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Title:
Cancer as a mitochondrial metabolic disease
Authors:
Seyfried, Thomas N.
Abstract:
Cancer is widely considered a genetic disease involving nuclear mutations in oncogenes and tumor suppressor genes. This view persists despite the numerous inconsistencies associated with the somatic mutation theory. In contrast to the somatic mutation theory, emerging evidence suggests that cancer is a mitochondrial metabolic disease, according to the original theory of Otto Warburg. The findings are reviewed from nuclear cytoplasm transfer experiments that relate to the origin of cancer. The evidence from these experiments is difficult to reconcile with the somatic mutation theory, but is consistent with the notion that cancer is primarily a mitochondrial metabolic disease.
Published:
July 6, 2015
Title:
Emerging drugs for the treatment of anxiety
Authors:
Murrough, James W; Yaqubi, Sahab; Sayed, Sehrish; Charney, Dennis S
Abstract:
Introduction—Anxiety disorders are among the most prevalent and disabling psychiatric disorders in the United States and worldwide. Basic research has provided critical insights into the mechanism regulating fear behavior in animals and a host of animal models have been developed in order to screen compounds for anxiolytic properties. Despite this progress, no mechanistically novel agents for the treatment of anxiety have come to market in more than two decades.
Published:
July 2, 2015
Title:
NREM-sleep Associated Epileptiform Discharges Disappeared Following a Shift toward the Paleolithic Ketogenic Diet in a Child with Extensive Cortical Malformation
Authors:
Clemens, Zsofia; Kelemen, Anna; Tóth, Csaba
Abstract:
Purpose: Although the classical ketogenic diet is an effective treatment in childhood epilepsy, it is difficult to maintain on the long term due to side-effects and dislike. Methods: Here we report a case of a child with frequent epileptiform discharges confined to non-rapid-eye-movement (NREM) sleep and extensive cortical malformation. The child was started on a modified version of the classical ketogenic diet we refer to as the paleolithic ketogenic diet. Results: Subsequent follow-up electroencephalograms showed complete normalization of brain electric activity along with cognitive improvement. Neither antiepileptic medication nor vitamin supplements were used. The child strongly adhered to the diet as assessed by regular urinary ketone tests and laboratory work ups. Currently she is on the diet for 17 months. Neither side effects nor clinical signs of nutrient deficiency were observed. Conclusion: We conclude that the paleolithic ketogenic diet was effective, safe and feasible in this case.
Published:
July 2, 2015
Title:
Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired nitric oxide signalling
Authors:
Scallan, Joshua P.; Hill, Michael A.; Davis, Michael J.
Abstract:
Aims Lymphatic vessel dysfunction is an emerging component of metabolic diseases and can lead to tissue lipid accumulation, dyslipidaemia, and oedema. While lymph leakage has been implicated in obesity and hypercholesterolaemia, whether similar lymphatic dysfunction exists in diabetes has not been investigated. Methods and results To measure the lymphatic integrity of transgenic mice, we developed a new assay that quantifies the solute permeability of murine collecting lymphatic vessels. Compared with age-matched wild-type (WT) controls, the permeability of collecting lymphatics from diabetic, leptin receptor-deficient (db/db) mice was elevated >130-fold. Augmenting nitric oxide (NO) production by suffusion of l-arginine rescued this defect. Using pharmacological tools and eNOS−/− mice, we found that NO increased WT lymphatic permeability, but reduced db/db lymphatic permeability. These conflicting actions of NO were reconciled by the finding that phosphodiesterase 3 (PDE3), normally inhibited by NO signalling, was active in db/db lymphatics and inhibition of this enzyme restored barrier function. Conclusion In conclusion, we identified the first lymphatic vascular defect in type 2 diabetes, an enhanced permeability caused by low NO bioavailability. Further, this demonstrates that PDE3 inhibition is required to maintain lymphatic vessel integrity and represents a viable therapeutic target for lymphatic endothelial dysfunction in metabolic disease.
Published:
June 30, 2015
Title:
Politicization of the Low-Carb High-Fat Diet in Sweden, Promoted On Social Media by Non-Conventional Experts
Authors:
Holmberg, Christopher
Abstract:
The low-carb high fat (LCHF) diet, a buzz diet in Sweden, is stirring dogmatic conflict between dieters and representatives from the National Food Agency (NFA), even gaining international reputation. After gathering materials from social media and press reports covering the popular diet, a thematic analysis has been conducted. The aim of this study was to investigate how three non-conventional experts and influential promoters of the LCHF movement transact their criticisms of current nutrition authorities, and how they utilize social media for their purpose. The diet has been highly politicized, creating distrust against the established scientific community. Findings indicate that events on the national level led to an increased public awareness of the LCHF diet, providing the supporters with invaluable opportunities to criticize the established nutritional community. This enabled certain prominent advocates of the diet to gain momentum while using features of social media to further the diet's believability.
Published:
June 30, 2015
Title:
#LowCarb #Ketogenic Diet Combats #Depression, #Bipolar Disorder, Aids #weightloss. http://www.celebrityhealthfitness.com/29028/low-carb-ketogenic-diet-combats-depression-bipolar-disorder-aids-weight-loss/ … via @samantha_chang #Keto #LCHF
Authors:
Sheila
Abstract:
Published:
June 19, 2015
Title:
Dental calculus reveals potential respiratory irritants and ingestion of essential plant-based nutrients at Lower Palaeolithic Qesem Cave Israel
Authors:
Hardy, Karen; Radini, Anita; Buckley, Stephen; Sarig, Rachel; Copeland, Les; Gopher, Avi; Barkai, Ran
Abstract:
Reconstructing detailed aspects of the lives of Lower Palaeolithic hominins, who lived during the Middle Pleistocene, is challenging due to the restricted nature of the surviving evidence, predominantly animal bones and stone tools. Qesem Cave, Israel (420e200 ka) is a site that has produced evidence for a wealth of innovative features including controlled use of fire, represented by a repeatedly used hearth. Numerous charred bone and stone tools as well as wood ash have been found throughout the ten metres of archaeological deposits. Here, we describe the presence of a range of potentially inhaled, and ingested, materials extracted from samples of dental calculus from the Qesem Cave hominins. These finds offer an insight into the environment in and around the cave, while micro-charcoal highlights the need for smoke management in enclosed environments. Plant fibres and a phytolith may be evidence of oral hygiene activities or of using the teeth to work raw materials. Starch granules and chemical compounds provide a direct link to ingested plant food items. This extends the evidence for consumption of plant foods containing essential nutrients including polyunsaturated fatty acids and carbohydrates, into the Lower Palaeolithic. Together, these results represent a significant breakthrough towards a better understanding of Middle Pleistocene dietary breadth and highlight some of the challenges facing the adoption of the habitual use of fire for cooking by the Qesem Cave hominins, as well as offering an insight into their ecological knowledge and technological adaptability.
