scholarly journals Screening of Altered Metabolites and Metabolic Pathways in Celiac Disease Using NMR Spectroscopy

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Ensieh Khalkhal ◽  
Mostafa Rezaei-Tavirani ◽  
Fariba Fathi ◽  
B. Fatemeh Nobakht M. Gh ◽  
Amir Taherkhani ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Nmr Spectroscopy ◽  
Metabolic Pathways ◽  
Screening Method ◽  
Invasive Procedure ◽  
Healthy Controls ◽  
Arginine Biosynthesis ◽  
Acid Biosynthesis ◽  
Isoleucine Biosynthesis ◽  
New Biomarkers

Background. Celiac disease (CeD) is an autoimmune intestinal disorder caused by gluten protein consumption in genetically predisposed individuals. As biopsy sampling is an invasive procedure, finding novel noninvasive serological markers for screening of at-risk CeD population is a priority. Metabolomics is helpful in monitoring metabolite changes in body fluids and tissues. In the present study, we evaluated serum metabolite levels of CeD patients relative to healthy controls with the aim of introducing new biomarkers for population screening. Method. We compared the serum metabolic profile of CeD patients ( n = 42 ) and healthy controls ( n = 22 ) using NMR spectroscopy and multivariate analysis. Result. 25 metabolites were identified by serum metabolic profiling. Levels of 3-hydroxyisobutyric acid and isobutyrate showed significant differences in CeD patients’ samples compared with healthy controls ( p < 0.05 ). According to pathway analysis, our data demonstrated that changes in nine metabolic pathways were significantly disrupted/affected in patients with CeD. These enriched pathways are involved in aminoacyl-tRNA biosynthesis; primary bile acid biosynthesis; nitrogen metabolism; glutamine and glutamate metabolism; valine, leucine, and isoleucine biosynthesis and degradation; taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and arginine biosynthesis. Conclusion. In summary, our results demonstrated that changes in the serum level of 25 metabolites may be useful in distinguishing CeD patients from healthy controls, which have the potential to be considered candidate biomarkers of CeD.

scholarly journals Metabolic profiling of liver and faeces in mice infected with echinococcosis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Mingxing Zhu ◽  
Xiancai Du ◽  
Hongxia Xu ◽  
Songhao Yang ◽  
Chan Wang ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Screening Method ◽  
Infection Model ◽  
Parasitic Disease ◽  
Biological Responses ◽  
Highly Sensitive ◽  
Isoleucine Biosynthesis ◽  
Phenylalanine Metabolism ◽  
Internal And External Factors

Abstract Background Echinococcosis is a severe zoonotic parasitic disease which severely affects the health of the hosts. The diagnosis of echinococcosis depends mainly on imaging examination. However, the patient is often in the late stage of the disease when the symptoms appear, thus limiting the early diagnosis of echinococcosis. The treatment and prognosis of the patients are hampered because of long-term asymptomatic latency. Metabolomics is a new discipline developed in the late 1990s. It reflects a series of biological responses in pathophysiological processes by demonstrating the changes in metabolism under the influence of internal and external factors. When the organism is invaded by pathogens, the alteration in the characteristics of metabolites in cells becomes extremely sensitive. Here, we used a metabolomics approach involving liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) to determine the molecular mechanism of cystic echinococcosis (CE) and to develop an effective method for CE diagnosis. Methods Twenty 8-week-old female BALB/c mice were divided into normal and Echinococcus granulosus infection groups. To develop the E. granulosus infection model, mice were infected with protoscoleces. Six weeks later, the abdomens of the mice showed significant bulging. An LC–MS/MS system-based metabolomics approach was used to analyse the liver and faeces to reveal the metabolic profiles of mice with echinococcosis. Results We found that the metabolism of nucleotides, alkaloids, amino acids, amides, and organic acids in mice is closely interrelated with E. granulosus infection. In the liver, the metabolic pathways of tyrosine and tryptophan biosynthesis; phenylalanine, valine, leucine and isoleucine biosynthesis; and phenylalanine metabolism were notably associated with the occurrence and development of hydatid disease, and in the faeces, pantothenate and CoA biosynthesis are thought to be closely associated with the development of CE. Conclusion The metabolomics approach used in this study provides a reference for a highly sensitive and specific diagnostic and screening method for echinococcosis. Graphic Abstract

scholarly journals Microbiota and Metabolomic Patterns in the Breast Milk of Subjects with Celiac Disease on a Gluten-Free Diet

