Pterostilbene targets the molecular oscillator RORγ to restore circadian rhythm oscillation and protect against sleep restriction induced metabolic disorders.

BACKGROUND: Considerable researches have directed toward metabolic disorders caused by sleep restriction (SR). SR-induced disruption of circadian metabolic rhythmicity is identified as an important pathophysiological mechanism. The flavonoid pterostilbene (PTE) is abundant in the traditional Chinese medicine dragon's blood with protective efficacy against obesity-related metabolic dysfunctions. Our previous study found that PTE ameliorates exercise intolerance and clock gene oscillation in the skeletal muscles subjected to SR. PURPOSE: This study aimed to explore whether PTE improves SR-induced metabolic disorders and delineate the relationship between PTE and the circadian clock. STUDY DESIGN AND METHODS: Two hundred male C57/B6J mice were kept awake for 20 h/d over five consecutive days and concurrently gavaged with 50, 100, or 200 mg/kg·bw/d PTE. Food consumption and body weight were monitored, and the metabolic status of the mice was evaluated by performing OGTT and ITT, measuring the serum lipid profiles and liver histopathology in response to SR. Daily behavior was analyzed by Clocklab™. The circadian rhythms of the liver clock genes and metabolic output genes were evaluated by cosine analysis. Binding between PTE and RORα/γ or NR1D1/2 was investigated by molecular docking. A luciferase reporter assay was used to determine the impact of PTE on Bmal1 transcription in SR-exposed mice co-transfected with Ad-BMAL1-LUC plus Ad-RORγ-mCherry or Ad-NR1D1-EGFP. RESULTS: PTE significantly ameliorated abnormal glucose and lipid metabolism (p < 0.05) in SR-exposed mice. PTE improved circadian behavior (p < 0.05) and rescued the circadian rhythm oscillation of the liver clock (p < 0.05) and metabolic output genes (p < 0.05) under SR condition. Molecular docking disclosed that PTE might interact with RORs, and PTE was found to increase Bmal1 promoter luciferase activity with RORE elements in the presence of Ad-RORγ-mCherry (p < 0.05). CONCLUSIONS: PTE may protect against SR-induced metabolic disorders by directly modulating RORγ to maintain circadian metabolic rhythm. The findings provide valuable insights into the potential use of PTE in the treatment of metabolic disorders associated with disruptions in the circadian rhythm.

Dihydromyricetin Ameliorates Nonalcoholic Fatty Liver Disease by Improving Mitochondrial Respiratory Capacity and Redox Homeostasis Through Modulation of SIRT3 Signaling.

Aims: Our previous clinical trial indicated that the flavonoid dihydromyricetin (DHM) could improve hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD), altough the potential mechanisms of these effects remained elusive. Here, we investigated the hepatoprotective role of DHM on high-fat diet (HFD)-induced NAFLD. Results: DHM supplementation could effectively ameliorate the development of NAFLD by inhibiting hepatic lipid accumulation both in HFD-fed wild-type mice and in palmitic acid-induced hepatocytes. We reveal for the first time that mitochondrial dysfunction characterized by ATP depletion and augmented oxidative stress could be reversed by DHM treatment. Moreover, DHM enhanced the mitochondrial respiratory capacity by increasing the expression and enzymatic activities of mitochondrial complexes and increased mitochondrial reactive oxygen species scavenging by restoring manganese superoxide dismutase (SOD2) activity. Interestingly, the benefits of DHM were abrogated in SIRT3 knockout (SIRT3KO) mice and in hepatocytes transfected with SIRT3 siRNA or treated with an SIRT3-specific inhibitor. We further showed that DHM could increase SIRT3 expression by activating the adenosine monophosphate-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC1α)/estrogen-related receptor-α (ERRα) signaling pathway. Innovation: Our work indicates that SIRT3 plays a critical role in the DHM-mediated beneficial effects that include ameliorating mitochondrial dysfunction and oxidative stress in a nutritional NAFLD model both in vivo and in vitro.Conclusion: Our results suggest that DHM prevents NAFLD by improving mitochondrial respiratory capacity and redox homeostasis in hepatocytes through a SIRT3-dependent mechanism. These results could provide a foundation to identify new DHM-based preventive and therapeutic strategies for NAFLD.

