ω-3PUFA及其诱导的外源性跨膜型TNFα对肿瘤细胞生长的影响

目的:探讨ω-3多不饱和脂肪酸(ω-3PUFA)及其诱导的外源性跨膜型TNFα对肿瘤细胞增殖和凋亡的影响。方法:将ω-3PUFA可调控的跨膜型TNFα真核表达载体转导入HL-60和MCF-7细胞,免疫荧光细胞化学方法检测ω-3PUFA对转染细胞外源基因表达的调控,生长曲线、流式细胞和DNA梯形带分析检测ω-3PUFA对转染细胞增殖能力和凋亡的影响。结果:在6.0×10-5mol/Lω-3PUFA诱导下转染细胞外源性跨膜型TNFα表达增加。HL-60和MCF-7细胞经6.0×10-5mol/Lω-3PUFA处理后增殖能力减弱,但只有HL-60细胞周期阻滞于G0/G1期及形成DNA梯形带。经ω-3PUFA处理后,以上变化在HL-60和MCF-7转染细胞中均更为显著。结论:ω-3PUFA诱导的外源性跨膜型TNFα基因产物可以增强ω-3多不饱和脂肪酸的抗肿瘤能力,而诱导细胞凋亡可能是其中重要机制之一。     

Dietary (n-3) long-chain polyunsaturated fatty acids inhibit ischemia and reperfusion arrhythmias and infarction in rat heart not enhanced by ischemic preconditioning

Ischemic preconditioning (IPC) and (n-3) PUFA are both cardioprotective. This study compared effects of dietary fish oil, IPC, and their interactions on heart function and injury during myocardial ischemia and reperfusion. Male Wistar rats were fed diets containing 10% wt:wt fat comprising either 7% high-docosahexaenoic acid (DHA) [22:6(n-3)] tuna fish oil + 3% olive oil [(n-3) PUFA]; 5% sunflower seed oil + 5% olive oil [(n-6) PUFA]; or 7% beef tallow + 3% olive oil [saturated fat (SF)] for 6 wk. In control experiments, isolated perfused hearts were subjected to 30-min regional ischemia and reperfused for 120 min. The IPC hearts were subjected to 3 cycles of 5-min global ischemia before the ischemia and reperfusion. Control (n-3) PUFA hearts had significantly lower heart rate, coronary flow, end diastolic pressure, maximum relaxation rate, and ischemic and reperfusion arrhythmias. In reperfusion, they had greater developed pressure and maximum relaxation rate and smaller infarct (10.9 +/- 0.6% ischemic zone, n = 6) than (n-6) PUFA (47.4 +/- 0.3%, n = 6) or SF (50.3 +/- 0.3%, n = 6). Compared with control, IPC significantly improved heart function and reduced infarct in (n-6) PUFA (11.8 +/- 0.4%, n = 6) and SF hearts (13.1 +/- 0.1%, n = 6). Heart function and infarct [(n-3) PUFA 9.6 +/- 0.1%, n = 6] did not differ among dietary IPC groups. Arrhythmias, significantly reduced by IPC in (n-6) PUFA and SF hearts, were significantly lower in (n-3) PUFA IPC hearts. Dietary fish oil induces a form of preconditioning, nutritional preconditioning, limiting ischemic cardiac injury, and myocardial infarction and endows cardioprotection as powerful as IPC, which provides no additional protection in (n-3) PUFA hearts.     

Similarities and differences between the effects of EPA and DHA on markers of atherosclerosis in human subjects

