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Title:
Sauna bathing and systemic inflammation
Authors:
Laukkanen, Jari A.; Laukkanen, Tanjaniina
Abstract:
© 2017 Springer Science+Business Media B.V., part of Springer Nature We aimed to investigate whether frequency of sauna bathing is associated with the levels of serum C-reactive protein. C-reactive protein is a leading blood marker of systemic inflammation. The study consisted of 2084 men (42–60 years) without acute or chronic inflammation. A total of 533 (25.6%), 1368 (65.6%), and 183 (8.8%) participants reported having a sauna bath once a week, 2–3 times, and 4–7 times per week; mean serum C-reactive protein levels were 2.41 (standard deviation 2.91), 2.00 (2.41), 1.65 (1.63) mmol/L, respectively. In a multivariable analysis adjusted for baseline age, body mass index, systolic blood pressure, smoking, type 2 diabetes, previous myocardial infarction, and serum low density lipoprotein cholesterol, alcohol consumption and physical activity, there was a significant inverse association between the frequency of sauna bathing and the level of C-reactive protein. Further studies are warranted to investigate the relationship between sauna bathing and systemic inflammation.
Published:
2018
Title:
Sauna bathing reduces the risk of stroke in Finnish men and women: A prospective cohort study
Authors:
Kunutsor, Setor K.; Khan, Hassan; Zaccardi, Francesco; Laukkanen, Tanjaniina; Willeit, Peter; Laukkanen, Jari A.
Abstract:
OBJECTIVE To assess the association between frequency of sauna bathing and risk of future stroke. METHODS Baseline habits of sauna bathing were assessed in 1,628 adult men and women aged 53-74 years (mean age, 62.7 years) without a known history of stroke in the Finnish Kuopio Ischemic Heart Disease prospective cohort study. Three sauna bathing frequency groups were defined: 1, 2-3, and 4-7 sessions per week. Hazard ratios (HRs) (95% confidence intervals [CIs]) were estimated for incident stroke. RESULTS During a median follow-up of 14.9 years, 155 incident stroke events were recorded. Compared with participants who had one sauna bathing session per week, the age- and sex-adjusted HR (95% CI) for stroke was 0.39 (0.18-0.83) for participants who had 4-7 sauna sessions per week. After further adjustment for established cardiovascular risk factors and other potential confounders, the corresponding HR (95% CI) was 0.39 (0.18-0.84) and this remained persistent on additional adjustment for physical activity and socioeconomic status at 0.38 (0.18-0.81). The association between frequency of sauna bathing and risk of stroke was not modified by age, sex, or other clinical characteristics (p for interaction \textgreater 0.10 for all subgroups). The association was similar for ischemic stroke but modest for hemorrhagic stroke, which could be attributed to the low event rate (n = 34). CONCLUSIONS This long-term follow-up study shows that middle-aged to elderly men and women who take frequent sauna baths have a substantially reduced risk of new-onset stroke.
Published:
2018
Title:
Sauna exposure leads to improved arterial compliance: Findings from a non-randomised experimental study
Authors:
Lee, Earric; Laukkanen, Tanjaniina; Kunutsor, Setor K.; Khan, Hassan; Willeit, Peter; Zaccardi, Francesco; Laukkanen, Jari A.
Abstract:
© 2017, © The European Society of Cardiology 2017. Background: Heat therapy has been suggested to improve cardiovascular function. However, the effects of hot sauna exposure on arterial compliance and the dynamics of blood flow and pressure have not been well documented. Thus, we investigated the short-term effects of sauna bathing on arterial stiffness and haemodynamics. Design: The design was an experimental non-randomised study. Methods: There were 102 asymptomatic participants (mean age, 51.9 years) who had at least one cardiovascular risk factor. Participants were exposed to a single sauna session (duration: 30 min; temperature: 73℃; humidity: 10–20%). Pulse wave velocity, augmentation index, heart rate, blood pressure, mean arterial pressure, pulse pressure, augmented pressure and left ventricular ejection time were assessed before, immediately after, and 30 min after a single sauna session. Results: Sauna bathing led to reductions in pulse wave velocity, blood pressure, mean arterial pressure and left ventricular ejection time. Mean pulse wave velocity value before sauna was 9.8 m/s and decreased to 8.6 m/s immediately after sauna bathing (p \textless 0.001 for difference), and was 9.0 m/s after the 30-minute recovery period (p \textless 0.001 for analysis of variance). Systolic blood pressure was 137 mm Hg before sauna bathing, decreasing to 130 mm Hg after sauna (p \textless 0.001), which remained sustained during the 30-minute recovery phase (p \textless 0.001 for analysis of variance). After a single sauna session, diastolic blood pressure decreased from 82 to 75 mm Hg, mean arterial pressure from 99.4 to 93.6 mm Hg and left ventricular ejection time from 307 to 278 m/s (p \textless 0.001 for all differences). Pulse pressure was 42.7 mm Hg before the sauna, 44.9 mm Hg immediately after the sauna, and reduced to 39.3 mm Hg after 30-minutes recovery (p \textless 0.001 for analysis of variance). Heart rate increased from 65 to 81 beats/min post-sauna (p \textless 0.001); there were no significant changes for augmented pressure and pulse pressure amplification. Conclusion: This study shows that pulse wave velocity, systolic blood pressure, diastolic blood pressure, mean arterial pressure, left ventricular ejection time and diastolic time decreased immediately after a 30-minute sauna session. Decreases in systolic blood pressure and left ventricular ejection time were sustained during the 30-minute recovery phase.
Published:
2018
Title:
Shifts on Gut Microbiota Associated to Mediterranean Diet Adherence and Specific Dietary Intakes on General Adult Population
Authors:
Garcia-Mantrana, Izaskun; Selma-Royo, Marta; Alcantara, Cristina; Collado, María C.
Abstract:
There is increasing evidence for the interaction between gut microbiome, diet, and health. It is known that dysbiosis is related to disease and that most of the times this imbalances in gut microbial populations can be promoted through diet. Western dietary habits, which are characterized by high intakes of calories, animal proteins, saturated fats, and simple sugars have been linked with higher risk of obesity, diabetes, cancer, and cardiovascular disease. However, little is known about the impact of dietary patterns, dietary components, and nutrients on gut microbiota in healthy people. The aim of our study is to determine the effect of nutrient compounds as well as adherence to a dietary pattern, as the Mediterranean diet (MD) on the gut microbiome of healthy adults. Consequently, gut microbiota composition in healthy individuals, may be used as a potential biomarker to identify nutritional habits as well as risk of disease related to these habits. Dietary information from healthy volunteers (n = 27) was recorded using the Food Frequency Questionnaire. Adherence to the MD was measured using the PREDIMED test. Microbiota composition and diversity were obtained by 16S rRNA gene sequencing and specific quantitative polymerase chain reaction. Microbial metabolic activity was determined by quantification of short chain fatty acids (SCFA) on high performance liquid chromatography (HPLC). The results indicated that a higher ratio of Firmicutes-Bacteroidetes was related to lower adherence to the MD, and greater presence of Bacteroidetes was associated with lower animal protein intake. High consumption of animal protein, saturated fats, and sugars affected gut microbiota diversity. A significant higher presence of Christensenellaceae was found in normal-weight individuals compared to those who were overweight. This was also the case in volunteers with greater adherence to the MD compared to those with lower adherence. Butyricimonas, Desulfovibrio, and Oscillospira genera were associated with a BMI
Published:
2018
Title:
Short-Term Repeatability of Insulin Resistance Indexes in Older Adults: The Atherosclerosis Risk in Communities Study
Authors:
Poon, Anna K.; Meyer, Michelle L.; Reaven, Gerald; Knowles, Joshua W.; Selvin, Elizabeth; Pankow, James S.; Couper, David; Loehr, Laura; Heiss, Gerardo
Abstract:
Context: The homeostatic model assessment of insulin resistance (HOMA-IR) and triglyceride (TG)/ high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) are insulin resistance indexes routinely used in clinical and population-based studies; however, their short-term repeatability is not well characterized. Objective: To quantify the short-term repeatability of insulin resistance indexes and their analytes, consisting of fasting glucose and insulin for HOMA-IR and TG and HDL-C for TG/HDL-C. Design: Prospective cohort study. Participants: A total of 102 adults 68 to 88 years old without diabetes attended an initial examination and repeated examination (mean, 46 days; range, 28 to 102 days). Blood samples were collected, processed, shipped, and assayed following a standardized protocol. Main Outcome Measures: Repeatability was quantified using the intraclass correlation coefficient (ICC) and within-person coefficient of variation (CV). Minimum detectable change (MDC 95) and minimum detectable difference with 95% confidence (MDD 95) were quantified. Results: For HOMA-IR, insulin, and fasting glucose, the ICCs were 0.70, 0.68, and 0.70, respectively; their respective within-person CVs were 30.4%, 28.8%, and 5.6%. For TG/HDL-C, TG, and HDL-C, the ICCs were 0.80, 0.68, and 0.91, respectively; their respective within-person CVs were 23.0%, 20.6%, and 8.2%. The MDC 95 was 2.3 for HOMA-IR and 1.4 for TG/HDL-C. The MDD 95 for a sample of n = 100 was 0.8 for HOMA-IR and 0.6 for TG/HDL-C. Conclusions: Short-term repeatability was fair to good for HOMA-IR and excellent for TG/HDL-C according to suggested benchmarks, reflecting the short-term variability of their analytes. These measurement properties can inform the use of these indexes in clinical and population-based studies.
