Animal Intervention Studies Research Articles

Perinatal programming of body weight control by leptin: putative roles of AMP kinase and muscle thermogenesis

Breastfeeding, compared with infant-formula feeding, confers later protection against obesity. Leptin represents a candidate for the programming of the lean phenotype as suggested by 1) the presence of leptin in breast milk and its absence in infant formula, 2) a human study that showed a negative correlation between leptin concentrations in breast milk and body weights of infants until 2 y of age, and 3) intervention studies in animals. Milk-borne leptin and leptin synthesized in adipose tissue and the stomach may contribute to leptinemia in newborns. Studies in rodents suggested that early leptin treatment may program either a lean or obese phenotype, probably depending on the dose, route of administration, and timing of exposure to high leptin concentrations, whereas these studies also suggested the importance of the physiologic postnatal surge in leptinemia for the programming effect. Leptin oral administration at physiologic doses to neonate rats during the entire lactation period had later positive effects that prevented the animals from overweight and obesity and other metabolic alterations, which were particularly associated with feeding of a high-fat diet. High leptin sensitivity, which is associated with leanness, and leptin resistance in obesity may be programmed by the early life environment. The differential sensitivity to leptin implies a contribution of leptin-inducible energy expenditure to the adult phenotype. Available data have suggested the involvement of nonshivering thermogenesis induced by a leptin-AMP-activated protein kinase axis in oxidative muscles, which is based on lipid metabolism. Additional studies on the programming effects of leptin, mainly in response to the oral intake of leptin, are required.

Docosahexaenoic Acid Supplementation Improved Lipocentric but Not Glucocentric Markers of Insulin Sensitivity in Hypertriglyceridemic Men

Increase in obesity and metabolic syndrome are associated with increases in insulin resistance (IR) and type 2 diabetes mellitus. Results from animal intervention studies and human epidemiological studies suggest that n-3 polyunsaturated fatty acids can prevent and reverse IR, but results from human intervention studies have varied. Results from some human and animal studies suggest that docosahexaenoic acid (22:6n-3; DHA) may be more effective than eicosapentaenoic acid (20:5n-3; EPA) in the prevention of IR. By using a placebo-controlled, parallel study design, we examined the effects of DHA supplementation (3 grams/day, 90 days) in the absence of EPA on glucocentric and lipocentric markers of IR in hypertriglyceridemic men (n=14-17/group). DHA supplementation increased fasting plasma glucose concentration by 4.7% (P<0.05), but did not alter other indices of IR based on fasting (insulin and homeostasis model assessment of insulin resistance [HOMA-IR]) or postprandial insulin and glucose concentrations (areas under curves for insulin and glucose, Matsuda index). Glucose increased by 2.7% in the placebo group and was not significant; increases in glucose in the two groups did not differ from each other. DHA decreased circulating concentrations of several lipocentric markers of IR, including plasma concentrations of nonesterified fatty acids (13.0%), small, dense low-density lipoprotein (LDL) particles (21.7%), and ratio of tryglycerides to high-density lipoprotein cholesterol (TG/HDL-C) (34.0%) (P<0.05). None of the variables changed in the placebo group. Our results suggest that lipocentric markers of IR are more responsive to DHA supplementation than the glucocentric markers. Future studies with DHA in prediabetic subjects and direct measures of insulin sensitivity are needed.

Cardioprotective Efficacy of a Novel Antioxidant Mix VitaePro Against Ex Vivo Myocardial Ischemia–Reperfusion Injury