Effect of combined use of a low-carbohydrate, high-protein diet with omega-3 polyunsaturated fatty acid supplementation on glycemic control in newly diagnosed type 2 diabetes: a randomized, double-blind, parallel-controlled trial.

Background: The combined effect of a low-carbohydrate, high-protein (LCHP) diet and omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation on patients with type 2 diabetes (T2D) is not known. Objective: The aim of this study was to evaluate the effect of an LCHP diet combined with ω-3 (LCHP+ω-3) on glycemic control in patients with T2D. Design: In this randomized, double-blind, parallel-controlled trial, 122 newly diagnosed participants with T2D were randomly assigned to receive a high-carbohydrate, low-protein diet with low ω-3 PUFAs [control (CON)], an LCHP, ω-3, or LCHP+ω-3 diet for 12 wk. The ratio of carbohydrate to protein was 42:28 in the LCHP and LCHP+ω-3 diet and 54:17 in the CON and ω-3 diet. The participants were given 6 g fish oil/d (containing 3.65 g docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid/d) in the ω-3 and LCHP+ω-3 diet groups or 6 g corn oil/d (placebo) in the CON and LCHP diet groups. Results: Compared with the CON diet group, greater decreases in glycated hemoglobin (HbA1c) and fasting glucose were observed in all of the other 3 diet groups at 12 wk. Of note, HbA1c reduction in the LCHP+ω-3 diet group (-0.51%; 95% CI: -0.64%, -0.37%) was greater than that in the LCHP (P = 0.03) and ω-3 (P = 0.01) diet groups at 12 wk. In terms of fasting glucose, only the LCHP+ω-3 diet group showed a significant decrease at 4 wk (P = 0.03 compared with CON). Moreover, the reduction in fasting glucose in the LCHP+ω-3 diet group (-1.32 mmol/L; 95% CI: -1.72, -0.93 mmol/L) was greater than that in the LCHP (P = 0.04) and ω-3 (P = 0.03) diet groups at 12 wk. Conclusions: The LCHP+ω-3 diet provided greater effects on HbA1c and fasting glucose and faster effects on fasting glucose than both the LCHP and ω-3 diets, indicating the potential necessity of combining an LCHP diet with ω-3 PUFAs in T2D control. This trial was registered at chictr.org.cn/ as ChiCTR-TRC-14004704.

Equol Attenuates Atherosclerosis in Apolipoprotein E-Deficient Mice by Inhibiting Endoplasmic Reticulum Stress via Activation of Nrf2 in Endothelial Cells.

The development of atherosclerosis is closely related to excessive endoplasmic reticulum stress (ERs). Equol reportedly protects against cardiovascular disease; however, the underlying mechanism for this protection remains unknown. Herein, the mechanisms contributing to the atheroprotective effect of equol were addressed using apolipoprotein E knockout (apoE-/-) mice fed a high-fat diet (HFD) with or without equol. Equol intervention reduced atherosclerotic lesions in the aorta in HFD-fed apoE-/- mice. Plasma lipid analysis showed that equol intervention reduced triglycerides, total cholesterol and LDL-cholesterol and increased HDL-cholesterol. Additionally, equol administration decreased lipid accumulation in the liver. Simultaneously, equol treatment inhibited cell apoptosis induced by t-BHP and thapsigargin in human umbilical vein endothelial cells (HUVECs). Furthermore, equol treatment attenuated palmitate, t-BHP or thapsigargin-induced upregulation of ER stress markers, including p-PERK, p-eIF2α, GRP78, ATF6 and CHOP proteins expression. The same tendency was also observed in aortic lysates in apoE-/- mice fed with equol plus HFD compared with HFD alone. Moreover, equol treatment dose dependently activated the Nrf2 signaling pathway under oxidative stress. Additionally, elevation of Nrf2 induction was found in aortic lysates in apoE-/- mice fed with a HFD diet containing equol compared with a HFD diet without equol. Importantly, Nrf2 siRNA interference induced CHOP and attenuated the effect of equol to inhibit t-BHP mediated CHOP induction, furthermore, abrogated cell apoptosis induced by t-BHP, suggesting a role for Nrf2 in the protective effect of equol in HUVECs. Collectively, these findings implicate that the improvement of atherosclerosis by equol through attenuation of ER stress is mediated, at least in part, by activating the Nrf2 signaling pathway.

