Increased dietary levels of α-linoleic acid inhibit mammary tumor growth and metastasis

Objective

The aim of this study was to determine whether α-linolenic acid (ALA ω-3 fatty acid) enriched diet affects growth parameters when applied to a syngeneic model of mammary carcinoma.

Materials and methods

BALB/c mice were divided and fed with: 1) a chia oil diet, rich in ALA or 2) a corn oil diet, rich in linoleic acid (LA ω-6 fatty acid). Mice were subcutaneously inoculated with a tumor cell line LM3, derived from a murine mammary adenocarcinoma.

Results

After 35 days, tumor incidence, weight, volume and metastasis number were lower in the ALA-fed mice, while tumor latency time was higher, and the release of pro-tumor metabolites derived from ω-6 fatty acids decreased in the tumor. Compared to the control group, a lower number of mitosis, a higher number of apoptotic bodies and higher T-lymphocyte infiltration were consistently observed in the ALA group. An ALA-rich diet decreased the estrogen receptor (ER) α expression, a recognized breast cancer promotor while showing an opposite effect on ERβ in tumor lysates.

Conclusion

These data support the anticancer effect of an ALA-enriched diet, which might be used as a dietary strategy in breast cancer prevention.

     

Prenatal lead levels, plasma amyloid β levels, and gene expression in young adulthood

Background: Animal studies suggest that early-life lead exposure influences gene expression and production of proteins associated with Alzheimer’s disease (AD).Objectives: We attempted to assess the relationship between early-life lead exposure and potential biomarkers for AD among young men and women. We also attempted to assess whether early-life lead exposure was associated with changes in expression of AD-related genes.Methods: We used sandwich enzyme-linked immunosorbent assays (ELISA) to measure plasma concentrations of amyloid β proteins Aβ₄₀ and Aβ₄₂ among 55 adults who had participated as newborns and young children in a prospective cohort study of the effects of lead exposure on development. We used RNA microarray techniques to analyze gene expression.Results: Mean plasma Aβ₄₂ concentrations were lower among 13 participants with high umbilical cord blood lead concentrations (≥ 10 μg/dL) than in 42 participants with lower cord blood lead concentrations (p = 0.08). Among 10 participants with high prenatal lead exposure, we found evidence of an inverse relationship between umbilical cord lead concentration and expression of ADAM metallopeptidase domain 9 (ADAM9), reticulon 4 (RTN4), and low-density lipoprotein receptor-related protein associated protein 1 (LRPAP1) genes, whose products are believed to affect Aβ production and deposition. Gene network analysis suggested enrichment in gene sets involved in nerve growth and general cell development.Conclusions: Data from our exploratory study suggest that prenatal lead exposure may influence Aβ-related biological pathways that have been implicated in AD onset. Gene network analysis identified further candidates to study the mechanisms of developmental lead neurotoxicity.     

α-Linolenic acid, linoleic acid and heart failure in women

α-Linolenic acid (18?:?3n-3) intake and linoleic acid (18?:?2n-6) intake have been associated with lower rates of CHD, though results have not been consistent. The relationship of these fatty acids with incident heart failure (HF) is not well established. We examined the hypothesis that women with higher intakes of 18?:?3n-3 and 18?:?2n-6 would have lower rates of HF hospitalisation and mortality. We measured 18?:?3n-3 and 18?:?2n-6 intake in 36?234 Swedish Mammography Cohort participants aged 48-83 years using FFQ and followed participants through Swedish inpatient and cause-of-death registers from 1 January 1998 until 31 December 2006. Cox models were used to calculate incidence rate ratios (RR) and 95?% CI. Because of multicollinearity, 18?:?3n-3 and 18?:?2n-6 were examined separately. Over 9 years, 596 women were hospitalised and fifty-five died due to HF. In models accounting for age and other covariates, the RR for HF comparing the top quintile of 18?:?3n-3 (median 1·50?g/d) with the bottom quintile (median 0·88?g/d) was 0·91 (95?% CI 0·71, 1·17, P trend?=?0·41). The RR comparing the top quintile of 18?:?2n-6 (median 7·8?g/d) with the bottom quintile (median 4·6?g/d) was 1·14 (95?% CI 0·88, 1·46, P trend?=?0·36). We did not find evidence for the interaction of 18?:?3n-3 and 18?:?2n-6 with each other or with long-chain n-3 fatty acids. In conclusion, these data do not support our hypothesis that 18?:?3n-3 and 18?:?2n-6 are associated with HF. However, these results may not be generalisable to populations with higher intakes of 18?:?3n-3.     

