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Chuanjie Wu, Chuanhui Li, Wenbo Zhao, Nanchang Xie, Feng Yan, Yajun Lian, Li Zhou, Xiaoya Xu, Yong Liang, Lu Wang, Ming Ren, Sijie Li, Xuan Cheng, Lu Zhang, Qingfeng Ma, Haiqing Song, Ran Meng, Xunming Ji
OBJECTIVES: To investigate whether the plasma level of trimethylamine N -oxide (TMAO), a proatherosclerotic intestinal microbiota metabolite, can be a predictor of ischemic brain injury secondary to carotid artery stenting (CAS). METHODS: In this multicenter, prospective cohort study, we enrolled patients with severe carotid artery stenosis (>70%) who were prepared for CAS. Plasma TMAO level was measured within 3 days before CAS, and MRI was performed 1 to 3 days after CAS...
March 14, 2018: Neurology
Lora J Kasselman, Nicholas A Vernice, Joshua DeLeon, Allison B Reiss
Cardiovascular disease associated with obesity and autoimmunity is the leading cause of death in these populations and significant residual risk remains despite current treatment approaches. Obesity, type 1 diabetes mellitus (T1DM), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) are linked to chronic inflammation, and subjects with these disorders have characteristic shifts in their gut microbiome composition. Recent data suggest that alterations in gut microbial and metabolic composition may be responsible, in part, for induction of chronic inflammation, thus promoting cardiovascular disease...
March 2, 2018: Atherosclerosis
Deepak Bhandari, Brett A Bowman, Anish B Patel, David M Chambers, Víctor R De Jesús, Benjamin C Blount
This work describes a quantitative high-throughput analytical method for the simultaneous measurement of small aliphatic nitrogenous biomarkers, i.e., 1,6-hexamethylenediamine (HDA), isophoronediamine (IPDA), β-methylamino-l-alanine (BMAA), and trimethylamine N-oxide (TMAO), in human urine. Urinary aliphatic diamines, HDA and IPDA, are potential biomarkers of environmental exposure to their corresponding diisocyanates. Urinary BMAA forms as a result of human exposure to blue-green algae contaminated food. And, TMAO is excreted in urine due to the consumption of carnitine- and choline-rich diets...
March 2, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Wei Ling Lau, Javad Savoj, Michael B Nakata, Nosratola D Vaziri
In chronic kidney disease (CKD), influx of urea and other retained toxins exerts a change in the gut microbiome. There is decreased number of beneficial bacteria that produce short-chain fatty acids, an essential nutrient for the colonic epithelium, concurrent with an increase in bacteria that produce uremic toxins such as indoxyl sulphate, p -cresyl sulphate, and trimethylamine-N-oxide (TMAO). Due to intestinal wall inflammation and degradation of intercellular tight junctions, gut-derived uremic toxins translocate into the bloodstream and exert systemic effects...
March 15, 2018: Clinical Science (1979-)
Jasmohan S Bajaj, Genta Kakiyama, I Jane Cox, Hiroshi Nittono, Hajime Takei, Melanie White, Andrew Fagan, Edith A Gavis, Douglas M Heuman, Ho Chong Gilles, Phillip Hylemon, Simon D Taylor-Robinson, Cristina Legido-Quigley, Min Kim, Jin Xu, Roger Williams, Masoumeh Sikaroodi, William M Pandak, Patrick M Gillevet
Liver transplant (LT) improves daily function and ameliorates gut microbial composition. However, the effect of LT on microbial functionality, which can be related to overall patient benefit, is unclear and could affect the post-LT course. AIMS: To determine the effect of LT on gut microbial functionality focusing on endotoxemia, bile acid (BA), ammonia metabolism and lipidomics. METHOD: We enrolled outpatient cirrhotic patients on the LT list and followed them till 6 months post-LT...
March 3, 2018: Liver Transplantation
Zehong Wei, Huihui Zhou, Yanjiao Zhang, Qin Zhang, Wenbing Zhang, Kangsen Mai
A previous study showed that flesh quality of large yellow croaker (LYC) was improved by feeding dietary hydroxyproline (Hyp, 0·69 %). The aim of the present study was to explore the underlying mechanisms using transcriptomics and metabolomics analysis. The metabolomics analysis showed that muscle metabolite profiles could be clearly separated between the basal diet and Hyp supplementation diet. Metabolites including betaine, Hyp, lactate, glucose-6-phosphate, trimethylamine N-oxide, taurine, creatine, inosine monophosphate, histamine and serine made significant contribution to the separation...
February 2018: British Journal of Nutrition
C Antza, S Stabouli, V Kotsis
The human gut microbiota is being composed of more than one hundred trillion microbial cells, including aerobic and anaerobic species as well as gram-positive and negative species. Animal based evidence suggests that the change of normal gut microbiota is responsible for several clinical implications including blood pressure increase and kidney function reduction. Trimethylamine-N-Oxide, short-chain fatty acids and inflammatory factors are originated from the gut microbes and may induce changes in arteries, kidneys and blood pressure...