Capsaicin-containing chili improved postprandial hyperglycemia, hyperinsulinemia, and fasting lipid disorders in women with gestational diabetes mellitus and lowered the incidence of large-for-gestational-age newborns.

BACKGROUND & AIMS: Gestational diabetes mellitus (GDM) may increase the future health risks of women and their offspring. The aim of this study was to determine the effect of capsaicin supplementation on blood glucose, lipid metabolism and pregnancy outcomes in women with GDM. METHODS: Forty-four pregnant women with GDM at 22-33 gestational weeks were randomly assigned to the capsaicin group (5 mg/d of capsaicin) or to the placebo group (0 mg/d of capsaicin) for 4 weeks in a randomized, double-blind, placebo-controlled trial. The concentrations of fasting plasma glucose and serum insulin, 2-h postprandial plasma glucose (2-h PG) and serum insulin (2-h INS), and fasting serum lipids, liver and kidney function parameters, and calcitonin gene-related peptide (CGRP) were measured at 0 and 4 weeks. The maternal and neonatal outcomes were also recorded. RESULTS: Forty-two women completed the trial. Compared to the placebo group, 2-h PG and 2-h INS concentrations and 2-h postprandial HOMA-IR (2-h HOMA-IR) levels, and the fasting serum total cholesterol and triglycerides concentrations significantly decreased in the capsaicin group after treatment (P < 0.05). Moreover, the fasting serum apolipoprotein B and CGRP concentrations significantly increased in the capsaicin group (P < 0.05). The changes in the 2-h PG and 2-h INS concentrations and in the 2-h HOMA-IR were negatively correlated with the change in the serum CGRP concentration (P < 0.05). Furthermore, the incidence of large-for-gestational-age (LGA) newborns was significantly lower in the capsaicin group than in the placebo group (P = 0.022). CONCLUSIONS: Capsaicin-containing chili supplementation regularly improved postprandial hyperglycemia and hyperinsulinemia as well as fasting lipid metabolic disorders in women with GDM, and it decreased the incidence of LGA newborns.

Fish Oil Supplements Lower Serum Lipids and Glucose in Correlation with a Reduction in Plasma Fibroblast Growth Factor 21 and Prostaglandin E2 in Nonalcoholic Fatty Liver Disease Associated with Hyperlipidemia: A Randomized Clinical Trial.