We have reviewed effects of long chain (LC) n-3 PUFA on markers of atherosclerosis in human subjects with a focus on individual effects of EPA and DHA. Initial results from epidemiological studies suggested that LC n-3 PUFA from fish oils (FO) reduced incidence of CVD; those results have been confirmed in interventional studies. Dietary intervention with n-3 PUFA decreased fasting and postprandial TAG, number of remnant-like chylomicron particles, large VLDL, and total and small dense LDL particles. It increased mean size of LDL particles by increasing number of large and decreasing those of small dense particles. With some exceptions, n-3 PUFA decreased blood pressure (BP) and heart rate (HR), flow-mediated dilation (FMD) and plasma concentrations of inflammatory markers. n-3 PUFA also decreased circulating adhesion molecules and intima-media thickness (IMT) in some but not other studies. For IMT, results varied with the sex and artery being examined. EPA effects on FMD are endothelial cell dependent, while those of DHA seem to be endothelial cell independent. Individually, both EPA and DHA decreased TAG and inflammatory markers, but only DHA decreased HR, BP and number of small dense LDL particles. Results varied because of dose and duration of n-3 PUFA, EPA:DHA, health status of subjects and other reasons. Future studies are needed to determine optimal doses of EPA and DHA individually, their synergistic, additive or antagonistic effects, and to understand underlying mechanisms. In conclusion, n-3 PUFA decreased several risk factors for atherosclerosis without any serious adverse effects.     

Chlorpyrifos affects phenotypic outcomes in a model of mammalian neurodevelopment: critical stages targeting differentiation in PC12 cells

The organophosphate insecticide chlorpyrifos (CPF) adversely affects mammalian brain development through multiple mechanisms. To determine if CPF directly affects neuronal cell replication and phenotypic fate, and to identify the vulnerable stages of differentiation, we exposed PC12 cells, a model for mammalian neurodevelopment, to CPF concentrations spanning the threshold for cholinesterase inhibition (5-50 microM) and conducted evaluations during mitosis and in early and mid-differentiation. In undifferentiated cells, exposure to 5 microM CPF for 1-3 days reduced DNA synthesis significantly without eliciting cytotoxicity. At the same time, CPF increased the expression of tyrosine hydroxylase (TH), the enzymatic marker for the catecholamine phenotype, without affecting choline acetyltransferase (ChAT), the corresponding marker for the cholinergic phenotype. Upon exposure to nerve growth factor (NGF), PC12 cells developed neuritic projections in association with vastly increased TH and ChAT expression accompanying differentiation into the two phenotypes. CPF exposure begun at the start of differentiation significantly reduced ChAT but not TH activity. In contrast, when CPF was added in mid-differentiation (4 days of NGF pretreatment), ChAT was unaffected and TH was increased slightly. Thus, CPF exerts stage-specific effects, reducing DNA synthesis in the undifferentiated state, impairing development of the cholinergic phenotype at the start of differentiation, and promoting expression of the catecholaminergic phenotype both in undifferentiated and differentiated cells. CPF administration in vivo produces deficits in the number of neurons and cholinergic function, and because we were able to reproduce these effects in vitro, our results suggest that CPF directly influences the phenotypic fate of neuronal precursors.     

Translational research with progesterone receptor modulator motivated by the use of levonorgestrel-releasing intrauterine system

The use of levonorgestrel-releasing intrauterine system (LNG-IUS) is effective for management of menorrhagic women with uterine myomas because of reduction in menorrhagia. However, the size of myomas during use of LNG-IUS increased in some but decreased in other instances. This prompted us to characterize the effects of progesterone (P4) on cultured leiomyoma cell growth. Treatment with P4 resulted in increase in epidermal growth factor (EGF) expression in cultured leiomyoma cells, whereas treatment with E2 augmented EGF-R expression in those cells. This indicates that P4 and E2 act in combination to stimulate myoma growth through induction of EGF/EGF-R expression. Bcl-2 expression in leiomyoma cells was up-regulated by P4. Furthermore, P4 augmented proliferating cell nuclear antigen expression in cultured leiomyoma cells but not in cultured normal myometrial cells. This fact let us to examine the effects of progesterone receptor modulator (PRM) on leiomyoma cell proliferation and apoptosis in comparison with normal myometrial cells. Our studies revealed that CDB-2914 inhibits the proliferation, stimulates apoptosis of cultured leiomyoma cells, and inhibits the expression of angiogenic factors (vascular endothelial growth factor and adrenomedullin) and their receptors in cultured leimyoma cells, without affecting those in cultured normal myometrial cells. We then evaluated the effects of CDB-2914 on extracellular matrix (ECM) components in cultured leiomyoma cells. CDB-2914 increased ECM metalloproteinase inducer, matrix metalloproteinase (MMP)-1, MMP-8 contents and decreased tissue inhibitors of MMP (TIMP)-1, TIMP-2 contents as well as type I and type III collagen contents in cultured leiomyoma cells, without comparable effects on cultured normal myometrial cells. These findings demonstrate that PRM not only inhibits the proliferation and stimulates apoptosis of cultured leiomyoma cells but also suppresses collagen synthesis in a cell-type specific manner. This is meaningful for understanding the molecular mechanism of the usefulness of PRM in the treatment of uterine fibroids.     