Published:
2018
Title:
Skeletal muscle insulin resistance is induced by 4-hydroxy-2-hexenal, a by-product of n-3 fatty acid peroxidation
Authors:
Soulage, Christophe O.; Sardón Puig, Laura; Soulère, Laurent; Zarrouki, Bader; Guichardant, Michel; Lagarde, Michel; Pillon, Nicolas J.
Abstract:
AIMS/HYPOTHESIS: Oxidative stress is involved in the pathophysiology of insulin resistance and its progression towards type 2 diabetes. The peroxidation of n-3 polyunsaturated fatty acids produces 4-hydroxy-2-hexenal (4-HHE), a lipid aldehyde with potent electrophilic properties able to interfere with many pathophysiological processes. The aim of the present study was to investigate the role of 4-HHE in the development of insulin resistance. METHODS: 4-HHE concentration was measured in plasma from humans and rats by GC-MS. Insulin resistance was estimated in healthy rats after administration of 4-HHE using hyperinsulinaemic-euglycaemic clamps. In muscle cells, glucose uptake was measured using 2-deoxy-D-glucose and signalling pathways were investigated by western blotting. Intracellular glutathione was measured using a fluorimetric assay kit and boosted using 1,2-dithiole-3-thione (D3T). RESULTS: Circulating levels of 4-HHE in type 2 diabetic humans and a rat model of diabetes (obese Zucker diabetic fatty rats), were twice those in their non-diabetic counterparts (33 vs 14 nmol/l, p < 0.001), and positively correlated with blood glucose levels. During hyperinsulinaemic-euglycaemic clamps in rats, acute intravenous injection of 4-HHE significantly altered whole-body insulin sensitivity and decreased glucose infusion rate (24.2 vs 9.9 mg kg-1 min-1, p < 0.001). In vitro, 4-HHE impaired insulin-stimulated glucose uptake and signalling (protein kinase B/Akt and IRS1) in L6 muscle cells. Insulin-induced glucose uptake was reduced from 186 to 141.9 pmol mg-1 min-1 (p
Published:
2018
Title:
Statin wars: Have we been misled about the evidence? A narrative review
Authors:
Demasi, Maryanne
Abstract:
AbsTRACT Statins are the most widely prescribed, cholesterol-lowering drugs in the world. Despite the expiration of their patents, revenue for statins is expected to rise, with total sales on track to reach an estimated US$1 trillion by 2020. A bitter dispute has erupted among doctors over suggestions that statins should be prescribed to millions of healthy people at low risk of heart disease. There are concerns that the benefits have been exaggerated and the risks have been underplayed. Also, the raw data on the efficacy and safety of statins are being kept secret and have not been subjected to scrutiny by other scientists. This lack of transparency has led to an erosion of public confidence. Doctors and patients are being misled about the true benefits and harms of statins, and it is now a matter of urgency that the raw data from the clinical trials are released.
Published:
2018
Title:
Targeting Colon Luminal Lipid Peroxidation Limits Colon Carcinogenesis Associated with Red Meat Consumption
Authors:
Martin, Océane C. B.; Naud, Nathalie; Taché, Sylviane; Debrauwer, Laurent; Chevolleau, Sylvie; Dupuy, Jacques; Chantelauze, Céline; Durand, Denis; Pujos-Guillot, Estelle; Blas-Y-Estrada, Florence; Urbano, Christine; Kuhnle, Gunter G. C.; Santé-Lhoutellier, Véronique; Sayd, Thierry; Viala, Didier; Blot, Adeline; Meunier, Nathalie; Schlich, Pascal; Attaix, Didier; Guéraud, Françoise; Scislowski, Valérie; Corpet, Denis E.; Pierre, Fabrice H. F.
Abstract:
Red meat is probably carcinogenic to humans (WHO/IARC class 2A), in part through heme iron-induced lipoperoxidation. Here, we investigated whether red meat promotes carcinogenesis in rodents and modulates associated biomarkers in volunteers, speculating that an antioxidant marinade could suppress these effects via limitation of the heme induced lipid peroxidation. We gave marinated or non-marinated beef with various degrees of cooking to azoxymethane-initiated rats, Min mice, and human volunteers (crossover study). Mucin-depleted foci were scored in rats, adenoma in Min mice. Biomarkers of lipoperoxidation were measured in the feces and urine of rats, mice, and volunteers. The organoleptic properties of marinated meat were tested. Fresh beef increased colon carcinogenesis and lipoperoxidation in rats and mice and lipoperoxidation in humans. Without an adverse organoleptic effect on meat, marinade normalized peroxidation biomarkers in rat and mouse feces, reduced peroxidation in human feces and reduced the number of Mucin-depleted foci in rats and adenoma in female Min mice. This could lead to protective strategies to decrease the colorectal cancer burden associated with red meat consumption. Cancer Prev Res; 11(9); 569-80. ©2018 AACR.
Published:
2018
Title:
Targeting RAGE Signaling in Inflammatory Disease
Authors:
Hudson, Barry I.; Lippman, Marc E.
Abstract:
The receptor for advanced glycation end-products (RAGE) is a multiligand pattern recognition receptor implicated in diverse chronic inflammatory states. RAGE binds and mediates the cellular response to a range of damage-associated molecular pattern molecules (DAMPs) including AGEs, HMGB1, S100s, and DNA. RAGE can also act as an innate immune sensor of microbial pathogen-associated molecular pattern molecules (PAMPs) including bacterial endotoxin, respiratory viruses, and microbial DNA. RAGE is expressed at low levels under normal physiology, but it is highly upregulated under chronic inflammation because of the accumulation of various RAGE ligands. Blocking RAGE signaling in cell and animal models has revealed that targeting RAGE impairs inflammation and progression of diabetic vascular complications, cardiovascular disease (CVD), and cancer progression and metastasis. The clinical relevance of RAGE in inflammatory disease is being demonstrated in emerging clinical trials of novel small-molecule RAGE inhibitors.
Published:
2018
Title:
Targeting the MYCN-PARP-DNA Damage Response Pathway in Neuroendocrine Prostate Cancer
Authors:
Zhang, Wei; Liu, Bo; Wu, Wenhui; Li, Likun; Broom, Bradley M.; Basourakos, Spyridon P.; Korentzelos, Dimitrios; Luan, Yang; Wang, Jianxiang; Yang, Guang; Park, Sanghee; Azad, Abul Kalam; Cao, Xuhong; Kim, Jeri; Corn, Paul G.; Logothetis, Christopher J.; Aparicio, Ana M.; Chinnaiyan, Arul M.; Navone, Nora; Troncoso, Patricia; Thompson, Timothy C.
Abstract:
Purpose: We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphologic criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for neuroendocrine prostate cancer (NEPC).Experimental Design and Results: Using comparative bioinformatics analyses of CRPC-Adeno and CRPC-Neuro RNA sequence data from public data sets and a panel of 28 PDX models, we identified a MYCN-PARP-DNA damage response (DDR) pathway that is enriched in CRPC with neuroendocrine differentiation (NED) and CRPC-Neuro. ChIP-PCR assay revealed that N-MYC transcriptionally activates PARP1, PARP2, BRCA1, RMI2, and TOPBP1 through binding to the promoters of these genes. MYCN or PARP1 gene knockdown significantly reduced the expression of MYCN-PARP-DDR pathway genes and NED markers, and inhibition with MYCNsi and/or PARPsi, BRCA1si, or RMI2si significantly suppressed malignant activities, including cell viability, colony formation, and cell migration, in C4-2b4 and NCI-H660 cells. Targeting this pathway with AURKA inhibitor PHA739358 and PARP inhibitor olaparib generated therapeutic effects similar to those of gene knockdown in vitro and significantly suppressed tumor growth in both C4-2b4 and MDACC PDX144-13C subcutaneous models in vivoConclusions: Our results identify a novel MYCN-PARP-DDR pathway that is driven by N-MYC in a subset of CRPC-Adeno and in NEPC. Targeting this pathway using in vitro and in vivo CRPC-Adeno and CRPC-Neuro models demonstrated a novel therapeutic strategy for NEPC. Further investigation of N-MYC-regulated DDR gene targets and the biological and clinical significance of MYCN-PARP-DDR signaling will more fully elucidate the importance of the MYCN-PARP-DDR signaling pathway in the development and maintenance of NEPC. Clin Cancer Res; 24(3); 696-707. ©2017 AACR.
Published:
2018
Title:
The Anticonvulsant Effects of Ketogenic Diet on Epileptic Seizures and Potential Mechanisms
Authors:
Zhang, Yifan; Xu, Jingwei; Zhang, Kun; Yang, Wei; Li, Bingjin
Abstract:
BACKGROUND: Epilepsy is a syndrome of brain dysfunction induced by the aberrant excitability of certain neurons. Despite advances in surgical technique and anti-epileptic drug in recent years, recurrent epileptic seizures remain intractable and lead to a serious morbidity in the world. The ketogenic diet refers to a high-fat, low-carbohydrate and adequate-protein diet. Currently, its beneficial effects on epileptic seizure reduction have been well established. However, the detailed mechanisms underlying the anti-epileptic effects of ketogenic diet are still poorly understood. In this article, the possible roles of ketogenic diet on epilepsy were discussed. METHODS: Data was obtained from the websites including Web of Science, Medline, Pubmed, Scopus, based on these keywords: "Ketogenic diet" and "epilepsy". RESULTS: As shown in both clinical and basic studies, the therapeutic effects of ketogenic diet might involve neuronal metabolism, neurotransmitter function, neuronal membrane potential and neuron protection against ROS. CONCLUSION: In this review, we systematically reviewed the effects and possible mechanisms of ketogenic diet on epilepsy, which may optimize the therapeutic strategies against epilepsy.