UNLABELLED: Fish oil has been used effectively in the treatment of cardiovascular disease via triglyceride reduction and inflammation modulation. This study aimed to assess the effects of fish oil on patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. Eighty participants with NAFLD associated with hyperlipidemia were randomly assigned to consume fish oil (n=40, 4 g/d) or corn oil capsules (n=40, 4 g/d) for 3 months in a double-blind, randomized clinical trial. Blood levels of lipids, glucose and insulin, liver enzymes, kidney parameters and cytokines at baseline and the end of the study were measured. Seventy people finished the trial. Plasma concentrations of eicosapentaenoic acid and docosahexaenoic acid significantly increased in the fish oil group after intervention. After adjustment for age, gender and BMI, fish oil significantly decreased fasting serum concentrations of total cholesterol, triglyceride, apolipoprotein B and glucose (by (mean±SD) 0.49±0.43 mmol/L, 0.58±0.89 mmol/L, 0.28±0.33 g/L and 0.76±0.56 mmol/L, respectively, P<0.05), as well as alanine aminotransferase and γ-glutamyl transpeptidase levels (by (median (interquartile)) 9.0(0.5, 21.5) and 7.0(2.2, 20.0) IU/L, respectively, P<0.05), significantly increased serum adiponectin levels (by 1.29±0.62 µg/mL, P<0.001), and reduced serum levels of tumor necrosis factor α, leukotrienes B4, fibroblast growth factor 21 (FGF21), cytokeratin 18 fragment M30 and prostaglandin E2 (by 1.70±1.18 pg/mL, 0.59±0.28 ng/mL, 121±31 pg/mL, 83±60 IU/L and 10.9±2.3 pg/mL, respectively, P<0.001). Corn oil had no effect except for increasing serum creatinine concentrations by 7.7±8.9 µmol/L (P=0.008). The effects of fish oil on lipids, glucose and γ-glutamyl transpeptidase were positively correlated with the reductions of serum FGF21 and prostaglandin E2 concentrations after adjustment for age, gender and BMI (r = 0.275 to 0.360 and 0.261 to 0.375, respectively, P<0.05). In conclusion, our findings suggest that fish oil can benefit metabolic abnormalities associated with NAFLD treatment. TRIAL REGISTRATION: ChiCTR-TRC-12002380.

Dihydromyricetin improves glucose and lipid metabolism and exerts anti-inflammatory effects in nonalcoholic fatty liver disease: A randomized controlled trial.

Ampelopsis grossedentata, a medicinal and edible plant, has been widely used in China for hundreds of years, and dihydromyricetin is the main active ingredient responsible for its various biological actions. We investigated the effects of dihydromyricetin on glucose and lipid metabolism, inflammatory mediators and several biomarkers in nonalcoholic fatty liver disease. In a double-blind clinical trial, sixty adult nonalcoholic fatty liver disease patients were randomly assigned to receive either two dihydromyricetin or two placebo capsules (150 mg) twice daily for three months. The serum levels of alanine, aspartate aminotransferase, γ-glutamyl transpeptidase, glucose, low-density lipoprotein-cholesterol and apolipoprotein B, and the homeostasis model assessment of insulin resistance (HOMA-IR) index were significantly decreased in the dihydromyricetin group compared with the placebo group. In the dihydromyricetin group, the serum levels of tumor necrosis factor-alpha, cytokeratin-18 fragment and fibroblast growth factor 21 were decreased, whereas the levels of serum adiponectin were increased at the end of the study. We conclude that dihydromyricetin supplementation improves glucose and lipid metabolism as well as various biochemical parameters in patients with nonalcoholic fatty liver disease, and the therapeutic effects of dihydromyricetin are likely attributable to improved insulin resistance and decreases in the serum levels of tumor necrosis factor-alpha, cytokeratin-18, and fibroblast growth factor 21.

Resveratrol improves hepatic steatosis by inducing autophagy through the cAMP signaling pathway.