(n-3) Polyunsaturated fatty acids promote activation-induced cell death in murine T lymphocytes

Previous studies showing dietary (n-3) polyunsaturated fatty acids (PUFA) attenuate T cell immune-mediated inflammatory diseases led us to hypothesize that (n-3) PUFA promote activation-induced cell death (AICD) in T cells. Because T cell subsets display a differential resistance to AICD, we compared the effects of (n-3) PUFA feeding on T cells stimulated in vitro to express different cytokine profiles. Mice were fed either diets lacking (n-3) PUFA (control) or (n-3) PUFA-containing diets for 14 d. Splenic T cells were stimulated with alphaCD3/alphaCD28, phorbol myristate acetate (PMA)/Ionomycin or alphaCD3/PMA for 48 h, followed by reactivation with the same stimuli for 5 h. Apoptosis was measured using Annexin V/propidium iodide. (n-3) PUFA were selectively incorporated into membrane phospholipid pools. Cytokine analyses revealed that (n-3) PUFA enhanced AICD only in T cells expressing a T helper cell (Th)1-like cytokine profile after stimulation with PMA/Ionomycin compared to mice fed the (n-6) PUFA control diet (P = 0.0008). In contrast, no increase in apoptosis was seen in T cells stimulated with alphaCD3/PMA, which exhibited a Th2 cytokine profile. These data demonstrate that the ability of (n-3) PUFA to promote AICD is dependent on the activation stimulus. In conclusion, we have identified a novel mechanism by which (n-3) PUFA modulate T cell-mediated immunity by selective deletion of Th1-like cells while maintaining or enhancing the Th2-mediated humoral immune response.     

The effect of n - 3 PUFA/gamma-cyclodextrin complex on serum lipids in healthy volunteers--a randomized, placebo-controlled, double-blind trial

OBJECTIVES: This study was carried out to examine whether serum triglyceride concentrations were decreased by administration of n-3 polyunsaturated fatty acid (PUFA)/gamma-cyclodextrin (gamma-CD) complex-containing capsules as reported previously with n-3PUFA without gamma-CD. STUDY DESIGN: A placebo-controlled double-blind study with healthy subjects (n=35) and hypertriglyceridemic subjects (n=7) of 35-66 years of age was performed. The subjects were randomized to a group (n-3 group) supplemented with n-3PUFA/gamma-CD-containing capsules (660 mg EPA + 280 mg DHA/day) or a control group supplemented with capsules containing essentially no n-3 PUFA for 8 weeks with stratification by sex, age, and serum triglyceride levels in a double blind manner. Fasting blood samples were obtained at the start of administration and 4 and 8 weeks afterward. RESULTS: EPA concentrations in the total phospholipid fraction of red blood cells increased significantly in all subjects in the n-3 group, whereas no changes were seen in the control group. Triglyceride levels were significantly decreased (-17%) in the n-3 group compared with the control group at week 8. The following serum lipids did not significantly change over time: total-cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol. Only two subjects in the n-3 group guessed at the end of the study that their capsules were active. CONCLUSION: n-3 PUFA/gamma-CD complex lowered triglyceride levels in normal and slightly hypertriglyceridemic subjects. There was a possibility that gamma-CD might at least partly cover the smell and aftertaste of fish oil.     

