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Title:
Maternal Sleep in Pregnancy and Postpartum Part I: Mental, Physical, and Interpersonal Consequences
Authors:
Christian, Lisa M.; Carroll, Judith E.; Teti, Douglas M.; Hall, Martica H.
Abstract:
Purpose of Review Sleep is a critical restorative behavior which occupies approximately one third of people’s lives. Extensive data link sleep health with disease and mortality risk in the general population. During pregnancy and following childbirth, unique factors contribute to overall sleep health. In addition, there are unique implications of poor sleep during these time periods. Recent Findings Poor maternal sleep may contribute to risk for adverse birth outcomes as well as poor maternal physical and mental health in pregnancy, postpartum, and longer term during childrearing. Moreover, the extent to which notable racial disparities in sleep contribute to disparities in adverse perinatal health outcomes remains to be fully explicated.
Published:
2019-03
Title:
Maternal Sleep in Pregnancy and Postpartum Part II: Biomechanisms and Intervention Strategies
Authors:
Carroll, Judith E.; Teti, Douglas M.; Hall, Martica H.; Christian, Lisa M.
Abstract:
Purpose of Review As described in Part I of this two-part review, maternal sleep has wide-ranging implications for maternal health and overall family functioning. In addition, poor sleep quality and insufficient sleep are highly prevalent and characterized by considerable racial disparities.
Published:
2019-03
Title:
Procyanidin—Cell Wall Interactions within Apple Matrices Decrease the Metabolization of Procyanidins by the Human Gut Microbiota and the Anti-Inflammatory Effect of the Resulting Microbial Metabolome In Vitro
Authors:
Le Bourvellec, Carine; Bott, Romain; Renard, Catherine M. G. C.; Dufour, Claire; Bagano Vilas Boas, Priscilla; Chatel, Jean-Marc; Lepercq, Pascale; Comtet-Marre, Sophie; Ruiz, Philippe; Mosoni, Pascale; Auffret, Pauline
Abstract:
B-type oligomeric procyanidins in apples constitute an important source of polyphenols in the human diet. Their role in health is not known, although it is suggested that they generate beneficial bioactive compounds upon metabolization by the gut microbiota. During apple processing, procyanidins interact with cell-wall polysaccharides and form stable complexes. These interactions need to be taken into consideration in order to better assess the biological effects of fruit constituents. Our objectives were to evaluate the impact of these interactions on the microbial metabolization of cell walls and procyanidins, and to investigate the potential anti-inflammatory activity of the resulting metabolome, in addition to analyzing the taxonomical changes which the microbiota undergo. In vitro fermentation of three model apple matrices with microbiota from 4 healthy donors showed that the binding of procyanidins to cell-wall polysaccharides, whether covalently or non-covalently, substantially reduced procyanidin degradation. Although cell wall-unbound procyanidins negatively affected carbohydrate fermentation, they generated more hydroxyphenylvaleric acid than bound procyanidins, and increased the abundance of Adlercreutzia and Gordonibacter genera. The best results in terms of production of anti-inflammatory bioactive metabolites were observed from the apple matrix with no bonds between procyanidins and cell wall polysaccharides, although the matrix with non-covalent bonds was not far behind.
Published:
2019-03
Title:
The obese adipose tissue microenvironment in cancer development and progression
Authors:
Quail, Daniela F.; Dannenberg, Andrew J.
Abstract:
Obesity is associated with both increased cancer incidence and progression in multiple tumour types, and is estimated to contribute to up to 20% of cancer-related deaths. These associations are driven, in part, by metabolic and inflammatory changes in adipose tissue that disrupt physiological homeostasis both within local tissues and systemically. However, the mechanisms underlying the obesity–cancer relationship are poorly understood. In this Review, we describe how the adipose tissue microenvironment (ATME) evolves during body-weight gain, and how these changes might influence tumour initiation and progression. We focus on multiple facets of ATME physiology, including inflammation, vascularity and fibrosis, and discuss therapeutic interventions that have the potential to normalize the ATME, which might be translationally relevant for cancer prevention and therapy. Given that the prevalence of obesity is increasing on an international scale, translational research initiatives are urgently needed to provide mechanistic explanations for the obesity–cancer relationship, and how to best identify high-risk individuals without relying on crude measures, such as BMI.
Published:
2019-03
Title:
A Randomized Trial Comparing Extended-Release Injectable Suspension and Oral Naltrexone, Both Combined With Behavioral Therapy, for the Treatment of Opioid Use Disorder
Authors:
Sullivan, Maria A.; Bisaga, Adam; Pavlicova, Martina; Carpenter, Kenneth M.; Choi, C. Jean; Mishlen, Kaitlyn; Levin, Frances R.; Mariani, John J.; Nunes, Edward V.
Abstract:
Published:
2019-02
Title:
Advanced glycation end products are elevated in estrogen receptor-positive breast cancer patients, alter response to therapy, and can be targeted by lifestyle intervention
Authors:
Walter, Katherine R.; Ford, Marvella E.; Gregoski, Mathew J.; Kramer, Rita M.; Knight, Kendrea D.; Spruill, Laura; Nogueira, Lourdes M.; Krisanits, Bradley A.; Phan, Van; La Rue, Amanda C.; Lilly, Michael B.; Ambs, Stefan; Chan, King; Turner, Tonya F.; Varner, Heidi; Singh, Shweta; Uribarri, Jaime; Garrett-Mayer, Elizabeth; Armeson, Kent E.; Hilton, Ebony J.; Clair, Mark J.; Taylor, Marian H.; Abbott, Andrea M.; Findlay, Victoria J.; Peterson, Lindsay L.; Magwood, Gayenell; Turner, David P.
Abstract:
Purpose Lifestyle factors associated with personal behavior can alter tumor-associated biological pathways and thereby increase cancer risk, growth, and disease recurrence. Advanced glycation end products (AGEs) are reactive metabolites produced endogenously as a by-product of normal metabolism. A Western lifestyle also promotes AGE accumulation in the body which is associated with disease phenotypes through modification of the genome, protein crosslinking/dysfunction, and aberrant cell signaling. Given the links between lifestyle, AGEs, and disease, we examined the association between dietary-AGEs and breast cancer. Methods We evaluated AGE levels in bio-specimens from estrogen receptor-positive (ER+) and estrogen receptor-negative (ER−) breast cancer patients, examined their role in therapy resistance, and assessed the ability of lifestyle intervention to reduce circulating AGE levels in ER+ breast cancer survivors. Results An association between ER status and AGE levels was observed in tumor and serum samples. AGE treatment of ER+ breast cancer cells altered ERα phosphorylation and promoted resistance to tamoxifen therapy. In a proof of concept study, physical activity and dietary intervention was shown to be viable options for reducing circulating AGE levels in breast cancer survivors. Conclusions There is a potential prognostic and therapeutic role for lifestyle derived AGEs in breast cancer. Given the potential benefits of lifestyle intervention on incidence and mortality, opportunities exist for the development of community health and nutritional programs aimed at reducing AGE exposure in order to improve breast cancer prevention and treatment outcomes.
Published:
2019-02
Title:
Comparing SRM and SWATH Methods for Quantitation of Bovine Muscle Proteomes
Authors:
Wu, Wei; Dai, Rui-Tong; Bendixen, Emoke
Abstract:
Mass spectrometry (MS) has become essential for efficient and accurate quantification of proteins and proteomes and, thus, a key technology throughout all biosciences. However, validated MS methods are still scarce for meat quality research applications. The objective of this work was to develop and compare two targeted proteomic methods, namely, selected reaction monitoring (SRM) and sequential window acquisition of all theoretical spectra (SWATH), for the quantification of 11 bovine muscle proteins that may be indicators of meat color. Both methods require evaluation of spectra from proteotypic and quantotypic peptides, and we here report our evaluation of which peptides and MS parameters are best suited for robust quantification of these 11 proteins. We observed that the SRM approach provides better reproducibility, linearity, and sensitivity than SWATH and is therefore ideal for targeted quantification of low-abundance proteins, while the SWATH approach provides a more time-efficient method for targeted protein quantification of high-abundance proteins and, additionally, supports the search for novel biomarkers.