Published:
June 17, 2015
Title:
Holocene Demographic Changes and the Emergence of Complex Societies in Prehistoric Australia
Authors:
Williams, Alan N.; Ulm, Sean; Turney, Chris S. M.; Rohde, David; White, Gentry
Abstract:
A continental-scale model of Holocene Australian hunter-gatherer demography and mobility is generated using radiocarbon data and geospatial techniques. Results show a delayed expansion and settlement of much of Australia following the termination of the late Pleistocene until after 9,000 years ago (or 9ka). The onset of the Holocene climatic optimum (9-6ka) coincides with rapid expansion, growth and establishment of regional populations across ~75% of Australia, including much of the arid zone. This diffusion from isolated Pleistocene refugia provides a mechanism for the synchronous spread of pan-continental archaeological and linguistic attributes at this time (e.g. Pama-Nyungan language, Panaramitee art style, backed artefacts). We argue longer patch residence times were possible at the end of the optimum, resulting in a shift to more sedentary lifestyles and establishment of low-level food production in some parts of the continent. The onset of El Niño - Southern Oscillation (ENSO; 4.5-2ka) restricted low-level food production, and resulted in population fragmentation, abandonment of marginal areas, and reduction in ranging territory of ~26%. Importantly, climate amelioration brought about by more pervasive La Niña conditions (post-2ka), resulted in an intensification of the mobility strategies and technological innovations that were developed in the early- to mid-Holocene. These changes resulted in population expansion and utilization of the entire continent. We propose that it was under these demographically packed conditions that the complex social and religious societies observed at colonial contact were formed.
Published:
June 16, 2015
Title:
Body composition in Pan paniscus compared with Homo sapiens has implications for changes during human evolution
Authors:
Zihlman, Adrienne L.; Bolter, Debra R.
Abstract:
During human evolution, the body changed in shape, partially to accommodate bipedal locomotion. Concurrently, brain size underwent a three-fold increase recorded in evidence from fossils and from comparative anatomy of chimpanzees, Homo sapiens’ closest living relatives. Because soft tissues like muscle, skin, and fat do not fossilize, and little information is available on these components for the genus Pan, reconstructing tissue changes has primarily relied on what is known about humans. This study presents unique quantitative data on major body components of muscle, bone, skin, and fat of 13 bonobos (Pan paniscus) for interpreting evolutionary forces that have shaped the human form for survival in a savanna mosaic environment., The human body has been shaped by natural selection during the past 4–5 million years. Fossils preserve bones and teeth but lack muscle, skin, fat, and organs. To understand the evolution of the human form, information about both soft and hard tissues of our ancestors is needed. Our closest living relatives of the genus Pan provide the best comparative model to those ancestors. Here, we present data on the body composition of 13 bonobos (Pan paniscus) measured during anatomical dissections and compare the data with Homo sapiens. These comparative data suggest that both females and males (i) increased body fat, (ii) decreased relative muscle mass, (iii) redistributed muscle mass to lower limbs, and (iv) decreased relative mass of skin during human evolution. Comparison of soft tissues between Pan and Homo provides new insights into the function and evolution of body composition.
Published:
June 15, 2015
Title:
Body composition in Pan paniscus compared with Homo sapiens has implications for changes during human evolution
Authors:
Zihlman, Adrienne L.; Bolter, Debra R.
Abstract:
The human body has been shaped by natural selection during the past 4–5 million years. Fossils preserve bones and teeth but lack muscle, skin, fat, and organs. To understand the evolution of the human form, information about both soft and hard tissues of our ancestors is needed. Our closest living relatives of the genus Pan provide the best comparative model to those ancestors. Here, we present data on the body composition of 13 bonobos (Pan paniscus) measured during anatomical dissections and compare the data with Homo sapiens. These comparative data suggest that both females and males (i) increased body fat, (ii) decreased relative muscle mass, (iii) redistributed muscle mass to lower limbs, and (iv) decreased relative mass of skin during human evolution. Comparison of soft tissues between Pan and Homo provides new insights into the function and evolution of body composition.
Published:
June 15, 2015
Title:
Nonalcoholic fatty liver disease: a systematic review
Authors:
Rinella, Mary E.
Abstract:
IMPORTANCE: Nonalcoholic fatty liver disease and its subtype nonalcoholic steatohepatitis affect approximately 30% and 5%, respectively, of the US population. In patients with nonalcoholic steatohepatitis, half of deaths are due to cardiovascular disease and malignancy, yet awareness of this remains low. Cirrhosis, the third leading cause of death in patients with nonalcoholic fatty liver disease, is predicted to become the most common indication for liver transplantation. OBJECTIVES: To illustrate how to identify patients with nonalcoholic fatty liver disease at greatest risk of nonalcoholic steatohepatitis and cirrhosis; to discuss the role and limitations of current diagnostics and liver biopsy to diagnose nonalcoholic steatohepatitis; and to provide an outline for the management of patients across the spectrum of nonalcoholic fatty liver disease. EVIDENCE REVIEW: PubMed was queried for published articles through February 28, 2015, using the search terms NAFLD and cirrhosis, mortality, biomarkers, and treatment. A total of 88 references were selected, including 16 randomized clinical trials, 44 cohort or case-control studies, 6 population-based studies, and 7 meta-analyses. FINDINGS: Sixty-six percent of patients older than 50 years with diabetes or obesity are thought to have nonalcoholic steatohepatitis with advanced fibrosis. Even though the ability to identify the nonalcoholic steatohepatitis subtype within those with nonalcoholic fatty liver disease still requires liver biopsy, biomarkers to detect advanced fibrosis are increasingly reliable. Lifestyle modification is the foundation of treatment for patients with nonalcoholic steatosis. Available treatments with proven benefit include vitamin E, pioglitazone, and obeticholic acid; however, the effect size is modest (
Published:
June 8, 2015
Title:
A Comparison of the Mouse and Human Lipoproteome: Suitability of the Mouse Model for Studies of Human Lipoproteins
Authors:
Gordon, Scott M.; Li, Hailong; Zhu, Xiaoting; Shah, Amy S.; Lu, L. Jason; Davidson, W. Sean
Abstract:
Plasma levels of low density lipoproteins (LDL) and high density lipoproteins (HDL) exhibit opposing associations with cardiovascular disease in human populations and mouse models have been heavily used to derive a mechanistic understanding of these relationships. In humans, recent mass spectrometry studies have revealed that the plasma lipoproteome is significantly more complex than originally appreciated. This is particularly true for HDL which contains some 90 distinct proteins, a majority of which play functional roles that go beyond those expected for simple lipid transport. Unfortunately, the mouse lipoproteome remains largely uncharacterized—a significant gap given the heavy reliance on the model. Using a gel filtration chromatography and mass spectrometry analysis that targets phospholipid-bound plasma proteins, we compared the mouse lipoproteome and its size distribution to a previous, identical human analysis. We identified 113 lipid associated proteins in the mouse. In general, the protein diversity in the LDL and HDL size ranges was similar in mice versus humans, though some distinct differences were noted. For the majority of proteins, the size distributions, that is, whether a given protein was associated with large versus small HDL particles, for example, were also similar between species. Again, however, there were clear differences exhibited by a minority of proteins that may reflect metabolic differences between species. Finally, by correlating the lipid and protein size profiles, we identified five proteins that closely track with the major HDL protein, apolipoprotein A-I across both species. Thus, mice have most of the minor proteins identified in human lipoproteins that play key roles in inflammation, innate immunity, proteolysis and its inhibition, and vitamin transport. This provides support for the continued use of the mouse as a model for many aspects of human lipoprotein metabolism.,
