Gangliosides as Signaling Regulators in Cancer

At the plasma membrane, gangliosides, a group of glycosphingolipids, are expressed along with glycosphingolipids, phospholipids, and cholesterol in so-called lipid rafts that interact with signaling receptors and related molecules. Most cancers present abnormalities in the intracellular signal transduction system involved in tumor growth, invasion, and metastasis. To date, the roles of gangliosides as regulators of signal transduction have been reported in several cancer types. Gangliosides can be expressed by the exogenous ganglioside addition, with their endogenous expression regulated at the enzymatic level by targeting specific glycosyltransferases. Accordingly, the relationship between changes in the composition of cell surface gangliosides and signal transduction has been investigated by controlling ganglioside expression. In cancer cells, several types of signaling molecules are positively or negatively regulated by ganglioside expression levels, promoting malignant properties. Moreover, antibodies against gangliosides have been shown to possess cytotoxic effects on ganglioside-expressing cancer cells. In the present review, we highlight the involvement of gangliosides in the regulation of cancer cell signaling, and we explore possible therapies targeting ganglioside-expressing cancer.     

Peripheral Vascular Abnormalities in Anorexia Nervosa: A Psycho-Neuro-Immune-Metabolic Connection

Immune, neuroendocrine, and autonomic nervous system dysregulation in anorexia nervosa lead to cardiovascular complications that can potentially result in increased morbidity and mortality. It is suggested that a complex non-invasive assessment of cardiovascular autonomic regulation—cardiac vagal control, sympathetic vascular activity, and cardiovascular reflex control—could represent a promising tool for early diagnosis, personalized therapy, and monitoring of therapeutic interventions in anorexia nervosa particularly at a vulnerable adolescent age. In this view, we recommend to consider in the diagnostic route, at least in the subset of patients with peripheral microvascular symptoms, a nailfold video-capillaroscopy as an easy not invasive tool for the early assessing of possible cardiovascular involvement.     

In anorexia nervosa and associated factors in female adolescents city in south of Brazil

The objective was to identify the prevalence of anorexia nervosa symptoms and its associations with body mass index (BMI) and body size satisfaction among female adolescents. It is a cross-sectional population based study of 407 adolescents aged between 14 and 19, including the BMI assessment, the Eating Attitude Test and the Silhouette Scale. The association between the dependent and independent variables was performed by the univariate analyses and followed by a multivariate analysis with adjusted logistic model. The prevalence of symptoms of anorexia nervosa was 15.97%, and the adolescents who are dissatisfied with their body image have 2.56 (IC 1,11-5,83) times increased risk of developing symptoms of anorexia. Most of them are eutrophic (83.78%), and there was no connection between the presence of symptoms of anorexia and the BMI. The results suggest that body dissatisfaction is related to the symptoms of anorexia, which indicates the need of a multidisciplinary performance with the population.     

HDL Cholesterol and Non-Cardiovascular Disease: A Narrative Review

High density lipoprotein (HDL) cholesterol has traditionally been considered the “good cholesterol”, and most of the research regarding HDL cholesterol has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within atherosclerotic cardiovascular disease. Randomized trials aiming at increasing HDL cholesterol have, however, failed and left questions to what role HDL cholesterol plays in human health and disease. Recent observational studies involving non-cardiovascular diseases have shown that high levels of HDL cholesterol are not necessarily associated with beneficial outcomes as observed for age-related macular degeneration, type II diabetes, dementia, infection, and mortality. In this narrative review, we discuss these interesting associations between HDL cholesterol and non-cardiovascular diseases, covering observational studies, human genetics, and plausible mechanisms.     

Dietary fat in the prevention of cardiovascular disease — a review

In developed countries atherosclerotic cardiovascular disease is the reason for about 50% of all deaths. With growing prosperity coronary heart disease (CHD) is becoming the major cause of premature death. Most complications of atherosclerosis occur unexpectedly and more than 50% of the patients developing a myocardial infarction do not survive more than one year. Because of the severe morbidity and high mortality primary prevention is likely to be the only solution. Epidemiological studies show a strong, positive relationship between plasma cholesterol concentrations and the incidence of CHD. People who immigrate from low‐risk to high‐risk areas usually acquire similar plasma cholesterol levels as the native population and a similar CHD risk. This demonstrates that environmental rather than genetic factors lead to the differences in cardiovascular risk and supports the notion that nutrition and lifestyle play a major role. The association between dietary intake of fat and cholesterol and the extent of atherosclerosis and CHD has been recognized in previous studies. The amount of saturated fat in the diet correlates stronger with the incidence of CHD than with total fat intake. The consumption of unsaturated fatty acids, however, appears to be beneficial, since it is inversely correlated with the plasma cholesterol concentration and risk of myocardial infarction. Lately additional nutritional factors like trans fatty acids with a negative influence on risk as well as positive factors like linolenic acid have attracted much attention. In conclusion, as a challenge to public health, preventive medicine needs to focus on changes in dietary habits with priority, particularly fat modification. A nutrition low in total fat primarily avoiding saturated and trans fatty acids, but rich in fruit and vegetables should be recommended.     

