An Optimized Method for LC-MS-Based Quantification of Endogenous Organic Acids: Metabolic Perturbations in Pancreatic Cancer.

Accurate and reliable quantification of organic acids with carboxylic acid functional groups in complex biological samples remains a major analytical challenge in clinical chemistry. Issues such as spontaneous decarboxylation during ionization, poor chromatographic resolution, and retention on a reverse-phase column hinder sensitivity, specificity, and reproducibility in multiple-reaction monitoring (MRM)-based LC-MS assays. We report a targeted metabolomics method using phenylenediamine derivatization for quantifying carboxylic acid-containing metabolites (CCMs).

Machine-learning-based integrative -'omics analyses reveal immunologic and metabolic dysregulation in environmental enteric dysfunction.

Environmental enteric dysfunction (EED) is a subclinical enteropathy challenging to diagnose due to an overlap of tissue features with other inflammatory enteropathies. EED subjects ( = 52) from Pakistan, controls ( = 25), and a validation EED cohort ( = 30) from Zambia were used to develop a machine-learning-based image analysis classification model. We extracted histologic feature representations from the Pakistan EED model and correlated them to transcriptomics and clinical biomarkers.

Effect of variable left ventricular ejection fraction assessed by equilibrium radionuclide angiocardiography using different software packages on the diagnosis of cardiotoxicity in patients with cancer.

Background: The equilibrium radionuclide angiocardiography (ERNA) scan is an established imaging modality for assessing left ventricular ejection fraction (LVEF) in oncology patients. This study aimed to explore the interchangeability of two commercially available software packages (MIM and JS) for LVEF measurement for a cancer-therapy-related cardiac dysfunction (CTRCD) diagnosis.

Methods: This is a single-center retrospective study among 322 patients who underwent ERNA scans.

Herbal Approaches to Pediatric Functional Abdominal Pain.

Chronic abdominal pain is one of the most common problems seen by both pediatricians and pediatric gastroenterologists. Abdominal-pain-related functional gastrointestinal disorders (AP-FGIDs) are diagnosed in children with chronic and recurrent abdominal pain meeting clinical criteria set forth in the Rome IV criteria. AP-FGIDs affect approximately 20% of children worldwide and include functional dyspepsia (FD), irritable bowel syndrome (IBS), functional abdominal pain (FAP), and abdominal migraine.

Feruloyl esterase Fae1 is required specifically for host colonisation by the rice-blast fungus Magnaporthe oryzae.

Plant cell wall acts as a primary barrier for microbial pathogens during infection. A cell wall-degrading enzyme thus may be a crucial virulence factor, as it may aid the pathogen in successful host invasion. Nine genes coding for feruloyl esterases (Fae), likely involved in plant cell wall degradation, have been annotated in the genome of the cereal-blast fungus Magnaporthe oryzae.

Discovery of Metabolic Biomarkers Predicting Radiation Therapy Late Effects in Prostate Cancer Patients.

Patients presenting with prostate cancers undergo clinical staging evaluations to determine the extent of disease to guide therapeutic recommendations. Management options may include watchful waiting, surgery, or radiation therapy. Thus, initial risk stratification of prostate cancer patients is important for achieving optimal therapeutic results or cancer cure and preservation of quality of life.

Metabolomic Studies of Tissue Injury in Nonhuman Primates Exposed to Gamma-Radiation.

Exposure to ionizing radiation induces a complex cascade of systemic and tissue-specific responses that lead to functional impairment over time in the surviving population. However, due to the lack of predictive biomarkers of tissue injury, current methods for the management of survivors of radiation exposure episodes involve monitoring of individuals over time for the development of adverse clinical symptoms and death. Herein, we report on changes in metabolomic and lipidomic profiles in multiple tissues of nonhuman primates (NHPs) that were exposed to a single dose of 7.

Plasma-derived extracellular vesicles yield predictive markers of cranial irradiation exposure in mice.

Ionizing radiation exposure to the brain is common for patients with a variety of CNS related malignancies. This exposure is known to induce structural and functional alterations to the brain, impacting dendritic complexity, spine density and inflammation. Over time, these changes are associated with cognitive decline.