Published:
June 4, 2015
Title:
Assessing Needs and Feasibility of Diabetes Self-management Coaching at Faith-Based Organizations for Indo-Guyanese Immigrants
Authors:
Hosler, Akiko S.; Solanki, Malini N.; Savadatti, Sanghamitra
Abstract:
PurposeThe purpose of this study is to explore barriers and needs related to diabetes care and the feasibility of diabetes self-management (DSM) ?coaching? at faith-based organizations (FBOs) for the Indo-Guyanese community in Schenectady, New York.MethodsParticipants were recruited though flyers and mass mailings, and in-depth interviews were conducted at their homes by a team of culturally matched interviewers using a semi-structured questionnaire. Characteristics of participants were compared with existing population-based data to confirm their representativeness. Responses were transcribed, coded, and summarized, and findings are presented along with selective quotations. Key dimensions of feasibility were scored and charted for visualization.ResultsFindings revealed barriers regarding diet-related knowledge and skills, access to structured DSM education, hyperglycemia control, and environmental support for physical activity. Participants responded positively to receiving free DSM coaching at their FBOs. All participants preferred a qualified health care professional such as certified diabetes educator as their coach and wanted coaching in all aspects of DSM; however, food preparation/diet was the most frequently requested specific topic. Participants uniformly disliked contact with the coach through e-mails and text messages but liked receiving periodic telephone calls at home by the coach. Overall, DSM coaching at FBOs rated high on the key dimensions of feasibility, namely, affordability, accessibility, acceptability, cultural relevance, and safety.ConclusionsThis study sheds light on the feasibility of an FBO-based DSM intervention for the Indo-Guyanese. It offers insights into developing culturally appropriate DSM intervention format and strategy.
Published:
May 31, 2015
Title:
Exploring the relationship between lifestyles, diets and genetic adaptations in humans
Authors:
Valente, Cristina; Alvarez, Luis; Marks, Sarah J.; Lopez-Parra, Ana M.; Parson, Walther; Oosthuizen, Ockie; Oosthuizen, Erica; Amorim, António; Capelli, Cristian; Arroyo-Pardo, Eduardo; Gusmão, Leonor; Prata, Maria J.
Abstract:
Background One of the most important dietary shifts underwent by human populations began to occur in the Neolithic, during which new modes of subsistence emerged and new nutrients were introduced in diets. This change might have worked as a selective pressure over the metabolic pathways involved in the breakdown of substances extracted from food. Here we applied a candidate gene approach to investigate whether in populations with different modes of subsistence, diet-related genetic adaptations could be identified in the genes AGXT, PLRP2, MTRR, NAT2 and CYP3A5. Results At CYP3A5, strong signatures of positive selection were detected, though not connected to any dietary variable, but instead to an environmental factor associated with the Tropic of Cancer. Suggestive signals of adaptions that could indeed be connected with differences in dietary habits of populations were only found for PLRP2 and NAT2. Contrarily, the demographic history of human populations seemed enough to explain patterns of diversity at AGXT and MTRR, once both conformed the evolutionary expectations under selective neutrality. Conclusions Accumulated evidence indicates that CYP3A5 has been under adaptive evolution during the history of human populations. PLRP2 and NAT2 also appear to have been modelled by some selective constrains, although clear support for that did not resist to a genome wide perspective. It is still necessary to clarify which were the biological mechanisms and the environmental factors involved as well as their interactions, to understand the nature and strength of the selective pressures that contributed to shape current patterns of genetic diversity at those loci. Electronic supplementary material The online version of this article (doi:10.1186/s12863-015-0212-1) contains supplementary material, which is available to authorized users.
Published:
May 27, 2015
Title:
Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models
Authors:
Bianchi, Giovanna; Martella, Roberto; Ravera, Silvia; Marini, Cecilia; Capitanio, Selene; Orengo, Annamaria; Emionite, Laura; Lavarello, Chiara; Amaro, Adriana; Petretto, Andrea; Pfeffer, Ulrich; Sambuceti, Gianmario; Pistoia, Vito; Raffaghello, Lizzia; Longo, Valter D.
Abstract:
Tumor chemoresistance is associated with high aerobic glycolysis rates and reduced oxidative phosphorylation, a phenomenon called “Warburg effect” whose reversal could impair the ability of a wide range of cancer cells to survive in the presence or absence of chemotherapy. In previous studies, Short-term-starvation (STS) was shown to protect normal cells and organs but to sensitize different cancer cell types to chemotherapy but the mechanisms responsible for these effects are poorly understood. We tested the cytotoxicity of Oxaliplatin (OXP) combined with a 48hour STS on the progression of CT26 colorectal tumors. STS potentiated the effects of OXP on the suppression of colon carcinoma growth and glucose uptake in both in vitro and in vivo models. In CT26 cells, STS down-regulated aerobic glycolysis, and glutaminolysis, while increasing oxidative phosphorylation. The STS-dependent increase in both Complex I and Complex II-dependent O2 consumption was associated with increased oxidative stress and reduced ATP synthesis. Chemotherapy caused additional toxicity, which was associated with increased succinate/Complex IIdependent O2 consumption, elevated oxidative stress and apoptosis .
Published:
May 19, 2015
Title:
Fasting potentiates the anticancer activity of tyrosine kinase inhibitors by strengthening MAPK signaling inhibition
Authors:
Caffa, Irene; D’Agostino, Vito; Damonte, Patrizia; Soncini, Debora; Cea, Michele; Monacelli, Fiammetta; Odetti, Patrizio; Ballestrero, Alberto; Provenzani, Alessandro; Longo, Valter D.; Nencioni, Alessio
Abstract:
Tyrosine kinase inhibitors (TKIs) are now the mainstay of treatment in many types of cancer. However, their benefit is frequently short-lived, mandating the search for safe potentiation strategies. Cycles of fasting enhance the activity of chemo-radiotherapy in preclinical cancer models and dietary approaches based on fasting are currently explored in clinical trials. Whether combining fasting with TKIs is going to be potentially beneficial remains unknown. Here we report that starvation conditions increase the ability of commonly administered TKIs, including erlotinib, gefitinib, lapatinib, crizotinib and regorafenib, to block cancer cell growth, to inhibit the mitogen-activated protein kinase (MAPK) signaling pathway and to strengthen E2F-dependent transcription inhibition. In cancer xenografts models, both TKIs and cycles of fasting slowed tumor growth, but, when combined, these interventions were significantly more effective than either type of treatment alone. In conclusion, cycles of fasting or of specifically designed fasting-mimicking diets should be evaluated in clinical studies as a means to potentiate the activity of TKIs in clinical use.