SCOPE: Resveratrol (RSV), a natural polyphenol, has been reported to attenuate nonalcoholic fatty liver disease (NAFLD); however, its underlying mechanism is unclear. Autophagy was recently identified as a critical protective mechanism during NAFLD development. Therefore, we investigated the role of autophagy in the beneficial effects of RSV on hepatic steatosis. METHODS AND RESULTS: Via Oil red O staining, triglyceride, and ß-hydroxybutyrate detection, we found that RSV decreased palmitate-induced lipid accumulation and stimulated fatty acid ß-oxidation in hepatocytes. Based on Western blot assay, confocal microscopy and transmission electron microscopy, we found that RSV induced autophagy in hepatocytes, whereas autophagy inhibition markedly abolished RSV-mediated hepatic steatosis improvement. Moreover, RSV increased cAMP levels and the levels of SIRT1 (sirtuin 1), pPRKA (phosphorylated protein kinase A), and pAMPK (phosphorylated AMP-activated protein kinase), as well as SIRT1 activity in HepG2 cells. Incubation with inhibitors of AC (adenylyl cyclase), PRKA, AMPK, SIRT1, or with AC, PRKA, AMPK, or SIRT1 siRNA abolished RSV-mediated autophagy. Similar results were obtained in mice with hepatic steatosis. CONCLUSION: RSV improved hepatic steatosis partially by inducing autophagy via the cAMP-PRKA-AMPK-SIRT1 signaling pathway, which provides new evidence regarding RSV's effects on NAFLD treatment.

Activation of nuclear factor erythroid 2-related factor 2 and PPARγ plays a role in the genistein-mediated attenuation of oxidative stress-induced endothelial cell injury.

We investigate the cytoprotective effects and the molecular mechanism of genistein in oxidative stress-induced injury using an endothelial cell line (EA.hy926). An oxidative stress model was established by incubating endothelial cells with H2O2. According to the present results, genistein pretreatment protected endothelial cells against H2O2-induced decreases in cell viability and increases in apoptosis. Genistein also prevented the inhibition of B-cell lymphoma 2 and the activation of caspase-3 induced by H2O2. Genistein increased superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels and attenuated the decrease in these antioxidants during oxidative stress. We also found that genistein induced the promoter activity of both nuclear factor erythroid 2-related factor 2 (Nrf2) and PPARγ. Additionally, genistein induced the nuclear translocation of Nrf2 and PPARγ. While genistein caused the up-regulation of both Nrf2 and PPARγ, it also activated and up-regulated the protein expression and transcription of a downstream protein, haem oxygenase-1 (HO-1). Moreover, the use of Nrf2 small interfering RNA transfection and HO-1- or PPARγ-specific antagonists (Znpp and GW9662, respectively) blocked the protective effects of genistein on endothelial cell viability during oxidative stress. Therefore, we conclude that oxidative stress-induced endothelial cell injury can be attenuated by treatment with genistein, which functions via the regulation of the Nrf2 and PPARγ signalling pathway. Additionally, the endogenous antioxidants SOD, CAT and GSH appear to play a role in the antioxidant activity of genistein. The present findings suggest that the beneficial effects of genistein involving the activation of cytoprotective antioxidant genes may represent a novel strategy in the prevention and treatment of cardiovascular endothelial damage.

Effects of taurine on glial cells apoptosis and taurine transporter expression in retina under diabetic conditions.

Taurine, a ß-aminosulfonic acid, has been reported to reduce the risk of a number of diseases, including cardiovascular disease, diabetes, and also perhaps to reduce neurodegeneration in the elderly. The transport of taurine is known to be mediated by taurine transporter (TauT). The purpose of this study is to examine the effects of taurine on glial cells apoptosis and on TauT expression in retina of diabetic rats and retinal glial cells cultured with high glucose. TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining analysis showed that the number of TUNEL-positive cells in taurine treated diabetic rats was significantly lower than those of untreated diabetic rats over the 8-, and 12-week time courses, respectively (all P < 0.001). No TUNEL-positive cells were observed in retina of control groups and taurine treated control groups. In cultured retinal glial cells, the apoptosis in high glucose-treated cells was significantly increased vs the control. When the cells were incubated with high glucose and taurine at 0.1, 1.0 and 10 mmol/l, the percentage of apoptosis was significantly decreased to 16.4, 5.7 and 7.6% respectively (all P < 0.05). With supplementation of taurine in diet and culture medium, higher expression of TauT in retina of diabetic rats and cultured retinal glial cells under diabetic conditions were detected by western-blotting (P < 0.05). Taken together, our data suggest that diabetes or high glucose induced retinal glial cells apoptosis can be inhibited by taurine, and that taurine reverses the diabetes-induced or high glucose-induced decrease in TauT expression.

