PubMed

Related Articles Resistance exercise stimulates mixed muscle protein synthesis in lean and obese young adults. Physiol Rep. 2018 07;6(14):e13799 Authors: Hulston CJ, Woods RM, Dewhurst-Trigg R, Parry SA, Gagnon S, Baker L, James LJ, Markey O, Martin NRW, Ferguson RA, van Hall G Abstract Obese individuals exhibit a diminished muscle protein synthesis response to nutrient stimulation when compared with their lean counterparts. However, the effect of obesity on exercise-stimulated muscle protein synthesis remains unknown. Nine lean (23.5 ± 0.6 kg/m2 ) and 8 obese (33.6 ± 1.2 kg/m2 ) physically active young adults participated in a study that determined muscle protein synthesis and intracellular signaling at rest and following an acute bout of resistance exercise. Mixed muscle protein synthesis was determined by combining stable isotope tracer ([13 C6 ]phenylalanine) infusion with serial biopsies of the vastus lateralis. A unilateral leg resistance exercise model was adopted so that resting and postexercise measurements of muscle protein synthesis could be obtained simultaneously. Obesity was associated with higher basal levels of serum insulin (P < 0.05), plasma triacylglycerol (P < 0.01), plasma cholesterol (P < 0.01), and plasma CRP (P < 0.01), as well as increased insulin resistance determined by HOMA-IR (P < 0.05). However, resting and postexercise rates of muscle protein synthesis were not significantly different between lean and obese participants (P = 0.644). Furthermore, resistance exercise stimulated muscle protein synthesis (~50% increase) in both groups (P < 0.001), with no difference between lean and obese (P = 0.809). Temporal increases in the phosphorylation of intracellular signaling proteins (AKT/4EBP1/p70S6K) were observed within the exercised leg (P < 0.05), with no differences between lean and obese. These findings suggest a normal anabolic response to muscle loading in obese young adults. PMID: 30009507 [PubMed - indexed for MEDLINE]

Related Articles Pseudoqc: A Regression-Based Simulation Software for Correction and Normalization of Complex Metabolomics and Proteomics Datasets. Proteomics. 2019 Aug 31;:e1900264 Authors: Wang S, Yang H Abstract Various types of unwanted and uncontrollable signal variations in mass spectrometry (MS)-based metabolomics and proteomics datasets severely disturb the accuracies of metabolite and protein profiling. Therefore, pooled quality control (QC) samples are often employed in quality management processes, which are indispensable to the success of metabolomics and proteomics experiments, especially in high-throughput cases and long-term projects. However, data consistency and QC sample stability are still difficult to guarantee because of the experimental operation complexity and differences between experimenters. To make things worse, numerous proteomics projects do not take QC samples into consideration at the beginning of experimental design. Herein, we present a powerful and interactive web-based software, named pseudoQC, to simulate QC sample data for actual metabolomics and proteomics datasets using four different machine learning-based regression methods. The simulated data are used for correction and normalization of the two published datasets, and the obtained results suggest that nonlinear regression methods perform better than linear ones. Additionally, the above software is available as a web-based graphical user interface (GUI) and can be utilized by scientists without a bioinformatics background. pseudoQC is open-source software and freely available at https://www.omicsolution.org/wukong/pseudoQC/. This article is protected by copyright. All rights reserved. PMID: 31474000 [PubMed - as supplied by publisher]

Related Articles Resveratrol-mediated glycemic regulation is blunted by curcumin and is associated to modulation of gut microbiota. J Nutr Biochem. 2019 Jul 30;72:108218 Authors: Sreng N, Champion S, Martin JC, Khelaifia S, Christensen JE, Padmanabhan R, Azalbert V, Blasco-Baque V, Loubieres P, Pechere L, Landrier JF, Burcelin R, Sérée E Abstract The polyphenols resveratrol (RSV) and curcumin (Cur) are phytoalexines and natural antibiotics with numerous pharmacological functions and metabolic impacts. Recent evidences show a broad control of gut microbiota by polyphenols which could influence glycemic regulation. The aim of this work is to estimate the respective effect of RSV and Cur alone or in association on the control of glycemia and on gut microbiota. A 5-week chronic treatment of hyperglycemic mice with RSV and/or Cur resulted in a differential effect on glucose tolerance test and modified gut microbiome. We precisely identified groups of bacteria representing a specific signature of the glycemic effect of RSV. Inferred metagenomic analysis and metabolic pathway prediction showed that the sulfur and branched-chain amino-acid (BCAA) metabolic activities are tightly correlated with the efficacy of RSV for the control of glycaemia. The impact on BCAA metabolism was further validated by serum metabolomics analysis. Altogether, we show that polyphenols specifically impact gut microbiota and corresponding metabolic functions which could be responsible for their therapeutic role. PMID: 31473511 [PubMed - as supplied by publisher]

