Interlaboratory comparison of standardised metabolomics and lipidomics analyses in human and rodent blood using the MxP Quant 500 kit.

Metabolomics and lipidomics are pivotal in understanding phenotypic variations beyond genomics. However, quantification and comparability of mass spectrometry (MS)-derived data are challenging. Standardised assays can enhance data comparability, enabling applications in multi-center epidemiological and clinical studies.

Integrative metabolomics-genomics analysis identifies key networks in a stem cell-based model of schizophrenia.

Schizophrenia (SCZ) is a neuropsychiatric disorder, caused by a combination of genetic and environmental factors. The etiology behind the disorder remains elusive although it is hypothesized to be associated with the aberrant response to neurotransmitters, such as dopamine and glutamate. Therefore, investigating the link between dysregulated metabolites and distorted neurodevelopment holds promise to offer valuable insights into the underlying mechanism of this complex disorder.

Transcriptional networks underlying a primary ovarian insufficiency disorder in alligators naturally exposed to EDCs.

Interactions between the endocrine system and environmental contaminants are responsible for impairing reproductive development and function. Despite the taxonomic diversity of affected species and attendant complexity inherent to natural systems, the underlying signaling pathways and cellular consequences are mostly studied in lab models. To resolve the genetic and endocrine pathways that mediate affected ovarian function in organisms exposed to endocrine disrupting contaminants in their natural environments, we assessed broad-scale transcriptional and steroidogenic responses to exogenous gonadotropin stimulation in juvenile alligators (Alligator missippiensis) originating from a lake with well-documented pollution (Lake Apopka, FL) and a nearby reference site (Lake Woodruff, FL).

Intrinsic and extrinsic factors interact during development to influence telomere length in a long-lived reptile.

The mechanisms connecting environmental conditions to plasticity in biological aging trajectories are fundamental to understanding individual variation in functional traits and life history. Recent findings suggest that telomere biology is especially dynamic during early life stages and has long-term consequences for subsequent reproduction and survival. However, our current understanding is mostly derived from studies investigating ecological and anthropogenic factors separately, leaving the effects of complex environmental interactions unresolved.

Bile acids targeted metabolomics and medication classification data in the ADNI1 and ADNIGO/2 cohorts.

Alzheimer's disease (AD) is the most common cause of dementia. The mechanism of disease development and progression is not well understood, but increasing evidence suggests multifactorial etiology, with a number of genetic, environmental, and aging-related factors. There is a growing body of evidence that metabolic defects may contribute to this complex disease.

A plasma metabolite panel as biomarkers for early primary breast cancer detection.

In recent years, metabolites have attracted substantial attention as promising novel biomarkers of various diseases. However, breast cancer plasma metabolite studies are still in their infancy. Here, we investigated the potential of metabolites to serve as minimally invasive, early detection markers of primary breast cancer.

Altered bile acid profile associates with cognitive impairment in Alzheimer's disease-An emerging role for gut microbiome.

Introduction: Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and a specific role for the gut-brain axis in neurodegeneration. Bile acids (BAs), products of cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer's disease (AD).

Assessment of Plasma Amino Acid Dynamics in Response to ACTH Stimulation by Liquid Chromatography Tandem-Mass Spectrometry.

Background: The adrenocorticotropic hormone (ACTH) stimulation test is a widely used diagnostic tool to assess the adrenal gland function. Beyond that the ACTH test can be used in stress research to induce a biochemical stress response under standardized conditions. To study the impact of the stress response on protein metabolism, time-course plasma amino acid profiling in healthy individuals was performed with high performance liquid chromatography tandem-mass spectrometry (HPLC-MS/MS).

A validated liquid chromatography-high resolution-tandem mass spectrometry method for the simultaneous quantitation of tryptophan, kynurenine, kynurenic acid, and quinolinic acid in human plasma.

Tryptophan (TRP) catabolism via the kynurenine pathway is considered to represent a major link between inflammation and various diseases, including neurodegenerative disorders, depression, schizophrenia, multiple sclerosis, cardiovascular disease, and cancer. The kynurenine pathway and levels of TRP and its metabolites kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN) are well regulated under physiological conditions but may be altered as part of the activated immune response. A simple, sensitive, and specific liquid chromatography-time of flight mass spectrometry method was developed for determining levels of the four compounds in human plasma samples.

Bile acid quantification of 20 plasma metabolites identifies lithocholic acid as a putative biomarker in Alzheimer's disease.

Introduction: There is still a clear need for a widely available, inexpensive and reliable method to diagnose Alzheimer's disease (AD) and monitor disease progression. Liquid chromatography-mass spectrometry (LC-MS) is a powerful analytic technique with a very high sensitivity and specificity.

Objectives: The aim of the present study is to measure concentrations of 20 bile acids using the novel Kit from Biocrates Life Sciences based on LC-MS technique.

Targeted metabolomics and medication classification data from participants in the ADNI1 cohort.

Alzheimer's disease (AD) is the most common neurodegenerative disease presenting major health and economic challenges that continue to grow. Mechanisms of disease are poorly understood but significant data point to metabolic defects that might contribute to disease pathogenesis. The Alzheimer Disease Metabolomics Consortium (ADMC) in partnership with Alzheimer Disease Neuroimaging Initiative (ADNI) is creating a comprehensive biochemical database for AD.

Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma.

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow.

Metabolomic profiling of ascending thoracic aortic aneurysms and dissections - Implications for pathophysiology and biomarker discovery.