Dietary taurine supplementation prevents glial alterations in retina of diabetic rats.

The preventive effect of dietary taurine supplementation on glial alterations in retina of streptozotocin-induced diabetic rats was examined in this study. Blood glucose content, content of taurine, glutamate and -amino butyric acid (GABA) and expression of glial fibrillary acid protein (GFAP), vascular endothelial growth factor (VEGF), glutamate transporter (GLAST), glutamine synthetase (GS) and glutamate decarboxylase (GAD) in retina were determined in diabetic rats fed without or with 5% taurine in a controlled trial lasting 12 weeks, with normal rats fed without or with 5% taurine served as controls. Dietary taurine supplementation could not lower glucose concentration in blood (P > 0.05), but caused an elevation of taurine content and a decline in levels of glutamate and GABA in retina of diabetic rats (P < 0.05). The content of GABA in normal control group was not altered by taurine supplementation. With supplementation of taurine in diet, lower expression of GFAP and VEGF while higher expression of GLAST, GS and GAD in retina of diabetic rats were determinated by RT-PCR, Western-blotting and immunofluorescence (P < 0.05). GFAP, VEGF, GLAST, GS and GAD expressions in normal controls were not altered by taurine treatment. This may have prospective implications of using taurine to treat complications in diabetic retinopathy.

Effects of different dietary fatty acids on the fatty acid compositions and the expression of lipid metabolic-related genes in mammary tumor tissues of rats.

In this study, the effects of dietary fatty acids on the fatty acid compositions and lipid metabolic-related genes expression in N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinogenesis were evaluated. The 50-day-old female Sprague-Dawley rats were intervened by different dietary fats (15% wt/wt), including saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n-6 polyunsaturated fatty acid (PUFA), n-3 PUFA, 1:1 n-6/n-3, 5:1 n-6/n-3, 10:1 n-6/n-3, and 1:2:1 S/M/P (1:1 n-6/n-3), alone or in combination with MNU. There was no mammary tumor occurrence in the control and MNU-treated n-3 PUFA groups after 18 wk. n-3 PUFA diet retarded the weight growth of rats. 1:1 n-6/n-3 diet significantly reduced the MNU-induced tumor incidence and tumor multiplicity compared with SFA, MUFA, n-6 PUFA, 5:1 n-6/n-3, 10:1 n-6/n-3 and 1:2:1 S/M/P diets (42.86% vs. 83.33%-92.31%, 0.79 vs. 2.62-2.85, P < 0.01). Additionally, 1:1 n-6/n-3 diet substantially increased cis-5,8,11,14,17-eicosapentaenoic acid and cis-4,7,10,13,16,19-docosahexaenoic acid levels, whereas it decreased C20:4 level and the mRNA expressions of fatty acid synthase, Cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) in mammary tissues (P < 0.05). These results suggest that 1:1 n-6/n-3 in the diet is effective in the prevention of mammary tumor development by increasing the n-3 PUFA content and reducing the expression of lipid metabolic-related genes.

Dietary taurine supplementation ameliorates diabetic retinopathy via anti-excitotoxicity of glutamate in streptozotocin-induced Sprague-Dawley rats.

The purpose of this study was to investigate whether taurine ameliorate the diabetic retinopathy, and to further explore the underlying mechanisms. The Sprague-Dawley rats were injected with streptozotocin to establish experimental diabetic model, then fed without or with 1.2% taurine for additional 4-12 weeks. After that, the protective effects of dietary taurine supplementation on diabetic retinopathy were estimated. Our results showed that chronic taurine supplement effectively improved diabetic retinopathy as changes of histopathology and ultrastructure. The supplementation could not lower plasma glucose concentration (P > 0.05), but caused an elevation in taurine content and a decline in levels of glutamate and gamma-aminobutyric acid (GABA) in diabetic retina (P < 0.05). Moreover, chronic taurine supplementation increased glutamate transporter (GLAST) expression (P < 0.05), decreased intermediate filament glial fibrillary acidic protein (GFAP) and N-methyl-D: -aspartate receptor subunit 1 (NR1) expression in diabetic retina (P < 0.05). These results demonstrated that chronic taurine supplementation ameliorates diabetic retinopathy via anti-excitotoxicity of glutamate in rats.

