Publications by authors named "Richard Beger"
Introduction: In 2015, the FDA released a Drug Safety Communication regarding a possible link between opioid exposure during early pregnancy and an increased risk of fetal neural tube defects (NTDs). At the time, the indications for opioid use during pregnancy were not changed due to incomplete maternal toxicity data and limitations in human and animal studies. To assess these knowledge gaps, largescale animal studies are ongoing; however, state-of-the-art technologies have emerged as promising tools to assess otherwise non-standard endpoints.
View Article and Find Full Text PDFIntroduction: Coronavirus disease 2019 (COVID-19) has widely varying clinical severity. Currently, no single marker or panel of markers is considered standard of care for prediction of COVID-19 disease progression. The goal of this study is to gain mechanistic insights at the molecular level and to discover predictive biomarkers of severity of infection and outcomes among COVID-19 patients.
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- Different analytical methods in metabolomics and lipidomics include untargeted, targeted, and semi-targeted approaches, with Ultra High Performance Liquid Chromatography-Mass Spectrometry being a key tool due to its efficiency in detecting metabolites.
- The review aims to clarify the differences among these methods in terms of determining metabolite quantities and to discuss their respective advantages and limitations related to accuracy and precision.
- The choice of method is influenced by factors such as prior knowledge of metabolites, the need for peak responses or absolute concentrations, and the desired number of metabolites to analyze, with each method providing different reporting capabilities.
Article Synopsis
- Stable isotopic labeling and mass spectrometry are used in quantitative proteomics to aid in disease research, drug discovery, and biomarker identification.
- The trypsin-catalyzed O/O labeling technique is highlighted for its low sample consumption, simple process, and cost-effectiveness, making it advantageous for proteomic studies.
- The chapter outlines a protocol using this method to identify proteins related to liver damage from acetaminophen in rats, involving protein extraction, digestion, labeling, and advanced analysis of peptide fractions.
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- Black cohosh extract is marketed as a dietary supplement to help relieve menopause symptoms and may protect against bone loss in postmenopausal women; however, its interactions with bisphosphonates like risedronate are unclear.
- A study on female rats examined the effects of black cohosh, risedronate, and their combination on bone mineral density over 24 weeks after ovariectomy.
- Results showed that while high doses of risedronate significantly increased bone mineral density, black cohosh extract had no significant effects alone or in combination with risedronate.
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- Untargeted metabolomics is a method that effectively analyzes small molecules in biological systems but faces challenges in data quality evaluation; using pooled quality control (QC) samples can help monitor and correct analytical variance during experiments.!* -
- A literature review of 109 published studies shows that the metabolomics community has widely adopted pooled QC samples across various biological types, but many studies fail to report their effectiveness in improving data quality.!* -
- The review reveals missing or unclear details in the QC framework, which hampers the ability to fully understand the quality control steps taken in these studies, indicating both strengths and areas for improvement in the field's reporting practices.!*
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- Microbicidal violet-blue light (405 nm) effectively reduces blood-borne pathogens in human plasma and platelets, showing promise for pathogen inactivation in stored blood products.
- The safety of using this light for treating platelet concentrates was evaluated through metabolomics analyses, focusing on changes in key metabolites in both platelets and plasma.
- Results indicate that fundamental platelet functions remain intact despite the generation of reactive oxygen species (ROS) during treatment, confirming that 405 nm light is a potent microbicide without needing additional photosensitizers.
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- - The text emphasizes the importance of high-quality data from metabolic phenotyping studies, highlighting that proper quality control (QC) protocols and accurate reporting are crucial for the credibility and future analysis of results.
- - The guidance aims to help researchers effectively communicate their quality assessment and QC procedures in untargeted metabolomics, particularly with regard to QC samples, ensuring that these details are clear and replicable.
- - Key reporting practices for QC protocols include the types, preparation, and usage of QC materials, as well as outlining acceptance criteria and sample handling methods, with recommendations for varying levels of reporting detail.
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- * In this study, researchers used metabolomics to analyze changes in metabolism and gut bacteria after treating mice with cefoperazone (Cef), finding that MR1 KO mice experienced less disruption to their microbiota.