Related Articles A metabolomics study on effects of polyaromatic compounds in oil sand extracts on the respiratory, hepatic and nervous systems using three human cell lines. Environ Res. 2019 Aug 19;178:108680 Authors: Sarma SN, Kimpe LE, Doyon VC, Blais JM, Chan HM Abstract Polyaromatic compounds (PACs) are by-products of combustion and are the major pollutants from the oil and gas industry. However, the mechanism of PACs induced toxicity still remains elusive. The aim of this study was to elucidate the effects of a typical mixture of PACs found in oil sand extract (OSE) on the respiratory, hepatic and nervous systems in humans using in vitro cell culture models followed by non-targeted metabolomics analysis. OSE collected from Alberta, Canada was fractionated into PAC and alkane fractions, and their effects after 24 h exposure on the cell viability measured by MTT assay in three human cell lines (A549, HepG2, and SK-N-SH) were studied. The PAC fractions showed significant dose-dependent cytotoxicity. A549 cells showed the highest sensitivity to OSE extracts, followed by SK-N-SH and HepG2. In contrast, the alkane fractions showed no effects on cell viability. The three human cell lines were further exposed with the PACs at 10% and 20% lethal concentration for 24 h. Metabolomics analysis of the cell extracts indicated that PACs treatments showed different disruptions on possible metabolic pathways on the three cell lines. PACs altered the sex steroid hormone metabolism and regulated the levels of leukotrienes metabolites in all three cell types. The amino acids L-cysteine, L-glutamine, L-tyrosine that are known to cause respiratory effects were significantly up-regulated in A549 cells. The PACs treated HepG2 cells showed down-regulation in metabolites responsible for the inflammatory mediation. Treatment of the differentiated SK-N-SH cells showed up-regulated metabolites involved with butanoate, fatty acid, and pyrimidine metabolism. Leukotriene metabolites were found to be significantly increased in all PACs treated cells. In conclusion, our results showed that PACs in OSE can alter the metabolism of the human lung, liver and neuronal cells and may induce toxicity in multiple target organs. PMID: 31473503 [PubMed - as supplied by publisher]

Related Articles Dynamic Metabolomics for Engineering Biology: Accelerating Learning Cycles for Bioproduction. Trends Biotechnol. 2019 Aug 28;: Authors: Vavricka CJ, Hasunuma T, Kondo A Abstract Metabolomics is a powerful tool to rationally guide the metabolic engineering of synthetic bioproduction pathways. Current reports indicate great potential to further develop metabolomics-directed synthetic bioproduction. Advanced mass metabolomics methods including isotope flux analysis, untargeted metabolomics, and system-wide approaches are assisting the characterization of metabolic pathways and enabling the biosynthesis of more complex products. More importantly, a design, build, test, and learn (DBTL) cycle is accelerating synthetic biology research and is highly compatible with metabolomics data to further expand bioproduction capability. However, learning processes are currently the weakest link in this workflow. Therefore, guidelines for the development of metabolic learning processes are proposed based on bioproduction examples. Linking dynamic mass spectrometry (MS) methodologies together with automated learning workflows is encouraged. PMID: 31473013 [PubMed - as supplied by publisher]

