Association between ERCC1 and ERCC2 gene polymorphisms and susceptibility to pancreatic cancer.

We conducted a study to investigate the association between ERCC1 (rs3212986) and ERCC2 (rs13181) gene polymorphisms and the risk of pancreatic cancer in a Chinese population. A total of 217 pancreatic cancer patients and 244 control subjects were recruited from the Nuclear Industry 215 Hospital of Shaanxi Province between February 2013 and December 2014. Genomic DNA was extracted from peripheral blood samples using a TIANamp Blood DNA Kit (Tiangen, Beijing, China) according to the manufacturer's instructions. The ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length of polymorphism. Unconditional logistic regression analyses showed that subjects with the CC genotype of ERCC1 rs3212986 were susceptible to the development of pancreatic cancer when compared with subjects with the AA genotype (OR = 2.57, 95%CI = 1.34-5.02). The ERCC1 rs3212986 gene polymorphism was associated with increased risk of pancreatic cancer in the dominant (OR = 1.54, 95%CI = 1.05-2.28) and recessive (OR = 2.22, 95%CI = 1.20-4.19) models. However, no significant difference was found between the ERCC2 rs13181 polymorphism and the risk of pancreatic cancer in the codominant, dominant, and recessive models. We suggest that the ERCC1 rs3212986 polymorphism increases susceptibility to pancreatic cancer in the codominant, dominant, and recessive models, although further studies are needed to confirm our findings.

Melatonin, energy metabolism, and obesity: a review.

Melatonin is an old and ubiquitous molecule in nature showing multiple mechanisms of action and functions in practically every living organism. In mammals, pineal melatonin functions as a hormone and a chronobiotic, playing a major role in the regulation of the circadian temporal internal order. The anti-obesogen and the weight-reducing effects of melatonin depend on several mechanisms and actions. Experimental evidence demonstrates that melatonin is necessary for the proper synthesis, secretion, and action of insulin. Melatonin acts by regulating GLUT4 expression and/or triggering, via its G-protein-coupled membrane receptors, the phosphorylation of the insulin receptor and its intracellular substrates mobilizing the insulin-signaling pathway. Melatonin is a powerful chronobiotic being responsible, in part, by the daily distribution of metabolic processes so that the activity/feeding phase of the day is associated with high insulin sensitivity, and the rest/fasting is synchronized to the insulin-resistant metabolic phase of the day. Furthermore, melatonin is responsible for the establishment of an adequate energy balance mainly by regulating energy flow to and from the stores and directly regulating the energy expenditure through the activation of brown adipose tissue and participating in the browning process of white adipose tissue. The reduction in melatonin production, as during aging, shift-work or illuminated environments during the night, induces insulin resistance, glucose intolerance, sleep disturbance, and metabolic circadian disorganization characterizing a state of chronodisruption leading to obesity. The available evidence supports the suggestion that melatonin replacement therapy might contribute to restore a more healthy state of the organism.

Melatonin, vitamin E, and estrogen reduce damage induced by kainic acid in the hippocampus: potassium-stimulated GABA release.

Melatonin, vitamin E and estrogen have been shown to exert neuroprotective effects against kainic acid (KA)-induced damage in the hippocampus. The aim of the present study was to examine the changes in potassium-evoked gamma-aminobutyric acid (GABA) release in the hippocampus of KA-treated rats and to test the possible protective effects of melatonin, vitamin E or estrogen. Following the treatment of mice with KA, a marked reduction in potassium-evoked [3H]GABA release was observed. Melatonin or estrogen prevented the reduction in potassium-evoked GABA release due to kainate administration. Vitamin E also exhibited some protective effect, but it was less than that provided by melatonin or estrogen. Melatonin, estrogen and, to a lesser extent, vitamin E reduce the physiological toxicity of KA. Since KA is believed to cause neuronal alterations via oxidative processes, it is assumed that the free radical scavenging and oxidative properties of melatonin, estrogen and vitamin E account for the protective effects of these agents.