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2243
Author(s):  
Katherine L. Olshan ◽  
Ali R. Zomorrodi ◽  
Meritxell Pujolassos ◽  
Jacopo Troisi ◽  
Nayeim Khan ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Breast Milk ◽  
Milk Composition ◽  
Gluten Free Diet ◽  
Intestinal Microbiome ◽  
Healthy Controls ◽  
Gluten Free ◽  
Bacterial Strains ◽  
Shotgun Metagenomics ◽  
Functional Pathways

The intestinal microbiome may trigger celiac disease (CD) in individuals with a genetic disposition when exposed to dietary gluten. Research demonstrates that nutrition during infancy is crucial to the intestinal microbiome engraftment. Very few studies to date have focused on the breast milk composition of subjects with a history of CD on a gluten-free diet. Here, we utilize a multi-omics approach with shotgun metagenomics to analyze the breast milk microbiome integrated with metabolome profiling of 36 subjects, 20 with CD on a gluten-free diet and 16 healthy controls. These analyses identified significant differences in bacterial and viral species/strains and functional pathways but no difference in metabolite abundance. Specifically, three bacterial strains with increased abundance were identified in subjects with CD on a gluten-free diet of which one (Rothia mucilaginosa) has been previously linked to autoimmune conditions. We also identified five pathways with increased abundance in subjects with CD on a gluten-free diet. We additionally found four bacterial and two viral species/strains with increased abundance in healthy controls. Overall, the differences observed in bacterial and viral species/strains and in functional pathways observed in our analysis may influence microbiome engraftment in neonates, which may impact their future clinical outcomes.

scholarly journals Liquid Biopsy in Hepatocellular Carcinoma: Where Are We Now?

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2274
Author(s):  
Filippo Pelizzaro ◽  
Romilda Cardin ◽  
Barbara Penzo ◽  
Elisa Pinto ◽  
Alessandro Vitale ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liquid Biopsy ◽  
Predictive Biomarkers ◽  
Invasive Procedure ◽  
Therapeutic Monitoring ◽  
Comprehensive Overview ◽  
Improve Patient Survival ◽  
Prognostic Tests ◽  
Prognostic Stratification ◽  
New Biomarkers

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death worldwide. Diagnostic, prognostic, and predictive biomarkers are urgently needed in order to improve patient survival. Indeed, the most widely used biomarkers, such as alpha-fetoprotein (AFP), have limited accuracy as both diagnostic and prognostic tests. Liver biopsy provides an insight on the biology of the tumor, but it is an invasive procedure, not routinely used, and not representative of the whole neoplasia due to the demonstrated intra-tumoral heterogeneity. In recent years, liquid biopsy, defined as the molecular analysis of cancer by-products, released by the tumor in the bloodstream, emerged as an appealing source of new biomarkers. Several studies focused on evaluating extracellular vesicles, circulating tumor cells, cell-free DNA and non-coding RNA as novel reliable biomarkers. In this review, we aimed to provide a comprehensive overview on the most relevant available evidence on novel circulating biomarkers for early diagnosis, prognostic stratification, and therapeutic monitoring. Liquid biopsy seems to be a very promising instrument and, in the near future, some of these new non-invasive tools will probably change the clinical management of HCC patients.

scholarly journals ASICS: an R package for a whole analysis workflow of 1D 1H NMR spectra