Liver function parameters,cholesterol, and phospholipid α-linoleic acid are associated with adipokine levels in overweight and obese adults

Dysregulation of adipose hormones in obesity has been associated with the hastened development of metabolic syndrome and associated chronic disease sequalae including cardiovascular disease and type 2 diabetes mellitus. This study aims to identify common biochemical and anthropometric markers that impact adipose hormones, including adiponectin and leptin. Based on previous literature, it was hypothesized that these would be adversely impacted by liver function parameters, and adiponectin levels would be positively correlated with phospholipid Ω-3 fatty acids. Forty nondiabetic adult subjects (body mass index, ≥25.0 kg/m²) were recruited. Fasting plasma samples were taken to assess adipokine levels, glucose metabolism, electrolytes, liver enzymes, and blood lipids. Basic anthropometric measurements were also recorded. Adiponectin levels were positively correlated with high-density lipoprotein cholesterol and negatively correlated with anthropometric measures, insulin, liver enzymes, triglycerides, and very low–density lipoprotein cholesterol but not body mass index. Conversely, plasma leptin levels were positively correlated with anthropometric measures, C-reactive protein, high-density lipoprotein cholesterol, and plasma phospholipid proportions of Ω-3 α linoleic acid but inversely correlated with creatinine levels. These results support other data regarding correlations between adiponectin and relative adipose distribution. Correlations with specific liver enzymes may indicate that adiponectin levels are tied to fatty acid deposition in the liver; however, liver/kidney damage though further mechanistic clarification is required. Leptin levels were associated with measures of adiposity but not liver enzymes. Each of these variables, along with blood lipids, may serve as potential future therapeutic targets for the prevention and management of obesity and related comorbidities.     

Ameliorative effects of konjac glucomannan on human faecal β-glucuronidase activity, secondary bile acid levels and faecal water toxicity towards Caco-2 cells

Konjac glucomannan (KGM) has been shown to increase human colon microbial ecology and reduce faecal toxicity in mice. The main goal of the present study was to assess the effects of a KGM supplement into a low-fibre diet on precancerous markers of colon cancer in a double-blind, placebo- and diet-controlled study. Adult volunteers consumed defined diets supplemented with konjac (4·5?g/d) or placebo (maize starch) for 4 weeks. Stools collected before and at the end of the supplementation were analysed for β-glucosidase, β-galactosidase and β-glucuronidase activities, microflora and bile acids. Faecal water was co-incubated with Caco-2 cells, a model of human colonocytes, to determine the cytotoxicity and DNA-damaging effect as assessed by the comet assay. The results indicated that the KGM supplement significantly decreased faecal β-glucuronidase activity by 25·6 (se 7·8)?% and faecal secondary bile acid level by 42·4 (se 11·8)?%. In contrast, consuming the defined diet supplemented with placebo for 4 weeks did not improve these determinants. The KGM-supplemented diet, but not the placebo diet, significantly increased the survival rate (%) of Caco-2 cells co-incubated with faecal water for 1 and 3?h, respectively. In addition, KGM significantly reduced the DNA damage induced by the faecal water alone or in combination with H2O2. The faecal bifidobacteria and lactobacilli levels increased only with the KGM-supplemented diet. Therefore, we conclude that supplementation of KGM into a low-fibre diet improved the faecal microbial ecology and metabolites, which may contribute to the reduced toxicity of faecal water and precancerous risk factors of human colon cancer.     