Published:
2019-02
Title:
Review of Two Popular Eating Plans within the Multiple Sclerosis Community: Low Saturated Fat and Modified Paleolithic
Authors:
Wahls, Terry L.; Chenard, Catherine A.; Snetselaar, Linda G.
Abstract:
The precise etiology of multiple sclerosis (MS) is unknown but epidemiologic evidence suggests this immune-mediated, neurodegenerative condition is the result of a complex interaction between genes and lifetime environmental exposures. Diet choices are ...
Published:
2019-02
Title:
The arrival of circadian medicine
Authors:
Panda, Satchidananda
Abstract:
Circadian rhythm research is beginning to show how rhythms sustain health. Genome-wide transcriptome, metabolome and proteome studies have improved our understanding of circadian regulation. This knowledge is leveraged for behavioural interventions that optimize daily rhythms, the timing of drug delivery and the targeting of clock components to prevent or treat chronic diseases. A reference human circadian transcriptome atlas elucidated tissue-specific circadian regulation1.The human plasma proteome shows diurnal changes and shift work affects a subset of these temporal changes4,5.A high-fat diet disrupts the temporal coordination of transcripts and metabolites across multiple organs in rodents6.Time-restricted eating among men at risk of prediabetes improves blood glucose control and reduces blood pressure without causing weight loss7.Timed administration of drugs without changing dosage can improve potency of anti-inflammatory drugs and pharmacological targeting of circadian clock is a new approach to treat cancer9,10.
Published:
2019-02
Title:
A short-term intervention combining aerobic exercise with medium-chain triglycerides (MCT) is more ketogenic than either MCT or aerobic exercise alone: a comparison of normoglycemic and prediabetic older women
Authors:
Vandenberghe, Camille; Castellano, Christian-Alexandre; Maltais, Mathieu; Fortier, Mélanie; St-Pierre, Valérie; Dionne, Isabelle J.; Cunnane, Stephen C.
Abstract:
The objectives of this study were to determine (i) whether a 5-day aerobic exercise (AE) program combined with a medium-chain triglyceride (MCT) supplement would increase the plasma ketone response in older women more than either intervention alone and (ii) whether ketonemia after these combined or separate treatments was alike in normoglycemic (NG) and prediabetic (PD) women. Older women (NG, n = 10; PD, n = 9) underwent a 4-h metabolic study after each of 4 different treatments: (i) no treatment (control), (ii) 5 days of MCT alone (30 g·day-1), (iii) 1 session of 30 min of AE alone, and (iv) 5 days of MCT and AE combined (MCT+AE). Blood was sampled every 30 min over 4 h for analysis. In NG, MCT+AE induced the highest area under the curve (AUC) for plasma ketones (835 ± 341 μmol·h·L-1); this value was 69% higher than that observed with MCT alone (P < 0.05). AUCs were not different between MCT alone and MCT+AE in PD, but both treatments induced a significantly higher AUC than the control or AE alone (P
Published:
2019-01
Title:
An Overview of Animal Models Related to Schizophrenia
Authors:
Winship, Ian R.; Dursun, Serdar M.; Baker, Glen B.; Balista, Priscila A.; Kandratavicius, Ludmyla; Maia-de-Oliveira, Joao Paulo; Hallak, Jaime; Howland, John G.
Abstract:
Schizophrenia is a heterogeneous psychiatric disorder that is poorly treated with current therapies. In this brief review, we provide an update regarding the use of animal models to study schizophrenia in an attempt to understand its aetiology and develop novel therapeutic strategies. Tremendous progress has been made developing and validating rodent models that replicate the aetiologies, brain pathologies, and behavioural abnormalities associated with schizophrenia in humans. Here, models are grouped into 3 categories—developmental, drug induced, and genetic—to reflect the heterogeneous risk factors associated with schizophrenia. Each of these models is associated with varied but overlapping pathophysiology, endophenotypes, behavioural abnormalities, and cognitive impairments. Studying schizophrenia using multiple models will permit an understanding of the core features of the disease, thereby facilitating preclinical research aimed at the development and validation of better pharmacotherapies to alter the progression of schizophrenia or alleviate its debilitating symptoms.
Published:
2019-01
Title:
Antipsychotic Use During Pregnancy and the Risk of Gestational Diabetes Mellitus: A Systematic Review
Authors:
Uguz, Faruk
Abstract:
Purpose: This study aimed to review the current literature examining a potential relationship between the use of antipsychotic drugs during pregnancy and gestational diabetes mellitus (GDM).
Published:
2019-01
Title:
Association of Triglyceride-Lowering LPL Variants and LDL-C–Lowering LDLR Variants With Risk of Coronary Heart Disease
Authors:
Ference, Brian A.; Kastelein, John J. P.; Ray, Kausik K.; Ginsberg, Henry N.; Chapman, M. John; Packard, Chris J; Laufs, Ulrich; Oliver-Williams, Clare; Wood, Angela M; Butterworth, Adam S; Di Angelantonio, Emanuele; Danesh, John; Nicholls, Stephen J; Bhatt, Deepak L; Sabatine, Marc S; Catapano, Alberico L
Abstract:
Published:
2019-01
Title:
Associations Between Dietary Protein Sources, Plasma BCAA and Short-Chain Acylcarnitine Levels in Adults
Authors:
Rousseau, Michèle; Guénard, Frédéric; Garneau, Véronique; Allam-Ndoul, Bénédicte; Lemieux, Simone; Pérusse, Louis; Vohl, Marie-Claude
Abstract:
Elevated plasma branched-chain amino acids (BCAA) and C3 and C5 acylcarnitines (AC) levels observed in individuals with insulin resistance (IR) might be influenced by dietary protein intakes. This study explores the associations between dietary protein sources, plasma BCAA levels and C3 and C5 ACs in normal weight (NW) or overweight (OW) individuals with or without metabolic syndrome (MS). Data from 199 men and women aged 18–55 years with complete metabolite profile were analyzed. Associations between metabolic parameters, protein sources, plasma BCAA and AC levels were tested. OW/MS+ consumed significantly more animal protein (p = 0.0388) and had higher plasma BCAA levels (p < 0.0001) than OW/MS− or NW/MS− individuals. Plasma BCAA levels were not associated with BCAA intakes in the whole cohort, while there was a trend for an association between plasma BCAA levels and red meat or with animal protein in OW/MS+. These associations were of weak magnitude. In NW/MS− individuals, the protein sources associated with BCAA levels varied greatly with adjustment for confounders. Plasma C3 and C5 ACs were associated with plasma BCAA levels in the whole cohort (p
Published:
2019-01
Title:
Changes in inflammatory bowel disease subtype during follow-up and over time in 44,302 patients
Authors:
Everhov, Åsa H.; Sachs, Michael C.; Malmborg, Petter; Nordenvall, Caroline; Myrelid, Pär; Khalili, Hamed; Elmberg, Maria; Ekbom, Anders; Askling, Johan; Jakobsson, Gustav; Halfvarson, Jonas; Ludvigsson, Jonas F.; Olén, Ola
Abstract:
AIM: To investigate inflammatory bowel disease (IBD) register-based subtype classifications over a patient's disease course and over time. METHODS: We examined International Classification of Diseases coding in patients with ≥2 IBD diagnostic listings in the National Patient Register 2002-2014 (n = 44,302). RESULTS: 18% of the patients changed diagnosis (17% of adults, 29% of children) during a median follow-up of 3.8 years. Of visits with diagnoses of Crohn's disease (CD) or ulcerative colitis (UC), 97% were followed by the same diagnosis, whereas 67% of visits with diagnosis IBD-unclassified (IBD-U) were followed by another IBD-U diagnosis. Patients with any diagnostic change changed mostly once (47%) or twice (31%), 39% from UC to CD, 33% from CD to UC and 30% to or from IBD-U. Using a classification algorithm based on the first two diagnoses ('incident classification'), suited for prospective cohort studies, the proportion adult patients with CD, UC, and IBD-U 2002-2014 were 29%, 62%, and 10% (43%, 45%, and 12% in children). A classification model incorporating additional information from surgeries and giving weight to the last 5 years of visits ('prevalent classification'), suited for description of a study population at end of follow-up, classified 31% of adult cases as CD, 58% as UC and 11% as IBD-U (44%, 38%, and 18% in children). CONCLUSIONS: IBD subtype changed in 18% during follow-up. The proportion with CD increased and UC decreased from definition at start to end of follow-up. IBD-U was more common in children.
