Rabbit Anti-Human NOS3 (a.a. 756-1161) Polyclonal antibody

Several studies have focused on the impaired role of endothelial nitric oxide synthase (NOS3) gene polymorphism and its association to erectile dysfunction (ED). However, currently controversial results have been reported due to their significant heterogeneity. The present study aimed to assess the genotypic distribution and the allelic frequency of Intron 4 VNTR and Glu298Asp gene polymorphisms in vasculogenic ED patients compared to healthy controls of a specific region of Turkey. A total of 75 patients with ED (median age: 56, IQR:10.5) and 75 healthy controls (median age: 56, IQR:10.5) were prospectively analyzed. All subjects were equally evaluated by the same physician with detailed history-taking, physical examination, International Index of Erectile Function (IIEF) questionnaire, and blood tests (incl. glucose, testosterone, triglyceride and total cholesterol level). Those with an IIEF score under 26 were considered to have ED, by classifying them according to their scores as mild (22-25), moderate (11-21) and severe (1-10) ED. Color doppler ultrasonography was carried out in patients with an IIEF score <22. Hypertension, diabetes mellitus, coronary artery disease, and smoking status were significantly associated with the ED group compared to control subjects with p values of <0.001, <0.001, 0.002 and <0.001, respectively. Overall genotype frequencies was 47 (31%) a/a, 22 (15%) a/b, 82 (55%) b/b for Intron 4 VNTR and 56 (37%) GG, 78 (52%) GT, 16 (11%) TT for the Glu298Asp polymorphism. The frequencies of Intron 4 VNTR a/a allele and Glu298Asp GT allele were associated with severe ED, while a/b and TT were associated with moderate or mild, and b/b and GG were associated with no ED. In contrast to Glu298Asp, statistically significant differences in genotypic frequencies of Intron 4 VNTR gene polymorphism between ED and control subjects was established.

Hepatocellular carcinoma (HCC) represents 80% of the primary hepatic neoplasms. It is the sixth most frequent neoplasm, the fourth cause of cancer-related death, and 7% of registered malignancies. Sorafenib is the first line molecular targeted therapy for patients in advanced stage of HCC. The present study shows that Sorafenib exerts free radical scavenging properties associated with the downregulation of nuclear factor E2-related factor 2 (Nrf2)-regulated thioredoxin 1 (Trx1) expression in liver cancer cells. The experimental downregulation and/or overexpression strategies showed that Trx1 induced activation of nitric oxide synthase (NOS) type 3 (NOS3) and S-nitrosation (SNO) of CD95 receptor leading to an increase of caspase-8 activity and cell proliferation, as well as reduction of caspase-3 activity in liver cancer cells. In addition, Sorafenib transiently increased mRNA expression and activity of S-nitrosoglutathione reductase (GSNOR) in HepG2 cells. Different experimental models of hepatocarcinogenesis based on the subcutaneous implantation of HepG2 cells in nude mice, as well as the induction of HCC by diethylnitrosamine (DEN) confirmed the relevance of Trx1 downregulation during the proapoptotic and antiproliferative properties induced by Sorafenib. In conclusion, the induction of apoptosis and antiproliferative properties by Sorafenib were related to Trx1 downregulation that appeared to play a relevant role on SNO of NOS3 and CD95 in HepG2 cells. The transient increase of GSNOR might also participate in the deactivation of CD95-dependent proliferative signaling in liver cancer cells.