Pharmacokinetic and Metabolomic Studies with BIO 300, a Nanosuspension of Genistein, in a Nonhuman Primate Model.

Genistein is a naturally occurring phytoestrogen isoflavone and is the active drug ingredient in BIO 300, a radiation countermeasure under advanced development for acute radiation syndrome (H-ARS) and for the delayed effects of acute radiation exposure (DEARE). Here we have assessed the pharmacokinetics (PK) and safety of BIO 300 in the nonhuman primate (NHP). In addition, we analyzed serum samples from animals receiving a single dose of BIO 300 for global metabolomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS).

Liquid Chromatography-Mass Spectrometry-Based Metabolomics of Nonhuman Primates after 4 Gy Total Body Radiation Exposure: Global Effects and Targeted Panels.

Rapid assessment of radiation signatures in noninvasive biofluids may aid in assigning proper medical treatments for acute radiation syndrome (ARS) and delegating limited resources after a nuclear disaster. Metabolomic platforms allow for rapid screening of biofluid signatures and show promise in differentiating radiation quality and time postexposure. Here, we use global metabolomics to differentiate temporal effects (1-60 d) found in nonhuman primate (NHP) urine and serum small molecule signatures after a 4 Gy total body irradiation.

Plasma Derived Exosomal Biomarkers of Exposure to Ionizing Radiation in Nonhuman Primates.

Exposure to ionizing radiation induces a cascade of molecular events that ultimately impact endogenous metabolism. Qualitative and quantitative characterization of metabolomic profiles is a pragmatic approach to studying the risks of radiation exposure since it provides a phenotypic readout. Studies were conducted in irradiated nonhuman primates (NHP) to investigate metabolic changes in plasma and plasma-derived exosomes.

Exposure to Ionizing Radiation Causes Endoplasmic Reticulum Stress in the Mouse Hippocampus.

It is well known that ionizing radiation-induced toxicity to normal tissue has functional consequences in the brain. However, the underlying molecular alterations have yet to be elucidated. We have previously reported cognitive impairments with concomitant changes in dendritic complexity, spine density and inflammation in mice at 6-24 weeks postirradiation.

Metabolomics based predictive classifier for early detection of pancreatic ductal adenocarcinoma.

The availability of robust classification algorithms for the identification of high risk individuals with resectable disease is critical to improving early detection strategies and ultimately increasing survival rates in PC. We leveraged high quality biospecimens with extensive clinical annotations from patients that received treatment at the Medstar-Georgetown University hospital. We used a high resolution mass spectrometry based global tissue profiling approach in conjunction with multivariate analysis for developing a classification algorithm that would predict early stage PC with high accuracy.

A Metabolomic and Lipidomic Serum Signature from Nonhuman Primates Administered with a Promising Radiation Countermeasure, Gamma-Tocotrienol.

The development of radiation countermeasures for acute radiation syndrome (ARS) has been underway for the past six decades, leading to the identification of multiple classes of radiation countermeasures. However, to date, only two growth factors (Neupogen and Neulasta) have been approved by the United States Food and Drug Administration (US FDA) for the mitigation of hematopoietic acute radiation syndrome (H-ARS). No radioprotector for ARS has been approved by the FDA yet.

Metabolomic biomarkers of pancreatic cancer: a meta-analysis study.

Pancreatic cancer (PC) is an aggressive disease with high mortality rates, however, there is no blood test for early detection and diagnosis of this disease. Several research groups have reported on metabolomics based clinical investigations to identify biomarkers of PC, however there is a lack of a centralized metabolite biomarker repository that can be used for meta-analysis and biomarker validation. Furthermore, since the incidence of PC is associated with metabolic syndrome and Type 2 diabetes mellitus (T2DM), there is a need to uncouple these common metabolic dysregulations that may otherwise diminish the clinical utility of metabolomic biosignatures.

Validity of the construct of post-traumatic stress disorder in a low-income country: interview study of women in Gujarat, India.

The validity of the clinical construct of post-traumatic stress disorder (PTSD) has been questioned in non-Western cultures. This report describes in-depth interviews exploring the experiences of women who were traumatised by the communal riots in Ahmedabad, India, in March 2002. Three specific narratives are presented which describe experiences that closely resemble re-experiencing, avoidance and hyperarousal.