Effects of two plant growth regulators, indole-3-acetic acid and β-naphthoxyacetic acid, on genotoxicity in Drosophila SMART assay and on proliferation and viability of HEK293 cells from the perspective of carcinogenesis

In this study, the mutagenic and recombinogenic effects of indole-3-acetic acid (IAA), a plant growth regulator naturally synthesized in plants but produced synthetically, and β-naphthoxyacetic acid (BNOA), a synthetic plant growth regulator widely used in agricultural regions, were investigated using the somatic mutation and recombination test (SMART) in Drosophila wings. The effect of the same plant growth regulators against the proliferation and viability of a human immortalized embryonic kidney HEK293 cells which is at the early stage of carcinogenesis were also examined with MTT and trypan-blue exclusion assays. For the SMART assay, two different crosses were used: a standard and a high-bioactivation (HB) cross, involving the flare-3 and the multiple wing hairs markers. The HB cross involved flies characterized by an increased cytochrome P-450-dependent bioactivation capacity, which permits the more efficient biotransformation of promutagens and procarcinogens. In both crosses, the wings of the two types of progeny, inversion-free marker heterozygotes and balancer heterozygotes, were analyzed. The results show that IAA and BNOA are not mutagenic or recombinogenic in the wing cells of Drosophila. Furthermore, neither plant growth regulator affected the proliferation rate of HEK293 cells; however, both of them induced cell death at high concentrations.     

Modulation of leptin levels by oxidized linoleic acid: a connection to atherosclerosis?

The objective of the study was to determine the effects of oxidized linoleic acid (Ox-LA) on plasma leptin and to determine the relationship between plasma leptin levels and atherosclerosis in animals treated with Ox-LA. Low-density lipoprotein (LDL) receptor knockout (LDL r(-/-)) mice were fed a high fat diet with or without Ox-LA for 11 weeks. Plasma leptin levels in the high fat group consuming Ox-LA were significantly higher (14,052?±?601?pg/mL vs. 10,950?±?541?pg/mL; P?相似文献   

Effect of domestic cooking on human bioavailability of naringenin,chlorogenic acid,lycopene and β-carotene in cherry tomatoes

Summary Background Epidemiological data showed that tomato and tomato product (sauce, paste) consumption is associated with a protective effect against the development of some chronic-degenerative diseases. Tomato antioxidant bioactive molecules such as carotenoids and polyphenols could be responsible, at least in part, for the healthy effect observed. The bioavailability of these compounds is an essential requirement to sustain their in vivo role. While it is well known that many factors can influence the bioaccessibility of carotenoids from the food matrix, there is little information about the factors affecting phenolic compounds bioaccessibility. Aim of the study This investigation was carried out to evaluate the effect of domestic cooking on the bioavailability in humans of antioxidant molecules after the administration of a test meal containing cherry tomatoes. Methods A cross-over design was conducted. Subjects (3 females and 2 males) consumed experimental meals containing fresh and cooked cherry tomatoes. Blood collection was performed at different time intervals (0, 2, 4, 6, 8 and 24 h). Results Carotenoid and phenol plasma concentrations were measured. Plasma levels of lycopene and -carotene were not significantly different with respect to the baseline after ingestion of both the test meals, while plasma concentrations of naringenin and chlorogenic acid increased significantly with respect to the baseline (P<0.05) after administration of cooked cherry tomatoes, but not after administration of fresh cherry tomatoes. Conclusions The present study indicated that domestically cooked tomatoes significantly increase naringenin and chlorogenic acid plasma levels. Considering that both naringenin and chlorogenic acid are widely studied for their potential healthy properties, evidence of their bioavailability and of the factors influencing their bioaccessibility is an important tool to sustain the possibility that these polyphenols play a biological role in human physiology.     

Aminotransferase levels,body mass index,and the risk of diabetes: a prospective cohort study

Purpose

To investigate whether the relationship between body mass index (BMI) and incident diabetes is modified by different alanine or aspartate aminotransferases (ALT or AST) levels.

Empirically driven definitions of “good,” “moderate,” and “poor” levels of functioning in the treatment of schizophrenia

Purpose

This study used an empirical approach to identify and validate the classification of patients with schizophrenia in “good,” “moderate,” or “poor” functioning groups based on the assessment of functional measures.