Published:
May 19, 2015
Title:
History of Salads and Salad Dressings
Authors:
Stradley, Linda
Abstract:
History of Salads: What exactly is the definition of salad? Everyone's definition of salad seems to be different. Salads can be an entree or side dish that is prepared and
Published:
May 19, 2015
Title:
Selenium and chronic diseases: a nutritional genomics perspective
Authors:
Méplan, Catherine
Abstract:
Mechanistic data have revealed a key role for selenium (Se) and selenoproteins in biological pathways known to be altered in multifactorial diseases, such as cellular maintenance, response to oxidative stress and correct protein folding. Although epidemiological studies indicate that low Se intake is linked to increased risk for various chronic diseases, supplementation trials have given confusing outcomes, suggesting that additional genetic factors could affect the relationship between Se and health. Genetic data support this hypothesis, as risk for several chronic diseases, in particular cancer, was linked to a number of single nucleotide polymorphisms (SNP) altering Se metabolism, selenoprotein synthesis or activity. Interactions between SNPs in selenoprotein genes, SNPs in related molecular pathways and biomarkers of Se status were found to further modulate the genetic risk carried by the SNPs. Taken together, nutritional genomics approaches uncovered the potential implication of some selenoproteins as well as the influence of complex interactions between genetic variants and Se status in the aetiology of several chronic diseases. This review discusses the results from these genetic associations in the context of selenoprotein functions and epidemiological investigations and emphasises the need to assess in future studies the combined contribution of Se status, environmental stress, and multiple or individual SNPs to disease risk.
Published:
May 14, 2015
Title:
The Natural Olive Constituent Oleuropein Induces Nutritional Cardioprotection in Normal and Cholesterol-Fed Rabbits: Comparison with Preconditioning
Authors:
Andreadou, Ioanna; Benaki, Dimitra; Efentakis, Panagiotis; Bibli, Sofia-Iris; Milioni, Alkistis-Ioanna; Papachristodoulou, Anastasia; Zoga, Anastasia; Skaltsounis, Alexios-Leandros; Mikros, Emmanuel; Iliodromitis, Efstathios K.
Abstract:
Ischemic preconditioning, which is mediated by cell signaling molecules, protects the heart from ischemia-reperfusion injury by limiting the infarct size. Oleuropein, the main polyphenolic constituent of olives, reduced the infarct size in normal and cholesterol-fed rabbits when it was administered at a nutritional dose. The aim of the present study was to compare the effects of oleuropein and preconditioning in terms of the cell signaling and metabolism pathways underlying myocardial protection. Rabbits were randomly divided into six groups: the control group received 5% dextrose for six weeks, the preconditioning group was subjected to two cycles of preconditioning with 5 min ischemia/10 min reperfusion, the O6 group was treated with oleuropein for six weeks, the Chol group was fed a cholesterol-enriched diet and 5% dextrose for six weeks, and the CholO6 and CholO3 groups were treated with cholesterol and oleuropein for six and three weeks, respectively; oleuropein was dissolved in 5 % dextrose solution and was administered orally at a dose of 20 mg x kg-1 x day-1. All animals were subsequently subjected to 30 min myocardial ischemia followed by 10 min of reperfusion. At that time, myocardial biopsies were taken from the ischemic areas for the assessment of oxidative and nitrosative stress biomarkers (malondialdehyde and nitrotyrosine), and determination of phosphorylation of signaling molecules involved in the mechanism of preconditioning (PI3K, Akt, eNOS, AMPK, STAT3). The tissue extracts NMR metabolic profile was recorded and further analyzed by multivariate statistics. Oxidative biomarkers were significantly reduced in the O6, CholO6, and CholO3 groups compared to the control, preconditioning, and Chol groups. Considering the underlying signaling cascade, the phosphorylation of PI3K, Akt, eNOS, AMPK, and STAT-3 was significantly higher in the preconditioning and all oleuropein-treated groups compared to the control and Chol groups. The NMR-based metabonomic study, performed through the analysis of spectroscopic data, depicted differences in the metabolome of the various groups with significant alterations in purine metabolism. In conclusion, the addition of oleuropein to a normal or hypercholesterolemic diet results in a preconditioning-like intracellular effect, eliminating the deleterious consequences of ischemia and hypercholesterolemia, followed by a decrease of oxidative stress biomarkers. This effect is exerted through inducing preconditioning-involved signaling transduction. Nutritional preconditioning may support the low cardiovascular morbidity and mortality associated with the consumption of olive products.
Published:
May 14, 2015
Title:
Screening for dysglycaemia in patients with coronary artery disease as reflected by fasting glucose, oral glucose tolerance test, and HbA1c: a report from EUROASPIRE IV--a survey from the European Society of Cardiology
Authors:
Gyberg, Viveca; De Bacquer, Dirk; Kotseva, Kornelia; De Backer, Guy; Schnell, Oliver; Sundvall, Jouko; Tuomilehto, Jaakko; Wood, David; Rydén, Lars; EUROASPIRE IV Investigators
Abstract:
AIMS: Three methods are used to identify dysglycaemia: fasting plasma glucose (FPG), 2-h post-load plasma glucose (2hPG) from the oral glucose tolerance test (OGTT), and glycated haemoglobin A1c (HbA1c). The aim was to describe the yield and concordance of FPG, HbA1c, and 2hPG alone, or in combination, to identify dysglycaemia in patients with coronary artery disease. METHODS AND RESULTS: In EUROASPIRE IV, a cross-sectional survey of patients aged 18-80 years with coronary artery disease in 24 European countries, 4004 patients with no reported history of diabetes had FPG, 2hPG, and HbA1c measured. All participants were divided into different glycaemic categories according to the ADA and WHO criteria for dysglycaemia. Using all screening tests together, 1158 (29%) had undetected diabetes. Out of them, the proportion identified by FPG was 75%, by 2hPG 40%, by HbA1c 17%, by FPG + HbA1c 81%, and by OGTT (=FPG + 2hPG) 96%. Only 7% were detected by all three methods FPG, 2hPG, and HbA1c. The ADA criteria (FPG + HbA1c) identified 90% of the population as having dysglycaemia compared with 73% with the WHO criteria (OGTT = FPG + 2hPG). Screening according to the ADA criteria for FPG + HbA1c identified 2643 (66%) as having a 'high risk for diabetes', while the WHO criteria for FPG + 2hPG identified 1829 patients (46%). CONCLUSION: In patients with established coronary artery disease, the OGTT identifies the largest number of patients with previously undiagnosed diabetes and should be the preferred test when assessing the glycaemic state of such patients.