Published:
2019-01
Title:
Growth and Persistence of Place-Based Mortality in the United States: The Rural Mortality Penalty
Authors:
Cosby, Arthur G.; McDoom-Echebiri, M. Maya; James, Wesley; Khandekar, Hasna; Brown, Willie; Hanna, Heather L.
Abstract:
Objectives. To examine 47 years of US urban and rural mortality trends at the county indicate that the rural penalty is broad level, controlling for effects of education, income, poverty, and race. based and occurs in all 5 leading causes of death: Methods. We obtained (1) Centers for Disease Control and Prevention WONDER (Wide-ranging ONline Data for Epidemiologic Research) data (1970–2016) on 104 million deaths; (2) US Census data on education, poverty, and race; and (3) Bureau of Economic Analysis data on income. We calculated ordinary least square regression models, including interaction models, for each year. We graphed standardized parameter estimates for 47 years. Results. Rural–urban mortality disparities increased from the mid-1980s through 2016. We found education, race, and rurality to be strong predictors; we found strong interactions between percentage poverty and percentage rural, indicating that the largest penalty was in high-poverty, rural counties. Conclusions. The rural–urban mortality disparity was persistent, growing, and large when compared to other place-based disparities. The penalty had evolved into a highpoverty, rural penalty that rivaled the effects of education and exceeded the effects of race by 2016.
Published:
2019-01
Title:
Having few remaining teeth is associated with a low nutrient intake and low serum albumin levels in middle-aged and older Japanese individuals: findings from the NIPPON DATA2010
Authors:
Nakamura, Mieko; Ojima, Toshiyuki; Nagahata, Tomomi; Kondo, Imako; Ninomiya, Toshiharu; Yoshita, Katsushi; Arai, Yusuke; Ohkubo, Takayoshi; Murakami, Keiko; Nishi, Nobuo; Murakami, Yoshitaka; Takashima, Naoyuki; Okuda, Nagako; Kadota, Aya; Miyagawa, Naoko; Kondo, Keiko; Okamura, Tomonori; Ueshima, Hirotsugu; Okayama, Akira; Miura, Katsuyuki; Group, NIPPON DATA2010 Research
Abstract:
CONCLUSIONS: Having few remaining teeth was associated with a low nutrient intake and low serum albumin levels in middle-aged and older Japanese adults, and these associations were more evident in individuals with low SES.
Published:
2019-01
Title:
Insulin Resistance Is a Risk Factor for Mild Cognitive Impairment in Elderly Adults with T2DM
Authors:
Zhao, Hongjun; Wu, Chenglong; Zhang, Xiaoping; Wang, Liping; Sun, Jianhong; Zhuge, Fuyuan
Abstract:
Objective: The aim of this study was to investigate the clinical effects of insulin resistance (IR) in the development of mild cognitive impairment (MCI) in elderly adults with Type 2 diabetes mellitus (T2DM). Methods: Seventy-eight patients with T2DM were recruited and divided into MCI group (<26, n=48) and normal group (≥26, n=30) according to the Montreal Cognitive Assessment (MoCA) score. The fasting plasma glucose (FPG), HbA1c, and fasting plasma C-peptide (FPC) were examined and compared between the two groups. The Pancreatic islets function (HOMA-islet) and Insulin Resistance Index (HOMA-IR) were also calculated for the two groups. Using the HOMA-IR and HOMA-islet as the reference, the predicted values for MCI in T2DM patients were calculated by sensitivity, specificity and area under the receiver operating characteristic (ROC) curve. Results: The MoCA scores were statistically different between the MCI and control groups (23.79±1.15 vs 28.50±1.01, p<0.05). The serum FPG and FPC were 10.38±2.36 mmol/L and 0.79±0.34 ng/mL in the MCI group which were significant different from those of the control group (8.96±2.55 mmol/L and 1.04±0.38 ng/mL; p<0.05). The HOMA-IR and HOMA-islet were 10.08±2.64 and 94.67±29.12 for the MCI group and 8.16±2.46 and 130.30±38.43 for the control group; both were statistically different (p<0.05). The serum HbA1c was 11.02±2.59% and 9.37±2.00% for the MCI and control groups (significantly different with p<0.5). A significant positive correlation was found between MoCA score and HOMA-islet (rpearson=0.44; p
Published:
2019-01
Title:
Intakes of Vitamin B-12 from Dairy Food, Meat, and Fish and Shellfish Are Independently and Positively Associated with Vitamin B-12 Biomarker Status in Pregnant Dutch Women
Authors:
Denissen, Karlijn F M; Heil, Sandra G; Eussen, Simone J P M; Heeskens, Jim P J; Thijs, Carel; Mommers, Monique; Smits, Luc J M; Dongen, Martien C J M van; Dagnelie, Pieter C; van Dongen, Martien C J M
Abstract:
Background: The effect of vitamin B-12 from different animal foods on vitamin B-12 biomarker status has not previously been evaluated in pregnant women.Objective: We examined the association of vitamin B-12 intake from dairy, meat, fish (including shellfish), and eggs with circulating concentrations of vitamin B-12 biomarkers and with the presence of vitamin B-12 deficiency in 1266 pregnant women participating in the KOALA Birth Cohort Study.Methods: Blood samples were collected in weeks 34-36 of pregnancy, and vitamin B-12 intake from foods and supplements was estimated with a semiquantitative food-frequency questionnaire (FFQ). Total vitamin B-12, holotranscobalamin (holoTC), and methylmalonic acid (MMA) were determined in plasma. Vitamin B-12 deficiency was defined as holoTC 0.45 μmol/L. Associations were evaluated with linear and logistic regression analyses, adjusting for potential confounders.Results: Significant dose-response relations were observed between vitamin B-12 intake from dairy, meat, and fish and plasma vitamin B-12, holoTC, and MMA [P-trend for (shell)fish with MMA = 0.002; P-trend for dairy, meat, and fish with all other markers
Published:
2019-01
Title:
Mechanisms Preserving Insulin Action during High Dietary Fat Intake
Authors:
Lundsgaard, Anne-Marie; Holm, Jacob B.; Sjøberg, Kim A.; Bojsen-Møller, Kirstine N.; Myrmel, Lene S.; Fjære, Even; Jensen, Benjamin A.H.; Nicolaisen, Trine S.; Hingst, Janne R.; Hansen, Sine L.; Doll, Sophia; Geyer, Philip E.; Deshmukh, Atul S.; Holst, Jens J.; Madsen, Lise; Kristiansen, Karsten; Wojtaszewski, Jørgen F.P.; Richter, Erik A.; Kiens, Bente
Abstract:
Published:
2019-01
Title:
Metabolomics and Microbiomes as Potential Tools to Evaluate the Effects of the Mediterranean Diet
Authors:
Jin, Qi; Black, Alicen; Kales, Stefanos N.; Vattem, Dhiraj; Ruiz-Canela, Miguel; Sotos-Prieto, Mercedes
Abstract:
The approach to studying diet–health relationships has progressively shifted from individual dietary components to overall dietary patterns that affect the interaction and balance of low-molecular-weight metabolites (metabolome) and host-enteric microbial ecology (microbiome). Even though the Mediterranean diet (MedDiet) has been recognized as a powerful strategy to improve health, the accurate assessment of exposure to the MedDiet has been a major challenge in epidemiological and clinical studies. Interestingly, while the effects of individual dietary components on the metabolome have been described, studies investigating metabolomic profiles in response to overall dietary patterns (including the MedDiet), although limited, have been gaining attention. Similarly, the beneficial effects of the MedDiet on cardiometabolic outcomes may be mediated through gut microbial changes. Accumulating evidence linking food ingestion and enteric microbiome alterations merits the evaluation of the microbiome-mediated effects of the MedDiet on metabolic pathways implicated in disease. In this narrative review, we aimed to summarize the current evidence from observational and clinical trials involving the MedDiet by (1) assessing changes in the metabolome and microbiome for the measurement of diet pattern adherence and (2) assessing health outcomes related to the MedDiet through alterations to human metabolomics and/or the microbiome.