Insulin-like growth factor-1 attenuates apoptosis and protects neurochemical phenotypes of dorsal root ganglion neurons with paclitaxel-induced neurotoxicity in vitro

Paclitaxel (PT)-induced neurotoxicity is a significant problem associated with successful treatment of cancers. Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays an important role in promoting axonal growth from dorsal root ganglion (DRG) neurons. Whether IGF-1 has protective effects on neurite growth, cell viability, neuronal apoptosis and neuronal phenotypes in DRG neurons with PT-induced neurotoxicity is still unclear. In this study, primary cultured rat DRG neurons were used to assess the effects of IGF-1 on DRG neurons with PT-induced neurotoxicity. The results showed that PT exposure caused neurite retraction in a dose-dependent manner. PT exposure caused a decrease of cell viability and an increase in the ratio of apoptotic cells which could be reversed by IGF-1. The percentage of calcitonin gene-related peptide immunoreactive (CGRP-IR) neurons and neurofilament (NF)-200-IR neurons, mRNA, and protein levels of CGRP and NF-200 decreased significantly after treatment with PT. IGF-1 administration had protective effects on CGRP-IR neurons, but not on NF-200-IR neurons. Either extracellular signal-regulated protein kinase (ERK1/2) inhibitor PD98059 or phosphatidylinositol 3-kinase (PI3 K) inhibitor LY294002 blocked the effect of IGF-1. The results imply that IGF-1 may attenuate apoptosis to improve neuronal cell viability and promote neurite growth of DRG neurons with PT-induced neurotoxicity. Moreover, these results support an important neuroprotective role of exogenous IGF-1 on distinct subpopulations of DRG neurons which is responsible for skin sensation. The effects of IGF-1 might be through ERK1/2 or PI3 K/Akt signaling pathways. These findings provide experimental evidence for IGF-1 administration to alleviate neurotoxicity of distinct subpopulations of DRG neurons induced by PT.     

维生素C对神经元细胞生长的时间剂量效应

目的研究不同处理时间和不同剂量的维生素C(VC)对神经元细胞生长的影响。方法体外原代培养的新生SD乳鼠大脑皮层神经元细胞,在细胞生活的不同时间(D1、D4、D7、D14)加入不同浓度的VC(0～800μmol/L)共培养,用MTT法检测细胞存活率,并选取D7加入VC共培养的细胞作后续研究,观察VC对神经元细胞的突起数目、长度、胞体面积和长轴长度的影响。结果MTT结果显示:D1加入VC,800μmol/L处理组使细胞存活率降低;D4或D14加入VC,400μmol/L处理组使细胞存活率提高,而800μmol/L处理组使细胞存活率降低;D7加入VC,200、400μmol/L组的MTT值明显高于对照组,800μmol/L组的MTT值低于对照组。进一步观察发现,在D7加入VC,无论浓度如何,对细胞突起的数目无明显影响;而200、400、800μmol/L处理组能使突起长度、细胞胞体面积和长轴长度较对照组显著增高,作两两比较,400μmol/L组高于其他组。结论在细胞生长的D7加入400μmol/L的VC,其对神经元细胞的生长有明显的促进作用。     

Comparison of n-3 polyunsaturated fatty acid contents of wild and cultured Australian abalone

The fatty acid contents of wild and cultured Australian adult blacklip abalone, Haliotis rubra, were analysed by gas liquid chromatography. Wild abalone contained significantly higher levels of total n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3) and alpha-linolenic acid (18:3n-3) than cultured abalone (P<0.05). The predominant n-3 PUFA was docosapentaenoic acid in wild abalone, while in cultured abalone a high level of eicosapentaenoic acid was found. The concentration of docosahexaenoic acid (22:6n-3) was low in both wild and cultured abalone, and cultured abalone had a significantly higher percentage composition of this fatty acid than wild abalone (P<0.01). Significantly higher levels of arachidonic acid (20:4n-6), 22:2n-6, 22:4n-6 and total n-6 PUFA were also found in wild abalone than in cultured animals (P<0.05). The ratio of n-3 PUFA to n-6 PUFA was the same in wild and cultured abalone. Manipulation of nutrient sources of cultured abalone may influence their lipid composition. Consumption of either wild or cultured abalone will contribute to dietary n-3 PUFA intake, with benefits to human health.     