Related Articles Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids. Microbiome. 2019 Aug 31;7(1):126 Authors: Wang S, Martins R, Sullivan MC, Friedman ES, Misic AM, El-Fahmawi A, De Martinis ECP, O'Brien K, Chen Y, Bradley C, Zhang G, Berry ASF, Hunter CA, Baldassano RN, Rondeau MP, Beiting DP Abstract BACKGROUND: The microbiome has been implicated in the initiation and persistence of inflammatory bowel disease. Despite the fact that diet is one of the most potent modulators of microbiome composition and function and that dietary intervention is the first-line therapy for treating pediatric Crohn's disease, the relationships between diet-induced remission, enteropathy, and microbiome are poorly understood. Here, we leverage a naturally-occurring canine model of chronic inflammatory enteropathy that exhibits robust remission following nutritional therapy, to perform a longitudinal study that integrates clinical monitoring, 16S rRNA gene amplicon sequencing, metagenomic sequencing, metabolomic profiling, and whole genome sequencing to investigate the relationship between therapeutic diet, microbiome, and disease. RESULTS: We show that remission induced by a hydrolyzed protein diet is accompanied by alterations in microbial community structure marked by decreased abundance of pathobionts (e.g., Escherichia coli and Clostridium perfringens), reduced severity of dysbiosis, and increased levels of the secondary bile acids, lithocholic and deoxycholic acid. Physiologic levels of these bile acids inhibited the growth of E. coli and C. perfringens isolates, in vitro. Metagenomic analysis and whole genome sequencing identified the bile acid producer Clostridium hiranonis as elevated after dietary therapy and a likely source of secondary bile acids during remission. When C. hiranonis was administered to mice, levels of deoxycholic acid were preserved and pathology associated with DSS colitis was ameliorated. Finally, a closely related bile acid producer, Clostridium scindens, was associated with diet-induced remission in human pediatric Crohn's disease. CONCLUSIONS: These data highlight that remission induced by a hydrolyzed protein diet is associated with improved microbiota structure, an expansion of bile acid-producing clostridia, and increased levels of secondary bile acids. Our observations from clinical studies of exclusive enteral nutrition in human Crohn's disease, along with our in vitro inhibition assays and in vivo studies in mice, suggest that this may be a conserved response to diet therapy with the potential to ameliorate disease. These findings provide insight into diet-induced remission of gastrointestinal disease and could help guide the rational design of more effective therapeutic diets. PMID: 31472697 [PubMed - in process]

Related Articles Study of metabolic disorders associated with BDE-47 exposure in Drosophila model by MS-based metabolomics. Ecotoxicol Environ Saf. 2019 Aug 28;184:109606 Authors: Ji F, Wei J, Luan H, Li M, Cai Z Abstract Epidemiological and animal studies have revealed a possible linkage between 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) exposure and neurodegenerative disease such as Parkinson's disease (PD). However, whether or how BDE-47 would affect the PD progression remains unclear. Here, we carried out a metabolomics study based on liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) to investigate the possible contribution of BDE-47 exposure to PD progression in Drosophila (fly) model. Transgenic PD flies were exposed to BDE-47 through diet for 30 days. Global metabolomic analysis identified 48 altered metabolites after the exposure. These metabolites were mainly involved in tryptophan metabolism, phenylalanine metabolism, purine metabolism, and alanine, aspartate and glutamate metabolism. Further, by quantifying metabolites of interest using LC-MS/MS, we confirmed that the formation of neuro-protector kynurenic acid was slowed down while the formation of neurotoxin 3-hydroxy-kynurenine was speeded up on the 20th exposure day. Moreover, the levels of SAM/SAH (an index of methylation potential) and GSH/GSSG (an indicator of oxidative stress) were found to decrease on the 30th exposure day. Our results suggest that BDE-47 could induce imbalance of kynurenine metabolism and methylation potential, and oxidative stress, which might further accelerate PD progression. PMID: 31472382 [PubMed - as supplied by publisher]