Published:
2018
Title:
The Effect of Continuous Intravenous Glucagon on Glucose Requirements in Infants with Congenital Hyperinsulinism
Authors:
Hawkes, Colin P.; Lado, Juan J.; Givler, Stephanie; De Leon, Diva D.
Abstract:
Published:
2018
Title:
The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future
Authors:
Plog, Benjamin A.; Nedergaard, Maiken
Abstract:
The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudolymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters the brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here, we review the role of the glymphatic pathway in CNS physiology, the factors known to regulate glymphatic flow, and the pathologic processes in which a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, are also discussed.
Published:
2018
Title:
The Influence of Dietary Habits and Meat Consumption on Plasma 3-Methylhistidine-A Potential Marker for Muscle Protein Turnover
Authors:
Kochlik, Bastian; Gerbracht, Christiana; Grune, Tilman; Weber, Daniela
Abstract:
CONCLUSION: 1-MH concentrations in plasma seem to be suitable to display (white) meat consumption and its influence on 3-MH plasma concentration. 3-MH in plasma may be used as a biomarker for muscle protein turnover if subjects have not consumed meat in the previous 24 h. Copyright © 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Published:
2018
Title:
The Intestinal Epithelium: Central Coordinator of Mucosal Immunity
Authors:
Allaire, Joannie M.; Crowley, Shauna M.; Law, Hong T.; Chang, Sun-Young; Ko, Hyun-Jeong; Vallance, Bruce A.
Abstract:
The gastrointestinal (GI) tract represents a unique challenge to the mammalian immune system. It must tolerate the presence of the luminal microbiota and thus not respond to their products, but still protect the intestinal mucosa from potentially harmful dietary antigens and invading pathogens. The intestinal epithelium, composed of a single layer of cells, is crucial for preserving gut homeostasis and acts both as a physical barrier and as a coordinating hub for immune defense and crosstalk between bacteria and immune cells. We highlight here recent findings regarding communication between microbes and intestinal epithelial cells (IECs), as well as the immune mechanisms employed by distinct IEC subsets to promote homeostasis, emphasizing the central and active role that these cells play in host enteric defense.
Published:
2018
Title:
The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic Tissues
Authors:
Goetzman, Eric S.; Prochownik, Edward V.
Abstract:
That cancer cells show patterns of metabolism different from normal cells has been known for over 50 years. Yet it is only in the past decade or so that an appreciation of the benefits of these changes has begun to emerge. Altered cancer cell metabolism was initially attributed to defective mitochondria. However, we now realize that most cancers do not have mitochondrial mutations and that normal cells can transiently adopt cancer-like metabolism during periods of rapid proliferation. Indeed, an encompassing, albeit somewhat simplified, conceptual framework to explain both normal and cancer cell metabolism rests on several simple premises. First, the metabolic pathways used by cancer cells and their normal counterparts are the same. Second, normal quiescent cells use their metabolic pathways and the energy they generate largely to maintain cellular health and organelle turnover and, in some cases, to provide secreted products necessary for the survival of the intact organism. In contrast, undifferentiated cancer cells minimize the latter functions and devote their energy to producing the anabolic substrates necessary to maintain high rates of unremitting cellular proliferation. Third, as a result of the uncontrolled proliferation of cancer cells, a larger fraction of the metabolic intermediates normally used by quiescent cells purely as a source of energy are instead channeled into competing proliferation-focused and energy-consuming anabolic pathways. Fourth, cancer cell clones with the most plastic and rapidly adaptable metabolism will eventually outcompete their less well-adapted brethren during tumor progression and evolution. This attribute becomes increasingly important as tumors grow and as their individual cells compete in a constantly changing and inimical environment marked by nutrient, oxygen and growth factor deficits. Here, we review some of the metabolic pathways whose importance has gained center stage for tumor growth, particularly those under the control of the c-Myc (Myc) oncoprotein. We discuss how these pathways differ functionally between quiescent and proliferating normal cells, how they are kidnapped and corrupted during the course of transformation, and consider potential therapeutic strategies that take advantage of common features of neoplastic and metabolic disorders.
Published:
2018
Title:
The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids
Authors:
Jang, Cholsoon; Hui, Sheng; Lu, Wenyun; Cowan, Alexis J.; Morscher, Raphael J.; Lee, Gina; Liu, Wei; Tesz, Gregory J.; Birnbaum, Morris J.; Rabinowitz, Joshua D.
Abstract:
Excessive consumption of sweets is a risk factor for metabolic syndrome. A major chemical feature of sweets is fructose. Despite strong ties between fructose and disease, the metabolic fate of fructose in mammals remains incompletely understood. Here we use isotope tracing and mass spectrometry to track the fate of glucose and fructose carbons in vivo, finding that dietary fructose is cleared by the small intestine. Clearance requires the fructose-phosphorylating enzyme ketohexokinase. Low doses of fructose are ∼90% cleared by the intestine, with only trace fructose but extensive fructose-derived glucose, lactate, and glycerate found in the portal blood. High doses of fructose (≥1 g/kg) overwhelm intestinal fructose absorption and clearance, resulting in fructose reaching both the liver and colonic microbiota. Intestinal fructose clearance is augmented both by prior exposure to fructose and by feeding. We propose that the small intestine shields the liver from otherwise toxic fructose exposure.
Published:
2018
Title:
The Unconventional Career of Dr Muriel Bell
Authors:
Brown, Diana
Abstract:
Published:
2018
Title:
The association of diet, gut microbiota and colorectal cancer: what we eat may imply what we get
Authors:
Yang, J.; Yu, J.
Abstract:
Despite the success of colonoscopy screening and recent advances in cancer treatment, colorectal cancer (CRC) still remains one of the most commonly diagnosed and deadly cancers, with a significantly increased incidence in developing countries where people are adapting to Western lifestyle. Diet has an important impact on risk of CRC. Multiple epidemiological studies have suggested that excessive animal protein and fat intake, especially red meat and processed meat, could increase the risk of developing CRC while fiber could protect against colorectal tumorigenesis. Mechanisms have been investigated by animal studies. Diet could re-shape the community structure of gut microbiota and influence its function by modulating the production of metabolites. Butyrate, one of the short-chain fatty acids (SCFAs), which act as a favorable source for colonocytes, could protect colonic epithelial cells from tumorigenesis via anti-inflammatory and antineoplastic properties through cell metabolism, microbiota homeostasis, antiproliferative, immunomodulatory and genetic/epigenetic regulation ways. In contrast, protein fermentation and bile acid deconjugation, which cause damage to colonic cells through proinflammatory and proneoplastic ways, lead to increased risk of developing CRC. In conclusion, a balanced diet with an increased abundance of fiber should be adopted to reduce the risk and prevent CRC. © 2018, The Author(s).
Published:
2018
Title:
The carbohydrate-insulin model of obesity: Beyond “calories in, calories out”
Authors:
Ludwig, David S.; Ebbeling, Cara B.
Abstract:
Despite intensive research, the causes of the obesity epidemic remain incompletely understood and conventional calorie-restricted diets continue to lack long-term efficacy. According to the carbohydrate-insulin model (CIM) of obesity, recent increases in the consumption of processed, high-glycemic-load carbohydrates produce hormonal changes that promote calorie deposition in adipose tissue, exacerbate hunger, and lower energy expenditure. Basic and genetic research provides mechanistic evidence in support of the CIM. In animals, dietary composition has been clearly demonstrated to affect metabolism and body composition, independently of calorie intake, consistent with CIM predictions. Meta-analyses of behavioral trials report greater weight loss with reduced-glycemic load vs low-fat diets, though these studies characteristically suffer from poor long-term compliance. Feeding studies have lacked the rigor and duration to test the CIM, but the longest such studies tend to show metabolic advantages for low-glycemic load vs low-fat diets. Beyond the type and amount of carbohydrate consumed, the CIM provides a conceptual framework for understanding how many dietary and nondietary exposures might alter hormones, metabolism, and adipocyte biology in ways that could predispose to obesity. Pending definitive studies, the principles of a low-glycemic load diet offer a practical alternative to the conventional focus on dietary fat and calorie restriction.
Published:
2018
Title:
The clinical practice of risk reduction for Alzheimer's disease: A precision medicine approach
Authors:
Isaacson, Richard S.; Ganzer, Christine A.; Hristov, Hollie; Hackett, Katherine; Caesar, Emily; Cohen, Randy; Kachko, Robert; Meléndez-Cabrero, Josefina; Rahman, Aneela; Scheyer, Olivia; Hwang, Mu Ji; Berkowitz, Cara; Hendrix, Suzanne; Mureb, Monica; Schelke, Matthew W.; Mosconi, Lisa; Seifan, Alon; Krikorian, Robert
Abstract:
Like virtually all age-related chronic diseases, late-onset Alzheimer's disease (AD) develops over an extended preclinical period and is associated with modifiable lifestyle and environmental factors. We hypothesize that multimodal interventions that address many risk factors simultaneously and are individually tailored to patients may help reduce AD risk. We describe a novel clinical methodology used to evaluate and treat patients at two Alzheimer's Prevention Clinics. The framework applies evidence-based principles of clinical precision medicine to tailor individualized recommendations, follow patients longitudinally to continually refine the interventions, and evaluate N-of-1 effectiveness (trial registered at ClinicalTrials.gov NCT03687710). Prior preliminary results suggest that the clinical practice of AD risk reduction is feasible, with measurable improvements in cognition and biomarkers of AD risk. We propose using these early findings as a foundation to evaluate the comparative effectiveness of personalized risk management within an international network of clinician researchers in a cohort study possibly leading to a randomized controlled trial.