Methods

Using data from a study of schizophrenia outpatients, patients were classified into functional groups using cluster analysis based on the Heinrich–Carpenter Quality of Life Scale (QLS), the 36-item Short-Form Health Survey (SF-36) Mental Component Summary Score, and a productivity measure. A three-cluster solution was chosen. Concurrent, convergent, and discriminant validity were assessed. Criteria for classifying patient functioning as “good,” “moderate,” or “poor” were established using classification and regression tree analysis.

Results

The three clusters consistently differentiated patients on the QLS, SF-36 Mental Component Summary Score, and productivity measure. The clusters also differed on other functional measures and were concordant with previous functional classifications. Concurrent, convergent, and discriminant validity were good. “Good” functioning was identified as a QLS total score ≥84.5; “moderate” and “poor” functioning were separated by a cutoff score of 15.5 on the QLS intrapsychic foundation domain. Sensitivity ranged from 86 to 93 % and specificity from 89 to 99 %.

Conclusions

The heterogeneity in functioning of schizophrenia patients can be classified reliably in an empirical manner using specific cutoff scores on commonly used functional measures.     

Methyl-inositol, γ-aminobutyric acid and other health benefit compounds in the aril of litchi

The available components in the flesh of litchi seem insufficient to interpret its wide and significant physiological effects. Some unusual compounds, including myo-inositol, inositol methyl derivatives and γ-aminobutyric acid (GABA) were identified as main constituents in the flesh of litchi. Their concentrations varied among cultivars but remain relatively constant during development. Litchi flesh was shown to contain moderate myo-inositol (0.28–0.78?mg?g^?1 FW), ascorbic acid (0.08–0.39?mg?g^?1 FW) and phenolics (0.47–1.60?mg?g^?1 FW), but abundant l-quebrachitol (1.6–6.4?mg?g^?1 FW) and GABA (1.7–3.5?mg?g^?1 FW). The concentration of GABA in the flesh of litchi was about 100 times higher than in other fruits. And l-quebrachitol is not a common component in fruits. The biological and physiological activities of inositols, inositol derivatives and GABA have been extensively documented. These compounds are probably important compositional characteristic contributing to the widely shown health benefits of litchi.     

Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals

This review is part of a series intended for nonspecialists that will summarize evidence relevant to the question of whether causal relations exist between micronutrient deficiencies and brain function. Here, we focus on experiments that used cognitive or behavioral tests as outcome measures in experimental designs that were known to or were likely to result in altered brain concentrations of the n-3 fatty acid docosahexaenoic acid (DHA) during the perinatal period of "brain growth spurt." Experimental designs reviewed include observational breastfeeding studies and randomized controlled trials in humans and studies in rodents and nonhuman primates. This review is based on a large number of expert reviews and commentaries and on some 50 recent studies in humans and animals that have not yet been included in published reviews. Expert opinion regarding the strengths and weaknesses of the major experimental systems and uncertainties associated with interpreting results is summarized. On the basis of our reading of this literature, we conclude that evidence from several types of studies, particularly studies in animals, suggests that, within the context of specific experimental designs, changes in brain concentrations of DHA are positively associated with changes in cognitive or behavioral performance. Additional experimental information required to conclude that a causal association exists is discussed, as are uncertainties associated with applying results from specific experimental designs to the question of whether infant formula should be supplemented with DHA.     

Dynamic changes of myometrial activity,levels of PGF2α and E2 in rabbits after insertion of four types of IUDs

Myometrial activity, levels of PGF₂ and E₂ in uterine flushings were measured in rabbits before and after insertion of four types of IUDs. The results showed that IUDs could increase the uterine contraction during the early stages of insertion. Thereafter, the uterine activity tended to be stable. The sequences of uterine contractility generally were: Cu-IUD > SS-IUD > LNG-Cu-IUD > LNG-IUD. The measurement of prostaglandins, determined by RIA, indicated that the concentrations of PGF₂ and E₂ in Cu-IUD and SS-IUD groups were higher than those of controls for the early phase of insertion, which was not found after four months of use. Our results suggested that hyperactivity of the uterus in the early stage after insertion of IUDs might be relevant to side-effects like expulsion and pain. Copper released by Cu-IUD stimulates the uterine activity partially through increasing PGF₂ and E₂ contents. In rabbits wearing LNG-IUD or LNG-Cu-IUD, both PGF₂ and E₂ levels were low. The relatively low uterine mechanical and electrical activities were also observed in these two groups. Based on these data, it is concluded that development of LNG-Cu-IUD is feasible for reducing expulsion of IUDs.