Related Articles Toxicological screening and DNA sequencing detects contamination and adulteration in regulated herbal medicines and supplements for diet, weight loss and cardiovascular health. J Pharm Biomed Anal. 2019 Aug 23;176:112834 Authors: Crighton E, Coghlan ML, Farrington R, Hoban CL, Power MWP, Nash C, Mullaney I, Byard RW, Trengove R, Musgrave IF, Bunce M, Maker G Abstract Use of herbal medicines and supplements by consumers to prevent or treat disease, particularly chronic conditions continues to grow, leading to increased awareness of the minimal regulation standards in many countries. Fraudulent, adulterated and contaminated herbal and traditional medicines and dietary supplements are a risk to consumer health, with adverse effects and events including overdose, drug-herb interactions and hospitalisation. The scope of the risk has been difficult to determine, prompting calls for new approaches, such as the combination of DNA metabarcoding and mass spectrometry used in this study. Here we show that nearly 50% of products tested had contamination issues, in terms of DNA, chemical composition or both. Two samples were clear cases of pharmaceutical adulteration, including a combination of paracetamol and chlorpheniramine in one product and trace amounts of buclizine, a drug no longer in use in Australia, in another. Other issues include the undeclared presence of stimulants such as caffeine, synephrine or ephedrine. DNA data highlighted potential allergy concerns (nuts, wheat), presence of potential toxins (Neem oil) and animal ingredients (reindeer, frog, shrew), and possible substitution of bird cartilage in place of shark. Only 21% of the tested products were able to have at least one ingredient corroborated by DNA sequencing. This study demonstrates that, despite current monitoring approaches, contaminated and adulterated products are still reaching the consumer. We suggest that a better solution is stronger pre-market evaluation, using techniques such as that outlined in this study. PMID: 31472365 [PubMed - as supplied by publisher]

Related Articles A novel neutral loss/product ion scan-incorporated integral approach for the untargeted characterization and comparison of the carboxyl-free ginsenosides from Panax ginseng, Panax quinquefolius, and Panax notoginseng. J Pharm Biomed Anal. 2019 Aug 14;177:112813 Authors: Yang WZ, Shi XJ, Yao CL, Huang Y, Hou JJ, Han SM, Feng ZJ, Wei WL, Wu WY, Guo DA Abstract Differentiated composition in precursor ions for different subclasses of ginsenosides in the negative electrospray-ionization mode has been reported, which lays a foundation for the sorted and untargeted identification of ginsenosides. Carboxyl-free ginsenosides simultaneously from Panax ginseng, P. quinquefolius, and P. notoginseng, were comprehensively characterized and statistically compared. A neutral loss/product ion scan (NL-PIS) incorporated untargeted profiling approach, coupled to ultra-high performance liquid chromatography, was developed on a linear ion-trap/Orbitrap mass spectrometer for characterizing carboxyl-free ginsenosides. It incorporated in-source fragmentation (ISF) full scan-MS1, mass tag-MS2, and product ion scan-MS3. Sixty batches of ginseng samples were analyzed by metabolomics workflows for the discovery of ginsenoside markers. Using formic acid (FA) as the additive, carboxyl-free ginsenosides (protopanaxadiol-type, protopanaxatriol-type, and octillol-type) gave predominant FA-adducts, while rich deprotonated molecules were observed for carboxyl-containing ginsenosides (oleanolic acid-type and malonylated) when source-induced dissociation (SID) was set at 0 V. Based on the NL transition [M+FA‒H]- > [M-H]- and the characteristic sapogenin product ions, a NL-PIS approach was established. It took advantage of the efficient full-information acquisition of ISF-MS1 (SID: 50 V), the high specificity of mass tag (NL: 46.0055 Da)-induced MS2 fragmentation, and the substructure fragmentation of product ion scan-MS3. We could characterize 216 carboxyl-free ginsenosides, and 21 thereof were potentially diagnostic for the species differentiation. Conclusively, sorted and untargeted characterization of the carboxyl-free ginsenosides was achieved by the established NL-PIS approach. In contrast to the conventional NL or PIS-based survey scan strategies, the high-accuracy MSn data obtained can enable more reliable identification of ginsenosides. PMID: 31472326 [PubMed - as supplied by publisher]