Published:
2018
Title:
The complexity of mitochondrial outer membrane permeability and VDAC regulation by associated proteins
Authors:
Klepinin, Aleksandr; Ounpuu, Lyudmila; Mado, Kati; Truu, Laura; Chekulayev, Vladimir; Puurand, Marju; Shevchuk, Igor; Tepp, Kersti; Planken, Anu; Kaambre, Tuuli
Abstract:
Previous studies have shown that class II β-tubulin plays a key role in the regulation of oxidative phosphorylation (OXPHOS) in some highly differentiated cells, but its role in malignant cells has remained unclear. To clarify these aspects, we compared the bioenergetic properties of HL-1 murine sarcoma cells, murine neuroblastoma cells (uN2a) and retinoic acid - differentiated N2a cells (dN2a). We examined the expression and possible co-localization of mitochondrial voltage dependent anion channel (VDAC) with hexokinase-2 (HK-2) and βII-tubulin, the role of depolymerized βII-tubuline and the effect of both proteins in the regulation of mitochondrial outer membrane (MOM) permeability. Our data demonstrate that neuroblastoma and sarcoma cells are prone to aerobic glycolysis, which is partially mediated by the presence of VDAC bound HK-2. Microtubule destabilizing (colchicine) and stabilizing (taxol) agents do not affect the MOM permeability for ADP in N2a and HL-1 cells. The obtained results show that βII-tubulin does not regulate the MOM permeability for adenine nucleotides in these cells. HL-1 and NB cells display comparable rates of ADP-activated respiration. It was also found that differentiation enhances the involvement of OXPHOS in N2a cells due to the rise in their mitochondrial reserve capacity. Our data support the view that the alteration of mitochondrial affinity for ADNs is one of the characteristic features of cancer cells. It can be concluded that the binding sites for tubulin and hexokinase within the large intermembrane protein supercomplex Mitochondrial Interactosome, could be different between muscle and cancer cells.
Published:
2018
Title:
The effect of Ramadan fasting during pregnancy on perinatal outcomes: A systematic review and meta-analysis
Authors:
Glazier, Jocelyn D.; Hayes, Dexter J.L.; Hussain, Sabiha; D'Souza, Stephen W.; Whitcombe, Joanne; Heazell, Alexander E.P.; Ashton, Nick
Abstract:
BACKGROUND Although exempt, many pregnant Muslim women partake in the daily fast during daylight hours during the month of Ramadan. In other contexts an impoverished diet during pregnancy impacts on birth weight. The aim of this systematic review was to determine whether Ramadan fasting by pregnant women affects perinatal outcomes. Primary outcomes investigated were perinatal mortality, preterm birth and small for gestational age (SGA) infants. Secondary outcomes investigated were stillbirth, neonatal death, maternal death, hypertensive disorders of pregnancy, gestational diabetes, congenital abnormalities, serious neonatal morbidity, birth weight, preterm birth and placental weight. METHODS Systematic review and meta-analysis of observational studies and randomised controlled trials was conducted in EMBASE, MEDLINE, CINAHL, Web of Science, Google Scholar, the Health Management Information Consortium and Applied Social Sciences Index and Abstracts. Studies from any year were eligible. Studies reporting predefined perinatal outcomes in pregnancies exposed to Ramadan fasting were included. Cohort studies with no comparator group or that considered fasting outside pregnancy were excluded, as were studies assuming fasting practice based solely upon family name. Quality of included studies was assessed using the ROBINS-I tool for assessing risk of bias in non-randomised studies. Analyses were performed in STATA. RESULTS From 375 records, 22 studies of 31,374 pregnancies were included, of which 18,920 pregnancies were exposed to Ramadan fasting. Birth weight was reported in 21 studies and was not affected by maternal fasting (standardised mean difference [SMD] 0.03, 95% CI 0.00 to 0.05). Placental weight was significantly lower in fasting mothers (SMD -0.94, 95% CI -0.97 to -0.90), although this observation was dominated by a single large study. No data were presented for perinatal mortality. Ramadan fasting had no effect on preterm delivery (odds ratio 0.99, 95% CI 0.72 to 1.37) based on 5600 pregnancies (1193 exposed to Ramadan fasting). CONCLUSIONS Ramadan fasting does not adversely affect birth weight although there is insufficient evidence regarding potential effects on other perinatal outcomes. Further studies are needed to accurately determine whether Ramadan fasting is associated with adverse maternal or neonatal outcome.
Published:
2018
Title:
The effect of omega 3 fatty acid supplementation on premenstrual syndrome and health-related quality of life: a randomized clinical trial
Authors:
Behboudi-Gandevani, Samira; Hariri, Fatemeh-Zahra; Moghaddam-Banaem, Lida
Abstract:
INTRODUCTION: Most reproductive aged women suffer from somatic and mental disorders prior to menstruation. This study investigated whether omega-3 supplement improved premenstrual symptoms and health-related quality of life among reproductive aged women. METHODS: A multi-center, balanced (1:1), placebo-controlled, parallel-group randomized clinical trial was conducted in an urban academic institution. A sample consisting of 95 Iranian women aged 20-35 years who were suffering from premenstrual symptoms were randomly allocated into two groups. The treatment consisted of omega-3 supplement containing 1 g fish oil. Placebo was free of oil. The premenstrual symptoms' screening tool and 12-item short form health survey questionnaire were used for data collection. RESULTS: No statistically significant differences in the baseline characteristics of the groups were reported. Most premenstrual symptoms and their interference with daily activities were significantly reduced over the follow-up period. The mean score of overeating in the omega-3 supplement group and insomnia in the placebo group showed no difference between the groups. The longer use of omega-3 supplement provides improvement of premenstrual symptoms and activities. The mean scores of physical and mental components of quality of life were significantly improved in the omega-3 supplement and placebo groups. DISCUSSION: The treatment of premenstrual symptoms using omega-3 supplement reduced symptoms and ameliorated women's quality of life.
Published:
2018
Title:
The effects of fatty fish intake on adolescents' nutritional status and associations with attention performance: Results from the FINS-TEENS randomized controlled trial
Authors:
Handeland, K.; Skotheim, S.; Baste, V.; Graff, I.E.; Frøyland, L.; Lie, O.; Kjellevold, M.; Markhus, M.W.; Stormark, K.M.; Øyen, J.; Dahl, L.
Abstract:
Background: Adolescence involves changes in dietary habits that may induce imbalances in the intake of different nutrients. Fish is an important dietary source of omega-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFAs), vitamin D, several minerals and high-quality protein. By using secondary outcomes and exploratory analyses, the aims of this paper were to evaluate if nutritional biomarkers (red blood cell fatty acids, serum (s)-25(OH)D, s-ferritin and urinary iodine concentration (UIC)) were altered during a dietary intervention, and if they mediated previously reported changes in attention performance. In addition, to examine the status of the biomarkers and explore associations between dietary pattern, biomarkers and attention performance cross-sectionally at baseline. Methods: The Fish Intervention Studies-TEENS (FINS-TEENS) was a three-armed intervention trial, including adolescents from eight secondary schools (n = 415; age: 14-15y) in Bergen, Norway. Participants were individually randomized to receive either fish meals, meat meals or n-3 LCPUFA supplements, three times a week for a total of 12 weeks. Blood and urine samples were collected pre and post intervention and attention performance was assessed with the d2 test of attention. Analyses of covariance (ANCOVA) assessed differences between groups in changes of biomarkers and linear mixed models were applied in analyses of attention performance and biomarkers. The trial is registered in ClinicalTrials.gov (NCT02350322). Results: At baseline, the mean omega-3 index was 5.8 ± 1.3% and deficient status were identified for s-25(OH)D (54%), s-ferritin (10%) and UIC (40%). The intervention resulted in an increase in DHA and the omega-3 index which was larger in the supplement group compared to the fish and meat group (P < 0.01), and in the fish group compared to the meat group (P
Published:
2018
Title:
The fecal microbiome and metabolome differs between dogs fed Bones and Raw Food (BARF) diets and dogs fed commercial diets
Authors:
Schmidt, M.; Unterer, S.; Suchodolski, J.S.; Honneffer, J.B.; Guard, B.C.; Lidbury, J.A.; Steiner, J.M.; Fritz, J.; Kölle, P.
Abstract:
Introduction: Feeding a Bones and Raw Food (BARF) diet has become an increasing trend in canine nutrition. Bones and Raw Food diets contain a high amount of animal components like meat, offal, and raw meaty bones, combined with comparatively small amounts of plant ingredients like vegetables and fruits as well as different sorts of oil and supplements. While many studies have focused on transmission of pathogens via contaminated meat and on nutritional imbalances, only few studies have evaluated the effect of BARF diets on the fecal microbiome and metabolome. The aim of the study was to investigate differences in the fecal microbiome and the metabolome between dogs on a BARF diet and dogs on a commercial diet (canned and dry dog food). Methods: Naturally passed fecal samples were obtained from 27 BARF and 19 commercially fed dogs. Differences in crude protein, fat, fiber, and NFE (Nitrogen-Free Extract) between diets were calculated with a scientific nutrient database. The fecal microbiota was analyzed by 16S rRNA gene sequencing and quantitative PCR assays. The fecal metabolome was analyzed in 10 BARF and 9 commercially fed dogs via untargeted metabolomics approach. Results: Dogs in the BARF group were fed a significantly higher amount of protein and fat and significantly lower amount of NFE and fiber. There was no significant difference in alpha-diversity measures between diet groups. Analysis of similarity (ANOSIM) revealed a significant difference in beta-diversity (p
Published:
2018
Title:
The food metabolome and novel dietary biomarkers associated with diseases
Authors:
Arslan, O.E.; Palmon, P.