Circumstantial evidence frequently implicates oxygen-derived free radicals and oxidative stress as mediators of myocardial ischemia/reperfusion (I/R) injury. Therefore, external supplementation of natural antioxidants plays a main role as cardioprotective compounds. This study was designed to evaluate the cardioprotective effect of VitaePro (70mg/kg body weight, 21days), a novel antioxidant mix of astaxanthin, lutein and zeaxanthin in a rat ex vivo model of ischemia/reperfusion injury. The cardioprotective effect of VitaePro was also compared with vitamin E (70mg/kg body weight, 21days) treatment. Rats were randomized into control I/R (CIR), VitaePro I/R (VPIR) and Vitamin E I/R (VEIR). After 21days of oral treatment, isolated hearts from each group were subjected to 30min of ischemia followed by 2h of reperfusion. In the VPIR group compared to CIR and VEIR groups at 2h of reperfusion, increased left ventricular functional recovery, such as left ventricular developed pressure (92.7±0.7 vs. 85.3±0.3 and 89.4±1.2mm Hg), dp/dt max (2518.7±77.9 vs. 1962.5±24 and 2255.7±126.6mm Hg/s), and aortic flow (21.5±1.36 vs. 4.4±0.6 and 13.2±1.02ml/min) were observed. The infarct size (27.68±1.7 vs. 45.4±1.8 and 35.4±0.6%), apoptotic cardiomyocytes (61.7±10.6 vs. 194.1±14.8 and 118.7±15.4 counts/100 HPF) and thiobarbituric acid reactive substances levels (80±3 vs. 127±5 and 103± 2nM/mg tissue) also were decreased in VPIR group when compared to CIR and VEIR. As evidenced by the data, administration of vitamin E offered substantial cardioprotection to I/R injury, but VitaePro enhanced cardioprotection significantly more than vitamin E treatment. Taken in concert, the results of this study suggests that the oral ingestion of VitaePro protects myocardium from ischemia/reperfusion injury by decreasing oxidative stress and apoptosis, which may be of therapeutic benefit in the treatment of cardiovascular complications. However, further in vivo animal and human intervention studies are warranted before establishing any recommendations about usage of VitaePro for human cardiovascular complications.

The role of ruminant trans fat as a potential nutraceutical in the prevention of cardiovascular disease

Dietary trans fat has received increasing attention over the last few years. It is now appreciated that trans fatty acids (TFA) produced by ruminants (rTFA) via ‘a natural biohydrogenation reaction’ may have disparate health effects from those produced as a by-product of industrial processing present in partially hydrogenated vegetable oils. In this review, we discuss the most recent findings from human and animal intervention studies in order to evaluate the health implications and potential mechanisms of two major rTFA (t11-vaccenic acid and c9,t11-conjugated linoleic acid) in their purified form as well as in the format of dairy fat with regard to the development of cardiovascular diseases, with the aim to assess the potential of developing rTFA as novel components for functional foods.

Dental Infection and Vascular Disease

Periodontitis is a chronic inflammatory response to bacterial plaque in which the anchoring bone and soft tissues supporting teeth are destroyed, resulting in tooth mobility and loss. Dental caries involves the spread of infection from the dentine to the vascular dental pulp and periapical bony tissues, before involvement of adjacent soft tissues and spreading sepsis. Several case-controlled, cross-sectional, and cohort studies report correlation between periodontitis and increased cardiovascular, cerebrovascular, and peripheral artery disease, as determined by clinical disease, angiography, ultrasonography, and reduced flow-mediated dilation. Some studies report a similar relationship of atherosclerosis with periapical infection and potentially also with coronal caries, and this review identifies the need to investigate these associations further. Smoking and cadmium exposure are epidemiologically confounding environmental risk factors shared by atherosclerosis and periodontitis. Further complicating epidemiological studies are the risk factors for both atherosclerosis and periodontitis, with which periodontitis appears to have separate positive feedback relationships. These include diabetes, increased plasma lipid levels, hypertension, and white blood cell count. Animal and human intervention studies provide some direct support of a causal role for periodontitis in atherosclerosis, and possible mechanisms include bacterial invasion of arteries, specific atherogenic properties of oral bacteria, the acute phase response, and cytokine polymorphisms.

Antiarrhythmic effect mediated by κ-opioid receptor is associated with Cx43 stabilization*