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Resumen La actividad miométrica, los niveles de PGF₂ y E₂ en los accesos vasomotores uterinos fueron medidos en conejas antes y después de la colocación de cuatro tipos de dispositivos intrauterinos. Los resultados demostraron que los DIU pueden aumentar la contracción uterina al principio de la colocación, después de lo cual la actividad uterina tiende a estabilizarse. La escala de contractilidad del útero era generalmente la siguiente: DIU-Cu > DIU-SS > DIU-LNG-Cu > DIU-LNG. La medición de las prostaglandinas, determinadas por RIA, indicó que las concentraciones de PGF₂ y E₂ en el grupo de conejas con DIU SS y Cu eran, en el momento de la colocación, mayores que en el grupo testigo, no siendo más así después de cuatro meses de utilización. Nuestros resultados sugirieron que la hiperactividad del útero durante el período inmediatamente posterior a la colocación del DIU puede estar relacionada con efectos secundarios tales como expulsión y dolores. El cobre descargado por los DIU estimula la actividad uterina, en parte por el hecho de aumentar los niveles de PGF₂ y E₂. En las conejas con dispositivos de LNG o cobre, los niveles tanto de PGF₂ como de E₂ eran bajos. Se observaron asimismo en estos dos grupos actividades mecánicas y eléctricas relativamente bajas. Estos resultados llevaron a la conclusión de que el desarrollo de DIU de LNG-Cu es factible para reducir la expulsión.

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Resumé L'activité myométrique, les niveaux de PGF₂ et de E₂ dans les accès vasomoteurs utérins ont été mesurés sur des lapines avant et après l'insertion de quatre types de dispositifs intra-utérins. Les résultats ont montré que les DIU peuvent augmenter la contraction utérine au début de l'insertion, après quoi l'activité utérine tend à se stabiliser. L'échelle de contractilité de l'utérus était généralement la suivante: DIU-Cu > DIU-SS > DIU-LNG-Cu > DIU-LNG. La mesure des prostaglandines, déterminées par RIA, a indiqué que les concentrations de PGF₂ et E₂ dans le groupe de lapines munies de DIU SS et Cu étaient, au début de l'insertion, plus fortes que dans le groupe témoin, ce qui n'était plus le cas après quatre mois d'utilisation. Nos résultats laissent penser que l'hyperactivité de l'utérus pendant la période suivant immédiatement l'insertion du DIU peut avoir un rapport avec les effects secondaires tels que l'expulsion et les douleurs. Le cuivre libéré par les DIU au cuivre stimule l'activité utérine, en partie du fait de la teneur accrue en PGF₂ et E₂. Chez les lapines qui portaient des dispositifs au LNG ou au cuivre, les niveaux aussi bien de PGF₂ et de E₂ étaient faibles. On a également constaté dans ces deux groupes des activités mécaniques et électriques relativement faibles. Ces résultats ont ammené à conclure qu'une mise au point élaborée des DIU LNG-cu est réalisable en vue d'en réduire l'expulsion.

     

Combined effect of sesamin and α-lipoic acid on hepatic fatty acid metabolism in rats

Purpose

Dietary sesamin (1:1 mixture of sesamin and episesamin) decreases fatty acid synthesis but increases fatty acid oxidation in rat liver. Dietary α-lipoic acid lowers hepatic fatty acid synthesis. These changes can account for the serum lipid-lowering effect of sesamin and α-lipoic acid. It is expected that the combination of these compounds in the diet potentially ameliorates lipid metabolism more than the individual compounds. We therefore studied the combined effect of sesamin and α-lipoic acid on lipid metabolism in rats.

Methods

Male Sprague–Dawley rats were fed diets supplemented with 0 or 2 g/kg sesamin and containing 0 or 2.5 g/kg α-lipoic acid for 22 days.