Abstract:
The food metabolome is an area of research that is of rising interest, particularly the association of chronic diseases to dietary biomarkers. This chapter will review and assess the current literature of the novel biomarkers used to track dietary intake of carbohydrates, fats, proteins, vitamin C, and carotenoids, as well as to explore the relationship between dietary patterns and biomarkers associated with disease processes. There is good evidence for the use of certain novel biomarkers for each of the aforementioned dietary components. A review of the literature also reveals a relationship between a "Western" dietary pattern, characterized by higher intakes of red meat, processed meat, French fries, eggs, high-fat dairy products, sweets, and refined grains and that of increased risk for systemic inflammation, endothelial dysfunction, cardiovascular disease, metabolic syndrome, hypertension, and diabetes. Contrasting this is the "prudent" dietary pattern characterized by increased fruit, vegetables, poultry, fish, whole grains, and legumes which had improved biomarker profiles of the aforementioned diseases. Similar to the "Western" pattern is a diet with high saturated fat/high simple carbohydrate that correlates with increased biomarkers of Alzheimer's disease. There appears to be a large volume of literature investigating biomarkers of dietary intake and the relationship between dietary patterns and chronic diseases. However there is still need for literature looking into the relationship of novel biomarkers of fats, carbohydrates, protein, vitamin C, and carotenoids and the biomarkers of chronic diseases. © Springer Nature Singapore Pte Ltd. 2018.
Published:
2018
Title:
The future of nutrition: Nutrigenomics and nutrigenetics in obesity and cardiovascular diseases
Authors:
Peña-Romero, Alicia Cristina; Navas-Carrillo, Diana; Marín, Francisco; Orenes-Piñero, Esteban
Abstract:
Over time, the relationship between diet and health has aroused great interest, since nutrition can prevent and treat several diseases. It has been demonstrated that general recommendations on macronutrients and micronutrients do not affect to every individual in the same way because diet is an important environmental factor that interacts with genes. Thus, there is a growing necessity of improving a personalized nutrition to treat obesity and associated medical conditions, taking into account the interactions between diet, genes and health. Therefore, the knowledge of the interactions between the genome and nutrients at the molecular level, has led to the advent of nutritional genomics, which involves the sciences of nutrigenomics and nutrigenetics. In this review, we will comprehensively analyze the role of the most important genes associated with two interrelated chronic medical conditions, such as obesity and cardiovascular diseases.
Published:
2018
Title:
The impact of carbohydrate intake and its sources on hemoglobin A1c levels in Japanese patients with type 2 diabetes not taking anti-diabetic medication
Authors:
Haimoto, Hajime; Watanabe, Shiho; Komeda, Masashi; Wakai, Kenji
Abstract:
Background: Although postprandial glucose levels largely depend on carbohydrate intake, the impact of carbohydrate and its sources on hemoglobin A1c (HbA1c) levels has not been demonstrated in patients with type 2 diabetes (T2DM) probably because, in previous studies, more than 50% of patients were taking anti-diabetic medication, and the researchers used energy percent of carbohydrate as an indicator of carbohydrate intake. Patients and methods: We recruited 125 Japanese men (mean age 58±12 years) and 104 women (mean age 62±10 years) with T2DM who were not taking anti-diabetic medication and dietary therapy. We used 3-day dietary records to assess total carbohydrate intake and its sources, computed Spearman's correlation coefficients, and conducted multiple regression analyses for associations of carbohydrate sources with HbA1c by sex. Results: Mean HbA1c and total carbohydrate intake were 8.2%±1.9% and 272.0±84.6 g/day in men and 7.6%±1.3% and 226.7±61.5 g/day in women, respectively. We observed positive correlation of total carbohydrate intake (g/day) with HbA1c in men (rs=0.384) and women (rs=0.251), but no correlation for % carbohydrate in either sex. Regarding carbohydrate sources, we found positive correlations of carbohydrate from noodles (rs=0.231) and drinks (rs=0.325), but not from rice, with HbA1c in men. In women, carbohydrate from rice had a positive correlation (rs=0.317), but there were no correlations for carbohydrate from noodles and drinks. The association of total carbohydrate intake (g/day) and carbohydrate from soft drinks with HbA1c in men remained significant even after adjustment for total energy by multiple regression analyses. Conclusion: Our findings warrant interventional studies for moderate low-carbohydrate diets that focus on carbohydrate sources and sex differences in order to efficiently decrease HbA1c in patients with T2DM.
Published:
2018
Title:
The impact of nutrition and generally available products such as nicotine and alcohol on rheumatoid arthritis – review of the literature
Authors:
Grygielska, Jolanta; Raciborski, Filip; Kłak, Anna; Owoc, Jakub
Abstract:
Nutrition habits and diet may influence disease development and course. There are no specific recommendations related to rheumatic diseases for a diet that would facilitate treatment. However, some research results suggest that various nutrients may affect the health of patients, especially in the case of inflammatory rheumatic disease such as rheumatoid arthritis (RA). Scientists have been trying to find a relation between inflammatory rheumatic diseases and diet but have never come up with any firm conclusions that would help in determining the model of a diet for such patients. Nevertheless, there are some consistent results that refer to the influence of nutritional behaviours on symptoms of RA. The article presents a review of the research showing that certain nutrients may be beneficial for the course of disease among some RA patients.
Published:
2018
Title:
The interpretation and effect of a low-carbohydrate diet in the management of type 2 diabetes: A systematic review and meta-analysis of randomised controlled trials
Authors:
Huntriss, Rosemary; Campbell, Malcolm; Bedwell, Carol
Abstract:
Recently, the role of a low-carbohydrate diet in diabetes management has generated interest with claims being made regarding its superiority over the traditional high-carbohydrate, low-fat dietary approach. This systematic review and meta-analysis evaluated the interpretation and effect of a low-carbohydrate diet in the management of type 2 diabetes.
Published:
2018
Title:
The opportunity cost of animal based diets exceeds all food losses
Authors:
Shepon, Alon; Eshel, Gidon; Noor, Elad; Milo, Ron
Abstract:
Food loss is widely recognized as undermining food security and environmental sustainability. However, consumption of resource-intensive food items instead of more efficient, equally nutritious alternatives can also be considered as an effective food loss. Here we define and quantify these opportunity food losses as the food loss associated with consuming resource-intensive animal-based items instead of plant-based alternatives which are nutritionally comparable, e.g., in terms of protein content. We consider replacements that minimize cropland use for each of the main US animal-based food categories. We find that although the characteristic conventional retail-to-consumer food losses are ≈30% for plant and animal products, the opportunity food losses of beef, pork, dairy, poultry, and eggs are 96%, 90%, 75%, 50%, and 40%, respectively. This arises because plant-based replacement diets can produce 20-fold and twofold more nutritionally similar food per cropland than beef and eggs, the most and least resource-intensive animal categories, respectively. Although conventional and opportunity food losses are both targets for improvement, the high opportunity food losses highlight the large potential savings beyond conventionally defined food losses. Concurrently replacing all animal-based items in the US diet with plant-based alternatives will add enough food to feed, in full, 350 million additional people, well above the expected benefits of eliminating all supply chain food waste. These results highlight the importance of dietary shifts to improving food availability and security.
Published:
2018
Title:
The opportunity cost of animal based diets exceeds all food losses
Authors:
Shepon, Alon; Eshel, Gidon; Noor, Elad; Milo, Ron
Abstract:
Food loss is widely recognized as undermining food security and environmental sustainability. However, consumption of resource-intensive food items instead of more efficient, equally nutritious alternatives can also be considered as an effective food loss. Here we define and quantify these opportunity food losses as the food loss associated with consuming resource-intensive animal-based items instead of plant-based alternatives which are nutritionally comparable, e.g., in terms of protein content. We consider replacements that minimize cropland use for each of the main US animal-based food categories. We find that although the characteristic conventional retail-to-consumer food losses are ≈30% for plant and animal products, the opportunity food losses of beef, pork, dairy, poultry, and eggs are 96%, 90%, 75%, 50%, and 40%, respectively. This arises because plant-based replacement diets can produce 20-fold and twofold more nutritionally similar food per cropland than beef and eggs, the most and least resource-intensive animal categories, respectively. Although conventional and opportunity food losses are both targets for improvement, the high opportunity food losses highlight the large potential savings beyond conventionally defined food losses. Concurrently replacing all animal-based items in the US diet with plant-based alternatives will add enough food to feed, in full, 350 million additional people, well above the expected benefits of eliminating all supply chain food waste. These results highlight the importance of dietary shifts to improving food availability and security.