不同膳食脂肪酸对大鼠乳腺癌细胞核受体基因表达的影响

目的 探讨核受体基因表达在不同膳食脂肪酸影响大鼠乳腺癌发生中的作用。方法用8种不同膳食脂肪酸（饱和脂肪酸、单不饱和脂肪酸、n-6多不饱和脂肪酸、n-3多不饱和脂肪酸、1：1n-6／n-3多不饱和脂肪酸、5：1n-6／n-3多不饱和脂肪酸、10：1n-6／n-3多不饱和脂肪酸、1：2：1饱和脂肪酸／单不饱和脂肪酸／多不饱和脂肪酸其中n-6／n-3多不饱和脂肪酸1：1）喂养SD雌性幼年大鼠,采用50mg／kg的甲基亚硝基脲单次腹腔注射诱导大鼠乳腺癌发生,电镜观察大鼠乳腺细胞结构变化,BrdU体内标记法检测大鼠乳腺细胞增殖活性,RT—PCR分析乳腺组织过氧化物酶增殖活化受体（PPARβ和PPARγ）mRNA表达。结果 无乳腺癌诱发的各对照和n-3多不饱和脂肪酸诱癌组大鼠乳腺细胞超微结构正常,细胞增殖活性低。而有大鼠乳腺癌诱发的组织细胞内可见明显的腺癌标志,且高乳腺癌诱发的饱和脂肪酸、单不饱和脂肪酸、n-6多不饱和脂肪酸、5：1n-6／n-3多不饱和脂肪酸、10：1n-6／n-3多不饱和脂肪酸和1：2：1饱和脂肪酸／单不饱和脂肪酸／多不饱和脂肪酸喂养组大鼠乳腺细胞增殖活性升高（BrdU阳性率为21％～22％）,但1：1n-6／n-3多不饱和脂肪酸低诱癌组乳腺细胞增殖活性明显降低上述高乳腺癌诱发组（BrdU阳性率为13％,P〈0．05）。此外,过氧化物酶增殖活化受体作为与脂代谢密切相关的细胞核受体基因,1：1n-6／n-3多不饱和脂肪酸低诱癌组较相应对照组上调PPARβ和PPARγ mRNA表达力度明显弱于高乳腺癌诱发组。结论 不同膳食脂肪酸对PPAR基因表达的调节截然不同,这可能是差异性调节大鼠乳腺癌发生的分子机制之一。     

Effects of beryllium chloride on cultured cells

The effects of beryllium on cultured cells were investigated. Three cell-lines (HeLa-S3, Vero, HEL-R66) were used in these experiments and they were cultured in Eagle's MEM plus 5 or 10% FBS (Fetal Bovine Serum) containing beryllium in various concentrations. HeLa cells or Vero cells were able to grow in the medium with 10 micrograms Be/ml (1.1 mM). On the other hand, the growth of HEL cells were strongly inhibited, even when cultured in the medium with 1 microgram Be/ml (1.1 X 10(-1) mM) and the number of living cells showed markedly low level as compared to that of the control samples cultured in the medium without beryllium. The cytotoxic effects of beryllium on these cells, which were cultured for three days in the medium with beryllium, were observed. None of cytotoxic effects were found on HeLa cells cultured with 0.5 micrograms/ml (5.5 X 10(-2) mM) and on Vero cells cultured with 0.05 micrograms Be/ml (5.5 X 10(-3) mM), while HEL cells received cytotoxic effects even when cultured in the medium containing 0.05 micrograms Be/ml (5.5 X 10(-3) mM), and these effects on the cells appeared strong when cultured in the medium without FBS. It was revealed from these experiments that HEL cells are very sensitive in terms of toxic effects of beryllium. Therefore, there cells can be used for the toxicological study on low level concentrations of the metal.     

An enhanced apoptosis and a reduced angiogenesis are associated with the inhibition of lung colonisation in animals fed an n-3 polyunsaturated fatty acid-rich diet injected with a highly metastatic murine melanoma line