Published:
May 13, 2015
Title:
Two distinct etiologies of gastric cardia adenocarcinoma: interactions among pH, Helicobacter pylori, and bile acids
Authors:
Mukaisho, Ken-ichi; Nakayama, Takahisa; Hagiwara, Tadashi; Hattori, Takanori; Sugihara, Hiroyuki
Abstract:
Gastric cancer can be classified as cardia and non-cardia subtypes according to the anatomic site. Although the gastric cancer incidence has decreased steadily in several countries over the past 50 years, the incidence of cardia cancers and esophageal adenocarcinoma (EAC) continue to increase. The etiological factors involved in the development of both cardia cancers and EACs are associated with high animal fat intake, which causes severe obesity. Central obesity plays roles in cardiac-type mucosa lengthening and partial hiatus hernia development. There are two distinct etiologies of cardia cancer subtypes: one associated with gastroesophageal reflux (GER), which predominantly occurs in patients without Helicobacter pylori (H. pylori) infection and resembles EAC, and the other associated with H. pylori atrophic gastritis, which resembles non-cardia cancer. The former can be developed in the environment of high volume duodenal content reflux, including bile acids and a higher acid production in H. pylori–negative patients. N-nitroso compounds, which are generated from the refluxate that includes a large volume of bile acids and are stabilized in the stomach (which has high levels of gastric acid), play a pivotal role in this carcinogenesis. The latter can be associated with the changing colonization of H. pylori from the distal to the proximal stomach with atrophic gastritis because a high concentration of soluble bile acids in an environment of low acid production is likely to act as a bactericide or chemorepellent for H. pylori in the distal stomach. The manuscript introduces new insights in causative factors of adenocarcinoma of the cardia about the role of bile acids in gastro-esophageal refluxate based upon robust evidences supporting interactions among pH, H. pylori, and bile acids.
Published:
May 10, 2015
Title:
Food, Immunity, and the Microbiome
Authors:
Tilg, Herbert; Moschen, Alexander R.
Abstract:
There is increasing evidence that ingested diet-borne components are involved in the pathogenesis of disorders such as inflammatory bowel diseases, atherosclerosis, and type 2 diabetes. Nutrients can have short- and long-term effects in shaping the composition of the microbiota. Western diets (enriched in fat, phosphatidylcholine, and L-carnitine) promote inflammation and atherosclerosis through specific fatty acids and degradation products such as trimethylamine N-oxide. Other dietary factors such as carbazoles or tryptophan-enriched proteins have anti-inflammatory properties—partly via activation of aryl hydrocarbon receptors. The microbiota and its metabolic machinery produce a myriad of metabolites that serve as important messengers between the diet, microbiota, and host. Short-chain fatty acids affect immune responses and epithelial integrity via G-protein–coupled receptors and epigenetic mechanisms. By increasing our understanding of interactions between diet, immunity, and the microbiota, we might develop food-based approaches to prevent or treat many diseases. There now is scientific evidence to support the adage “we are what we eat,” and this process begins in early life.
Published:
April 30, 2015
Title:
Fasting blood glucose and HbA1c in children with ADHD
Authors:
Lindblad, Frank; Eickhoff, Malin; Forslund, Anders H.; Isaksson, Johan; Gustafsson, Jan
Abstract:
Reports of hypocortisolism and overweight in pediatric ADHD motivate an investigation of blood glucose regulation in this group. Fasting blood glucose and HbA1c were investigated in 10 children (10-15 years) with ADHD and 22 comparisons. Fasting blood glucose was similar in both groups. HbA1c values were higher in the ADHD-group. BMI-SDS was also higher in the ADHD-group but did not predict HbA1c. The results suggest an association between ADHD and an altered blood glucose homeostasis.
Published:
April 29, 2015
Title:
Fat, fibre and cancer risk in African Americans and rural Africans
Authors:
O'Keefe, Stephen J. D.; Li, Jia V.; Lahti, Leo; Ou, Junhai; Carbonero, Franck; Mohammed, Khaled; Posma, Joram M.; Kinross, James; Wahl, Elaine; Ruder, Elizabeth; Vipperla, Kishore; Naidoo, Vasudevan; Mtshali, Lungile; Tims, Sebastian; Puylaert, Philippe G. B.; DeLany, James; Krasinskas, Alyssa; Benefiel, Ann C.; Kaseb, Hatem O.; Newton, Keith; Nicholson, Jeremy K.; de Vos, Willem M.; Gaskins, H. Rex; Zoetendal, Erwin G.
Abstract:
Rates of colon cancer are much higher in African Americans (65:100,000) than in rural South Africans (
Published:
April 27, 2015
Title:
Acetone as biomarker for ketosis buildup capability--a study in healthy individuals under combined high fat and starvation diets
Authors:
Prabhakar, Amlendu; Quach, Ashley; Zhang, Haojiong; Terrera, Mirna; Jackemeyer, David; Xian, Xiaojun; Tsow, Francis; Tao, Nongjian; Forzani, Erica S.
Abstract:
BACKGROUND: Ketogenic diets are high fat and low carbohydrate or very low carbohydrate diets, which render high production of ketones upon consumption known as nutritional ketosis (NK). Ketosis is also produced during fasting periods, which is known as fasting ketosis (FK). Recently, the combinations of NK and FK, as well as NK alone, have been used as resources for weight loss management and treatment of epilepsy. METHODS: A crossover study design was applied to 11 healthy individuals, who maintained moderately sedentary lifestyle, and consumed three types of diet randomly assigned over a three-week period. All participants completed the diets in a randomized and counterbalanced fashion. Each weekly diet protocol included three phases: Phase 1 - A mixed diet with ratio of fat: (carbohydrate + protein) by mass of 0.18 or the equivalence of 29% energy from fat from Day 1 to Day 5. Phase 2- A mixed or a high-fat diet with ratio of fat: (carbohydrate + protein) by mass of approximately 0.18, 1.63, or 3.80 on Day 6 or the equivalence of 29%, 79%, or 90% energy from fat, respectively. Phase 3 - A fasting diet with no calorie intake on Day 7. Caloric intake from diets on Day 1 to Day 6 was equal to each individual's energy expenditure. On Day 7, ketone buildup from FK was measured. RESULTS: A statistically significant effect of Phase 2 (Day 6) diet was found on FK of Day 7, as indicated by repeated analysis of variance (ANOVA), F(2,20) = 6.73, p
Published:
April 21, 2015
Title:
Nature: A new heart for a new head in vertebrate cardiopharyngeal evolution
Authors:
Diogo, Rui; Kelly, Robert; Christiaen, Lionel; Levine, Michael; Ziermann, Janine; Molnar, Julia; Noden, Drew; Tzahor, Eldad
Abstract:
It has been more than 30 years since the publication of the new head hypothesis, which proposed that the vertebrate head is an evolutionary novelty resulting from the emergence of neural crest and cranial placodes. Neural crest generates the skull and associated connective tissues, whereas placodes produce sensory organs. However, neither crest nor placodes produce head muscles, which are a crucial component of the complex vertebrate head. We discuss emerging evidence for a surprising link between the evolution of head muscles and chambered hearts — both systems arise from a common pool of mesoderm progenitor cells within the cardiopharyngeal field of vertebrate embryos. We consider the origin of this field in non-vertebrate chordates and its evolution in vertebrates.