Published:
2019-01
Title:
Mitochondrial pyruvate import is a metabolic vulnerability in androgen receptor-driven prostate cancer
Authors:
Bader, David A.; Hartig, Sean M.; Putluri, Vasanta; Foley, Christopher; Hamilton, Mark P.; Smith, Eric A.; Saha, Pradip K.; Panigrahi, Anil; Walker, Christopher; Zong, Lin; Martini-Stoica, Heidi; Chen, Rui; Rajapakshe, Kimal; Coarfa, Cristian; Sreekumar, Arun; Mitsiades, Nicholas; Bankson, James A.; Ittmann, Michael M.; O’Malley, Bert W.; Putluri, Nagireddy; McGuire, Sean E.
Abstract:
Published:
2019-01
Title:
Myelin basic protein charge isomers change macrophage polarization
Authors:
Tsitsilashvili, Elene; Sepashvili, Maia; Chikviladze, Marika; Shanshiashvili, Lali; Mikeladze, David
Abstract:
Purpose: During a neuronal injury, a variety of immune cells infiltrate into the local microenvironment at the demyelination site. After the destruction of the intact myelin sheath, its major constituent myelin basic protein (MBP) dissociates from the plasma membrane and acts as a free ligand on the infiltrated immune cells. MBP exhibits charge microheterogeneity as a result of post-translational modifications, but the effect of various isomers of MBP on the activity of macrophages is not known. Materials and methods: MBP was isolated and purified from bovine brain white matter. RAW 264.7 macrophages were cultured in DMEM supplemented with heat-inactivated fetal bovine serum. For evaluation of macrophage polarization following treatment of RAW 264.7 cells with MBP charge isomers, inducible nitric oxide synthase (iNOS) expression (M1 phenotype marker) and arginase-1 expression (M2 phenotype marker) were determined in cell lysates by ELISA. To assess Rac activity, G-LISA Rac Activation Assay system was used. The expression of receptor for advanced glycation end-products (RAGE) and high mobility group box 1 (HMGB1) protein were assayed by Western blot analysis. Results: Our results have shown that minimally modified C1 component of MBP increases the expression of arginase-1 in cells, decreases the expression of iNOS, does not change the secretion of HMGB1 protein, but significantly elevates surface expression of RAGE, and in parallel, increases the activity of small GTPase Rac. On the other hand, highly modified deiminated isomer C8-MBP increases the secretion of HMGB1 protein but does not change the expression of arginase-1 or the content of RAGE. Conclusion: These data indicate that deiminated C8 isomer of MBP tends to polarize RAW macrophages into M1 phenotypes, whereas C1 enhances the activity of M2 phenotype markers.
Published:
2019-01
Title:
Role of autophagy in inherited metabolic and endocrine myopathies
Authors:
Tan, Ying; Gong, Yan; Dong, Maolong; Pei, Zhaohui; Ren, Jun
Abstract:
The prevalence of cardiometabolic disease has reached an exponential rate of rise over the last decades owing to high fat/high caloric diet intake and satiety life style. Although the presence of dyslipidemia, insulin resistance, hypertension and obesity mainly contributes to the increased incidence of cardiometabolic diseases, population-based, clinical and genetic studies have revealed a rather important role for inherited myopathies and endocrine disorders in the ever-rising metabolic anomalies. Inherited metabolic and endocrine diseases such as glycogen storage and lysosomal disorders have greatly contributed to the overall prevalence of cardiometabolic diseases. Recent evidence has demonstrated an essential role for proteotoxicity due to autophagy failure and/or dysregulation in the onset of inherited metabolic and endocrine disorders. Given the key role for autophagy in the degradation and removal of long-lived or injured proteins and organelles for the maintenance of cellular and organismal homeostasis, this mini-review will discuss the potential contribution of autophagy dysregulation in the pathogenesis of inherited myopathies and endocrine disorders, which greatly contribute to an overall rise in prevalence of cardiometabolic disorders. Molecular, clinical, and epidemiological aspects will be covered as well as the potential link between autophagy and metabolic anomalies thus target therapy may be engaged for these comorbidities.
Published:
2019-01
Title:
1H NMR-based metabolomics profiling and taste of stewed pork-hock in soy sauce
Authors:
Yang, Y.; Pan, D.; Sun, Y.; Wang, Y.; Xu, F.; Cao, J.
Abstract:
Stewed pork-hock in soy sauce is a representative meat product in China. Its taste quality is highly related to primary and secondary metabolites. This study researched the effects of stewing points (0, 30, 60 and 90 min) on the metabolites profile variation of stewed pork-hock in soy sauce by using 1H NMR spectroscopy with multivariate data analysis. The metabolome consisted of 25 metabolites, including amino acids, sugars, organic acids, nucleic acids and their derivatives. PC1 and PC2 explained a total of 90% and 7.8% of variables, respectively. Most amino acids, sucrose, β-glucose, acetate and creatinine increased during stewing, while creatine decreased. Fumarate kept extremely low content during the whole stewing process. The 60 and 90 min stewed points owned relatively higher levels of metabolites and sensory evaluation compared to other points. These results indicated that 1H NMR-based metabolomics is useful for a better understanding on the change of meat products during the stewing process, thus improving the stewing time to provide a better taste and higher product sales of stewed pork-hock in soy sauce. © 2018
Published:
2019
Title:
1H-NMR-based water-soluble low molecular weight compound characterization and fatty acid composition of boiled Wuding chicken during processing
Authors:
Xiao, Z.; Luo, Y.; Wang, G.; Ge, C.; Zhou, G.; Zhang, W.; Liao, G.
Abstract:
BACKGROUND: Boiled Wuding chicken was produced using whole chicken by washing, boiling 1 h with salt, deep frying, and boiling 2 h. The effect of the process on the water-soluble low molecular weight (WLOM) compound profiles of products was characterized using proton nuclear magnetic resonance spectroscopy, and the fatty acid composition of products was analyzed using gas chromatography–mass spectrometry. RESULTS: The metabolome was dominated by 49 WLOM compounds, and 22 fatty acid compounds were detected. Principal component (PC)1 and PC2 explained a total of 93.4% and 3% of variance respectively. Compared with the control group, the total WLOM compound and fatty acid contents of the chicken breast were significantly decreased in the other three processing stages (P < 0.05). Comprehensive multivariate data analysis showed significant differences about precursor substance between the different processing including creatine, lactate, creatinine, glucose, taurine, anserine, and acetate (P
Published:
2019
Title:
2-Deoxyglucose and Beta-Hydroxybutyrate: Metabolic Agents for Seizure Control
Authors:
Rho, Jong M.; Shao, Li-Rong; Stafstrom, Carl E.