[Role of Rho GTPase in inhibiting metastatic ability of human prostate cancer cell line PC-3 by omega-3 polyunsaturated fatty acid].

BACKGROUND & OBJECTIVE: Recently, researches refer to the influence of polyunsaturated fatty acid (PUFA) on cancer initiation and progression had been highly concerned. This study was to investigate the effects of 2 kinds of omega-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the metastatic ability of human prostate cancer cell line PC-3, and explore the role of Rho GTPase in inhibiting cancer metastasis by omega-3 PUFA. METHODS: MTT assay was used to determine the effects of omega-3 PUFA on the proliferation of PC-3 cells. Adhesion assay, invasion assay, and migration assay were used to observe the effects of omega-3 PUFA on the metastatic ability of PC-3 cells. Western blot was used to observe the effects of omega-3 PUFA on the expression of RhoA, Rac1, Rac2, and Cdc42 proteins in PC-3 cells. Laser confocal microscopy was used to investigate the effect of omega-3 PUFA on the reorganization of the microfilaments and microtubules marked by immunofluorescent cytochemistry technology. RESULTS: Both EPA and DHA inhibited the proliferation of PC-3 cells, and the proliferation inhibition rate increased along with the increase of the concentration and treatment time. When treated with 60 mumol/L EPA or DHA for 48 h, the abilities of adhesion, invasion and migration of PC-3 cells were inhibited (P<0.05). omega-3 PUFA significantly suppressed the expression of Rac1, Rac2 and Cdc42 proteins (P<0.05), influenced the distribution and structure of sytoskeletons. CONCLUSION: omega-3 PUFA could inhibit the metastatic ability of PC-3 cells through down-regulating the expression of Rho GTPase and inhibiting the cytoskeleton reorganization.

Dietary taurine reduces retinal damage produced by photochemical stress via antioxidant and anti-apoptotic mechanisms in Sprague-Dawley rats.

Taurine has been shown to be tissue protective in many models of oxidant-induced injury. However, its protective role against retinal damage induced by photochemical stress is less well known. The purpose of the present study was to investigate whether dietary taurine reduced retinal photochemical damage in Sprague-Dawley rats and to further explore the underlying molecular mechanisms of this action. Twenty rats fed AIN-93 formulation and maintained in the dark for 48 h were used as controls (n 20). Another forty rats were randomly divided into two groups and then treated with (n 20) or without 4 % taurine (n 20) for 15 d respectively. After treatment, these two groups were exposed to fluorescent light (3000 +/- 200 lux and 25 degrees C), and the protective effects of dietary taurine were then evaluated. The present results showed that dietary taurine effectively prevented retinal photochemical damage as assessed by changes of morphology. Also, the supplementation caused an increase of taurine in the retina, a decrease of malondialdehyde (P < 0.01), and elevation of superoxide dismutase (P < 0.01) and glutathione peroxidase activities in the retina (P < 0.01). Moreover, dietary taurine inhibited activator protein-1 (AP-1) (c-fos/c-jun subunits) expression (P < 0.05), up regulated NF-kappaB (p65) expression (P < 0.05), and decreased caspase-1 expression (P < 0.05) so as to reduce the apoptosis of photoreceptors in the retina (P < 0.05). These results suggest that dietary taurine reduced retinal damage produced by photochemical stress via antioxidant and anti-AP-1-NF-kappaB-caspase-1 apoptotic mechanisms in rats.