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To address preventive effects of n-3 PUFAs/LC n-3 PUFAs on CRTs, a randomized controlled trial was conducted. One-hundred four experimental group participants were advised to increase intake of n-3 PUFAs, including fish/shell fish, fish oil supplements and perilla oils, and to decrease consumption of n-6 PUFAs and fats/oils as a whole for 24 months. One-hundred one control group participants were only cautioned to reduce consumption of fats/oils as a whole. Random allocation was satisfactorily attained, and participants sufficiently complied with our regimen. Intakes, plasma concentrations, and compositions of the RBC and sigmoid colon membranes of n-3 PUFAs, LC n-3 PUFAs, EPA and DHA increased, and the ratios of n-6 PUFAs/n-3 PUFAs and AA/LC n-3 PUFAs decreased without any adverse response. Twenty-four months after the intervention, the multivariate-adjusted hazard ratio (95% confidence intervals) was estimated to be 0.805 (0.536–1.209) with a signal towards the reduced CRT incidence. [ABSTRACT FROM AUTHOR]

To clarify preventive effects of n-3 polyunsaturated fatty acids (PUFAs) against colorectal carcinogenesis, we performed a dietary intervention in patients polypectomized for colorectal adenomas/tumors. For the former the following dietary advice was given: (1) decrease intake of fat from 30 to 20% of the total; (2) decrease consumption of n-6PUFAs containing foods, and increase intake of n-3 PUFAs for 2 years. For the comparison group only decreased intake of fat (30–20%) was recommended. Samples of normal sigmoid colon mucosa, obtained by colonoscopic check once a year during the intervention period, were used to investigate COX-2, cell proliferation (Ki67 expression), p53, Bcl-2 and Bax by immunostaining and determine the apoptosis index (AI) by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL) in 21 and 20 patients in experimental and comparison groups, respectively, who completed the 2 years of the intervention. After 24 months, the AI and positive cells of Bax and the ratio of Bax/Bcl-2 in normal sigmoid colon mucosa for the experimental group was significantly increased, whereas this change was not found in comparison group. These observations demonstrated for the first time that increased intake of n-3 PUFAs promotes apoptosis of normal colon mucosa in human which is related to effect on Bax or the balance of Bax and Bcl-2. [Copyright &y& Elsevier]

Lung adenocarcinoma (AC) has been increasing over the last several decades in many countries, including China. Some of the glutathione S-transferases (GSTs) demonstrate polymorphisms which may play a role in lung AC susceptibility. Our previous study of a Chinese population found the GSTM1 null genotype to be associated with an increased risk of lung AC, and the combination of GSTM1 null genotype and CYP2E1 wild type conferred a significantly elevated risk. Here, we extended the study to investigate the potential role of GSTT1 and GSTP1 polymorphisms in likelihood of development of lung AC, either separately or in combination. This case-control study encompassed 112 cases with lung ACs and 119 age- and gender-matched cancer-free controls from Beijing. The frequencies for the GSTM1 null genotype were 61.6 and 50.4% among cases and controls, and for the GSTT1 null genotype 47.3 and 45.4%, respectively. The distribution of the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes was 59.8, 39.3 and 0.9% in cases, and 70.6, 28.6 and 0.8% in controls, respectively. No relationship between lung AC and the GSTT1 genotype was observed in the present study, either separately or in combination with the GSTM1 or GSTP1 genotypes. Although separate GSTM1 and GSTP1 polymorphisms were not statistically related to lung AC, the combination of GSTM1 null and GSTP1 Val was significantly associated with an elevated lung AC risk (OR=2.4, 95% CI 1.1–5.1). [Copyright &y& Elsevier]

Summary Recent evidence suggests that endoplasmic reticulum (ER) tubules mark the sites where the GTPase Drp1 promotes mitochondrial fission via a largely unknown mechanism. Here, we show that the SNARE protein syntaxin 17 (Syn17) is present on raft-like structures of ER-mitochondria contact sites and promotes mitochondrial fission by determining Drp1 localization and activity. The hairpin-like C-terminal hydrophobic domain, including Lys-254, but not the SNARE domain, is important for this regulation. Syn17 also regulates ER Ca 2+ homeostasis and interferes with Rab32-mediated regulation of mitochondrial dynamics. Starvation disrupts the Syn17-Drp1 interaction, thus favoring mitochondrial elongation during autophagy. Because we also demonstrate that Syn17 is an ancient SNARE, our findings suggest that Syn17 is one of the original key regulators for ER-mitochondria contact sites present in the last eukaryotic common ancestor. As such, Syn17 acts as a switch that responds to nutrient conditions and integrates functions for the ER and autophagosomes with mitochondrial dynamics. [ABSTRACT FROM AUTHOR]