Abstract:
Current anti-seizure drugs (ASDs) are believed to reduce neuronal excitability through modulation of ion channels and transporters that regulate excitability at the synaptic level. While most patients with epilepsy respond to ASDs, many remain refractory to medical treatment but respond favorably to a high-fat, low-carbohydrate metabolism-based therapy known as the ketogenic diet (KD). The clinical effectiveness of the KD has increasingly underscored the thesis that metabolic factors also play a crucial role in the dampening neuronal hyperexcitability that is a hallmark feature of epilepsy. This notion is further amplified by the clinical utility of other related metabolism-based diets such as the modified Atkins diet and the low-glycemic index treatment (LGIT). Traditional high-fat diets are characterized by enhanced fatty acid oxidation (which produces ketone bodies such as beta-hydroxybutyrate) and a reduction in glycolytic flux, whereas the LGIT is predicated mainly on the latter observation of reduced blood glucose levels. As dietary implementation is not without challenges regarding clinical administration and patient compliance, there is an inherent desire and need to determine whether specific metabolic substrates and/or enzymes might afford similar clinical benefits, hence validating the concept of a "diet in a pill." Here, we discuss the evidence for one glycolytic inhibitor, 2-deoxyglucose (2DG) and one metabolic substrate, β-hydroxybutyrate (BHB) exerting direct effects on neuronal excitability, highlight their mechanistic differences, and provide the strengthening scientific rationale for their individual or possibly combined use in the clinical arena of seizure management.
Published:
2019
Title:
A Long-Term, Open-Label Study to Evaluate the Safety and Tolerability of Brexpiprazole as Adjunctive Therapy in Adults With Major Depressive Disorder:
Authors:
Hobart, Mary; Zhang, Peter; Skuban, Aleksandar; Brewer, Claudette; Hefting, Nanco; Sanchez, Raymond; McQuade, Robert D.
Abstract:
Published:
2019
Title:
A Mobile Phone-Based Program to Promote Healthy Behaviors Among Adults With Prediabetes Who Declined Participation in Free Diabetes Prevention Programs: Mixed-Methods Pilot Randomized Controlled Trial
Authors:
Griauzde, Dina; Kullgren, Jeffrey T.; Liestenfeltz, Brad; Ansari, Tahoora; Johnson, Emily H.; Fedewa, Allison; Saslow, Laura R.; Richardson, Caroline; Heisler, Michele
Abstract:
BACKGROUND: Despite evidence that Diabetes Prevention Programs (DPPs) can delay or prevent progression to type 2 diabetes mellitus (T2DM), few individuals with prediabetes enroll in offered programs. This may be in part because many individuals with prediabetes have low levels of autonomous motivation (ie, motivation that arises from internal sources) to prevent T2DM. OBJECTIVE: This study aims to examine the feasibility and acceptability of a mobile health (mHealth) intervention designed to increase autonomous motivation and healthy behaviors among adults with prediabetes who previously declined participation free DPPs. In addition, the study aims to examine changes in autonomous motivation among adults offered 2 versions of the mHealth program compared with an information-only control group. METHODS: In this 12-week, parallel, 3-arm, mixed-methods pilot randomized controlled trial, participants were randomized to (1) a group that received information about prediabetes and strategies to prevent T2DM (control); (2) a group that received a mHealth app that aims to increase autonomous motivation among users (app-only); or (3) a group that received the app plus a physical activity tracker and wireless-enabled digital scale for self-monitoring (app-plus). Primary outcome measures included rates of intervention uptake (number of individuals enrolled/number of individuals assessed for eligibility), retention (number of 12-week survey completers/number of participants), and adherence (number of device-usage days). The secondary outcome measure was change in autonomous motivation (measured using the Treatment Self-Regulation Questionnaire), which was examined using difference-in-difference analysis. Furthermore, we conducted postintervention qualitative interviews with participants. RESULTS: Overall, 28% (69/244) of eligible individuals were randomized; of these, 80% (55/69) completed the 12-week survey. Retention rates were significantly higher among app-plus participants than participants in the other 2 study arms combined (P=.004, χ2). No significant differences were observed in adherence rates between app-only and app-plus participants (43 days vs 37 days; P=.34). Among all participants, mean autonomous motivation measures were relatively high at baseline (6.0 of 7.0 scale), with no statistically significant within- or between-group differences in follow-up scores. In qualitative interviews (n=15), participants identified reasons that they enjoyed using the app (eg, encouraged self-reflection), reasons that they did not enjoy using the app (eg, did not consider personal circumstances), and strategies to improve the intervention (eg, increased interpersonal contact). CONCLUSIONS: Among individuals with prediabetes who did not engage in free DPPs, this mHealth intervention was feasible and acceptable. Future work should (1) examine the effectiveness of a refined intervention on clinically relevant outcomes (eg, weight loss) among a larger population of DPP nonenrollees with low baseline autonomous motivation and (2) identify other factors associated with DPP nonenrollment, which may serve as additional potential targets for interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03025607; https://clinicaltrials.gov/ct2/show/NCT03025607 (Archived by WebCite at http://www.webcitation.org/73cvaSAie).
Published:
2019
Title:
A Pilot Low-Inflammatory Dietary Intervention to Reduce Inflammation and Improve Quality of Life in Patients With Familial Adenomatous Polyposis: Protocol Description and Preliminary Results
Authors:
Pasanisi, P.; Gariboldi, M.; Verderio, P.; Signoroni, S.; Mancini, A.; Rivoltini, L.; Milione, M.; Masci, E.; Ciniselli, C.M.; Bruno, E.; Macciotta, A.; Belfiore, A.; Ricci, M.T.; Gargano, G.; Morelli, D.; Apolone, G.; Vitellaro, M.
Abstract:
Patients with familial adenomatous polyposis (FAP) depend on a lifelong endoscopic surveillance programme and prophylactic surgery, and usually suffer nutritional problems. Intestinal inflammation has been linked to both FAP and colorectal cancer. Epidemiological studies show a relationship between diet and inflammation. Preventive dietary recommendations for FAP patients are so far lacking. We have designed a nonrandomized prospective pilot study on FAP patients to assess whether a low-inflammatory diet based on the Mediterranean diet principles and recipes, by interacting with the microbiota, reduces gastrointestinal markers of inflammation and improves quality of life. This report describes the scientific protocol of the study and reports the participants’ adherence to the proposed dietary recommendations. Thirty-four FAP patients older than 18 years, bearing the APC pathogenic variant, who underwent prophylactic total colectomy with ileo-rectal anastomosis were eligible into the study. During the 3-month dietary intervention, they reported improvements in their consumption of Mediterranean foods (vegetables, fruits, fish, and legumes), and a reduction in pro-inflammatory foods (red/processed meat and sweets); this led to a significant increase in their adherence to the Mediterranean diet. The improvement was accompanied by a decrease in the number of diarrhoeal discharges. These preliminary results are encouraging with regard to feasibility, dietary outcome measures, and safety. © The Author(s) 2019.
Published:
2019
Title:
A molecular portrait of epithelial-mesenchymal plasticity in prostate cancer associated with clinical outcome
Authors:
Stylianou, Nataly; Lehman, Melanie L.; Wang, Chenwei; Fard, Atefeh Taherian; Rockstroh, Anja; Fazli, Ladan; Jovanovic, Lidija; Ward, Micheal; Sadowski, Martin C.; Kashyap, Abhishek S.; Buttyan, Ralph; Gleave, Martin E.; Westbrook, Thomas F.; Williams, Elizabeth D.; Gunter, Jennifer H.; Nelson, Colleen C.; Hollier, Brett G.