Related Articles Metabolomics analysis reveals perturbations of cerebrocortical metabolic pathways in the Pahenu2 mouse model of phenylketonuria. CNS Neurosci Ther. 2019 Aug 31;: Authors: Lu LH, Xia ZX, Guo JL, Xiao LL, Zhang YJ Abstract AIMS: Phenylketonuria (PKU), which is caused by mutations in the phenylalanine hydroxylase (PAH) gene, is one of the most common inherited diseases of amino acid metabolism. Phenylketonuria is characterized by an abnormal accumulation of phenylalanine and its metabolites in body fluids and brain tissues, subsequently leading to severe brain dysfunction. Various pathophysiological and molecular mechanisms underlying brain dysfunction in PKU have been described. However, the metabolic changes and their impacts on the function of cerebral cortices of patients with PKU remain largely unknown. METHODS: We measured the levels of small molecule metabolites in the cerebrocortical tissues of PKU mice and wild-type control mice using liquid chromatography-mass spectrometry (LC-MS)-based metabolome analysis. Differential metabolites were further subjected to metabolic pathway and enrichment analysis. RESULTS: Metabolome analysis revealed 35 compounds among 143 detected metabolites were significantly changed in PKU mice as compared to those in their wild-type littermates. Metabolic pathway and enrichment analysis of these differential metabolites showed that multiple metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis; valine, leucine, and isoleucine biosynthesis; alanine, aspartate, and glutamate metabolism; purine metabolism; arginine and proline metabolism and methionine metabolism, were impacted in the cerebral cortices of PKU mice. CONCLUSIONS: The data revealed that multiple metabolic pathways in cerebral cortices of PKU mice were disturbed, suggesting that the disturbances of the metabolic pathways might contribute to neurological or neurodevelopmental dysfunction in PKU, which could thus provide new insights into brain pathogenic mechanisms in PKU as well as mechanistic insights for better understanding the complexity of the metabolic mechanisms of the brain dysfunction in PKU. PMID: 31471952 [PubMed - as supplied by publisher]

Related Articles Nutritional Deficiencies, Bariatric Surgery, and Serum Homocysteine Level: Review of Current Literature. Obes Surg. 2019 Aug 31;: Authors: Komorniak N, Szczuko M, Kowalewski B, Stachowska E Abstract Obesity is currently one of the biggest global health problems. In the case of severe obesity, bariatric surgeries are considered to be the most important method of treatment. The 2 most commonly performed bariatric surgery procedures include Roux-en-Y gastric bypass and sleeve gastrectomy. However, these methods are not free from complications, and the most common ones (moderately long or long term) are micronutrient deficiencies. The deficiency of vitamins B6, B12, and folic acid as cofactors of the folate cycle contributes to the development of hyperhomocysteinemia. It seems that apart from nutritional factors, there are other aspects that have a significant influence on the concentration of homocysteine in blood, such as the type of conducted bariatric surgery, the post-surgical concentration of betaine and creatinine, and the clearance of methionine (i.e., the mutations of the gene that encodes the MTHFR reductase as well as other genes associated with the process of methylation, e.g., methionine synthase). Their presence might be one of the causes of the increased concentration of homocysteine after surgery despite the fact that patients take vitamin-mineral supplementation. PMID: 31471768 [PubMed - as supplied by publisher]

Related Articles Xenobiotics metabolization in Salix alba leaves uncovered by mass spectrometry imaging. Metabolomics. 2019 Aug 30;15(9):122 Authors: Villette C, Maurer L, Wanko A, Heintz D Abstract INTRODUCTION: Micropollutants are increasingly monitored as their presence in the environment is rising due to human activities, and they are potential threats to living organisms. OBJECTIVES: This study aimed at understanding the role of plants in xenobiotics removal from polluted environments by following xenobiotics metabolism in leaf tissues. METHODS: Different classes of micropollutants were investigated using liquid chromatography (LC) coupled to quadrupole-time of flight (Q-TOF) high resolution mass spectrometry (HRMS). The tissue localization of xenobiotics in the leaves of a spontaneous (not planted by humans) Salix alba growing near the water flux was further investigated using matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI). RESULTS: The LC-Q-TOF analysis revealed the distribution of micropollutants in three different compartments of a tertiary treatment wetland. When further investing the metabolic profile of S. alba leaves using MSI, different distribution patterns were observed in specific leaf tissues. Xenobiotic metabolites were predicted and could also be tentatively identified in S. alba leaves, shedding new light on the metabolic processes at play in leaves to manage xenobiotics uptake from a polluted environment. CONCLUSION: Using complementary metabolomics approaches, this study performed a large-scale exploration of micropollutants spreading in the environment at the exit of a tertiary treatment wetland. The use of MSI coupled with the prediction of xenobiotic metabolites yielded novel insights into plant metabolism during chronical exposure to low doses of a mixture of micropollutants. PMID: 31471668 [PubMed - in process]