2019 ◽  
Vol 35 (21) ◽  
pp. 4356-4363 ◽  
Author(s):  
Gaëlle Lefort ◽  
Laurence Liaubet ◽  
Cécile Canlet ◽  
Patrick Tardivel ◽  
Marie-Christine Père ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Nmr Spectra ◽  
Complex Mixture ◽  
R Package ◽  
Statistical Analyses ◽  
Supplementary Information ◽  
Automatic Identification ◽  
Analysis Workflow ◽  
Expert Analysis ◽  
New Biomarkers

Abstract Motivation In metabolomics, the detection of new biomarkers from Nuclear Magnetic Resonance (NMR) spectra is a promising approach. However, this analysis remains difficult due to the lack of a whole workflow that handles spectra pre-processing, automatic identification and quantification of metabolites and statistical analyses, in a reproducible way. Results We present ASICS, an R package that contains a complete workflow to analyse spectra from NMR experiments. It contains an automatic approach to identify and quantify metabolites in a complex mixture spectrum and uses the results of the quantification in untargeted and targeted statistical analyses. ASICS was shown to improve the precision of quantification in comparison to existing methods on two independent datasets. In addition, ASICS successfully recovered most metabolites that were found important to explain a two level condition describing the samples by a manual and expert analysis based on bucketing. It also found new relevant metabolites involved in metabolic pathways related to risk factors associated with the condition. Availability and implementation ASICS is distributed as an R package, available on Bioconductor. Supplementary information Supplementary data are available at Bioinformatics online.

New ultrasonographic screening method for oropharyngeal dysphagia: tissue Doppler imaging

2018 ◽  
Vol 314 (1) ◽  
pp. G32-G38 ◽  
Author(s):  
Noriaki Manabe ◽  
Ken Haruma ◽  
Rui Nakato ◽  
Hiroaki Kusunoki ◽  
Tomoari Kamada ◽  
...  
Keyword(s):  
Tissue Doppler Imaging ◽  
Screening Method ◽  
Oropharyngeal Dysphagia ◽  
Regional Wall Motion ◽  
Tissue Doppler ◽  
Doppler Imaging ◽  
Esophageal Wall ◽  
Healthy Controls ◽  
Mean Velocity ◽  
High Resolution Manometry

Ultrasound tissue Doppler imaging (US-TDI) has been used to diagnose regional wall motion (WM) abnormalities in coronary artery disease but has not been applied to oropharyngeal diseases. This study aimed first to validate an US-TDI method to assess cervical esophageal (CE) WM and secondly to use the method to evaluate CE WM in patients with oropharyngeal dysphagia (OD). First, we enrolled 22 healthy men (mean age: 59.7 yr) who all underwent both US-TDI and videofluoroscopy (VF) and then esophageal high-resolution manometry (HRM) in the same week. We evaluated the reproducibility of the US-TDI and the relationship between US-TDI and other modalities (VF and HRM). Second, we enrolled 56 mild OD patients (mean age: 58.0 yr) and age- and sex-matched healthy controls. Difference in CE WM between these groups was evaluated by US-TDI. All healthy subjects underwent US-TDI, VF, and HRM successfully, with a sufficiently high reproducibility coefficient for this method, and significant correlation between US-TDI and VF/HRM parameters. US-TDI showed mean time to open CE wall and mean velocity of CE wall opening significantly differed between patients and healthy controls ( P < 0.01). In conclusion, we have developed a US-TDI method for easily assessing CE WM in daily practice and also found significant differences in CE WM between mild OD patients and healthy controls. NEW & NOTEWORTHY A new ultrasonographic screening method using tissue Doppler imaging for oropharyngeal dysphagia was found to be a reliable, reproducible, and well-tolerated method. There is a significant correlation between this new method and conventional methods. This method revealed that patients having mild symptoms of oropharyngeal dysphagia had already significantly delayed cervical esophageal wall opening.