Abstract:
The propensity of cancer cells to transition between epithelial and mesenchymal phenotypic states via the epithelial-mesenchymal transition (EMT) program can regulate metastatic processes, cancer progression, and treatment resistance. Transcriptional investigations using reversible models of EMT, revealed the mesenchymal-to-epithelial reverting transition (MErT) to be enriched in clinical samples of metastatic castrate resistant prostate cancer (mCRPC). From this enrichment, a metastasis-derived gene signature was identified that predicted more rapid cancer relapse and reduced survival across multiple human carcinoma types. Additionally, the transcriptional profile of MErT is not a simple mirror image of EMT as tumour cells retain a transcriptional "memory" following a reversible EMT. This memory was also enriched in mCRPC samples. Cumulatively, our studies reveal the transcriptional profile of epithelial-mesenchymal plasticity and highlight the unique transcriptional properties of MErT. Furthermore, our findings provide evidence to support the association of epithelial plasticity with poor clinical outcomes in multiple human carcinoma types.
Published:
2019
Title:
A peroxidized omega-3-enriched polyunsaturated diet leads to adipose and metabolic dysfunction
Authors:
Miller, James L.; Blaszkiewicz, Magdalena; Beaton, Cordell; Johnson, Cory P.; Waible, Stephen; Dubois, Amanda L.; Klemmer, Amanda; Kiebish, Michael; Townsend, Kristy L.
Abstract:
Consumption of diets that differ in fat type and amount, and sequestration of various fatty acids to tissues and organs likely have effects on overall physiology and metabolic health. However, the contributions of dietary lipids to brain-adipose communication and adipose tissue function are poorly understood. We designed six custom diets that differed only in amount and type of dietary fat, with high or low levels of saturated fatty acids (SFA), omega-6 polyunsaturated fatty acids (n-6 PUFA) or omega-3 (n-3) PUFA. Mice fed the n-3 PUFA diet for 16 weeks displayed a striking reduction in weight gain accompanied by smaller adipose depots and improved glucose sensitivity. Reduced body weight occurred despite lowered energy expenditure and no difference in food intake. Despite the apparent beneficial effects to whole body physiology, we have demonstrated for the first time that a peroxidized n-3-enriched diet led to lipotoxicity of white adipose tissue, as evidenced by increased fibrosis, lipofuscin, reduced anti-inflammatory markers and loss of proper nerve supply. While healthful, n-3 fats are prone to peroxidation, and we observed peroxidated lipid metabolites in the adipose tissue of mice on these diets. Furthermore, using a lipidomics approach, we have observed that brain, white adipose tissue and brown adipose tissue accumulate lipid metabolites differently. The brain remained mostly shielded from changes in dietary fat type and amount, but differences in adipose lipid metabolites across these six diets may have affected metabolic function and brain-adipose communication, as observed in this study.
Published:
2019
Title:
Addressing the pitfalls when designing intervention studies to discover and validate biomarkers of habitual dietary intake
Authors:
Lloyd, A.J.; Willis, N.D.; Wilson, T.; Zubair, H.; Chambers, E.; Garcia-Perez, I.; Xie, L.; Tailliart, K.; Beckmann, M.; Mathers, J.C.; Draper, J.
Abstract:
Introduction: Dietary exposure monitoring within populations is reliant on self-reported measures such as Food Frequency Questionnaires and diet diaries. These methods often contain inaccurate information due to participant misreporting, non-compliance and bias. Urinary metabolites derived from individual foods could provide additional objective indicators of dietary exposure. For biomarker approaches to have utility it is essential that they cover a wide-range of commonly consumed foods and the methodology works in a real-world environment. Objectives: To test that the methodology works in a real-world environment and to consider the impact of the major sources of likely variance; particularly complex meals, different food formulations, processing and cooking methods, as well as the dynamics of biomarker duration in the body. Methods: We designed and tested a dietary exposure biomarker discovery and validation strategy based on a food intervention study involving free-living individuals preparing meals and collecting urine samples at home. Two experimental periods were built around three consecutive day menu plans where all foods and drinks were provided (n = 15 and n = 36). Results: The experimental design was validated by confirming known consumption biomarkers in urinary samples after the first menu plan. We tested biomarker performance with different food formulations and processing methods involving meat, wholegrain, fruits and vegetables. Conclusion: It was demonstrated that spot urine samples, together with robust dietary biomarkers, despite major sources of variance, could be used successfully for dietary exposure monitoring in large epidemiological studies. © 2019, The Author(s).
Published:
2019
Title:
Advanced Glycation End Products (AGEs), Glutathione and Breast Cancer: Factors, Mechanism and Therapeutic Interventions
Authors:
Sharma, Anil K.; Sharma, Var R.; Gupta, Girish K.; Ashraf, Ghulam Md.; Kamal, Mohammad A.
Abstract:
BACKGROUND: Advanced Glycation End products (AGEs) are basically the end result of glycation of proteins and/or lipids in the presence of sugars. Specific cases of hyperglycemia have been reported with increased propensity of generation of AGEs. Many chronic and deadly diseases such as diabetes, cancer and neurodegenerative disorders have been known to be caused as a result of generation of AGEs. The role of glutathione (GSH) metabolism and its intricate association with AGEs have also been well established in breast cancer prognosis and treatment. To understand the etiology, mechanism and production of AGEs along with clinical relevance of Receptors for Advanced Glycation End-products (RAGE) and RAGE ligands, their interplay with GSH is of paramount importance especially in relation to breast cancer. METHODS: The available literature using PubMed, National Library of Medicine database, Web of Science and SCOPUS indexed, Science Direct and other prestigious journals have been systematically reviewed using the keywords: advanced glycation end-products, breast cancer, glutathione RAGE, and AGEs inhibitors. This narrative review of all the relevant papers with significant citations has led us to have greater insight into the action mechanism and potential therapeutic significance of AGEs inhibitors. RESULTS: Targeting breast cancer with the specific immunoglobulins and with other therapeutic interventions is needed to inhibit the generation of AGEs and manage glutathione expression, thus having strong implications in the management of breast cancer. Many RAGE ligands such as HMGB1, S100P, S100A8, S100A9 etc. have been known to enhance RAGE expression which may further lead to increased proliferation, migration and metastatic nature of tumor cells. Hence, RAGE and RAGE ligands in a close linkup with GSH may prove to be effective therapeutic markers of severity of breast cancer and for angiogenesis of tumor. CONCLUSION: This review provides a strong platform to comprehend the etiology, mechanism and production of AGEs and glutathione along with the agents which can block their production, paving a way for the therapeutic intervention and an amicable solution to treat and manage breast cancer.