Published:
2018
Title:
The regulatory effects of Acetyl-CoA distribution in the healthy and diseased brain
Authors:
Ronowska, Anna; Szutowicz, Andrzej; Bielarczyk, Hanna; Gul-Hinc, Sylwia; Klimaszewska-\Lata, Joanna; Dyś, Aleksandra; Zyśk, Marlena; Jankowska-Kulawy, Agnieszka
Abstract:
Brain neurons, to support their neurotransmitter functions, require a several times higher supply of glucose than non-excitable cells. Pyruvate, the end product of glycolysis, through pyruvate dehydrogenase complex reaction, is a principal source of acetyl-CoA, which is a direct energy substrate in all brain cells. Several neurodegenerative conditions result in the inhibition of pyruvate dehydrogenase and decrease of acetyl-CoA synthesis in mitochondria. This attenuates metabolic flux through TCA in the mitochondria, yielding energy deficits and inhibition of diverse synthetic acetylation reactions in all neuronal sub-compartments. The acetyl-CoA concentrations in neuronal mitochondrial and cytoplasmic compartments are in the range of 10 and 7 μmol/L, respectively. They appear to be from 2 to 20 times lower than acetyl-CoA Km values for carnitine acetyltransferase, acetyl-CoA carboxylase, aspartate acetyltransferase, choline acetyltransferase, sphingosine kinase 1 acetyltransferase, acetyl-CoA hydrolase, and acetyl-CoA acetyltransferase, respectively. Therefore, alterations in acetyl-CoA levels alone may significantly change the rates of metabolic fluxes through multiple acetylation reactions in brain cells in different physiologic and pathologic conditions. Such substrate-dependent alterations in cytoplasmic, endoplasmic reticulum or nuclear acetylations may directly affect ACh synthesis, protein acetylations, and gene expression. Thereby, acetyl-CoA may regulate the functional and adaptative properties of neuronal and non-neuronal brain cells. The excitotoxicity-evoked intracellular zinc excess hits several intracellular targets, yielding the collapse of energy balance and impairment of the functional and structural integrity of postsynaptic cholinergic neurons. Acute disruption of brain energy homeostasis activates slow accumulation of amyloid-β1-42 (Aβ). Extra and intracellular oligomeric deposits of Aβ affect diverse transporting and signaling pathways in neuronal cells. It may combine with multiple neurotoxic signals, aggravating their detrimental effects on neuronal cells. This review presents evidences that changes of intraneuronal levels and compartmentation of acetyl-CoA may contribute significantly to neurotoxic pathomechanisms of different neurodegenerative brain disorders.
Published:
2018
Title:
The role of SIRT3 in the brain under physiological and pathological conditions
Authors:
Sidorova-Darmos, Elena; Sommer, Rosa; Eubanks, James H.
Abstract:
Sirtuin enzymes are a family of highly seven conserved protein deacetylases, namely SIRT1 through SIRT7, whose enzymatic activities require the cofactor nicotinamide adenine dinucleotide (NAD+). Sirtuins reside in different compartments within cells, and their activities have been shown to regulate a number of cellular pathways involved in but not limited to stress management, apoptosis and inflammatory responses. Given the importance of mitochondrial functional state in neurodegenerative conditions, the mitochondrial SIRT3 sirtuin, which is the primary deacetylase within mitochondria, has garnered considerable recent attention. It is now clear that SIRT3 plays a major role in regulating a host of mitochondrial molecular cascades that can contribute to both normal and pathophysiological processes. However, most of the currently available knowledge on SIRT3 stems from studies in non-neuronal cells, and the consequences of the interactions between SIRT3 and its targets in the CNS are only beginning to be elucidated. In this review, we will summarize current advances relating to SIRT3, and explore how its known functions could influence brain physiology.
Published:
2018
Title:
The role of adipose tissue in cardiovascular health and disease
Authors:
Oikonomou, Evangelos K.; Antoniades, Charalambos
Abstract:
Accumulating knowledge on the biology and function of the adipose tissue has led to a major shift in our understanding of its role in health and disease. The adipose tissue is now recognized as a crucial regulator of cardiovascular health, mediated by the secretion of several bioactive products, including adipocytokines, microvesicles and gaseous messengers, with a wide range of endocrine and paracrine effects on the cardiovascular system. The adipose tissue function and secretome are tightly controlled by complex homeostatic mechanisms and local cell–cell interactions, which can become dysregulated in obesity. Systemic or local inflammation and insulin resistance lead to a shift in the adipose tissue secretome from anti-inflammatory and anti-atherogenic towards a pro-inflammatory and pro-atherogenic profile. Moreover, the interplay between the adipose tissue and the cardiovascular system is bidirectional, with vascular-derived and heart-derived signals directly affecting adipose tissue biology. In this Review, we summarize the current knowledge of the biology and regional variability of adipose tissue in humans, deciphering the complex molecular mechanisms controlling the crosstalk between the adipose tissue and the cardiovascular system, and their possible clinical translation. In addition, we highlight the latest developments in adipose tissue imaging for cardiovascular risk stratification and discuss how therapeutic targeting of the adipose tissue can improve prevention and treatment of cardiovascular disease.
Published:
2018
Title:
The role of gut microbiota and diet on uremic retention solutes production in the context of chronic kidney disease
Authors:
Koppe, L.; Fouque, D.; Soulage, C.O.
Abstract:
Uremic retention solutes (URS) are associated with cardiovascular complications and poor survival in chronic kidney disease. The better understanding of the origin of a certain number of these toxins enabled the development of new strategies to reduce their production. URS can be classified according to their origins (i.e., host, microbial, or exogenous). The discovery of the fundamental role that the intestinal microbiota plays in the production of many URS has reinstated nutrition at the heart of therapeutics to prevent the accumulation of URS and their deleterious effects. The intestinal microbiota is personalized and is strongly influenced by dietary habits, such as the quantity and the quality of dietary protein and fibers. Herein, this review out lines the role of intestinal microbiota on URS production and the recent discoveries on the effect of diet composition on the microbial balance in the host with a focus on the effect on URS production. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Published:
2018
Title:
The role of the gut microbiome in systemic inflammatory disease
Authors:
Clemente, J.C.; Manasson, J.; Scher, J.U.
Abstract:
The role of the gut microbiome in models of inflammatory and autoimmune disease is now well characterized. Renewed interest in the human microbiome and its metabolites, as well as notable advances in host mucosal immunology, has opened multiple avenues of research to potentially modulate inflammatory responses. The complexity and interdependence of these diet-microbe-metabolite-host interactions are rapidly being unraveled. Importantly, most of the progress in the field comes from new knowledge about the functional properties of these microorganisms in physiology and their effect in mucosal immunity and distal inflammation. This review summarizes the preclinical and clinical evidence on how dietary, probiotic, prebiotic, and microbiome based therapeutics affect our understanding of wellness and disease, particularly in autoimmunity. © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to.
Published:
2018
Title:
Therapeutic lifestyle change diet enriched in legumes reduces oxidative stress in overweight type 2 diabetic patients: a crossover randomised clinical trial
Authors:
Mirmiran, P.; Hosseinpour-Niazi, S.; Azizi, F.
Abstract:
The objective of this study was to investigate whether a diet rich in legumes are associated with oxidative stress among type 2 diabetic patients. In a randomized, controlled, crossover clinical trial, 31 type 2 diabetic patients were randomly assigned to receive 2 diets, each for a period of 8 weeks: (1) The legume-free therapeutic lifestyle change (TLC) diet and (2) the legume-based TLC diet. Both diets were similar except that 2 servings of red meat were replaced by different types of legumes 3 days per week in the legume-based TLC diet. Oxidative stress biomarkers were measured at baseline and after 8 weeks. Compared to the legume-free TLC diet, the legume-based TLC diet significantly decreased malondialdehyde (-0.22 versus -0.68 mumol/l; P=0.002), oxidized-LDL (-0.9 versus -2.3 mU/l; P=0.05) and increased nitric oxide (0.40 versus 0.96 mM/l; P=0.03) and catalase activity (1.2 versus 2.1 Iu/ml; P=0.05).
Published:
2018
Title:
Towards utilization of the human genome and microbiome for personalized nutrition
Authors:
Bashiardes, Stavros; Godneva, Anastasia; Elinav, Eran; Segal, Eran
Abstract:
Generalized dietary and lifestyle guidelines have been formulated and published for decades now from a variety of relevant agencies in an attempt to guide people towards healthy choices. As the pandemic rise in metabolic diseases continues to increase, it has become clear that the one-fit-for-all diet approach does not work and that there is a significant variation in inter-individual responses to diet and lifestyle interventions. Recent technological advances have given an unprecedented insight into the sources of this variation, pointing towards our genome and microbiome as potentially and previously under-explored culprits contributing to individually unique dietary responses. Variations in our genome influence the bioavailability and metabolism of nutrients between individuals, while inter-individual compositional variation of commensal gut microbiota leads to different microbe functional potential, metabolite production and metabolism modulation. Quantifying and incorporating these factors into a comprehensive personalized nutrition approach may enable practitioners to rationally incorporate individual nutritional recommendations in combating the metabolic syndrome pandemic.
Published:
2018
Title:
Trabecular Anisotropy in the Primate Mandibular Condyle Is Associated with Dietary Toughness
Authors:
Coiner‐Collier, Susan; Vogel, Erin R.; Scott, Robert S.
Abstract:
Past attempts to establish a relationship between mandibular morphology and different dietary categories (e.g., frugivore, folivore, insectivore) have had mixed results, possibly because descriptive dietary categories are too broad and obscure variation within primate diets. Another potential reason is that not all aspects of skeletal architecture, especially trabecular anisotropy, have factored into functional assessments of dietary inputs into jaw form. Recent emphasis on quantifying food mechanical properties (FMPs) has provided an alternative to reliance on dietary categories. We used data on FMPs to test for correlations among dietary toughness and Young's modulus and the trabecular structure of the mandibular condyle, which is loaded during feeding and should reflect differences in masticatory stresses associated with different dietary FMPs. Adult primate mandibles from 11 species were imaged using high-resolution X-ray computed tomography, and trabecular structure was analyzed with BoneJ and Quant3D to assess common three-dimensional trabecular parameters. Results of phylogenetic generalized least squares analysis suggested a positive correlation between the degree of anisotropy (DA) and toughness, and weaker correlations between FMPs and various other trabecular variables. Because the DA contributes to the mechanical properties of bone, these results suggest a functional relationship between dietary toughness and trabecular anisotropy in the mandibular condyle. Such a perspective underscores the need to consider all aspects of skeletal morphology in evaluating the links between diet and jaw biomechanics. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.