Relation of total cholesterol in serum tocopherols, probabilistic study in Mexican children

Epidemiological studies have shown the effect of nutritional status of tocopherols and development of cardiovascular diseases that now are more frequent during early years of life. In this work we evaluated the association between the total cholesterol and serum levels of tocopherols in a population of Mexican children in whom we measured the oxidant status and antioxidant capacity (December 2003). In 1155 children (12-59 months) residents of urban and rural locations we quantified in serum alpha-tocopherol, gamma-tocopherol and total cholesterol; the antioxidant capacity and oxidative status were evaluated with the production of TBARS. Children with serum cholesterol < 170 mg/dL had an average of 472.5 +/- 179.6 microg/dL tocopherol in serum and > or = 240 mg/dL cholesterol recorded an average of 577.3 +/- 200.8 microg/dL. However, when tocopherols were expressed in relation to total cholesterol (micromol/mmol) found that children with < 170 mg/dL had the highest ratios (3.06 +/-1.19) which places them in an adequate nutritional status of tocopherol, unlike the group with > or = 240 mg/dL of cholesterol in whom the relationship was low (1.93 +/- 0.69). There were no differences in serum antioxidant capacity, but if in the production of TBARS for children with > or = 200 mg/dL cholesterol. In preschools the increases in total cholesterol limits the availability of serum tocopherol for circulating lipids, this condition over time could determine the early development of vascular injury mediated by oxidative stress.     

The evidence for the antiatherogenicity of high density lipoprotein in man

It has long been recognized that patients with clinical coronary heart disease (CHD) have, on average, higher concentrations of plasma very low density and low density lipoproteins than do healthy subjects. The same, studies clearly demonstrated that coronary victims tend also to have low plasma concentrations of high density lipoprotein (HDL). It is only recently, however, that the possible significance of this second observation has been examined. Direct evidence for an inverse relationship between HDL cholesterol concentration and the prevalence of clinical CHD, independent of other plasma lipoproteins, has been provided by the Honolulu Heart and Cooperative Lipoprotein Phenotyping Studies. The Tromsø Heart and Framingham Studies subsequently demonstrated that this relationship precedes the clinical manifestation of coronary disease. More recently, angiographic studies have confirmed that the severity of existing coronary atherosclerosis is inversely related to HDL cholesterol concentration. Other investigations have shown that coronary victims also have low mean concentrations of apolipoproteins AI and AII (the major protein components of HDL), although the reduction of apoAI concentration may be less marked than that of HDL cholesterol, and preliminary findings from Tromsø have suggested that apolipoprotein AI may be less powerful than HDL cholesterol as a predictor of CHD. Such observations have supported the proposal that HDL may exert a protective effect against coronary atherosclerosis. Final confirmation (or otherwise) of this hypothesis, however, must await the results of carefully controlled animal experiments and of regression studies in patients with angiographically defined atherosclerosis.     

Soya protein and athersclerosis

Cholesterol-free, semipurified diets produce hypercholesterolemia and atherosclerosis in rabbits when casein is used as dietary protein, but not when the casein is replaced by soya protein. In general, animal proteins produce higher levels of plasma cholesterol in rabbits than plant proteins. At least part of this difference appears to be related to differences in the amino acid composition of the proteins. Rabbits fed soya protein had a faster turnover of plasma cholesterol, absorbed cholesterol from the intestine less readily, and excreted more fecal neutral sterols and bile acids than rabbits fed casein. Differences in composition and turnover of plasma lipoproteins were also observed. Some, but not all, studies on humans with either normal or elevated levels of plasma cholesterol have shown that these levels can be lowered by replacing animal protein in the diet by soya protein. Epidemiological data have also provided evidence of an association between coronary heart disease and amount of animal protein in the diet. Relatively small changes in the diet can substantially decrease the ratio of animal to plant protein, and this may offer a means of lowering serum cholesterol levels and decreasing the high incidence of coronary heart disease in industrialized countries. The use of soya protein for this purpose minimizes the risk of essential amino acid deficiency, because its amino acid composition tends to complement that of cereal proteins, which are the major source of plant protein in most human diets.     