Published:
2019
Title:
Alternol eliminates excessive ATP production by disturbing Krebs cycle in prostate cancer
Authors:
Li, Changlin; He, Chenchen; Xu, Ying; Xu, Haixia; Tang, Yuzhe; Chavan, Hemantkumar; Duan, Shaofeng; Artigues, Antonio; Forrest, Marcus Laird; Krishnamurthy, Partha; Han, Suxia; Holzbeierlein, Jeffrey M.; Li, Benyi
Abstract:
Background Alternol is a natural compound isolated from fermentation products of a mutant fungus. Our previous studies demonstrated that Alternol specifically kills cancer cells but spares benign cells. Methods To investigate the mechanism underlying alternol-induced cancer cell-specific killing effect, we took a comprehensive strategy to identify Alternol's protein targets in prostate cancer cells, including PC-3, C4-2, and 22RV1, plus benign BPH1 cell lines. Major experimental techniques included biotin-streptavidin pulldown assay coupled with mass-spectrometry, in vitro enzyme activity assay for Krebs cycle enzymes and gas chromatography-mass spectrometry (GC-MS) for metabolomic analysis. Results Among 14 verified protein targets, four were Krebs cycle enzymes, fumarate hydratase (FH), malate dehydrogenase-2 (MDH2), dihydrolipoamide acetyltransferase (DLAT) in pyruvate dehydrogenase complex (PDHC) and dihydrolipoamide S-succinyltransferase (DLST) in a-ketoglutarate dehydrogenase complex (KGDHC). Functional assays revealed that PDHC and KGDHC activities at the basal level were significantly higher in prostate cancer cells compared to benign prostate BPH1 cells, while alternol treatment reduced their activities in cancer cells close to the levels in BPH1 cells. Although FH and MDH2 activities were comparable among prostate cancer and benign cell lines at the basal level, Alternol treatment largely increased their activities in cancer cells. Metabolomic analysis revealed that Alternol treatment remarkably reduced the levels of malic acid, fumaric acid, and isocitric acid and mitochondrial respiration in prostate cancer cells. Alternol also drastically reduced mitochondrial respiration and ATP production in PC-3 cells in vitro or in xenograft tissues but not in BPH1 cells or host liver tissues. Conclusions Alternol interacts with multiple Krebs cycle enzymes, resulting in reduced mitochondrial respiration and ATP production in prostate cancer cells and xenograft tissues, providing a novel therapeutic strategy for prostate cancer treatment.
Published:
2019
Title:
Alzheimer's “Prevention” vs. “Risk Reduction”: Transcending Semantics for Clinical Practice
Authors:
Rajji, Tarek K.; Kaiser, Scott; Melendez, Juan A.; Hodes, John F.; Kaufman, Yakir; Patel, Smita; Saif, Nabeel; Galvin, James E.; Rahman, Aneela; Merrill, David A.; Meléndez-Cabrero, Josefina; Fosnacht Morgan, Anne Marie; Bellara, Sonia; Oakley, Carlee I.; O'Keefe, James H.; Lu, Peilin; Hristov, Hollie; Krikorian, Robert; Isaacson, Richard S.
Abstract:
Published:
2019
Title:
Anti-Inflammatory Effect of an Apigenin-Maillard Reaction Product in Macrophages and Macrophage-Endothelial Cocultures
Authors:
Zhou, Qian; Xu, Hui; Yu, Wenzhe; Li, Edmund; Wang, Mingfu
Abstract:
Chronic inflammation is involved in the progression of various diseases, while dietary flavonoids are reported to possess antioxidative and anti-inflammatory properties against age-related diseases. Previously, an apigenin-Maillard reaction product, dimethylglyoxal apigenin (DMA), was identified by us and demonstrated to be antioxidative. In this study, we investigated the inhibitory effect of DMA on advanced glycation end product- (AGE-) induced inflammation in macrophages and macrophage-endothelial cocultures. Results showed that DMA remarkably inhibited the mRNA and protein expression of receptor for AGEs (RAGE), thereby inhibiting the production of ROS and proinflammatory cytokines, including tumor necrosis factor- (TNF-) α, interleukin (IL) 1, IL 6, and monocyte chemoattractant protein- (MCP-) 1 in RAW 264.7 cells. In the coculture system which was performed in the Boyden chamber, macrophage infiltration and adhesion to endothelial cells were significantly suppressed by DMA. Further study indicated that DMA decreased AGE-evoked IL 6 and MCP-1 secretion, which might be achieved through RAGE and its downstream-regulated transforming growth factor- (TGF-) β1 and intercellular adhesion molecule (ICAM) 1 expression in the coculture system. In conclusion, our study demonstrates that DMA, a thermally induced compound, has anti-inflammatory activity in both macrophages and macrophage-endothelial cocultures, offering a promising approach for slowing down the development of chronic diseases.
Published:
2019
Title:
Antioxidant treatment induces reductive stress associated with mitochondrial dysfunction in adipocytes
Authors:
Peris, Eduard; Micallef, Peter; Paul, Alexandra; Palsdottir, Vilborg; Enejder, Annika; Bauzá-Thorbrügge, Marco; Olofsson, Charlotta S.; Wernstedt Asterholm, Ingrid
Abstract:
β-Adrenergic stimulation of adipose tissue increases mitochondrial density and activity (browning) that are associated with improved whole-body metabolism. Whereas chronically elevated levels of reactive oxygen species (ROS) in adipose tissue contribute to insulin resistance, transient ROS elevation stimulates physiological processes such as adipogenesis. Here, using a combination of biochemical and cell and molecular biology-based approaches, we studied whether ROS or antioxidant treatment affects β3-adrenergic receptor (β3-AR) stimulation-induced adipose tissue browning. We found that β3-AR stimulation increases ROS levels in cultured adipocytes, but, unexpectedly, pretreatment with different antioxidants (N-acetylcysteine, vitamin E, or GSH ethyl ester) did not prevent this ROS increase. Using fluorescent probes, we discovered that the antioxidant treatments instead enhanced β3-AR stimulation-induced mitochondrial ROS production. This pro-oxidant effect of antioxidants was, even in the absence of β3-AR stimulation, associated with decreased oxygen consumption and increased lactate production in adipocytes. We observed similar antioxidant effects in WT mice: N-acetylcysteine blunted β3-AR stimulation-induced browning of white adipose tissue and reduced mitochondrial activity in brown adipose tissue even in the absence of β3-AR stimulation. Furthermore, N-acetylcysteine increased the levels of peroxiredoxin 3 and superoxide dismutase 2 in adipose tissue, indicating increased mitochondrial oxidative stress. We interpret this negative impact of antioxidants on oxygen consumption in vitro and adipose tissue browning in vivo as essential adaptations that prevent a further increase in mitochondrial ROS production. In summary, these results suggest that chronic antioxidant supplementation can produce a paradoxical increase in oxidative stress associated with mitochondrial dysfunction in adipocytes.
Published:
2019
Title:
Assessing Validity of Self-Reported Dietary Intake within a Mediterranean Diet Cluster Randomized Controlled Trial among US Firefighters
Authors:
Sotos-Prieto, M.; Christophi, C.; Black, A.; Furtado, J.D.; Song, Y.; Magiatis, P.; Papakonstantinou, A.; Melliou, E.; Moffatt, S.; Kales, S.N.
Abstract:
Collecting dietary intake data is associated with challenges due to the subjective nature of self-administered instruments. Biomarkers may objectively estimate the consumption of specific dietary items or help assess compliance in dietary intervention studies. Our aim was to use a panel of plasma and urine biomarkers to assess the validity of self-reported dietary intake using a modified Mediterranean Diet Scale (mMDS) among firefighters participating in Feeding America's Bravest (FAB), an MD cluster-randomized controlled trial. In our nested biomarker pilot study, participants were randomly selected from both the MD intervention group (n = 24) and the control group (n = 24) after 12-months of dietary intervention. At baseline data collection for the pilot study (t = 12-months of FAB), participants in the control group crossed-over to receive the MD intervention (active intervention) for 6-months. Participants in the intervention group continued in a self-sustained continuation phase (SSP) of the intervention. Food frequency questionnaires (FFQ), 13-item-mMDS questionnaires, 40 plasma fatty acids, inflammatory biomarkers and urinary hydroxytyrosol and tyrosol were analyzed at both time points. Spearman's correlation, t-tests and linear regression coefficients were calculated using SAS software. Overall, the mMDS derived from the FFQ was highly correlated with the specific 13-domain-mMDS (r = 0.74). The concordance between the two questionnaires for low and high adherence to MD was high for all the participants in the parent trial (κ = 0.76). After 6 months of intervention in the pilot study, plasma saturated fatty acid decreased in both groups (active intervention: -1.3 ± 1.7; p = 0.002; SSP: -1.12 ± 1.90; p = 0.014) and oleic acid improved in the SSP (p = 0.013). Intake of olive oil was positively associated with plasma omega-3 (p = 0.004) and negatively with TNF-α (p
Published:
2019
Title:
Balance of saccharolysis and proteolysis underpins improvements in stool quality induced by adding a fiber bundle containing bound polyphenols to either hydrolyzed meat or grain-rich foods
Authors:
Jackson, M.I.; Jewell, D.E.