Objective: Our basic understanding of ascending thoracic aortic aneurysm (ATAA) pathogenesis is still very limited, hampering early diagnosis, risk prediction, and development of treatment options. "Omics"-technologies, ideal to reveal tissue alterations from the normal physiological state due to disease have hardly been applied in the field. Using a metabolomic approach, with this study the authors seek to define tissue differences between controls and various forms of ATAAs.

Metabolic network failures in Alzheimer's disease: A biochemical road map.

Introduction: The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, and nonprofit organizations to develop new research directions to transform our understanding of Alzheimer's disease (AD) and propel the development of critically needed therapies. In response to their recommendations, big data at multiple levels are being generated and integrated to study network failures in disease. We used metabolomics as a global biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance.

Achievements and Future Directions of the APFCB Mass Spectrometry Harmonisation Project on Serum Testosterone.

As an outcome of the 2010 Asian Pacific Conference for Chromatography and Mass Spectrometry in Hong Kong, a collaborative working group was formed to promote the harmonisation of mass spectrometry methods. The Mass Spectrometry Harmonisation Working Group resides under the combined auspices of the Asia-Pacific Federation for Clinical Biochemistry and Laboratory Medicine (APFCB) and the Australasian Association of Clinical Biochemists (AACB). A decision was made to initially focus attention on serum steroids due to the common interest of members in this area; with the first steroid to assess being testosterone.

Progress in Metabolomics Standardisation and its Significance in Future Clinical Laboratory Medicine.

Today, the technology of 'targeted' based metabolomics is pivotal in the clinical analysis workflow as it provides information of metabolic phenotyping (metabotypes) by enhancing our understanding of metabolism of complex diseases, biomarker discovery for disease development, progression, treatment, and drug function and assessment. This review is focused on surveying and providing a gap analysis on metabolic phenotyping with a focus on targeted based metabolomics from an instrumental, technical discussing the instrumentation, pre- to post- analytical aspects as well as an overall future necessity for biomarker discovery and future (pre-) clinical routine application.

Inter-Laboratory Robustness of Next-Generation Bile Acid Study in Mice and Humans: International Ring Trial Involving 12 Laboratories.

Background: The increasing relevance of individual bile acids quantification in biological samples requires analytical standardization to guarantee robustness and reliability of laboratory results. We have organized the first international ring trial, carried out in 12 laboratories, to evaluate the newly developed LC-MS/MS-based test kit for bile acid analysis.

Methods: Each laboratory received a Biocrates® Bile Acids Kit including system suitability test (SST) protocol.

The ratio of phosphatidylcholines to lysophosphatidylcholines in plasma differentiates healthy controls from patients with Alzheimer's disease and mild cognitive impairment.

Background: Metabolomic processes have been identified as being strongly linked to the development of Alzheimer's disease (AD). Thus, lipid metabolites appear to be highly useful as diagnostic substrates for the diagnosis of AD and mild cognitive impairment (MCI) in plasma.

Methods: We analyzed plasma samples from controls (n = 35), MCI (n = 33), and AD patients (n = 43) using the AbsoluteIDQ p180 Kit (Biocrates Life Sciences), which included quantitative analysis of 40 acylcarnitines, 21 amino acids, 19 biogenic amines, 15 sphingolipids, 90 glycerophospholipids, and sum of hexoses.

Sphingomyelin SM(d18:1/18:0) is significantly enhanced in cerebrospinal fluid samples dichotomized by pathological amyloid-β42, tau, and phospho-tau-181 levels.

Alzheimer's disease (AD) is a severe and chronic neurodegenerative disorder of the brain. The laboratory diagnosis is limited to the analysis of three biomarkers in cerebrospinal fluid (CSF): amyloid-β42 (Aβ42), total tau, and phospho-tau-181 (P-tau-181). However, there is a need to find more biomarkers in CSF that can improve the sensitivity and specificity.

Standardized LC-MS/MS based steroid hormone profile-analysis.

In order to overcome many limitations of immunoassays, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has the potential to find its place in the clinical laboratory medicine for quantification of steroid hormones. A prerequisite for the application of a new analytical procedure in clinical diagnostics is standardization to minimize analytical intra- and interlaboratory variability and inaccuracy. We evaluate a newly standardized HPLC-MS/MS assay in kit-format, developed for routine determination of 16 steroid hormones in human serum samples.

Targeted metabolomics for biomarker discovery.

Metabolomics is a truly interdisciplinary field of science, which combines analytical chemistry, platform technology, mass spectrometry, and NMR spectroscopy with sophisticated data analysis. Applied to biomarker discovery, it includes aspects of pathobiochemistry, systems biology/medicine, and molecular diagnostics and requires bioinformatics and multivariate statistics. While successfully established in the screening of inborn errors in neonates, metabolomics is now widely used in the characterization and diagnostic research of an ever increasing number of diseases.

Complexity and pitfalls of mass spectrometry-based targeted metabolomics in brain research.

Current quantitative metabolomic research in brain tissue is challenged by several analytical issues. To compare data of metabolite pattern, ratios of individual metabolite concentrations and composed classifiers characterizing a distinct state, standardized workup conditions, and extraction medium are crucial. Differences in physicochemical properties of individual compounds and compound classes such as polarity determine extraction yields and, thus, ratios of compounds with varying properties.

Metabolomic analyses of plasma reveals new insights into asphyxia and resuscitation in pigs.

Background: Currently, a limited range of biochemical tests for hypoxia are in clinical use. Early diagnostic and functional biomarkers that mirror cellular metabolism and recovery during resuscitation are lacking. We hypothesized that the quantification of metabolites after hypoxia and resuscitation would enable the detection of markers of hypoxia as well as markers enabling the monitoring and evaluation of resuscitation strategies.