Fatty acid profile and affective dysregulation in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with a high co-occurrence with affective dysregulation. Affective disorders have been associated with specific changes in the PUFA and cholesterol profile. In IBS, similar changes may be present as have been reported in patients with affective disorders. This exploratory study investigates (i) the level of affective dysregulation (AD) in IBS patients and healthy controls; (ii) PUFA and cholesterol profiles in IBS patients compared with controls; and (iii) associations between PUFA and cholesterol parameters with the level of AD. Blood samples were obtained for determination of the FA composition of plasma phospholipids and serum cholesterol in 23 diarrheapredominant IBS patients and 23 healthy matched controls. AD was scored using the Symptom Check List depression scale, the Hospital Anxiety and Depression Scale, and the Hamilton Depression Rating Scale. The level of AD was higher in IBS patients compared with controls. PUFA and cholesterol profiles did not differ significantly between groups. Total n−3 PUFA and cholesterol were significantly negatively associated and the ratio of n−6 to n−3 PUFA and the ratio of arachidonic acid to EPA were significantly positively associated with the level of AD. The findings of the present study reveal that AD was higher in IBS patients compared with healthy controls and that changes in PUFA and cholesterol profiles were significantly associated with the level of AD. These results warrant further studies regarding the role of PUFA and cholesterol status in the co-occurrence of AD and functional gastrointestinal disorders.     

Effects of Microbiota Imbalance in Anxiety and Eating Disorders: Probiotics as Novel Therapeutic Approaches

Anxiety and eating disorders produce a physiological imbalance that triggers alterations in the abundance and composition of gut microbiota. Moreover, the gut–brain axis can be altered by several factors such as diet, lifestyle, infections, and antibiotic treatment. Diet alterations generate gut dysbiosis, which affects immune system responses, inflammation mechanisms, the intestinal permeability, as well as the production of short chain fatty acids and neurotransmitters by gut microbiota, which are essential to the correct function of neurological processes. Recent studies indicated that patients with generalized anxiety or eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorders) show a specific profile of gut microbiota, and this imbalance can be partially restored after a single or multi-strain probiotic supplementation. Following the PRISMA methodology, the current review addresses the main microbial signatures observed in patients with generalized anxiety and/or eating disorders as well as the importance of probiotics as a preventive or a therapeutic tool in these pathologies.     

Hyperlipidemia and premature arteriosclerosis

In the last decade, understanding of the relationship between plasma lipoprotein concentrations and arteriosclerosis has advanced considerably. Prospective and case-control epidemiologic studies in the general population have established a direct correlation between low density lipoprotein and an inverse correlation between high density lipoprotein concentrations and the risk of coronary disease. Detailed studies of patients and families with genetic hypercholesterolemia, hypertriglyceridemia, and combined hypercholesterolemia hypertriglyceridemia have identified subpopulations at particular risk. Skin fibroblast lines from patients with genetic hyperlipidemias have been used to provide important new information on the regulation by plasma lipoproteins of cellular cholesterol metabolism. We are entering a phase of investigation where epidemiological and biochemical data supplement each other in such a way that the old hypothesis linking plasma lipids to atherosclerosis has new life.     

Issues concerning the monitoring of statin therapy in hypercholesterolemic subjects with high plasma lipoprotein (a) levels

Most studies on the topic have shown that statin therapy decreases plasma LDL levels but not those of lipoprotein(a) [Lp(a)]. This specificity of action, although previously noted, has not been systematically investigated. In the current study we approached this problem by monitoring LDL- and Lp(a) cholesterol in 80 hypercholesterolemic subjects with high Lp(a) levels, at entry and 8 mon after initiation of statin therapy. We found that commonly used direct and indirect LDL cholesterol assays gave an LDL cholesterol value that comprised both true LDL- and Lp(a) cholesterol. We estimated these two analytes from the values of Lp(a) protein determined by FLISA and from knowledge of the Lp(a) chemical composition, complemented by data from immunochemical and ultracentrifugal analyses. Statin therapy, while not affecting plasma Lp(a) protein levels (21.7±10.4, before, and 22.0±10.1 mg/dL, after), caused a decrease in the estimated or true LDL cholesterol (P<0.0001) to values in some cases as low as 10 mg/dL. This drop in true LDL was validated by the decrease in the LDL band in the ultracentrifugation profiles, and its magnitude was proportional to the degree of total cholesterol lowering and to the pretreatment true LDL/Lp(a) cholesterol weight ratio. We conclude that true LDL but not Lp(a) cholesterol is affected by statin therapy and that this specific response cannot be monitored by current LDL cholesterol assays and must, rather, rely on estimates of these two analytes.     