Published:
2018
Title:
Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinoma
Authors:
Ye, Huilin; Zhou, Quanbo; Zheng, Shangyou; Li, Guolin; Lin, Qing; Wei, Lusheng; Fu, Zhiqiang; Zhang, Bin; Liu, Yimin; Li, Zhihua; Chen, Rufu
Abstract:
Tumor-associated macrophages (TAMs) are frequently found near pancreatic cancer cells, but it is uncertain whether they are involved in pancreatic cancer progression and the Warburg effect. Here, we show that CCL18 secreted by TAMs facilitates malignant progression and induced a glycolytic phenotype in pancreatic cancer, partially owing to paracrine induction of VCAM-1 in pancreatic cancer cells. Reciprocally, VCAM-1-induced lactate production from pancreatic cancer cells with enhanced aerobic glycolysis activates macrophages to a TAM-like phenotype, forming a positive feedback loop. VCAM-1 was found to be highly expressed in human pancreatic ductal adenocarcinoma (PDAC) tissues and cell lines, and is associated with disease progression and predicts clinical outcome in PDAC patients. Flow cytometry analysis further demonstrated that VCAM-1 downregulation induced an accumulation of PDAC cells in G0/G1 phase, accompanied by a significant decrease in S phase. Downregulation of VCAM-1 significantly inhibited proliferation, colony formation, migration, and invasion of PDAC cells in vitro, whereas the ectopic expression of VCAM-1 had the opposite effect. VCAM-1 on pancreatic cancer cells might tethers THP-1 monocytes to cancer cells via counter-receptor interaction, providing a survival advantage to pancreatic cancer cells that infiltrate leukocyte-rich microenvironments. Furthermore, downregulation of VCAM-1 could repress tumor growth in mouse xenograft models. In particular, our results highlighted the contribution of VCAM-1 to the maintenance of the Warburg effect in PDAC cells. Finally, we investigated the clinical correlations of CCL18 and VCAM-1 in human PDAC specimens. In summary, these findings indicate that the CCL18/PITPNM3/NF-kB/VCAM-1 regulatory network might provide a potential new therapeutic strategy for PDAC.
Published:
2018
Title:
Turning the Waiting Room into a Classroom: Weekly Classes Using a Vegan or a Portion-Controlled Eating Plan Improve Diabetes Control in a Randomized Translational Study
Authors:
Barnard, Neal D.; Levin, Susan M.; Gloede, Lise; Flores, Rosendo
Abstract:
BACKGROUND: In research settings, plant-based (vegan) eating plans improve diabetes management, typically reducing weight, glycemia, and low-density lipoprotein (LDL) cholesterol concentrations to a greater extent than has been shown with portion-controlled eating plans. OBJECTIVE: The study aimed to test whether similar benefits could be found using weekly nutrition classes in a typical endocrinology practice, hypothesizing that a vegan eating plan would improve glycemic control, weight, lipid concentrations, blood pressure, and renal function and would do so more effectively than a portion-controlled eating plan. DESIGN: In a 20-week trial, participants were randomly assigned to a low-fat vegan or portion-controlled eating plan. PARTICIPANTS/SETTING: Individuals with type 2 diabetes treated in a single endocrinology practice in Washington, DC, participated (45 starters, 40 completers). INTERVENTION: Participants attended weekly after-hours classes in the office waiting room. The vegan plan excluded animal products and added oils and favored low-glycemic index foods. The portion-controlled plan included energy intake limits for weight loss (typically a deficit of 500 calories/day) and provided guidance on portion sizes. MAIN OUTCOME MEASURES: Body weight, hemoglobin A1c (HbA1c), plasma lipids, urinary albumin, and blood pressure were measured. STATISTICAL ANALYSES PERFORMED: For normally distributed data, t tests were used; for skewed outcomes, rank-based approaches were implemented (Wilcoxon signed-rank test for within-group changes, Wilcoxon two-sample test for between-group comparisons, and exact Hodges-Lehmann estimation to estimate effect sizes). RESULTS: Although participants were in generally good metabolic control at baseline, body weight, HbA1c, and LDL cholesterol improved significantly within each group, with no significant differences between the two eating plans (weight: -6.3 kg vegan, -4.4 kg portion-controlled, between-group P=0.10; HbA1c, -0.40 percentage point in both groups, P=0.68; LDL cholesterol -11.9 mg/dL vegan, -12.7 mg/dL portion-controlled, P=0.89). Mean urinary albumin was normal at baseline and did not meaningfully change. Blood pressure changes were not significant. CONCLUSIONS: Weekly classes, integrated into a clinical practice and using either a low-fat vegan or portion-controlled eating plan, led to clinical improvements in individuals with type 2 diabetes.
Published:
2018
Title:
Untargeted Metabolomics Identifies Novel Potential Biomarkers of Habitual Food Intake in a Cross-Sectional Study of Postmenopausal Women
Authors:
Wang, Ying; Gapstur, Susan M.; Carter, Brian D.; Hartman, Terryl J.; Stevens, Victoria L.; Gaudet, Mia M.; McCullough, Marjorie L.
Abstract:
Background: Recent studies suggest that untargeted metabolomics is a promising tool to identify novel biomarkers of individual foods. However, few large cross-sectional studies with comprehensive data on habitual diet and circulating metabolites have been conducted. Objective: We aimed to identify potential food biomarkers and evaluate their predictive accuracy. Methods: We conducted a cross-sectional analysis of consumption of 91 food groups or items, assessed by a 152-item food-frequency questionnaire, in relation to 1186 serum metabolites measured by mass spectrometry-based platforms from 1369 nonsmoking postmenopausal women (mean age = 68.3 y). Diet-metabolite associations were selected by Pearson's partial correlation analysis (P 0.2). The predictive accuracy of the selected food metabolites was evaluated from the area under the curve (AUC) calculated from receiver operating characteristic analysis conducted among women in the top and bottom quintiles of dietary intake. Results: We identified 379 diet-metabolite associations. Forty-two food groups or items were correlated with 199 serum metabolites. We replicated 63 metabolites as biomarkers of habitual food intake reported in previous cross-sectional studies. Among those not previously shown to be associated with habitual diet, several are biologically plausible and were reported in acute feeding studies including: banana and dopamine 3-O-sulfate (r = 0.34, AUC = 76%) and dopamine 4-O-sulfate (r = 0.33, AUC = 74%), garlic and alliin (r = 0.24, AUC = 69%), N-acetylalliin (r = 0.27, AUC = 70%), and S-allylcysteine (r = 0.23, AUC = 69). Two unannotated metabolites were the strongest predictors for dark fish (X-02269, r = 0.51, AUC = 94%) and coffee intake (X-21442, r = 0.62, AUC = 98%). Conclusion: In this comprehensive, cross-sectional analysis of habitual food intake and serum metabolites among postmenopausal women, we identified several potentially novel food biomarkers and replicated others. Our findings contribute to the limited literature on food-based biomarkers and highlight the significant and promising role that large cohort studies with archived blood samples could play in this field. This study was registered at clinicaltrials.gov as NCT03282812.
Published:
2018
Title:
Urinary composition predicts diuretic efficiency of hypertonic saline solution with furosemide therapy and heart failure prognosis
Authors:
Ando, Tomotaka; Okuhara, Yoshitaka; Orihara, Yoshiyuki; Nishimura, Koichi; Yamamoto, Kyoko; Masuyama, Tohru; Hirotani, Shinichi
Abstract:
© 2018, Springer Japan KK, part of Springer Nature. Recently, we and other group have reported that furosemide administration along with hypertonic saline solution enhanced diuretic efficiency of furosemide. However, little is known about factors which associated with high diuretic efficiency by hypertonic saline solution with furosemide therapy. To identify predictors of diuretic efficiency in the hypertonic saline solution with furosemide therapy, we recruited 30 consecutive hospitalized heart failure (HF) patients with volume overload (77 ± 10 years, systolic blood pressure \textgreater 90 mmHg, and estimated glomerular filtration rate \textgreater 15 ml/min/1.73 m2). Hypertonic saline with furosemide solution, consisting of 500 ml of 1.7% hypertonic saline solution with 40 mg of furosemide, was administered continuously over 24 h. The patients were divided into two groups on the basis of 24-h urine volume (UV) after initiation of diuretic treatment ≥ 2000 ml (high urine volume: HUV) and \textless 2000 ml (low urine volume: LUV). The basal clinical characteristics of both groups were analyzed and the predictors of HUV after receiving the treatment were identified. There were not significant differences between two groups in baseline clinical characteristics and medication. Univariate logistic analysis revealed that blood urea nitrogen/creatinine ratio, urine urea nitrogen/creatinine ratio (UUN/UCre), fractional excretion of sodium, and tricuspid annular plane systolic excursion positively associated with HUV. Multivariate logistic regression analysis revealed that UUN/UCre at baseline was independently associated with HUV, and UUN/UCre best predicts HUV by the therapy with a cut-off value of 6.16 g/dl/g Cre (AUC 0.910, 95% CI 0.696–0.999, sensitivity 80%, specificity 87%). The Kaplan–Meier curves revealed significant difference for HF rehospitalization and death rate at 180 days between patients with UUN/UCre ≥ 6.16 g/dl/g Cre and those with UUN/UCre \textless 6.16 g/dl/g Cre (log-rank P = 0.0489). UUN/UCre at baseline strongly predicted of diuretic efficiency in the hypertonic saline solution with furosemide therapy, and was associated with HF prognosis.