February 26, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Monia Savi, Leonardo Bocchi, Letizia Bresciani, Angela Falco, Federico Quaini, Pedro Mena, Furio Brighenti, Alan Crozier, Donatella Stilli, Daniele Del Rio
One of the most recently proposed candidates as a potential trigger for cardiovascular diseases is trimethylamine- N -oxide (TMAO). Possible direct effects of TMAO on myocardial tissue, independent of vascular damage, have been only partially explored so far. In the present study, we assessed the detrimental direct effects of TMAO on cardiomyocyte contractility and intracellular calcium dynamics, and the ability of urolithin B-glucuronide (Uro B-gluc) in counteracting TMAO-induced cell damage. Cell mechanics and calcium transients were measured, and ultrastructural analysis was performed in ventricular cardiomyocytes isolated from the heart of normal adult rats...
March 1, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Bridget M Stroup, Nivedita Nair, Sangita G Murali, Katarzyna Broniowska, Fran Rohr, Harvey L Levy, Denise M Ney
Background: Individuals with phenylketonuria (PKU) have a risk of cognitive impairment and inflammation. Many follow a low-phenylalanine (low-Phe) diet devoid of animal protein in combination with medical foods (MFs). Objective: To assess lipid metabolism in participants with PKU consuming amino acid MFs (AA-MFs) or glycomacropeptide MFs (GMP-MFs), we conducted fatty acid and metabolomics analyses. Methods: We used subsets of fasting plasma and urine samples from our randomized crossover trial in which participants with early-treated classical and variant (milder) PKU consumed a low-Phe diet combined with AA-MFs or GMP-MFs for 3 wk each...
February 1, 2018: Journal of Nutrition
Zhaoqian Su, Gopal Ravindhran, Cristiano Luis Dias
Effects of Trimethylamine-N-oxide (TMAO) on hydrophobic and charge-charge interactions are investigated using molecular dynamics simulations. Recently, these interactions in model peptides and in the Trp-Cage miniprotein have been reported to be strongly affected by TMAO. Neopentane dimers and Na+ Cl- are used, here, as models for hydrophobic and charge-charge interactions, respectively. Distance-dependent interactions, i.e., potential of mean force, are computed using an umbrella sampling protocol at different temperatures which allows us to determine enthalpy and entropic energies...
February 26, 2018: Journal of Physical Chemistry. B
Faith N Lambert, Jason R Treberg, W Gary Anderson, Catherine Brandt, Andrew N Evans
Although secondary stress physiology of elasmobranchs is fairly well studied, gaps remain in our understanding of species differences, including stress recovery. We examined the physiological stress response to air exposure in Atlantic stingrays (Hypanus sabinus) using a serial sampling method requiring minimal handling. Many elasmobranch stress studies exclusively quantify glucose, although there is evidence that elasmobranchs are unusually reliant on ketone bodies. Therefore, we also tested the hypothesis that ketone bodies play a significant role in the elasmobranch stress response by examining plasma β-hydroxybutyrate...
February 23, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Karin Julius, Samy R Al-Ayoubi, Michael Paulus, Metin Tolan, Roland Winter
Investigating the correlation between structure and activity of oligomeric enzymes at high pressure is essential for understanding intermolecular interactions and reactivity of proteins in cellulo of organisms thriving at extreme environmental conditions as well as for biotechnological applications, such as high-pressure enzymology. In a combined experimental effort employing small-angle X-ray scattering, FT-IR and fluorescence spectroscopy as well as stopped-flow enzyme kinetics in concert with high-pressure techniques, we reveal the pressure-induced conformational changes of the dimeric enzyme horse liver alcohol dehydrogenase (LADH) on the quaternary, secondary and tertiary structural level...
February 26, 2018: Physical Chemistry Chemical Physics: PCCP
Stefano Ciciliot, Mattia Albiero, Stefano Campanaro, Nicol Poncina, Serena Tedesco, Valentina Scattolini, Francesca Dalla Costa, Andrea Cignarella, Monica Vettore, Iole Maria Di Gangi, Sara Bogialli, Angelo Avogaro, Gian Paolo Fadini
The 66 kDa isoform of the mammalian Shc gene promotes adipogenesis, and p66Shc-/- mice accumulate less body weight than wild-type (WT) mice. As the metabolic consequences of the leaner phenotype of p66Shc-/- mice is debated, we hypothesized that gut microbiota may be involved. We confirmed that p66Shc-/- mice gained less weight than WT mice when on a high-fat diet (HFD), but they were not protected from insulin resistance and glucose intolerance. p66Shc deletion significantly modified the composition of gut microbiota and their modification after an HFD...