Both epidemiological and experimental studies indicate that dietary n-3 PUFA inhibit carcinogenesis and tumour growth. Metastatic diffusion has also been found to be affected in animals fed diets containing purified n-3 PUFA or fish oil. In the present study, we investigated whether the metastatic diffusion of a highly metastatic variant (F10-SR cells) isolated from the B16 melanoma F10 line was affected by feeding host animals a diet containing 5 % fish oil. In these animals, compared with those fed a diet containing 5 % maize oil, there was a reduced number of metastatic pulmonary colonies. The immunohistochemical analysis of appropriate markers revealed that the antimetastatic effect of dietary n-3 PUFA was not related to a reduction of proliferation, but rather to an enhanced apoptotic activity. The reduction of von Willebrand factor immunoreactivity found in pulmonary colonies of F10-SR cells grown in fish oil-fed animals indicates that a decrease of angiogenesis contributes to the antimetastatic effect of dietary n-3 PUFA. This conclusion stands in spite of the higher expression of vascular endothelial growth factor observed in pulmonary colonies grown in fish oil-fed animals.     

Omega 3 polyunsaturated fatty acids and body weight

In animal studies, n-3 PUFA have been shown to influence body composition and to reduce the accumulation of body fat, thereby affecting body weight homeostasis. In addition, it has been suggested that an additional supply of n-3 PUFA during pregnancy or lactation, or both, would have a beneficial effect on birth weight and infant growth and development. The purpose of the present study was to systematically review interventional clinical trials on the effects of dietary n-3 PUFA supplementation on body weight in adult subjects and in infants whose mothers were supplemented with these fatty acids during pregnancy and/or lactation. A systematic search, focused on n-3 PUFA and body weight, and limited to controlled clinical trials, was performed in different databases. The quality of all included studies was assessed against set criteria, and results of eligible trials were compared. There were few studies targeting this topic. In adults, all of the five studies included, except for one, show no change in body weight by dietary supplementation with n-3 PUFA. Within those trials conducted in pregnant and/or lactating women in which a main outcome was birth weight or growth in infancy, two showed a modest increase in birth weight and the rest showed no effect. None of the trials showed an effect of maternal n-3 PUFA supplementation on infant's weight at the short term. However, it should be noted that a number of limitations, including a variety of experimental designs, type and doses of n-3 PUFA, and high attrition rates, among others, make impossible to draw robust conclusions from this review.     

Comparison of n-3 polyunsaturated fatty acid contents of wild and cultured Australian abalone

The fatty acid contents of wild and cultured Australian adult blacklip abalone, Haliotis rubra, were analysed by gas liquid chromatography. Wild abalone contained significantly higher levels of total n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3) and α-linolenic acid (18:3n-3) than cultured abalone (P<0.05). The predominant n-3 PUFA was docosapentaenoic acid in wild abalone, while in cultured abalone a high level of eicosapentaenoic acid was found. The concentration of docosahexaenoic acid (22:6n-3) was low in both wild and cultured abalone, and cultured abalone had a significantly higher percentage composition of this fatty acid than wild abalone (P<0.01). Significantly higher levels of arachidonic acid (20:4n-6), 22:2n-6, 22:4n-6 and total n-6 PUFA were also found in wild abalone than in cultured animals (P<0.05). The ratio of n-3 PUFA to n-6 PUFA was the same in wild and cultured abalone. Manipulation of nutrient sources of cultured abalone may influence their lipid composition. Consumption of either wild or cultured abalone will contribute to dietary n-3 PUFA intake, with benefits to human health.     

Membrane raft organization is more sensitive to disruption by (n-3) PUFA than nonraft organization in EL4 and B cells

Model membrane and cellular detergent extraction studies show (n-3) PUFA predominately incorporate into nonrafts; thus, we hypothesized (n-3) PUFA could disrupt nonraft organization. The first objective of this study was to determine whether (n-3) PUFA disrupted nonrafts of EL4 cells, an extension of our previous work in which we discovered an (n-3) PUFA diminished raft clustering. EPA or DHA treatment of EL4 cells increased plasma membrane accumulation of the nonraft probe 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate by ~50-70% relative to a BSA control. F?rster resonance energy transfer imaging showed EPA and DHA also disrupted EL4 nanometer scale nonraft organization by increasing the distance between nonraft molecules by ~25% compared with BSA. However, changes in nonrafts were due to an increase in cell size; under conditions where EPA or DHA did not increase cell size, nonraft organization was unaffected. We next translated findings on EL4 cells by testing if (n-3) PUFA administered to mice disrupted nonrafts and rafts. Imaging of B cells isolated from mice fed low- or high-fat (HF) (n-3) PUFA diets showed no change in nonraft organization compared with a control diet (CD). However, confocal microscopy revealed the HF (n-3) PUFA diet disrupted lipid raft clustering and size by ~40% relative to CD. Taken together, our data from 2 different model systems suggest (n-3) PUFA have limited effects on nonrafts. The ex vivo data, which confirm previous studies with EL4 cells, provide evidence that (n-3) PUFA consumed through the diet disrupt B cell lipid raft clustering.     