Published:
April 21, 2015
Title:
AGE/RAGE/Akt pathway contributes to prostate cancer cell proliferation by promoting Rb phosphorylation and degradation
Authors:
Bao, Ji-Ming; He, Min-Yi; Liu, Ya-Wei; Lu, Yong-Jie; Hong, Ying-Qia; Luo, Hai-Hua; Ren, Zhong-Lu; Zhao, Shan-Chao; Jiang, Yong
Abstract:
Metabolomic research has revealed that metabolites play an important role in prostate cancer development and progression. Previous studies have suggested that prostate cancer cell proliferation is induced by advanced glycation end products (AGEs) exposure, but the mechanism of this induction remains unknown. This study investigated the molecular mechanisms underlying the proliferative response of prostate cancer cell to the interaction of AGEs and the receptor for advanced glycation end products (RAGE). To investigate this mechanism, we used Western blotting to evaluate the responses of the retinoblastoma (Rb), p-Rb and PI3K/Akt pathway to AGEs stimulation. We also examined the effect of knocking down Rb and blocking the PI3K/Akt pathway on AGEs induced PC-3 cell proliferation. Our results indicated that AGE-RAGE interaction enhanced Rb phosphorylation and subsequently decreased total Rb levels. Bioinformatics analysis further indicated a negative correlation between RAGE and RB1 expression in prostate cancer tissue. Furthermore, we observed that AGEs stimulation activated the PI3K/Akt signaling pathway and that blocking PI3K/Akt signaling abrogated AGEs-induced cell proliferation. We report, for the first time, that AGE-RAGE interaction enhances prostate cancer cell proliferation by phosphorylation of Rb via the PI3K/Akt signaling pathway.
Published:
April 14, 2015
Title:
Degradation and antioxidant activities of peptides and zinc-peptide complexes during in vitro gastrointestinal digestion
Authors:
Wang, Chan; Li, Bo; Wang, Bo; Xie, Ningning
Abstract:
The degradation characteristics of three peptides (Ser-Met, Asn-Cys-Ser, and glutathione) and their zinc-peptide complexes were studied using a two-stage in vitro digestion model. Enzyme-resistant peptides and zinc-peptide complexes, antioxidant activities, and free amino acids released by digestive enzymes, were measured in this study. The results revealed that the three peptides and their zinc-peptide complexes were resistant to pepsin but not to pancreatin. Pancreatin can partly hydrolyse both peptides and zinc-peptide complexes, but more than half of them remaining in their original form after gastrointestinal digestion. The coordination of zinc improved the enzymatic resistance of the peptide due to lower solubility of complexes and affected the hydrolytic site of pepsin and pancreatin. Zinc-Asn-Cys-Ser, which is highly resistant to enzymatic hydrolysis and maintains Zn in a soluble form, may have potential to improve Zn bioavailability.
Published:
April 14, 2015
Title:
The effect of vegetarian diet on skin autofluorescence measurements in haemodialysis patients
Authors:
Nongnuch, Arkom; Davenport, Andrew
Abstract:
CVD remains the major cause of death for dialysis patients. Dialysis patients have both traditional and nontraditional risk factors, including the retention of advanced glycation end products (AGE). Tissue AGE can be measured by skin autofluorescence (SAF) and are a reliable measurement of chronic exposure. Dietary intake of AGE may be lower in vegetarian patients than in non-vegetarian patients, so we determined whether vegetarian patients had lower SAF than non-vegetarian patients. We measured SAF in 332 adult haemodialysis patients using a UV technique in a standardised manner. Information about patients' demographic data, laboratory results and current medicinal prescriptions was collected retrospectively from the hospital's computerised database. The mean patient age was 65·2 (SD 15·1) years, 64 % were men, 42 % were diabetic, and 66 % were Caucasian. The mean SAF was 3·26 (SD 0·95) arbitrary units (AU), and SAF was lower in vegetarians as compared to non-vegetarians (2·71 (SD 0·6) v. 3·31 (SD 0·97) AU, P= 0·002). SAF was negatively correlated on both univariate (r -0·17, P= 0·002) and multiple linear regression (β coefficient -0·39, 95 % CI -0·7, -0·07, P= 0·019). SAF, a marker of tissue AGE deposition, was reduced in vegetarian haemodialysis patients after correction for known confounders, which suggests that a vegetarian diet may reduce exposure to preformed dietary AGE. Dietary manipulation could potentially reduce tissue AGE and SAF as well as CVD risk, but further prospective studies are warranted to confirm the present findings.
Published:
April 13, 2015
Title:
Gilbert's Syndrome Successfully Treated with the Paleolithic Ketogenic Diet
Authors:
Tóth, Csaba; Clemens, Zsofia
Abstract:
Gilbert’s syndrome (GS) is a common hyperbilirubinaemia syndrome caused by reduced conjugation of serum bilirubin by the liver. Although it is considered as a common and harmless condition not requiring treatment symptoms associated with GS may be unfavorable. Here we present a case of GS where high level of total and direct bilirubin, yellowish discoloration of the sclera as well as associated symptoms including migraine, fatigue and granulomatosus dermatitis were reversed following a shift toward the popular paleolithic and then toward the paleolithic ketogenic diet.
Published:
April 11, 2015
Title:
Vitamin D-dependent induction of cathelicidin in human macrophages results in cytotoxicity against high-grade B cell lymphoma
Authors:
Bruns, Heiko; Büttner, Maike; Fabri, Mario; Mougiakakos, Dimitrios; Bittenbring, Jörg T.; Hoffmann, Markus H.; Beier, Fabian; Pasemann, Shirin; Jitschin, Regina; Hofmann, Andreas D.; Neumann, Frank; Daniel, Christoph; Maurberger, Anna; Kempkes, Bettina; Amann, Kerstin; Mackensen, Andreas; Gerbitz, Armin
Abstract:
Infiltration by macrophages represents a characteristic morphological hallmark in high-grade lymphatic malignancies such as Burkitt's lymphoma (BL). Although macrophages can, in principle, target neoplastic cells and mediate antibody-dependent cellular cytotoxicity (ADCC), tumor-associated macrophages (TAMs) regularly fail to exert direct cytotoxic functions. The underlying mechanisms responsible for this observation remain unclear. We demonstrate that inflammatory M1 macrophages kill proliferating high-grade B cell lymphoma cells by releasing the antimicrobial peptide cathelicidin in a vitamin D-dependent fashion. We show that cathelicidin directly induces cell death by targeting mitochondria of BL cells. In contrast, anti-inflammatory M2 macrophages and M2-like TAMs in BL exhibit an altered vitamin D metabolism, resulting in a reduced production of cathelicidin and consequently in inability to lyse BL cells. However, treatment of M2 macrophages with the bioactive form of vitamin D, 1,25D3, or a vitamin D receptor agonist effectively induces cathelicidin production and triggers tumoricidal activity against BL cells. Furthermore, rituximab-mediated cytotoxicity of vitamin D-treated M2 macrophages is cathelicidin-dependent. Finally, vitamin D treatment of 25-hydroxyvitamin D (25D)-deficient volunteers in vivo or primary TAMs in vitro improves rituximab-mediated ADCC against B cell lymphoma cells. These data indicate that activation of the vitamin D signaling pathway activates antitumor activity of TAMs and improves the efficacy of ADCC.