Acute myocardial ischemia induces electrical and chemical uncoupling of gap junctions, which contributes to conduction abnormalities and re-entrant arrhythmias. We tested the hypothesis that structure and function of Connexin43 may vibrate during acute myocardial ischemia and reperfusion and κ-opioid receptor stimulation may stabilize the alteration of Connexin43. An animal intervention study was conducted with comparison to a control group. University preclinical research laboratory. Age-, weight-, and sex-matched Sprague-Dawley rats. Adult rat hearts were subjected to ischemia or ischemia/reperfusion, which was induced by temporary occlusion of the left main coronary artery. U50488H was given 10 mins before tissue specimens were taken or before ischemia (1.5 mg/kg, intravenous) and nor-BNI was given 15 mins before tissue specimens were taken or before ischemia (2 mg/kg, intravenous). Tissue samples came from left ventricular myocardium of the rat hearts. Electrocardiogram, immunohistochemistry, immunoblotting, and reverse transcription-polymerase chain reaction were used to measure changes of arrhythmias, protein, and gene expression of Connexin43, respectively. κ-opioid receptor activation with U50 decreased arrhythmia in a model of myocardial ischemia and reperfusion. In normal hearts, immunohistochemical data showed reduced amount and lateralization of Connexin43 induced by κ-opioid receptor activation, whereas immunoblotting data demonstrated no significant changes between control and U50 group. During ischemia, however, Connexin43 protein underwent dephosphorylation and degradation, and Connexin43 mRNA was upregulated. These alterations were significantly attenuated on κ-opioid receptor stimulation. During ischemia and reperfusion, Connexin43 protein underwent dephosphorylation and degradation and recovered slowly during reperfusion. Activation of κ-opioid receptor accelerated recovery of phosphorylated and total Connexin43. In normal rat hearts, Connexin43 translocates from intercellular junctions to intracellular locations on κ-opioid receptor activation. In rat hearts experiencing acute myocardial ischemia and reperfusion, protein and gene expression of Connexin43 undergo vibration. This phenomenon is stabilized when κ-opioid receptor is activated and by the fact that κ-opioid receptor produces antiarrhythmic effects.

Recent advances on Ilex paraguariensis research: Minireview

Ilex paraguariensis dried and minced leaves are made into a brewed tea, prepared in a sui generis manner by large populations in South America, having evolved from a tea drunk by the Guarani ethnic group to a beverage that has a social and almost ritualistic role in some South American modern societies. It is used both as a source of caffeine, in lieu or in parallel with tea and coffee, but also as a therapeutic agent for its alleged pharmacological properties. Although with some exceptions, research on biomedical properties of this herb has had a late start and strongly lags behind the impressive amount of literature on green tea and coffee. However, in the past 15 years, there was a several-fold increase in the literature studying Ilex paraguariensis properties showing effects such as antioxidant properties in chemical models and ex vivo lipoprotein studies, vaso-dilating and lipid reduction properties, antimutagenic effects, controversial association with oropharyngeal cancer, anti-glycation effects and weight reduction properties. Lately, promising results from human intervention studies have surfaced and the literature offers several developments on this area. The aim of this review is to provide a concise summary of the research published in the past three years, with an emphasis on translational studies, inflammation and lipid metabolism. Ilex paraguariensis reduces LDL-cholesterol levels in humans with Ilex paraguariensis dyslipoproteinemia and the effect is synergic with that of statins. Plasma antioxidant capacity as well as expression of antioxidant enzymes is positively modulated by intervention with Ilex paraguariensis in human cohorts. A review on the evidence implicating Ilex paraguariensis heavy consumption with some neoplasias show data that are inconclusive but indicate that contamination with alkylating agents during the drying process of the leaves should be avoided. On the other hand, several new studies confirm the antimutagenic effects of Ilex paraguariensis in different models, from DNA double breaks in cell culture models to mice studies. Novel interesting work has emerged showing significant effect on weight reduction both in mice and in rat models. Some mechanisms involved are inhibition of pancreatic lipase, activation of AMPK and uncoupling of electron transport. Intervention studies in animals have provided strong evidence of anti-inflammatory effects of Ilex paraguariensis, notably protecting cigarette-induced lung inflammation acting on macrophage migration and inactivating matrix-metalloproteinase. Research on the effects of Ilex paraguariensis in health and disease has confirmed its antioxidant, anti-inflammatory, antimutagenic and lipid-lowering activities. Although we are still waiting for the double-blind, randomized prospective clinical trial, the evidence seems to provide support for beneficial effects of mate drinking on chronic diseases with inflammatory component and lipid metabolism disorders.

Does consuming isoflavones reduce or increase breast cancer risk?