Related Articles Cadmium and selenate exposure affects the honey bee microbiome and metabolome, and bee-associated bacteria show potential for bioaccumulation. Appl Environ Microbiol. 2019 Aug 30;: Authors: Rothman JA, Leger L, Kirkwood JS, McFrederick QS Abstract Honey bees are important insect pollinators used heavily in agriculture and can be found in diverse environments. Bees may encounter toxicants such as cadmium and selenate by foraging on plants growing in contaminated areas, which can result in negative health effects. Honey bees are known to have a simple and consistent microbiome that conveys many benefits to the host, and toxicant exposure may impact this symbiotic microbial community. We used 16s rRNA gene sequencing to assay the effects that sublethal cadmium and selenate treatments had over seven days and found that both treatments significantly but subtly altered the composition of the bee microbiome. Next, we exposed bees to cadmium and selenate then used untargeted LC-MS metabolomics to show that chemical exposure changed the bees' metabolite profiles and that compounds which may be involved in detoxification, proteolysis, and lipolysis were more abundant in treatments. Lastly, we exposed several strains of bee-associated bacteria in liquid culture and found that each strain removed cadmium from their media, but only Lactobacillus Firm-5 microbes assimilated selenate, indicating the possibility that these microbes may reduce metal and metalloid burden on their host. Overall, our study shows that metal and metalloid exposure can affect the honey bee microbiome and metabolome, and that strains of bee-associated bacteria can bioaccumulate these toxicants.Importance Bees are important insect pollinators who may encounter environmental pollution when foraging upon plants grown in contaminated areas. Despite the pervasiveness of pollution, little is known about the effects of these toxicants on honey bee metabolism and their symbiotic microbiomes. Here, we investigated the impact of selenate and cadmium exposure on the gut microbiome and metabolome of honey bees. We found that exposure to these chemicals subtly altered the overall composition of the bees' microbiome and metabolome, and that exposure to toxicants may negatively impact both host and microbe. As the microbiome of animals can reduce mortality upon metal or metalloid challenge, we grew bee-associated bacteria in media spiked with selenate or cadmium. We show that some bacteria can remove these toxicants from their media in vitro and suggest that bacteria may reduce metal burden in their hosts. PMID: 31471302 [PubMed - as supplied by publisher]

Related Articles On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis. Ann Rheum Dis. 2019 Aug 30;: Authors: Kissel T, van Schie KA, Hafkenscheid L, Lundquist A, Kokkonen H, Wuhrer M, Huizinga TW, Scherer HU, Toes R, Rantapää-Dahlqvist S Abstract OBJECTIVE: Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains). Recently, we showed that N-glycosylation sites, which are required for the incorporation of V-domain glycans, are introduced following somatic hypermutation. However, it is currently unclear when V-domain glycosylation occurs. Further, it is unknown which factors might trigger the generation of V-domain glycans and whether such glycans are relevant for the transition towards RA. Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients. METHODS: ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chrmatography(UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative). RESULTS: V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset. Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG. CONCLUSION: Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life. Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA. PMID: 31471298 [PubMed - as supplied by publisher]

Related Articles Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans. Cell Metab. 2019 Aug 20;: Authors: Stekovic S, Hofer SJ, Tripolt N, Aon MA, Royer P, Pein L, Stadler JT, Pendl T, Prietl B, Url J, Schroeder S, Tadic J, Eisenberg T, Magnes C, Stumpe M, Zuegner E, Bordag N, Riedl R, Schmidt A, Kolesnik E, Verheyen N, Springer A, Madl T, Sinner F, de Cabo R, Kroemer G, Obermayer-Pietsch B, Dengjel J, Sourij H, Pieber TR, Madeo F Abstract Caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study (ClinicalTrials.gov identifier: NCT02673515), we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average. No adverse effects occurred even after >6 months. ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improving the fat-to-lean ratio, and increased β-hydroxybutyrate, even on non-fasting days. On fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated. We found reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF. These results shed light on the physiological impact of ADF and supports its safety. ADF could eventually become a clinically relevant intervention. PMID: 31471173 [PubMed - as supplied by publisher]

