in plasma and myocardium in SF-treated group were significantly lower than those in diabetic control group. Expression of connective tissue growth factor (CTGF) in myocardium in SF-treated group was apparently lower than that in diabetic control group. Compared with normal control group, electron micrographs of myocardium in diabetic control group showed apparently abnormality, while that was significantly ameliorated in SF-treated group. The study demonstrated that SF has a cardioprotective effect via increasing SOD activity and NO levels in plasma and myocardium, inhibiting oxidative stress in plasma and myocardium, and inhibiting the expression of CTGF in myocardium in diabetes rats

Hypoxia-inducible factor-1α gene polymorphisms and cancer risk: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>The results from the published studies on the association between <it>hypoxia-inducible factor -1α </it>(HIF-1α) polymorphisms and cancer risk are conflicting. In this meta-analysis, we aimed to investigate the association between <it>HIF-1α </it>1772 C/T and 1790 G/A polymorphisms and cancer.</p> <p>Methods</p> <p>The meta-analysis for 1772 C/T polymorphism included 4131 cancer cases and 5387 controls, and for 1790 G/A polymorphism included 2058 cancer cases and 3026 controls. Allelic and genotypic comparisons between cases and controls were evaluated. Subgroup analyses by cancer types, ethnicity, and gender were also performed. We included prostate cancer in male subgroup, and female specific cancers in female subgroup.</p> <p>Results</p> <p>For the 1772 C/T polymorphism, the analysis showed that the T allele and genotype TT were significantly associated with higher cancer risk: odds ratio (OR) = 1.29 [95% confidence interval (CI, 1.01, 1.65)], P = 0.04, P_{heterogeneity}< 0.00001, and OR = 2.18 [95% CI (1.32, 3.62)], P = 0.003, P_{heterogeneity}= 0.02, respectively. The effect of the genotype TT on cancer especially exists in Caucasians and female subjects: OR = 2.40 [95% CI (1.26, 4.59)], P = 0.008, P_{heterogeneity}= 0.02, and OR = 3.60 [95% CI (1.17, 11.11)], P = 0.03, P_{heterogeneity}= 0.02, respectively. For the 1790 G/A polymorphism, the pooled ORs for allelic frequency comparison and dominant model comparison suggested a significant association of 1790 G/A polymorphism with a decreased breast cancer risk: OR = 0.28 [95% CI (0.08, 0.90)], P = 0.03, P_{heterogeneity}= 0.45, and OR = 0.29 [95% CI (0.09, 0.97)], P = 0.04, P_{heterogeneity}= 0.41, respectively. The frequency of the <it>HIF-1α </it>1790 A allele was very low and only two studies were included in the breast cancer subgroup.</p> <p>Conclusions</p> <p>Our meta-analysis suggests that the <it>HIF-1α </it>1772 C/T polymorphism is significantly associated with higher cancer risk, and 1790 G/A polymorphism is significantly associated with decreased breast cancer risk. The effect of the 1772 C/T polymorphism on cancer especially exists in Caucasians and female subjects. Only female specific cancers were included in female subgroup, which indicates that the 1772 C/T polymorphism is significantly associated with an increased risk for female specific cancers. The association between the 1790 G/A polymorphism and lower breast cancer risk could be due to chance.</p

Tumor Necrosis Factor Receptor-Associated Protein 1 Protects against Mitochondrial Injury by Preventing High Glucose-Induced mPTP Opening in Diabetes

Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide. Renal tubular epithelial cell apoptosis and tubular atrophy have been recognized as indicators of the severity and progression of DKD, while the mechanism remains elusive. Tumor necrosis factor receptor-associated protein 1 (TRAP1) plays critical roles in apoptosis. The aim of this study was to investigate the protective role TRAP1 plays in DKD and to study the potential underlying mechanisms. TRAP1 expression was decreased, and mitochondria were injured in NRK-52e cells under high-glucose (HG) conditions. The overexpression of TRAP1 ameliorated HG-induced apoptosis, increased cell viability, maintained mitochondrial morphology, adenosine triphosphate (ATP) levels, and mitochondrial membrane potential (MMP), and buffered oxidative stress, whereas TRAP1 knockdown aggravated these effects. The protective effects of TRAP1 may be exerted via the inhibition of mitochondrial permeability transition pore (mPTP) opening, and the damage caused by TRAP1 knockdown can be partially reversed by treatment with the mPTP opening inhibitor cyclosporin A (CsA). In vivo, TRAP1 expression upregulation by AAV2/9 injection prevented renal dysfunction, ameliorated histopathological changes, maintained mitochondrial morphology and function, and reduced apoptosis and reactive oxygen species (ROS) in STZ-treated DKD rats. Thus, our results suggest that TRAP1 ameliorates diabetes-induced renal injury by preventing abnormal mPTP opening and maintaining mitochondrial structure and function, which may be treated as a potential target for DKD treatment