Published:
2018
Title:
Urinary sodium excretion, blood pressure, cardiovascular disease, and mortality: a community-level prospective epidemiological cohort study
Authors:
Mente, Andrew; O'Donnell, Martin; Rangarajan, Sumathy; McQueen, Matthew; Dagenais, Gilles; Wielgosz, Andreas; Lear, Scott; Ah, Shelly Tse Lap; Wei, Li; Diaz, Rafael; Avezum, Alvaro; Lopez-Jaramillo, Patricio; Lanas, Fernando; Mony, Prem; Szuba, Andrzej; Iqbal, Romaina; Yusuf, Rita; Mohammadifard, Noushin; Khatib, Rasha; Yusoff, Khalid; Ismail, Noorhassim; Gulec, Sadi; Rosengren, Annika; Yusufali, Afzalhussein; Kruger, Lanthe; Tsolekile, Lungiswa Primrose; Chifamba, Jephat; Dans, Antonio; Alhabib, Khalid F.; Yeates, Karen; Teo, Koon; Yusuf, Salim
Abstract:
Background: WHO recommends that populations consume less than 2 g/day sodium as a preventive measure against cardiovascular disease, but this target has not been achieved in any country. This recommendation is primarily based on individual-level data from short-term trials of blood pressure (BP) without data relating low sodium intake to reduced cardiovascular events from randomised trials or observational studies. We investigated the associations between community-level mean sodium and potassium intake, cardiovascular disease, and mortality. Methods: The Prospective Urban Rural Epidemiology study is ongoing in 21 countries. Here we report an analysis done in 18 countries with data on clinical outcomes. Eligible participants were adults aged 35–70 years without cardiovascular disease, sampled from the general population. We used morning fasting urine to estimate 24 h sodium and potassium excretion as a surrogate for intake. We assessed community-level associations between sodium and potassium intake and BP in 369 communities (all \textgreater50 participants) and cardiovascular disease and mortality in 255 communities (all \textgreater100 participants), and used individual-level data to adjust for known confounders. Findings: 95 767 participants in 369 communities were assessed for BP and 82 544 in 255 communities for cardiovascular outcomes with follow-up for a median of 8·1 years. 82 (80%) of 103 communities in China had a mean sodium intake greater than 5 g/day, whereas in other countries 224 (84%) of 266 communities had a mean intake of 3–5 g/day. Overall, mean systolic BP increased by 2·86 mm Hg per 1 g increase in mean sodium intake, but positive associations were only seen among the communities in the highest tertile of sodium intake (p\textless0·0001 for heterogeneity). The association between mean sodium intake and major cardiovascular events showed significant deviations from linearity (p=0·043) due to a significant inverse association in the lowest tertile of sodium intake (lowest tertile \textless4·43 g/day, mean intake 4·04 g/day, range 3·42–4·43; change –1·00 events per 1000 years, 95% CI –2·00 to –0·01, p=0·0497), no association in the middle tertile (middle tertile 4·43–5·08 g/day, mean intake 4·70 g/day, 4·44–5.05; change 0·24 events per 1000 years, –2·12 to 2·61, p=0·8391), and a positive but non-significant association in the highest tertile (highest tertile \textgreater5·08 g/day, mean intake 5·75 g/day, \textgreater5·08–7·49; change 0·37 events per 1000 years, –0·03 to 0·78, p=0·0712). A strong association was seen with stroke in China (mean sodium intake 5·58 g/day, 0·42 events per 1000 years, 95% CI 0·16 to 0·67, p=0·0020) compared with in other countries (4·49 g/day, –0·26 events, –0·46 to –0·06, p=0·0124; p\textless0·0001 for heterogeneity). All major cardiovascular outcomes decreased with increasing potassium intake in all countries. Interpretation: Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate. Funding: Population Health Research Institute, Canadian Institutes of Health Research, Canadian Institutes of Health Canada Strategy for Patient-Oriented Research, Ontario Ministry of Health and Long-Term Care, Heart and Stroke Foundation of Ontario, and European Research Council.
Published:
2018
Title:
VDAC Regulation: A Mitochondrial Target to Stop Cell Proliferation
Authors:
Fang, Diana; Maldonado, Eduardo N.
Abstract:
Cancer metabolism is emerging as a chemotherapeutic target. Enhanced glycolysis and suppression of mitochondrial metabolism characterize the Warburg phenotype in cancer cells. The flux of respiratory substrates, ADP, and Pi into mitochondria and the release of mitochondrial ATP to the cytosol occur through voltage-dependent anion channels (VDACs) located in the mitochondrial outer membrane. Catabolism of respiratory substrates in the Krebs cycle generates NADH and FADH2 that enter the electron transport chain (ETC) to generate a proton motive force that maintains mitochondrial membrane potential (ΔΨ) and is utilized to generate ATP. The ETC is also the major cellular source of mitochondrial reactive oxygen species (ROS). αβ-Tubulin heterodimers decrease VDAC conductance in lipid bilayers. High constitutive levels of cytosolic free tubulin in intact cancer cells close VDAC decreasing mitochondrial ΔΨ and mitochondrial metabolism. The VDAC-tubulin interaction regulates VDAC opening and globally controls mitochondrial metabolism, ROS formation, and the intracellular flow of energy. Erastin, a VDAC-binding molecule lethal to some cancer cell types, and erastin-like compounds identified in a high-throughput screening antagonize the inhibitory effect of tubulin on VDAC. Reversal of tubulin inhibition of VDAC increases VDAC conductance and the flux of metabolites into and out of mitochondria. VDAC opening promotes a higher mitochondrial ΔΨ and a global increase in mitochondrial metabolism leading to high cytosolic ATP/ADP ratios that inhibit glycolysis. VDAC opening also increases ROS production causing oxidative stress that, in turn, leads to mitochondrial dysfunction, bioenergetic failure, and cell death. In summary, antagonism of the VDAC-tubulin interaction promotes cell death by a "double-hit model" characterized by reversion of the proproliferative Warburg phenotype (anti-Warburg) and promotion of oxidative stress.
Published:
2018
Title:
VDAC1 functions in Ca2+ homeostasis and cell life and death in health and disease
Authors:
Shoshan-Barmatz, Varda; Krelin, Yakov; Shteinfer-Kuzmine, Anna
Abstract:
In the outer mitochondrial membrane (OMM), the voltage-dependent anion channel 1 (VDAC1) serves as a mitochondrial gatekeeper, controlling the metabolic and energy cross-talk between mitochondria and the rest of the cell. VDAC1 also functions in cellular Ca2+ homeostasis by transporting Ca2+ in and out of mitochondria. VDAC1 has also been recognized as a key protein in mitochondria-mediated apoptosis, contributing to the release of apoptotic proteins located in the inter-membranal space (IMS) and regulating apoptosis via association with pro- and anti-apoptotic members of the Bcl-2 family of proteins and hexokinase. VDAC1 is highly Ca2+-permeable, transporting Ca2+ to the IMS and thus modulating Ca2+ access to Ca2+ transporters in the inner mitochondrial membrane. Intra-mitochondrial Ca2+ controls energy metabolism via modulating critical enzymes in the tricarboxylic acid cycle and in fatty acid oxidation. Ca2+ also determines cell sensitivity to apoptotic stimuli and promotes the release of pro-apoptotic proteins. However, the precise mechanism by which intracellular Ca2+ mediates apoptosis is not known. Here, the roles of VDAC1 in mitochondrial Ca2+ homeostasis are presented while emphasizing a new proposed mechanism for the mode of action of pro-apoptotic drugs. This view, proposing that Ca2+-dependent enhancement of VDAC1 expression levels is a major mechanism by which apoptotic stimuli induce apoptosis, position VDAC1 oligomerization at a molecular focal point in apoptosis regulation. The interactions of VDAC1 with many proteins involved in Ca2+ homeostasis or regulated by Ca2+, as well as VDAC-mediated control of cell life and death and the association of VDAC with disease, are also presented.
Published:
2018
Title:
Validation of Dried Blood Spot Cards to Determine Apple Phenolic Metabolites in Human Blood and Plasma After an Acute Intake of Red-Fleshed Apple Snack
Authors:
Yuste, Silvia; Macià, Alba; Ludwig, Iziar A.; Romero, María-Paz; Fernández-Castillejo, Sara; Catalán, Úrsula; Motilva, María-José; Rubió, Laura
Abstract:
SCOPE: The application of dried blood spot (DBS) cards for the study in human blood of dietary polyphenol bioavailability has been poorly studied. METHODS AND RESULTS: An analytical method based on blood sampling with DBS cards combined with LC-MS/MS has been developed and validated. To test the method validation, the phenolic metabolites are determined in human blood and plasma obtained after an acute intake of a red-fleshed apple snack in ten volunteers. Capillary blood by finger prick is compared to venous blood by venipuncture and whole blood is also compared to their corresponding venous plasma samples. Moreover, the venous plasma results using DBS cards are compared to those obtained by microElution solid phase extraction (µSPE). The main phenolic metabolites detected in blood and plasma samples are phloretin glucuronide, dihydroxyphenylpropionic acid sulphate, (methyl) catechol sulphate, catechol glucuronide, and hydroxyphenyl-γ-valerolactone glucuronide. No significant differences are observed between capillary blood, venous blood, and plasma samples using DBS, and neither between plasma samples analyzed by DBS or µSPE. CONCLUSIONS: Finger-prick blood sampling based on DBS appears to be a suitable alternative to the classic invasive venipuncture for the determination of circulating phenolic metabolites in nutritional postprandial studies.
Published:
2018
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