Published:
April 7, 2015
Title:
Estimating Neanderthal seasonality: Application of tooth mesowear and microwear to the Middle Palaeolithic levels from Portel-Ouest (France) and Teixoneres (Spain)
Authors:
Sánchez-Hernández, Carlos; Rivals, Florent; Blasco, Ruth; Rosell Ardèvol, Jordi
Abstract:
The research presented here investigates patterns of Neanderthal occupation in archaeo- logical sites, which purpose is to estimate seasonality through the application of tooth mesowear and microwear analysis. The aim is to contribute to a better understanding of the occupational patterns that occurred at the sites. The combination of tooth mesowear and microwear techniques has proven very useful for documenting both long and short term patterns in the paleodietary reconstruction of fossil mammals (Sánchez-Hernández et al. 2014). Tooth mesowear reflects the cumulative wear imposed on molars during a relatively long period of feeding activity (months-years). Tooth microwear is the analysis of microscopic scars produced by food on the occlusal surface and is more sensitive to short term fluctuations (hours-days) which may not be detectable if only mesowear is considered alone. The two methods are not commonly employed in Palaeolithic archaeology to study mammal remains but they can provide valuable information about ungulate immediate behavior and are useful to detect seasonal procurement of game ungulates by hominins. It is important to note that both mesowear and microwear are non-destructive methods and allow the study of faunal assemblages of large sample sizes. These two methods were applied to two Middle Palaeolithic sites. At Teixoneres Cave (Moià, Barcelona, Spain), the levels II and III have provided a significant record belonging to the Late Pleistocene (MIS 3) (Rosell et al. 2010). The stratigraphic sequence is dated between 100.3 ± 6.1 ka and ca. 14-16 ka BP (Tissoux et al. 2006). At Portel-Ouest (Loubens, Ariège, France), we sampled three levels, from level F dated to ca. 45 ka BP (MIS 3) to level B dated to 36.3 ± 5.4 ka BP. (Bahain 2007). The high inter-specific variation observed in the microwear pattern for levels III and IIIb from Teixoneres suggest that the horse and red deer have been hunted during different events/seasons. These results are identified and interpreted as the existence of a succession of short-term occupations during the year. At Portel-Ouest, estimation of variability of the microwear patterns estimated for ungulates (horse, reindeer, and red deer) indicates short occupations. These short term occupations at Teixoneres and Portel-Ouest are put in relation with high mobility that Neanderthals groups developed throughout the territory. The discrepancy in the results from mesowear and microwear suggest a strong seasonality in the occupation of the sites by Neanderthals. In addition, through a new approach analyzing the variability of the microwear pattern it was possible to estimate that those occupations were of short duration. This study establishes the usefulness of dental wear techniques as one of many valuable proxies to obtain information about hominin paleoecology.
Published:
April 6, 2015
Title:
The functional dimensions of earth oven cooking: An analysis of an accidently burned maize roast at the C. W. Cooper site in West-central Illinois
Authors:
Wilson, Gregory D.; VanDerwarker, Amber M.
Abstract:
Despite the prevalence of earth ovens, a subclass of pit features used for cooking, there is little consensus regarding how these cooking features were used or about the foodstuffs that were prepared in them. To provide a more detailed understanding of earth oven cooking in the archaeological record, we analyze the archaeobotanical contents, stratigraphy, and morphology of a cooking pit recently excavated at C. W. Cooper, an early Mississippian (a.d. 1150–1200) site in west-central Illinois in order to contribute to research on late Prehistoric foodways. Filled with nearly 100 ears of maize, this earth oven presents the opportunity to document the process of undertaking a maize roast. The volume of maize and its presence within a dense concentration of cooking, processing, and storage facilities allows us to consider the communal nature of outdoor earth oven cooking in the 12th century Central Illinois Valley and the socioeconomic dimensions of commensal politics more broadly during the Precolumbian era.
Published:
April 5, 2015
Title:
A high-fat diet rich in corn oil reduces spontaneous locomotor activity and induces insulin resistance in mice
Authors:
Wong, Chi Kin; Botta, Amy; Pither, Jason; Dai, Chuanbin; Gibson, William T.; Ghosh, Sanjoy
Abstract:
Over the last few decades, polyunsaturated fatty acid (PUFA), especially n-6 PUFA, and monounsaturated fatty acid content in ‘Western diets’ has increased manyfold. Such a dietary shift also parallels rising sedentary behavior and diabetes in the Western world. We queried if a shift in dietary fats could be linked to physical inactivity and insulin insensitivity in mice. Eight-week old female C57/Bl6 mice were fed either high-fat (HF) diets [40% energy corn oil (CO) or isocaloric olive oil (OO) diets] or chow (n=10/group) for 6 weeks, followed by estimation of spontaneous locomotor activity, body composition and in vivo metabolic outcomes. Although lean mass and resting energy expenditure stayed similar in both OO- and CO-fed mice, only CO-fed mice demonstrated reduced spontaneous locomotor activity. Such depressed activity in CO-fed mice was accompanied by a lower respiratory ratio, hyperinsulinemia and impaired glucose disposal following intraperitoneal glucose tolerance and insulin tolerance tests compared to OO-fed mice. Unlike the liver, where both HF diets increased expression of fat oxidation genes like PPARs, the skeletal muscle of CO-fed mice failed to up-regulate such genes, thereby supporting the metabolic insufficiencies observed in these mice. In summary, this study demonstrates a specific contribution of n-6 PUFA-rich oils like CO to the loss of spontaneous physical activity and insulin sensitivity in mice. If these data hold true for humans, this study could provide a novel link between recent increases in dietary n-6 PUFA to sedentary behavior and the development of insulin resistance in the Western world.
Published:
March 31, 2015
Title:
Effects of altered hepatic lipid metabolism on regulation of hepatic iNOS
Authors:
Stanimirovic, Julijana; Obradovic, Milan; Zafirovic, Sonja; Resanovic, Ivana; Bogdanovic, Nikola; Gluvic, Zoran; Mousa, Shaker A.; Isenovic, Esma R.
Abstract:
An altered hepatic lipid metabolism involves multifactorial pathologies such as hepatic inflammation, insulin resistance and oxidative stress. Immunity has an essential role in the regulation of glucose and lipid metabolism in the liver. Inducible nitric oxide (NO) synthase (iNOS) has been proposed as an important factor that interplays between immunity and energy metabolism and also in the pathogenesis of obesity-linked insulin resistance. In the liver, locally produced NO plays a protective role during inflammation, and the balance of NO protective and cytotoxic effects is very important. This review is focused on understanding the molecular mechanisms of iNOS regulation in the state of altered hepatic lipid metabolism, which is critical for developing new strategies for treatment of hepatic disorders.