Epidemiological studies suggest that consumption of phytoestrogens, in particular isoflavones, correlates with a lower incidence of breast cancer. However, data from human intervention studies have been less clear. Several meta-analyses have reported beneficial but relatively weak effects of isoflavone consumption on reduction of hot flushes and osteoporosis and improvement of cholesterol levels. However, the effects of isoflavones on early breast cancer markers differ between pre- and post-menopausal women. Conclusions on whether exposure of animals (mice and rats) to isoflavones protects against or promotes breast cancer development and growth vary between different studies. These results, taken together with the heterogeneous outcomes of human interventions, have led to a controversy surrounding the intake of isoflavone to reduce breast cancer risk. Here, we describe the results of recent human and animal intervention studies and discuss factors that might explain the variation in results. We also describe possible molecular mechanisms of action of isoflavones; distinguishing which mechanism(s) are involved is needed if we are to solve the controversy surrounding the actions of these compounds.

Epigenomics – Grand Challenge: Much more than the Developmental Origins of Adult Health and Disease

Epigenomics – Grand Challenge: Much more than the Developmental Origins of Adult Health and Disease

Salt and high blood pressure

HBP (high blood pressure) is the leading risk of death in the world. Unfortunately around the world, blood pressure levels are predicted to become even higher, especially in developing countries. High dietary salt is an important contributor to increased blood pressure. The present review evaluates the association between excess dietary salt intake and the importance of a population-based strategy to lower dietary salt, and also highlights some salt-reduction strategies from selected countries. Evidence from diverse sources spanning animal, epidemiology and human intervention studies demonstrate the association between salt intake and HBP. Furthermore, animal studies indicate that short-term interventions in humans may underestimate the health risks associated with high dietary sodium. Recent intervention studies have found decreases in cardiovascular events following reductions in dietary sodium. Salt intake is high in most countries and, therefore, strategies to lower salt intake could be an effective means to reduce the increasing burden of HBP and the associated cardiovascular disease. Effective collaborative partnerships between governments, the food industry, scientific organizations and healthcare organizations are essential to achieve the WHO (World Health Organization)-recommended population-wide decrease in salt consumption to less than 5 g/day. In the milieu of increasing cardiovascular disease worldwide, particularly in resource-constrained low- and middle-income countries, salt reduction is one of the most cost-effective strategies to combat the epidemic of HBP, associated cardiovascular disease and improve population health.

Conjugated linoleic acid isomer concentrations in milk from high‐ and low‐input management dairy systems

AbstractBACKGROUND: Different conjugated linoleic acid (CLA) isomers are known to have contrasting physiology or health effects and there is growing evidence that the profile of natural isomers in milk is influenced by the production system. This survey is the first to compare feeding regimes and concentrations of 14 CLA isomers in milk from three production systems in the UK.RESULTS: Total CLA and seven isomers (including C18:2 c9t11 which comprised &gt; 80% of total) were significantly higher in milk from both organically certified and non‐certified low input (LI) systems compared with milk from conventional high input farms. Sampling date also affected concentrations of total CLA and nine isomers; being lowest in March and highest in August. Seasonal differences were greater in milk from LI herds, thought to be due to changes in herbage and/or stage of lactation. Multivariate analysis showed a strong positive relationship between several CLA isomers and increasing levels of fresh forage in the diet.CONCLUSIONS: These results add to the evidence on how management adjustment may improve the profile of CLA isomers in milk fat, although animal or human intervention studies are required to identify the effects of consuming milk with different CLA levels and isomer profiles on human health. Copyright © 2009 Society of Chemical Industry

The influence of myocardial substrate on ventricular fibrillation waveform: A swine model of acute and postmyocardial infarction