- * The results showed higher carbohydrate levels in the WT mice's metabolism compared to the KO mice, and specific metabolic biomarkers, like GABA and riboflavin, were identified to give further insight into metabolic changes alongside metagenomics findings.
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used in the Comprehensive in vitro Proarrhythmia Assay (CiPA). The notable difference of the electrophysiological (EP) responses of hiPSC-CMs in serum and serum-free media (SFM) is puzzling and may impact regulatory decision-making on the cardiac safety of candidate drugs in inducing QT prolongation and torsade de pointes (TdP). In this study, we compared the EP responses of hiPSC-CMs to 10 CiPA compounds and moxifloxacin in serum and SFM; explained the potential reason behind the different EP responses-abiotic compound loss to plastic tubes/plates of hydrophobic compounds prepared in SFM; and investigated the impact of compound preparation methods on drug bioavailability in exposure media, which affects the TdP risk prediction of drugs tested in serum-containing and SFM.
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- The metabolomics quality assurance and quality control consortium (mQACC) focuses on developing and promoting appropriate reference materials (RMs) for quality assurance (QA) and quality control (QC) in untargeted metabolomics research.
- The review discusses the current status of RMs and methodologies in untargeted metabolomics and lipidomics, aiming for standardized results and better comparisons across studies and labs.
- Utilizing RMs can enhance data quality and consistency in metabolomics research, with ongoing efforts in developing new RMs and promoting educational initiatives to strengthen QA practices in the field.
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- - The study investigates how specific serum proteins can predict kidney recovery in patients with acute kidney injury requiring dialysis (AKI-D), showing that changes in protein levels are linked to recovery outcomes.
- - Serum samples from 72 patients revealed 119 proteins with altered levels; 53 were higher and 66 were lower in patients who recovered enough to stop dialysis compared to those who remained on it.
- - Key proteins like CXCL11 and Wnt-7a were identified as significantly associated with better recovery, even after considering other factors such as age and existing health conditions.
Serum metabolite profiles predict outcomes in critically ill patients receiving renal replacement therapy.
J Chromatogr B Analyt Technol Biomed Life Sci
December 2021
Article Synopsis
- Acute kidney injury (AKI) needing renal replacement therapy is linked to higher risks of dialysis dependence and mortality in critically ill patients.
- Serum samples analyzed from patients in a study showed that specific metabolites can predict mortality risk at both day 1 and day 8 of treatment, with accuracy improving over time.
- Findings suggest that lower levels of certain anti-inflammatory metabolites and higher levels of amino acids relate to poorer outcomes, highlighting potential biomarkers for kidney recovery and increased mortality.
Article Synopsis
- - The rapid development of new cellular and molecular technologies for assessing the safety of food, drugs, and personal care products is evolving, creating a need for their incorporation into regulatory processes.
- - There are concerns that these emerging technologies may not have been adequately tested for regulatory application, which could hinder their effective use in safety assessments.
- - To fully utilize these advancements, the regulatory community must devise strategies for evaluating these technologies and collaborate with developers, ensuring that regulatory decisions are informed and efficient.
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- Metabolomics is a versatile technology used to study metabolism and toxicity across various organisms and biological materials, such as blood and urine.
- It provides tools and resources for researchers, including data repositories and analysis tools, which enhance its application in precision medicine.
- The ACT Symposium review discusses the use of metabolomics in toxicity studies, including its role in understanding liver injury from acetaminophen and how it can inform pharmacokinetics, pharmacodynamics, and space research.
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- Omics methodologies are increasingly used in toxicology to explore toxicity mechanisms and support regulatory questions, but their acceptance is limited.
- Major barriers include non-transparent data processing and lack of standardized reporting, which hinders regulatory review.
- In 2017, the OECD began developing a formal reporting framework for omics data in toxicology to enhance transparency and usability in regulatory decision-making.
Introduction: The metabolomics quality assurance and quality control consortium (mQACC) evolved from the recognized need for a community-wide consensus on improving and systematizing quality assurance (QA) and quality control (QC) practices for untargeted metabolomics.
Objectives: In this work, we sought to identify and share the common and divergent QA and QC practices amongst mQACC members and collaborators who use liquid chromatography-mass spectrometry (LC-MS) in untargeted metabolomics.