Effect of copper supplementation on lipid profile of Venezuelan hyperlipemic patients

It has been assumed that most Western diets satisfy the requirement of copper/day because of ubiquitous presence of this element in most foods. Recent studies have shown that dietary copper (Cu) may often fall below the estimated daily requirements, what could determine a deficiency of this trace element. This deficiency is associated with hypercholesterolemia and hypertrigliceridemia, both in human and experimental animals. In the present intervention study was examined the effect of the administration of 5 mg of Cu/day in 73 patients (treated group), of both genders, with ages between 26 and 48 years, with high serum levels of total cholesterol and triglycerides without pharmacological treatment and compared with 73 hyperlipemic subjects non-treated with copper (control group) who were matched by gender, age, body weight, smoking habits, calories and fat intake, and physical activity. Before copper administration, a sample of blood was obtained for serum determinations of copper, zinc and lipids. At the end of the experimental period (45 days), a new sample of blood was taken for the corresponding determinations. The results suggest the existence of a marginal deficiency of the trace element in 38% of the subjects and demonstrate that copper supplementation decreases (p < 0.05) serum levels of total cholesterol (r = -0.976), triglycerides (r = -0.972), LDL-cholesterol (r = -0.961) and zinc (r = -0.980) with a slight increment (r = 0.894) of HDL-cholesterol. These findings demonstrate that copper can be used in the treatment of the patients with hypercholesterolemia and hypertriglyceridemia. The mechanisms by which Cu determines these changes are not known.     

Genetic variants in SLC22A1 are related to serum lipid levels in Mexican women

Dyslipidemia is the main risk factor for coronary artery disease and is characterized by alterations in concentrations of lipids, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triacylglycerols. The participation of several genes in the development of dyslipidemia has been evidenced. Genetic variants in SLC22A1 have been associated with elevated cholesterol and LDL-c levels. The aim of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) in the SLC22A1 gene with atherogenic risk lipid levels in Mexican women. Anthropometric and biochemical measurements were performed, and four SNPs in SLC22A1 were genotyped by real-time polymerase chain reaction. The Hardy–Weinberg equilibrium was verified, and haplotype frequencies were calculated. We found significant differences between the allele frequencies of the SNPs analyzed with those reported in Mexico and in the world, which could be due to differences in the historical admixture of the women studied. Generalized linear models were evaluated to determine the association between genotypes and haplotypes with lipids levels. We identified a significant increase in total cholesterol and LDL-c levels in women who were carriers of the GA and AG genotypes of the polymorphisms rs628031 and rs594709, respectively, significant effect that is also shown in a dominant inheritance model. Interestingly, we identified an important relationship of the AGC-GAT haplotype with the elevation in LDL-c levels and AGA-GAT haplotype with the elevation in HDL-c levels. On the other hand, we found a strong linkage disequilibrium between the polymorphisms studied. Our results show that variants in the SLC22A1 gene influence serum levels of atherogenic risk lipids, suggesting that these variants probably affect the function of organic cation transporter-1 and therefore, on the regulation of lipid metabolism.     

Epigenetic Aging and Colorectal Cancer: State of the Art and Perspectives for Future Research

Although translational research has identified a large number of potential biomarkers involved in colorectal cancer (CRC) carcinogenesis, a better understanding of the molecular pathways associated with biological aging in colorectal cells and tissues is needed. Here, we aim to summarize the state of the art about the role of age acceleration, defined as the difference between epigenetic age and chronological age, in the development and progression of CRC. Some studies have shown that accelerated biological aging is positively associated with the risk of cancer and death in general. In line with these findings, other studies have shown how the assessment of epigenetic age in people at risk for CRC could be helpful for monitoring the molecular response to preventive interventions. Moreover, it would be interesting to investigate whether aberrant epigenetic aging could help identify CRC patients with a high risk of recurrence and a worst prognosis, as well as those who respond poorly to treatment. Yet, the application of this novel concept is still in its infancy, and further research should be encouraged in anticipation of future applications in clinical practice.     