In cardiac arrest resulting from ventricular fibrillation, the ventricular fibrillation waveform may be a clue to its duration and predict the likelihood of shock success. However, ventricular fibrillation occurs in different myocardial substrates such as ischemia, heart failure, and structurally normal hearts. We hypothesized that ventricular fibrillation is altered by myocardial infarction and varies from the acute to postmyocardial infarction periods. An animal intervention study was conducted with comparison to a control group. This study took place in a university animal laboratory. Study subjects included 37 swine. Myocardial infarction was induced by occlusion of the midleft anterior descending artery. Ventricular fibrillation was induced in control swine, acute myocardial infarction swine, and in postmyocardial infarction swine after a 2-wk recovery period. Ventricular fibrillation was recorded in 11 swine with acute myocardial infarction, ten postmyocardial infarction, and 16 controls. Frequency (mean, median, dominant, and bandwidth) and amplitude-related content (slope, slope-amp [slope divided by amplitude], and amplitude-spectrum area) were analyzed. Frequencies at 5 mins of ventricular fibrillation were altered in both acute myocardial infarction (p < .001 for all frequency characteristics) and postmyocardial infarction swine (p = .015 for mean, .002 for median, .002 for dominant frequency, and <.001 for bandwidth). At 5 mins, median frequency was highest in controls, 10.9 +/- .4 Hz; lowest in acute myocardial infarction, 8.4 +/- .5 Hz; and intermediate in postmyocardial infarction, 9.7 +/- .5 Hz (p < .001 for acute myocardial infarction and p = .002 for postmyocardial infarction compared with control). Slope and amplitude-spectrum area were similar among the three groups with a shallow decline after minute 2, whereas slope-amp remained significantly altered for acute myocardial infarction swine at 5 mins (p = .003). Ventricular fibrillation frequencies depend on myocardial substrate and evolve from the acute through healing phases of myocardial infarction. Amplitude related measures, however, are similar among these groups. It is unknown how defibrillation may be affected by relying on the ventricular fibrillation waveform without considering myocardial substrate.

The Lipid lowering and Onset of Renal Disease (LORD) Trial: A randomized double blind placebo controlled trial assessing the effect of atorvastatin on the progression of kidney disease

BackgroundThere is evidence that dyslipidemia is associated with chronic kidney disease (CKD). Experimental studies have established that lipids are damaging to the kidney and animal intervention studies show statins attenuate this damage. Small clinical trials, meta-analyses, observational studies and post-hoc analyses of cardiovascular intervention studies all support the concept that statins can reduce kidney damage in humans. Based on this background, a double blind randomized placebo controlled trial was designed to assess the effectiveness of atorvastatin 10 mg on slowing the progression of kidney disease in a population of patients with CKD.Method/DesignThe Lipid lowering and Onset of Renal Disease (LORD) trial is a three-year, single center, multi-site, double blind, randomized, placebo controlled trial. The primary outcome measure is kidney function measured by eGFR calculated by both Modification of Diet in Renal Disease (MDRD) and Cockcroft and Gault equations. Secondary outcome measures include kidney function measured by 24-hour urine creatinine clearance and also 24-hour urinary protein excretion, markers of oxidative stress, inflammation and drug safety and tolerability.DiscussionThe results of this study will help determine the effectiveness and safety of atorvastatin and establish its effects on oxidative stress and inflammation in patients with CKD.Trial RegistrationANZCTRN012605000693628

Trans fatty acids, conjugated linoleic acids, and cardiovascular diseases

AbstractThis review focuses on human data about the link between cardiovascular risk and dietary trans and conjugated fatty acids. Some complementary data from animals are presented. Concerning trans monoene isomers, since 1990 they were extensively studied. Intervention studies have shown that they increased LDL‐cholesterol just like saturated fatty acids (palmitic, myristic, lauric acids). A recent meta‐analysis of 60 intervention studies emphasized that, unlike palmitic acid, these trans monoenes increased the total‐to‐HDL‐cholesterol ratio; as a result these trans isomers could increase the cardiovascular risk more than lauric, myristic and palmitic acids. Data from four epidemiological cohort studies suggest that a 2% increase in energy of daily intake of trans fatty acids significantly increases the incidence of cardiovascular diseases. Concerning conjugated linoleic acids (CLA), to date, there are no epidemiological data. Current knowledge is based on intervention studies in humans and animals and on in vitro studies. For the mixture of isomers (cis9, trans11 and trans10, cis12), clinical studies gave inconsistent results, and results on animal models differed from one species to another. For each isomer studied separately, their effects on the lipoprotein profile in humans were different. However, no dose effect was found whatever the isomer. Studies performed in healthy subjects and obese men presented convergent conclusions regarding the detrimental effects of trans10,cis12 CLA, but with rumenic acid (cis9, trans11 CLA) positive effects were observed in healthy subjects, not in obese subjects &amp;bock;pls check!&amp;bock;. Finally, results of studies lead to attribute a potential, general proatherogenic effect to trans10, cis12 CLA.