February 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sho Imoto, Harald Forbert, Dominik Marx
Solvation of trimethylamine-N-oxide (TMAO) by water is of great fundamental interest because this small molecule has both strongly hydrophilic and large hydrophobic groups at its opposite ends and, furthermore, stabilizes proteins against temperature and pressure denaturation. Since hydrophilic and hydrophobic groups affect the structural dynamics of the respective solvation water molecules in vastly different ways, we dissect their distinct influences on the THz spectrum of TMAO(aq) by using ab initio molecular dynamics simulations...
February 19, 2018: Physical Chemistry Chemical Physics: PCCP
Sahir Kalim, Ron Wald, Andrew T Yan, Marc B Goldstein, Mercedeh Kiaii, Dihua Xu, Anders H Berg, Clary Clish, Ravi Thadhani, Eugene P Rhee, Jeffrey Perl
BACKGROUND AND OBJECTIVES: In-center, extended duration nocturnal hemodialysis has been associated with variable clinical benefits, but the effect of extended duration hemodialysis on many established uremic solutes and other components of the metabolome is unknown. We determined the magnitude of change in metabolite profiles for patients on extended duration nocturnal hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a 52-week prospective, observational study, we followed 33 patients receiving conventional thrice weekly hemodialysis who converted to nocturnal hemodialysis (7-8 hours per session, three times per week)...
February 14, 2018: Clinical Journal of the American Society of Nephrology: CJASN
Divya Nayar, Nico F A van der Vegt
Water-mediated hydrophobic interactions play an important role in self-assembly processes, aqueous polymer solubility, and protein folding, to name a few. Cosolvents affect these interactions however the implications for hydrophobic polymer collapse and protein folding equilibria are not well-understood. This study examines cosolvent effects on the hydrophobic collapse equilibrium of a generic 32-mer hydrophobic polymer in urea, trimethylamine-N-oxide (TMAO), and acetone aqueous solutions using molecular dynamics simulations...
February 14, 2018: Journal of Physical Chemistry. B
Lilei Yu, Guannan Meng, Bing Huang, Xiaoya Zhou, Stavros Stavrakis, Menglong Wang, Xuefei Li, Liping Zhou, Yuhong Wang, Meng Wang, Zhenya Wang, Jielin Deng, Sunny S Po, Hong Jiang
BACKGROUND: Emerging evidence indicates gut microbes and their products could activate the autonomic nervous system (ANS), which plays important roles in the initiation and maintenance of atrial fibrillation (AF). Trimethylamine N-oxide (TMAO), a metabolite derived from gut microbes, is associated with cardiovascular diseases. The present study aimed to investigate the role of TMAO in the progression of AF. METHODS: In part 1: TMAO or saline was locally injected into 4 major atrial ganglionated plexi (GP) to clarify its effect on cardiac ANS and AF inducibility in normal canines...
March 15, 2018: International Journal of Cardiology
Weibang Yu, Chuncao Xu, Guomin Li, Weipeng Hong, Ziyi Zhou, Canxing Xiao, Yuanqi Zhao, Yefeng Cai, Min Huang, Jing Jin
Trimethylamine-N-oxide (TMAO) is derived from the gut microbiome and tissues metabolism of dietary choline and betaine. These molecules are closely related to the development of cardiovascular and cerebrovascular diseases. A rapid, sensitive and accurate method has been developed and validated for the simultaneous determination of trimethylamine N-oxide (TMAO), choline and betaine in human plasma using d9-trimethylamine N-oxide (TMAO), d9-choline, d9-betaine as the internal standard (IS). After methanol precipitation with 10 μL plasma samples, the analytes were extracted and then separated on Amide column (2...
February 2, 2018: Journal of Pharmaceutical and Biomedical Analysis
Marilisa Vigorita, Serena Cozzolino, Rosario Oliva, Giuseppe Graziano, Pompea Del Vecchio
Differential scanning calorimetry measurements performed on RNase A in aqueous binary solutions containing different concentrations of urea, tetramethylurea, guanidinium chloride, and guanidinium thiocyanate, and in aqueous ternary solutions, containing the same denaturants plus 1 M trimethylamine N-oxide, TMAO, demonstrate that the latter has a general counteracting ability at pH 7.0, but not at pH 4.0. Experimental data rule out the idea that counteraction originates from direct interactions between TMAO molecules and denaturing agents...
February 7, 2018: Biopolymers
Olumide A Odeyemi, Christopher M Burke, Christopher J S Bolch, Roger Stanley
Under the current commercial practice, live mussels only have 10days' shelf-life. Observed spoilage indices reduce consumers' acceptance, palatability and shelf-life of modified atmosphere packaged (MAP) live mussels. The aims of this study are to isolate specific spoilage bacteria from modified atmosphere packaged live mussels, evaluate isolates for microbial spoilage indices using qualitative methods and volatile metabolites production. Forty-six hydrogen sulphide producing bacteria were isolated and evaluated for trimethylamine n-oxide (TMAO) reduction, proteolytic and lipolytic activities and hydrogen sulphide production...
January 2018: Food Research International
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