Abstract:
Dietary fiber is a key component in gastrointestinal health maintenance partly due to its fermentation by the gut microbiome. The food-dependent effects of a novel fiber bundle added to hydrolyzed meat (HM) or grain-rich (GR) foods in healthy dogs (n = 16) or those with chronic enteritis/gastroenteritis (n = 16) were examined. Addition of fiber to either food improved stool quality in dogs regardless of health status; microbiome diversity of dogs with chronic enteritis/gastroenteritis became more similar to healthy dogs. The abundance of bacteria mediating beneficial saccharolytic processes (eg, Lachnospiraceae) significantly increased on addition of fiber to the GR food, while those mediating detrimental proteolytic catabolism (eg, Desulfovibrionaceae) significantly decreased. Fiber addition to the HM food led to significant changes in saccharolytic/proteolytic bacteria. Higher levels of free saccharides in feces upon fiber addition to either food indicated increased saccharolysis. Fiber addition to the GR food decreased levels of fecal free amino acids, indicating decreased proteolysis. Addition of fiber decreased fecal pH for both foods but likely by different mechanisms: addition of fiber to the HM food led to increased straight-chain short-chain fatty acids (SCFAs) and no significant change in proteolytic branched-chain SFCAs, while in the GR food, fiber mainly led to decreased proteolytic branched-chain SFCAs. Other postbiotics related to intestinal health were consistently altered when fiber was added to either food. Plant-derived bioactive molecules were enriched in feces from dogs fed either food with added fiber, which could account for the observed modulation of the canine gut microbiome and shifts in metabolic capacity. © 2019, © 2019 The Author(s). Published by Taylor & Francis.
Published:
2019
Title:
Biomarkers for major depressive and bipolar disorders using metabolomics: A systematic review
Authors:
MacDonald, Kellie; Krishnan, Ankur; Cervenka, Emily; Hu, Grace; Guadagno, Elena; Trakadis, Yannis
Abstract:
Major depressive disorder (MDD) and bipolar disorder (BD) lack robust biomarkers useful for screening purposes in a clinical setting. A systematic review of the literature was conducted on metabolomic studies of patients with MDD or BD through the use of analytical platforms such as in vivo brain imaging, mass spectrometry, and nuclear magnetic resonance. Our search identified a total of 7,590 articles, of which 266 articles remained for full-text revision. Overall, 249 metabolites were found to be dysregulated with 122 of these metabolites being reported in two or more of the studies included. A list of biomarkers for MDD and BD established from metabolites found to be abnormal, along with the number of studies supporting each metabolite and a comparison of which biological fluids they were reported in, is provided. Metabolic pathways that may be important in the pathophysiology of MDD and BD were identified and predominantly center on glutamatergic metabolism, energy metabolism, and neurotransmission. Using online drug registries, we also illustrate how metabolomics can facilitate the discovery of novel candidate drug targets.
Published:
2019
Title:
Bone status and adipokine levels in children on vegetarian and omnivorous diets
Authors:
Ambroszkiewicz, Jadwiga; Chełchowska, Magdalena; Szamotulska, Katarzyna; Rowicka, Grażyna; Klemarczyk, Witold; Strucińska, Małgorzata; Gajewska, Joanna
Abstract:
BACKGROUND & AIMS: Measurements of bone mineral density (BMD) reflect bone status but not the dynamics of bone turnover. Biochemical markers, which show global skeletal activity, were validated for the assessment of bone formation and resorption processes. Adipokines also play a significant role in the regulation of bone metabolism. OBJECTIVE: To assess body composition, bone mineral density, bone turnover markers and adipokine levels in relation to vegetarian and omnivorous diets. METHODS: The study included 53 vegetarian and 53 omnivorous prepubertal healthy children matched for age and sex (median age 7.0 years). Body composition and BMD were assessed by dual-energy X-ray absorptiometry. 25-hydroxyvitamin D and parathormone levels were measured by chemiluminescence method. Serum carboxy-terminal propeptide of type I collagen (CICP), total osteocalcin (OC) and its forms carboxylated (c-OC) and undercarboxylated (uc-OC), C-terminal cross-linking telopeptide of collagen type I (CTX), leptin and adiponectin levels were determined using immunoenzymatic assays. RESULTS: Both groups of children were comparable in terms of body composition, except for the percentage of fat mass, which was lower (19.24 vs. 21.77%, p = 0.018) in vegetarians. Mean values of total BMD z-score and lumbar spine BMD z-score were lower (-0.583 vs. -0.194, p = 0.009 and -0.877 vs. -0.496, p = 0.019, respectively) in vegetarians compared with omnivores. Serum leptin level was about 2-fold lower (1.39 vs. 2.94 ng/mL, p < 0.001) in vegetarians, however, adiponectin concentration was similar in both groups. Vegetarians had similar concentration of 25-hydroxyvitamin D, but higher parathormone (40.8 vs. 32.1 pg/mL, p = 0.015) and CTX (1.94 vs. 1.76 ng/mL, p = 0.077) levels than omnivores. Total osteocalcin and CICP concentrations were comparable in both groups, however, c-OC/uc-OC ratio was higher (1.43 vs. 1.04 ng/mL, p
Published:
2019
Title:
Brief Mindfulness Meditation Improves Emotion Processing
Authors:
Wu, Ran; Liu, Lin-Lin; Zhu, Hong; Su, Wen-Jun; Cao, Zhi-Yong; Zhong, Shi-Yang; Liu, Xing-Hua; Jiang, Chun-Lei
Abstract:
Mindfulness-based interventions have previously been shown to have positive effects on psychological well-being. However, the time commitment, teacher shortage, and high cost of classic mindfulness interventions may have hindered efforts to spread the associated benefits to individuals in developing countries. Brief mindfulness meditation (BMM) has recently received attention as a way to disseminate the benefits of mindfulness-based interventions. Most existing BMM methods are adaptations of the classic approach. Few studies have investigated the mechanisms underlying the beneficial effects of BMM. We developed a 15-min BMM named JW2016, which is based on the core concepts of mindfulness, Anapanasati (breath meditation of Buddhist Vipassana), our practical experience, and the results of scientific reports on meditation. We investigated the effects of this BMM on mood and emotion processing in an effort to create an effective, convenient, safe, and standardized BMM method that could benefit individuals with limited time or money to devote to meditation. Forty-six healthy participants (aged 18–25 years) were randomly allocated to the BMM group (n = 23) or the emotional regulation education (ERE) control group (n = 23). Forty-two of the study participants cooperated fully in all measurements and interventions (one time daily for seven consecutive days). Mood was measured with the Centre for Epidemiological Studies–Depression scale (CES-D) and the State Anxiety Inventory (SAI). Emotion processing was evaluated by assessing performance on an emotion intensity task, an emotional memory task, and an emotional dot-probe task. After intervention, the BMM group, but not the ERE group, showed a significant decreases in emotional intensity in response to positive as well as negative emotional stimuli, response time for emotional memory, and duration of attention bias toward negative emotional stimuli. Negative effects on mood state were found in the ERE group but not in the BMM group. This study demonstrated that BMM may improve aspects of emotion processing such as emotion intensity, emotional memory, and emotional attention bias. JW2016 BMM may be an effective, convenient, safe and standardized way to help practitioners remain focused and peaceful without any negative effect on emotion.
Published:
2019
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