The role of circadian genes in the pathogenesis of colorectal cancer.

Colorectal cancer (CRC) is the third most frequent cancer in human beings and is also the major cause of death among the other gastrointestinal cancers. The exact mechanisms of CRC development in most patients remains unclear. So far, several genetically, environmental and epigenetically risk factors have been identified for CRC development. The circadian rhythm is a 24-h rhythm that drives several biologic processes. The circadian system is guided by a central pacemaker which is located in the suprachiasmatic nucleus (SCN) in the hypothalamus. Circadian rhythm is regulated by circadian clock genes, cytokines and hormones like melatonin. Disruptions in biological rhythms are known to be strongly associated with several diseases, including cancer. The role of the different circadian genes has been verified in various cancers, however, the pathways of different circadian genes in the pathogenesis of CRC are less investigated. Identification of the details of the pathways in CRC helps researchers to explore new therapies for the malignancy.

Dietary omega-3 and -6 fatty acids affect the expression of prostaglandin E2 synthesis enzymes and receptors in mice uteri during the window of pre-implantation.

Considering possible effects of poly-unsaturated fatty acids (PUFA) on embryo implantation more likely through PGs, we investigated effects of dietary omega-3 and -6 PUFA on prostaglandin E2 (PGE2) signaling in mice uterus during pre-implantation period. The mRNA expressions of microsomal- and cytosolic- PGE synthase (mPGES and cPGES) and protein expressions of PGE receptor 2 and 4 (EP2 and EP4) were evaluated in uterus tissues of control as well as omega 3 and omega 6 received mice at days 1-5 of pregnancy. Expression of cPGES gene was not significantly different between groups but the mPGES expression on days 4 and 5 of pregnancy in supplemented groups was higher than controls. Omega-3 significantly decreased EP2 levels on days 3 and 4, while omega-6 caused an increase on days 3-5 of pregnancy. The levels of EP4 were significantly higher in the omega-6 group than other groups on days 4 and 5 of pregnancy. Also the implantation rate was higher in omega -6 compared to omega-3 group (p = 0.006). Moreover, there were significant correlations between implantation rate with expression levels of mPGES and EP2. Our results showed negative and positive effects of respectively dietary omega-3 and -6 PUFA on PGE2 signaling and implantation rate.

Effects of dietary omega-3 and -6 supplementations on phospholipid fatty acid composition in mice uterus during window of pre-implantation.

Since fatty acid composition of uterus phospholipids is likely to influence embryo implantation, this study was conducted to investigate the effects of dietary omega-3 and -6 fatty acids on implantation rate as well as uterine phospholipid fatty acids composition during mice pre-implantation period. Sixty female mice were randomly distributed into:1) control (standard pellet), 2) omega-3 (standard pellet + 10% w/w of omega-3 fatty acids) and 3) omega-6 (standard pellet + 10% w/w of omega-6 fatty acids). Uterine phospholipid fatty acid composition during the pre-implantation window (days 1-5 of pregnancy) was analyzed using gas-chromatography. The implantation rate on the fifth day of pregnancy was also determined. Our results showed that on days 1, 2 and 3 of pregnancy, the levels of arachidonic acid (ARA) as well as total omega-6 fatty acids were significantly higher and the levels of linolenic acid and total omega-3 fatty acids were statistically lower in the omega-6 group compared to the omega-3 group (p < 0.05). On the fourth day of pregnancy, only the ARA, total omega-6 fatty acids, and poly-unsaturated fatty acids levels were significantly different between the two dietary supplemented groups (p < 0.05). There were positive correlations between the levels of omega-6 fatty acids, especially ARA, with the implantation rate. The present study showed that diets rich in omega-3 and -6 fatty acids could differently modify uterine phospholipid fatty acid composition and uterine levels of phospholipid ARA, and that the total omega-6 fatty acids had a positive association with the implantation rate.