Lactate Transporters in the Context of Prostate Cancer Metabolism: What Do We Know?

Metabolic changes during malignant transformation have been noted for many years in tumours. Otto Warburg first reported that cancer cells preferentially rely on glycolysis for energy production, even in the presence of oxygen, leading to the production of high levels of lactate. The crucial role of lactate efflux and exchange within the tumour microenvironment drew attention to monocarboxylate transporters (MCTs). MCTs have been recognized as promising targets in cancer therapy, and their expression was described in a large variety of tumours; however, studies showing how these isoforms contribute to the acquisition of the malignant phenotype are scarce and still unclear regarding prostate cancer. In this review, we focus on the role for MCTs in cell metabolism, supporting the development and progression of prostate cancer, and discuss the exploitation of the metabolic nature of prostate cancer for therapeutic and diagnostic purposes.     

Plasma and lipoprotein fatty acid composition in glycogen storage disease type I

Nocturnal intragastric feeding has been shown to be an effective means to improve clinical and biochemical features in glycogen storage disease type I (GSD-I). In this study, we investigated the fatty acid patterns in a whole plasma and in circulating lipoproteins in patients on this therapy. The results demonstrated massive concentration of total fatty acids coupled with higher levels of triglycerides, free cholesterol, cholesterol ester and phospholipids. This hyperlipidemia involved all fatty acids without distinction of carbon or bond numbers. However, the increase was more pronounced for saturated than polyunsaturated fatty acids, as was demonstrated by the ratios of both oleic acid to linoleic acid (1.91±0.40 vs 0.80±0.09 in controls) and of ω3+ω6 to ω9 fatty acid families (0.92±0.11 vs 1.66±0.08 in controls). The fatty acid patterns in very low (VLDL), low (LDL) and high (HDL) density lipoprotein showed substantial differences in composition, reflecting an association between an abnormal lipoprotein pattern and essential fatty acid deficiency. Furthermore, GSD-I patients exhibited a significant increase in VLDL (17±2 vs 47±7 mg/dl) and LDL cholesterol (124±7 vs 206±24 mg/dl), coupled with a decrease in HDL cholesterol (49±4 vs 28±3 mg/dl). These data documenting high LDL cholesterol and low HDL cholesterol associated with an increased concentration and proportion of saturated fatty acids suggest that GSD-I patients on nocturnal intragastric feeding are at high risk for atherosclerosis and its complications.     

Influence of Benzo(a)pyrene on Different Epigenetic Processes

Epigenetic changes constitute one of the processes that is involved in the mechanisms of carcinogenicity. They include dysregulation of DNA methylation processes, disruption of post-translational patterns of histone modifications, and changes in the composition and/or organization of chromatin. Benzo(a)pyrene (BaP) influences DNA methylation and, depending on its concentrations, as well as the type of cell, tissue and organism it causes hypomethylation or hypermethylation. Moreover, the exposure to polyaromatic hydrocarbons (PAHs), including BaP in tobacco smoke results in an altered methylation status of the offsprings. Researches have indicated a potential relationship between toxicity of BaP and deregulation of the biotin homeostasis pathway that plays an important role in the process of carcinogenesis. Animal studies have shown that parental-induced BaP toxicity can be passed on to the F1 generation as studied on marine medaka (Oryzias melastigma), and the underlying mechanism is likely related to a disturbance in the circadian rhythm. In addition, ancestral exposure of fish to BaP may cause intergenerational osteotoxicity in non-exposed F3 offsprings. Epidemiological studies of lung cancer have indicated that exposure to BaP is associated with changes in methylation levels at 15 CpG; therefore, changes in DNA methylation may be considered as potential mediators of BaP-induced lung cancer. The mechanism of epigenetic changes induced by BaP are mainly due to the formation of CpG-BPDE adducts, between metabolite of BaP—BPDE and CpG, which leads to changes in the level of 5-methylcytosine. BaP also acts through inhibition of DNA methyltransferases activity, as well as by increasing histone deacetylases HDACs, i.e., HDAC2 and HDAC3 activity. The aim of this review is to discuss the mechanism of the epigenetic action of BaP on the basis of the latest publications.