维生素C对海马神经细胞生长影响的研究

本研究用新生大鼠脑海马区细胞进行体外培养，观察不同浓度（１０－３～１０－６ｍｏｌ／Ｌ）维生素Ｃ（ＶＣ）对海马细胞生长的影响。结果表明，培养１４天的细胞存活数在１０－６ｍｏｌ／Ｌ和１０－５ｍｏｌ／ＬＶＣ组与对照组（培养液中不加ＶＣ）之间无明显差别，１０－４ｍｏｌ／ＬＶＣ组明显高于对照组，而１０－３ｍｏｌ／ＬＶＣ组存活细胞很少。进一步观察可见１０－４ｍｏｌ／ＬＶＣ组细胞突起数目、长度、胞体面积和周长均高于对照组（Ｐ＜０．０５），细胞总蛋白相对含量明显增加。结果提示，１０－４ｍｏｌ／ＬＶＣ对体外培养海马神经细胞的生长有一定促进作用。     

PPARgamma1 as a molecular target of eicosapentaenoic acid in human colon cancer (HT-29) cells

Diets high in (n-3) PUFA decrease colon cancer development and suppress colon tumor growth, but the molecular mechanism through which these compounds act is largely unknown. We sought to determine whether PPARgamma1 serves as a molecular link between the physiological actions of eicosapentaenoic acid (EPA) in human colon cancer cells (HT-29). At nutritionally relevant concentrations, EPA stimulated a PPAR response element (PPRE) reporter assay in a dose-responsive manner in HT-29 cells. Cotreatment with GW9662 (GW), a PPARgamma antagonist, significantly inhibited this effect, whereas overexpressing the receptor enhanced it. EPA also stimulated the PPRE reporter in a PPARgamma negative cancer cell line (22Rv1) when the cells were cotransfected with a PPARgamma1 expression plasmid and this effect was again inhibited by GW. Furthermore, in vitro incubation of EPA with PPARgamma1 enhanced binding of the protein to DNA containing a PPRE. Next, we sought to determine whether EPA or a prostaglandin formed from EPA is the functional ligand of PPARgamma. Cotreatment in HT-29 and 22Rv1 cells with EPA and acetyl salicylic acid, an inhibitor of cyclooxygenase activity, activated the PPRE reporter at levels similar to EPA alone, suggesting that EPA itself is a ligand of PPARgamma. Finally, EPA suppressed HT-29 cell growth and this effect was significantly reversed by the addition of GW, suggesting that in part the physiological actions of EPA are the result of PPARgamma activation. These studies identify PPARgamma as a molecular mediator of (n-3) PUFA actions in colon cancer cells.     

Polyunsaturated fatty acid status in attention deficit hyperactivity disorder, depression, and Alzheimer's disease: towards an omega-3 index for mental health?

Interest in the role of polyunsaturated fatty acids (PUFAs), particularly long-chain (LC) omega-3 ( n -3) PUFAs, in mental health is increasing. This review investigates whether n -3 PUFA levels are abnormal in people with three prevalent mental health problems – attention deficit hyperactivity disorder, depression, and dementia. Data sources included PubMed, Web of Science, and bibliographies of papers published in English that describe PUFA levels in the circulation of individuals who have these mental health conditions. Although abnormal blood PUFA levels were reported in a number of studies, weighted comparisons of PUFA status showed no significant differences overall between people with mental health problems and controls. Whether those with low n -3 PUFA status are likely to be more responsive to n -3 PUFA supplementation is not yet resolved. Further studies assessing PUFA levels and mental status with greater uniformity are required in order to clarify the relationship between LC n -3 PUFA status and mental health.