Methods: All authors voluntarily participated in this collaborative research project by providing the details of and insights into the QA and QC practices used in their laboratories.
Article Synopsis
- Prostatitis primarily affects younger to middle-aged men, while older men are more prone to prostate cancer; this study investigates amino acids and lipids as potential biomarkers for chronic prostatitis, since prior research mostly focused on prostate cancer.
- The research involved profiling plasma samples from 148 rats that were exposed to estrogen and testosterone, analyzing data with advanced mass spectrometry techniques to identify lipid changes associated with chronic inflammation.
- Significant increases in specific lipids were found in the plasma of rats with chronic prostate inflammation, suggesting these lipids could serve as biomarkers for chronic prostatitis, although further studies are needed to validate these findings in humans.
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- Pharmacometabolomics (PMx) examines how an individual's metabolic profile, influenced by factors like genetics and health status, affects their response to drug treatments.* -
- The individual metabolic profile, known as "metabotype," helps identify patterns in drug efficacy and can classify patients as responders or non-responders, aiding in precision medicine.* -
- PMx research can facilitate the discovery of biomarkers during clinical trials, and these biomarkers can be submitted for FDA approval as outlined by the 21st Century Cures Act.*
Article Synopsis
- - MAIT cells, which recognize specific bacterial antigens via MR1, were found to play a role in maintaining a unique microbiota in MR1 knock-out (KO) mice, making them resistant to antibiotic disruption and colonization.
- - A study utilized LC/MS-based untargeted metabolomics to compare the bile acid (BA) profiles between MR1 KO and wild-type (WT) mice, assessing changes in intestinal and fecal samples before and after antibiotic treatment with cefoperazone (Cef).
- - Results indicated that KO mice had higher total BA intensity compared to WT mice, with KO mice showing smaller decreases in BA intensity after Cef treatment, while specific BA changes (increased taurocholic acid and decreased
Article Synopsis
- * Researchers discovered significant variations in transcript profiles of drug-metabolizing enzymes between male and female rats across different ages, highlighting the importance of sex in drug metabolism.
- * A study on selected drugs indicated that female rat hepatocytes exhibited much longer half-lives (37%-400% longer) for certain medications, suggesting that gene expression differences can predict sex-related variations in drug metabolism and toxicity.
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- Addiction involves the brain's reward system being altered by chemicals that create a compulsive need for substances, despite negative repercussions.
- The mu-opioid receptor (MOR) is particularly influential in addictions to powerful drugs like opioids and stimulants, while kappa (KOR) and delta (DOR) receptors can lead to negative reinforcement effects.
- New 3D-spectrometric models have been developed to predict how various substances interact with these receptors, which could help regulatory agencies assess health risks and aid pharmaceutical companies in developing addiction treatments.
Article Synopsis
- There is a shortage of standard reference materials for metabolomics in human fluids, due to issues with supply, characterization, and varying analysis methods.
- The proposed solution involves using untargeted metabolomic data profiles (like NMR and GC-MS) as reference materials, allowing researchers to compare their own data with standardized profiles.
- An interlaboratory study (ILS) showed that different labs identified consistent patterns in urine samples, indicating that this approach could improve testing and harmonization across different measurement platforms.
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- Clostridium difficile infection (CDI) often follows antibiotic use, which disrupts the gut's microbial balance.
- This study explored the role of Major histocompatibility complex-related protein 1 (MR1) in influencing gut immunity against CDI using wild-type and MR1-/- mice.
- Surprisingly, MR1-/- mice showed resistance to the infection, and their unique gut microbiome could be transferred to wild-type mice through fecal microbiota transplantation, indicating that MR1 affects gut flora and CDI vulnerability.
Article Synopsis
- The study investigates how various pre-analytical conditions, such as temperature and storage time of blood and plasma, affect the human plasma proteome in biomarker research.
- Researchers used whole blood from 16 healthy individuals and tested six different processing conditions to determine how they impacted the protein levels in the plasma.
- Findings revealed that certain conditions, like low centrifugal force and keeping blood at room temperature for 6 hours, caused significant changes in the plasma proteins, highlighting the need to control these variables for accurate biomarker measurements.