A Green Tea Catechin Extract Upregulates the Hepatic Low‐Density Lipoprotein Receptor in Rats

Green tea extracts have hypocholesterolaemic properties in epidemiological and animal intervention studies. Upregulation of the low-density lipoprotein (LDL) receptor may be one mechanism to explain this as it is the main way cholesterol is removed from the circulation. This study aimed to determine if a green tea extract could upregulate the hepatic LDL receptor in vivo in the rat. A green tea extract (GTE) enriched in its anti-oxidant constituents, the catechins, was fed to rats (n = 6) at concentrations of either 0, 0.5, 1.0 or 2.0% (w/w) mixed in with their normal chow along with 0.25% (w/w) cholesterol for 12 days. Administration of the GTE had no effect on plasma total or LDL cholesterol concentrations but high-density lipoprotein significantly increased (41%; p < 0.05). Interestingly, there was a significant increase in LDL receptor binding activity (2.7-fold) and LDL receptor protein (3.4-fold) in the 2% (w/w) treatment group compared to controls. There were also significant reductions in liver total and unesterified cholesterol (40%). Administration of the GTE significantly reduced cholesterol absorption (24%) but did not affect cholesterol synthesis. These results show that, despite no effect on plasma cholesterol, the GTE upregulated the LDL receptor in vivo. This appears to be via a reduction in liver cholesterol concentration and suggests that the green tea extract was able to increase the efflux of cholesterol from liver cells.

Adducin Polymorphisms and the Treatment of Hypertension

Hypertension is an important public health problem affecting more than 50 million individuals in the USA alone. The most common form, essential hypertension, results from the complex interplay between genetic predisposition and environmental influences. Epidemiological, migration, intervention and genetic studies in humans and animals provide very strong evidence of a causal link between high salt intake and high blood pressure. One of the candidate genes for salt-sensitive hypertension is adducin. Adducin is a heterodimeric cytoskeleton protein, the three subunits of which are encoded by genes (ADD1, ADD2 and ADD3) that map to three different chromosomes. A long series of parallel studies in the Milan hypertensive rat strain model of hypertension and humans indicated that an altered adducin function might cause hypertension through enhanced constitutive tubular sodium reabsorption. An example of a prospective efficacy of pharmacogenetics and pharmacogenomics is the detection and impact of adducin polymorphisms on hypertension. In particular, the selective advantages of diuretics in preventing myocardial infarction and stroke over other antihypertensive therapies that produce a similar blood pressure reduction in carriers of the mutated adducin may support new strategies aimed at optimizing the use of new antihypertensive agents for the prevention of hypertension-associated organ damage.

Role of Dietary Soy Protein in Obesity

Soy protein is an important component of soybeans and provides an abundant source of dietary protein. Among the dietary proteins, soy protein is considered a complete protein in that it contains ample amounts of all the essential amino acids plus several other macronutrients with a nutritional value roughly equivalent to that of animal protein of high biological value. Soy protein is unique among the plant-based proteins because it is associated with isoflavones, a group of compounds with a variety of biological properties that may potentially benefit human health. An increasing body of literature suggests that soy protein and its isoflavones may have a beneficial role in obesity. Several nutritional intervention studies in animals and humans indicate that consumption of soy protein reduces body weight and fat mass in addition to lowering plasma cholesterol and triglycerides. In animal models of obesity, soy protein ingestion limits or reduces body fat accumulation and improves insulin resistance, the hallmark of human obesity. In obese humans, dietary soy protein also reduces body weight and body fat mass in addition to reducing plasma lipids. Several potential mechanisms whereby soy protein may improve insulin resistance and lower body fat and blood lipids are discussed and include a wide spectrum of biochemical and molecular activities that favorably affect fatty acid metabolism and cholesterol homeostasis. The biologic actions of certain constituents of soy protein, particularly conglycinin, soyasaponins, phospholipids, and isoflavones, that relate to obesity are also discussed. In addition, the potential of soy protein in causing food allergy in humans is briefly discussed.