Results and conclusions

Sesamin and α-lipoic acid decreased serum lipid concentrations and the combination of these compounds further decreased the parameters in an additive fashion. These compounds reduced the hepatic concentration of triacylglycerol, the lignan being less effective in decreasing this value. The combination failed to cause a stronger decrease in hepatic triacylglycerol concentration. The combination of sesamin and α-lipoic acid decreased the activity and mRNA levels of hepatic lipogenic enzymes in an additive fashion. Sesamin strongly increased the parameters of hepatic fatty acid oxidation enzymes. α-Lipoic acid antagonized the stimulating effect of sesamin of fatty acid oxidation through reductions in the activity of some fatty acid oxidation enzymes and carnitine concentration in the liver. This may account for the failure to observe strong reductions in hepatic triacylglycerol concentration in rats given a diet containing both sesamin and α-lipoic acid.     

Homocysteine and methylmalonic acid levels in pregnant Nepali women. Should cobalamin supplementation be considered?

OBJECTIVE: The aim of this study was to investigate homocysteine and methylmalonic acid levels as markers of functional cobalamin and folate status in pregnant Nepali women. DESIGN: Cross-sectional study. SETTING: Patan Hospital, Kathmandu, Nepal. SUBJECTS: A sub-sample (n=382) of all pregnant women (n=2856) coming for their first antenatal visit in a 12 month period, 1994-1995. The selection of the sub-sample was based on maternal haematocrit values, categorised into three groups: severely, moderately and non-anaemic women. As serum levels of total homocysteine (s-tHcy) and methylmalonic acid (s-MMA) were similar in the three groups, pooled data are presented. Women who had already received micronutrient supplementation (n=54) were excluded. The remaining women (n=328) were included in the statistical analysis. RESULTS: Overall mean values (+/-s.d.) of s-tHcy and s-MMA were 9.5 (+/-4.2) micromol/l and 0.39 (+/-0.32) micromol/l, respectively. Elevated s-tHcy (>7.5 micromol/l) was found in 68% of the women, while 61% had elevated s-MMA (>0.26 micromol/l). Low s-cobalamin values (<150 pmol/l) were observed in 49% of the women, while only 7% had low s-folate values (< or =4.5 nmol/l). s-tHcy was significantly correlated with s-MMA (r=0.28, P<0.001), s-cobalamin (r=-0.30, P<0.001) and s-folate (r=-0.24, P<0.001). s-MMA was significantly associated with s-cobalamin (r=-0.40, P<0.001), but not with s-folate. CONCLUSIONS: Functional cobalamin deficiency was very common in the study population, while functional folate deficiency was rather uncommon. We suggest considering cobalamin supplementation to pregnant Nepali women. SPONSORSHIP: The Norwegian Research Council and the Norwegian Universities Committee for Development, Research and Education.     

Socio-demographic, lifestyle, gynecological, and obstetric predictors of serum or plasma concentrations of homocysteine, folic acid, and vitamins B12 and B6 among low-income women in São Paulo, Brazil

This study examined the socio-demographic, lifestyle, gynecological, and obstetric factors associated with serum or plasma concentrations of homocysteine, folic acid, and vitamins B12 and B6 among low-income women in S?o Paulo, Brazil. Serum concentrations of folic acid and vitamin B12 were measured by fluoroimmunoassay, while plasma vitamin B6 and homocysteine levels were measured by reversed-phase high performance liquid chromatography. Independent variables were initially selected by Pearson correlation or Kruskal-Wallis test (p < 0.20). Based on cut-off values, altered concentrations of homocysteine, folic acid, and vitamins B12 and B6 were found in 20%, 6%, 11%, and 67% of participants, respectively. Age was positively correlated with vitamin B6 and homocysteine plasma concentrations (p < 0.001). Body mass index was positively correlated with vitamin B6 plasma concentration (p < 0.001). Multiple linear regression models accounted for 10.2%, 5.8%, 14.4%, and 9.4% of folic acid, vitamins B12 and B6, and homocysteine plasma or serum concentrations, respectively. In this study, socio-demographic, lifestyle, gynecological, and obstetric variables showed important predictive value for serum or plasma levels of the biochemical indicators assessed.