scholarly journals Clinical Relevance of Serum Galactose Deficient IgA1 in Patients with IgA Nephropathy

2020 ◽  
Vol 9 (11) ◽  
pp. 3549
Author(s):  
Jin Sug Kim ◽  
Hyeon Seok Hwang ◽  
Sang Ho Lee ◽  
Yang Gyun Kim ◽  
Ju-Young Moon ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Clinical Relevance ◽  
Interstitial Fibrosis ◽  
Healthy Controls ◽  
Ckd Progression ◽  
Serum Samples ◽  
Tubular Atrophy ◽  
Appropriate Treatment ◽  
Cox Proportional Hazard Models ◽  
New Biomarkers

New biomarkers of IgA nephropathy (IgAN) are needed for non-invasive diagnosis and appropriate treatment. There is emerging evidence that galactose deficient IgA1 (Gd-IgA1) is a pivotal molecule in the pathogenesis of IgAN. However, few studies have investigated the role of Gd-IgA1 as a biomarker in IgAN. In this study, we investigated the clinical relevance of serum Gd-IgA1 levels in patients with IgAN. Two hundred and thirty biopsy-proven IgAN patients, 74 disease controls (patients with non-IgAN nephropathy), and 15 healthy controls were enrolled in this study. Levels of serum Gd-IgA1 were measured using an ELISA kit in serum samples obtained the day of renal biopsy. We compared levels of serum Gd-IgA1 according to the type of glomerular disease and analyzed the association between Gd-IgA1 levels and clinical and pathological parameters in patients with IgAN. We then divided IgAN patients into two groups according to Gd-IgA1 level and investigated the predictive value of Gd-IgA1 for progression of chronic kidney disease (CKD). Serum Gd-IgA1 levels were significantly higher in IgAN patients than disease controls and healthy controls. In patients with IgAN, serum Gd-IA1 levels were significantly correlated with estimated glomerular filtration rate, serum IgA level, and tubular atrophy/interstitial fibrosis. CKD progression was more frequent in IgAN patients with higher serum Gd-IgA1 levels than in those with lower serum Gd-IgA1 levels. Cox proportional hazard models showed that high GdIgA1 level was an independent risk factor for CKD progression after adjusting for several confounders. Our results suggest that serum Gd-IgA1 level is a useful diagnostic and prognostic marker in IgAN patients. Further studies with a larger sample size and longer follow-up duration are needed.

scholarly journals George Joseph Popjàk. 5 May 1914 — 30 December 1998

2000 ◽  
Vol 46 ◽  
pp. 403-424
Author(s):  
Muhammad Akhtar
Keyword(s):  
Metabolic Pathways ◽  
Fatty Acid Biosynthesis ◽  
Medical Training ◽  
Cholesterol Biosynthesis ◽  
Mevalonic Acid ◽  
Cholesterol Homeostasis ◽  
Joint Work ◽  
Acid Biosynthesis ◽  
Physiological Conditions ◽  
The Uk

George Joseph Popják was a leading biochemist who introduced radioisotopic techniques to the study of metabolic pathways in the UK, and fully exploited their use in his own researches. His earlier work clarified the origin of triglycerides and cholesterol in the foetus as well as in milk, and paved the way for far-reaching discoveries in these fields. His group was the first to demonstrate that fatty acid biosynthesis occurs not in the mitochondria by the mere reversal of the β-oxidation pathway, but by a new cytosolic enzyme system. With J.W. Cornforth he dominated the field of cholesterol biosynthesis for nearly two decades. Their joint work reached new heights when they made intellectually cunning contributions to the mechanism and stereochemistry of several enzymic reactions involved between mevalonic acid and squalene. His later work was concerned with the understanding of the factors that, under physiological conditions, maintain cholesterol homeostasis and the development of novel strategies that can be used in the treatment of hypercholesterolaemia. Popják's early medical training and his great mastery of chemical enzymology provided a powerful combination for tackling biomedically important problems at a molecular level.

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