Published:
March 31, 2015
Title:
Evidence for Pleistocene seed grinding at Lake Mungo, south-eastern Australia
Authors:
Fullagar, Richard; Hayes, Elspeth; Stephenson, Birgitta; Field, Judith; Matheson, Carney; Stern, Nicola; Fitzsimmons, Kathryn
Abstract:
Grinding stones and fragments have often been found in archaeological sites at Lake Mungo, south-western New South Wales, and their function has mostly been inferred on the basis of grindstone morphology. Of particular interest has been the antiquity of grass seed grinding, which is usually associated with deeply grooved, large sandstone dishes. Previous studies of grinding stones from the region have found no compelling evidence for seed grinding prior to the Pleistocene/Holocene boundary. One of the problems has been that the grinding stones have been found on deflated surfaces and have been difficult to accurately provenance and date. Here, we report a functional study of 17 sandstone artefacts, recently collected from the central part of the Mungo lunette, where a suite of OSL ages have provided bracketing age estimates for the stratigraphic units. Ten artefacts are attributed to Unit E deposited between c.25 and 14 ka. Four artefacts are attributed to Unit F, deposited c.8 ka. Three artefacts from the Golgol lag are of unknown age. Usewear indicates a likely seed grinding function for 14 of the artefacts. Use-related residues include starch, cellulose and collagen. The results of this study provide additional support for Pleistocene plant processing and seed grinding activities in Sahul.
Published:
March 31, 2015
Title:
Safety and efficacy of a multiphase dietetic protocol with meal replacements including a step with very low calorie diet
Authors:
Basciani, Sabrina; Costantini, Daniela; Contini, Savina; Persichetti, Agnese; Watanabe, Mikiko; Mariani, Stefania; Lubrano, Carla; Spera, Giovanni; Lenzi, Andrea; Gnessi, Lucio
Abstract:
To investigate safety, compliance, and efficacy, on weight loss and cardiovascular risk factors of a multiphasic dietary intervention based on meal replacements, including a period of very low calorie diet (VLCD) in a population of obese patients. Anthropometric parameters, blood tests (including insulin), dual-energy-X-ray absorptiometry (DXA), and questionnaires for the assessment of safety and compliance before and after (phase I) a 30-day VLCD, 700 kcal/day, normoproteic, 50 g/day carbohydrate, four meal replacements; (phase II) a 30-day low calorie diet (LCD), 820 kcal/day, three meal replacements plus a protein plate; (phase III) 60-day LCD, 1,100 kcal/day, two meal replacements plus two protein plates and reintroduction of small amounts of carbohydrates; (phase IV) 60-day hypocaloric balanced diet (HBD), 1,200 kcal/day, one meal replacement, two protein plates and the reintroduction of carbohydrates. 24 patients (17 females, 7 males, mean BMI 33.8 ± 3.2 kg/m2, mean age 35.1 ± 10.2 years) completed the study. The average weight loss was 15.4 ± 6.7 %, with a significant reduction of fat mass (from 32.8 ± 4.7 to 26.1 ± 6.3 % p < 0.05) and a relative increase of lean mass (from 61.9 ± 4.8 to 67.1 ± 5.9 % p
Published:
March 31, 2015
Title:
Biomarkers of selenium status
Authors:
Combs, Gerald F.
Abstract:
The essential trace element, selenium (Se), has multiple biological activities, which depend on the level of Se intake. Relatively low Se intakes determine the expression of selenoenzymes in which it serves as an essential constituent. Higher intakes have been shown to have anti-tumorigenic potential; and very high Se intakes can produce adverse effects. This hierarchy of biological activities calls for biomarkers informative at different levels of Se exposure. Some Se-biomarkers, such as the selenoproteins and particularly GPX3 and SEPP1, provide information about function directly and are of value in identifying nutritional Se deficiency and tracking responses of deficient individuals to Se-treatment. They are useful under conditions of Se intake within the range of regulated selenoprotein expression, e.g., for humans <55 μg/day and for animals
Published:
March 30, 2015
Title:
Tumor Cells Switch to Mitochondrial Oxidative Phosphorylation under Radiation via mTOR-Mediated Hexokinase II Inhibition - A Warburg-Reversing Effect
Authors:
Lu, Chung-Ling; Qin, Lili; Liu, Hsin-Chen; Candas, Demet; Fan, Ming; Li, Jian Jian
Abstract:
A unique feature of cancer cells is to convert glucose into lactate to produce cellular energy, even under the presence of oxygen. Called aerobic glycolysis [The Warburg Effect] it has been extensively studied and the concept of aerobic glycolysis in tumor cells is generally accepted. However, it is not clear if aerobic glycolysis in tumor cells is fixed, or can be reversed, especially under therapeutic stress conditions. Here, we report that mTOR, a critical regulator in cell proliferation, can be relocated to mitochondria, and as a result, enhances oxidative phosphorylation and reduces glycolysis. Three tumor cell lines (breast cancer MCF-7, colon cancer HCT116 and glioblastoma U87) showed a quick relocation of mTOR to mitochondria after irradiation with a single dose 5 Gy, which was companied with decreased lactate production, increased mitochondrial ATP generation and oxygen consumption. Inhibition of mTOR by rapamycin blocked radiation-induced mTOR mitochondrial relocation and the shift of glycolysis to mitochondrial respiration, and reduced the clonogenic survival. In irradiated cells, mTOR formed a complex with Hexokinase II [HK II], a key mitochondrial protein in regulation of glycolysis, causing reduced HK II enzymatic activity. These results support a novel mechanism by which tumor cells can quickly adapt to genotoxic conditions via mTOR-mediated reprogramming of bioenergetics from predominantly aerobic glycolysis to mitochondrial oxidative phosphorylation. Such a “waking-up” pathway for mitochondrial bioenergetics demonstrates a flexible feature in the energy metabolism of cancer cells, and may be required for additional cellular energy consumption for damage repair and survival. Thus, the reversible cellular energy metabolisms should be considered in blocking tumor metabolism and may be targeted to sensitize them in anti-cancer therapy.
Published:
March 24, 2015
Title:
Health Resources & Information
Authors:
theketowolf
Abstract:
Below are links to other articles or studies providing information on specific health conditions and how they have been found to be affected by a carb- and/or grain-limiting diet (SCD, GAPS, The Wa…
Published:
March 16, 2015
Title:
Native Peoples of the World: An Encylopedia of Groups, Cultures and Contemporary Issues : An Encylopedia of Groups, Cultures and Contemporary Issues
Authors:
Danver, Steven L.
Abstract:
This work examines the world's indigenous peoples, their cultures, the countries in which they reside, and the issues that impact these groups.
Published:
March 9, 2015
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