Related Articles Cell-autonomous, paracrine and neuroendocrine feedback regulation of autophagy by DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein): the obesity factor. Autophagy. 2019 Aug 30;: Authors: Bravo-San Pedro JM, Sica V, Martins I, Anagnostopoulos G, Maiuri C, Kroemer G Abstract DBI/ACBP (diazepam binding protein, acyl-CoA binding protein) participates in the regulation of fatty acid metabolism when it is localized within cells, whereas outside of cells it acts as a diazepam-binding protein. Recent results indicate that many different mammalian cell types release DBI/ACBP upon in vitro or in vivo starvation in a macroautophagy/autophagy-dependent fashion. The autophagy-associated release of DBI/ACBP elicits feedback inhibition of autophagy through 3 independent mechanisms. First, the depletion of DBI/ACBP from cells limits autophagy in a cell-autonomous fashion. Second, extracellular DBI/ACBP acts in a paracrine fashion to inhibit autophagy. Third, DBI/ACBP increasing in the systemic circulation acts as an activator of lipo-anabolism and feeding behavior, thus removing the cause of autophagy induction (starvation) and suppressing the phenomenon. DBI/ACBP expression is upregulated at the mRNA and protein levels in obese mice and humans, and its extracellular neutralization by antibodies controls food intake and increases lipo-catabolism. Current data support the contention that DBI/ACBP is an important pro-obesity factor. PMID: 31470770 [PubMed - as supplied by publisher]

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/08/31PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

36 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/08/30PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Metabolomics, transcriptomic and genetic-integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non-small cell lung cancer. Mol Oncol. 2019 Aug 28;: Authors: Hoang LT, Domingo-Sabugo C, Starren ES, Willis-Owen SAG, Morris-Rosendahl DJ, Nicholson AG, Cookson WOCM, Moffatt MF Abstract Lung cancer is the leading cause of cancer-related deaths in the world. The most prevalent subtype, accounting for 85% of cases, is non-small cell lung cancer (NSCLC). Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the most common subtypes. Despite recent advances in treatment, the low 5-year survival rate of NSCLC patients (approximately 13%) reflects the lack of early diagnostic biomarkers and incomplete understanding of the underlying disease mechanisms. We hypothesised that integration of metabolomic, transcriptomic and genetic profiles of tumours and matched normal tissues could help to identify important factors and potential therapeutic targets that contribute to tumorigenesis. We integrated omics profiles in tumours and matched adjacent normal tissues of patients with LUSC (N = 20) and LUAD (N = 17) using multiple system biology approaches. We confirmed the presence of previously described metabolic pathways in NSCLC, particularly those mediating the Warburg effect. In addition, through our combined omics analyses we found that metabolites and genes that contribute to haemostasis, angiogenesis, platelet activation and cell proliferation were predominant in both subtypes of NSCLC. The important roles of adenosine diphosphate (ADP) in promoting cancer metastasis through platelet activation and angiogenesis suggests this metabolite could be a potential therapeutic target. PMID: 31461552 [PubMed - as supplied by publisher]

Related Articles Delineating the role of FANCA in glucose-stimulated insulin secretion in β cells through its protein interactome. PLoS One. 2019;14(8):e0220568 Authors: Lagundžin D, Hu WF, Law HCH, Krieger KL, Qiao F, Clement EJ, Drincic AT, Nedić O, Naldrett MJ, Alvarez S, Woods NT Abstract Hyperinsulinemia affects 72% of Fanconi anemia (FA) patients and an additional 25% experience lowered glucose tolerance or frank diabetes. The underlying molecular mechanisms contributing to the dysfunction of FA pancreas β cells is unknown. Therefore, we sought to evaluate the functional role of FANCA, the most commonly mutated gene in FA, in glucose-stimulated insulin secretion (GSIS). This study reveals that FANCA or FANCB knockdown impairs GSIS in human pancreas β cell line EndoC-βH3. To identify potential pathways by which FANCA might regulate GSIS, we employed a proteomics approach to identify FANCA protein interactions in EndoC-βH3 differentially regulated in response to elevated glucose levels. Glucose-dependent changes in the FANCA interaction network were observed, including increased association with other FA family proteins, suggesting an activation of the DNA damage response in response to elevated glucose levels. Reactive oxygen species increase in response to glucose stimulation and are necessary for GSIS in EndoC-βH3 cells. Glucose-induced activation of the DNA damage response was also observed as an increase in the DNA damage foci marker γ-H2AX and dependent upon the presence of reactive oxygen species. These results illuminate the role of FANCA in GSIS and its protein interactions regulated by glucose stimulation that may explain the prevalence of β cell-specific endocrinopathies in FA patients. PMID: 31461451 [PubMed - in process]