Functional connections and pathways of coenzyme Q10‐inducible genes: An in‐silico study

Coenzyme Q10 (CoQ10, ubiquinone) is an essential cofactor in the electron transport chain, serves as a potent antioxidant in mitochondria and lipid membranes, and is often used as a dietary supplement for a number of diseases including cardiovascular diseases. Recently, we obtained evidence that CoQ10 (Kaneka Q10) affects the expression of hundreds of human genes. To decipher the functional and regulatory connections of these genes, a literature search combined with transcription factor binding site analysis was performed using Genomatix BiblioSphere and MatInspector. This in-silico analysis revealed 17 CoQ10-inducible genes which are functionally connected by signalling pathways of G-protein coupled receptors, JAK/STAT, integrin, and beta-arrestin. Promoter analysis of these CoQ10-inducible genes showed one group of NF B-regulated genes, namely IL5, thrombin, vitronectin receptor and C-reactive protein (CRP). Furthermore, a common promoter framework containing binding sites of the transcription factor families EVI1, HOXF, HOXC, and CLOX was identified in the promoters of IL5, CRP, and vitronectin receptor. The identified CoQ10-inducible genes and pathways play an important role in inflammatory response. Since these effects are based on an in-vitro study, the effect of CoQ10 on vascular health in vivo needs to be addressed in further animal and/or human intervention studies.

Antiproliferative effect of quercetin in the human U138MG glioma cell line

Recent epidemiological and dietary intervention studies in animals and humans have suggested that diet-derived flavonoids, in particular quercetin, may play a beneficial role by preventing or inhibiting tumorigenesis. The aim of this study was to evaluate whether quercetin may act differently on cancer and normal neuronal tissue. In order to investigate this, the U138MG human glioma cell line and hippocampal organotypic cultures were used. The study showed that quercetin induced in glioma cell cultures results in (a) a decrease in cell proliferation and viability, (b) necrotic and apoptotic cell death, (c) arrest in the G2 checkpoint of the cell cycle, and (d) a decrease of the mitotic index. Furthermore, we demonstrated that while quercetin promotes cancer regression it was able to protect the hippocampal organotypic cultures from ischemic damage. To sum up, our results suggest that quercetin induced growth inhibition and cell death in the U138MG human glioma cell line, while exerting a cytoprotective effect in normal cell cultures.

The Science of Soy: What Do We Really Know?

A stroll through nearly any American grocery store or pharmacy yields ample proof of the soybean’s increasing role in the U.S. diet. Food packaging offers statements about products’ soy content and the purported associated health benefits. Products such as tofu, soy milk, soy-based infant formula, and meatless “texturized vegetable protein” burgers are widely available. Shelves of dietary supplements and nutraceuticals are stocked with isoflavones, naturally occurring estrogenic compounds found in soy. The general impression is one of certainty that both soy and soy isoflavones deliver many health benefits, including prevention of cardiovascular disease, cancer, and osteoporosis, as well as treatment of menopausal symptoms. The science is less absolute, however, and still evolving. Soy provides a complete source of dietary protein, meaning that, unlike most plant proteins, it contains all the essential amino acids. According to the American Soybean Association, 3.14 billion bushels (85.5 million metric tons) of soybeans were harvested in the United States in 2004. Approximately half of the harvest was exported, and most of the remainder was crushed to produce oil and protein meal for domestic use. An April 2006 report from the USDA Economic Research Service indicates that only a small amount of whole soybeans are used to produce soy foods, and just 2% of soy protein meal is used for human consumption; the rest is used for animal feed. The Soyfoods Association of North America reports that U.S. sales of soy foods reached $3.9 billion in 2003, continuing an 11-year trend of 15% average annual increases. According to the United Soybean Board’s 2004–2005 Consumer Attitudes About Nutrition report, 25% of Americans consume soy foods or beverages at least once per week, and 74% view soy products as healthy. Nevertheless, Americans as a whole still consume very little soy protein. Based on 2003 data from the UN Food and Agriculture Organization, per-capita soy protein consumption is less than 1 gram (g) per day in most European and North American countries, although certain subpopulations such as vegetarians, Asian immigrants, and infants fed soy-based formula consume more. The Japanese, on the other hand, consume an average 8.7 g of soy protein per day; Koreans, 6.2–9.6 g; Indonesians, 7.4 g; and the Chinese, 3.4 g. Traditional soy foods include tofu, which is produced by pureeing cooked soybeans and precipitating the solids, and miso and tempeh, which are made by fermenting soybeans with grains. “Second generation” soy products involve chemical extractions and other processing, and include soy protein isolate and soy flour. These products become primary ingredients in items such as meatless burgers, dietary protein supplements, and infant formula, and are also used as nonnutritive additives to improve the characteristics of processed foods.