Nuclear Magnetic Resonance (NMR) spectroscopy is a quantitative analytical tool commonly utilized for metabolomics analysis. Quantitative NMR (qNMR) is a field of NMR spectroscopy dedicated to the measurement of analytes through signal intensity and its linear relationship with analyte concentration. Metabolomics-based NMR exploits this quantitative relationship to identify and measure biomarkers within complex biological samples such as serum, plasma, and urine. In this review of quantitative NMR-based metabolomics, the advancements and limitations of current techniques for metabolite quantification will be evaluated as well as the applications of qNMR in biomedical metabolomics. While qNMR is limited by sensitivity and dynamic range, the simple method development, minimal sample derivatization, and the simultaneous qualitative and quantitative information provide a unique landscape for biomedical metabolomics, which is not available to other techniques. Furthermore, the non-destructive nature of NMR-based metabolomics allows for multidimensional analysis of biomarkers that facilitates unambiguous assignment and quantification of metabolites in complex biofluids.

Objective: An intimate association exists between oxidative stress and inflammation. Because adipose tissue (AT) inflammation is intricately linked to metabolic disorders, it was hypothesized that reducing oxidative stress would be effective in ameliorating AT inflammation in obesity. Methods: Wild-type mice were fed a high-fat diet (HF) for 8 weeks followed by a 2-week treatment with nanoformulated copper/zinc superoxide dismutase (NanoSOD). The mice were divided into: 1) chow diet, 2) HF, and 3) HF 1 NanoSOD. Results: The HF 1 NanoSOD-treated mice showed a significant decrease in plasma and liver triglycerides when compared with HF-fed mice. Interestingly, NanoSOD reduced the expression of macrophage and inflammatory markers in visceral AT (VAT) and stromal cells derived from VAT. Moreover, the activation of proinflammatory signaling pathways, in particular, the extracellular signal-regulated kinases, was blunted in VAT on NanoSOD treatment. However, markers of oxidative stress were not altered significantly in the HF 1 NanoSOD group in the experimental conditions. Pretreatment of either macrophages or adipocytes significantly reduced the inflammatory response invoked in an in vitro coculture system, further supporting the role of NanoSOD in inhibiting obesity-linked inflammation. Conclusions: This data suggest that NanoSOD is effective not only in reducing AT macrophage accumulation and AT inflammation but also in promoting triglyceride metabolism in obesity.

Exposure to acute, damaging radiation may occur through a variety of events from cancer therapy and industrial accidents to terrorist attacks and military actions. Our understanding of how to protect individuals and mitigate the effects of radiation injury or Acute Radiation Syndrome (ARS) is still limited. There are only a few Food and Drug Administration-approved therapies for ARS; whereas, amifostine is limited to treating low dose (0.7–6 Gy) radiation poisoning arising from cancer radiotherapy. An early intervention is critical to treat ARS, which necessitates identifying diagnostic biomarkers to quickly characterize radiation exposure. Towards this end, a multiplatform metabolomics study was performed to comprehensively characterize the temporal changes in metabolite levels from mice and non-human primate serum samples following γ-irradiation. The metabolomic signature of amifostine was also evaluated in mice as a model for radioprotection. The NMR and mass spectrometry metabolomics analysis identified 23 dysregulated pathways resulting from the radiation exposure. These metabolomic alterations exhibited distinct trajectories within glucose metabolism, phospholipid biosynthesis, and nucleotide metabolism. A return to baseline levels with amifostine treatment occurred for these pathways within a week of radiation exposure. Together, our data suggests a unique physiological change that is independent of radiation dose or species. Furthermore, a metabolic signature of radioprotection was observed through the use of amifostine prophylaxis of ARS.

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Zika virus (ZIKV) is a major public health concern of international proportions. While the incidence of ZIKV infections has declined substantially in recent years, the potential for the reemergence or reintroduction remains high.

Due to the severe toxicity posed by chemotherapeutic drugs, adjuvant nutritional intervention has gained increased attention in the treatment of pancreatic cancer (PC). Amino acid (AA) metabolism is aberrantly regulated in PC and circulating histidine (His) levels are low in PC patients. We hypothesized that His uptake and/or metabolism is dysregulated in PC and that combining His with gemcitabine (Gem), a drug used in the treatment of PC, will enhance the anti-cancer effects of Gem. We performed in vitro and in vivo studies to determine the anticancer effect of the combination of His and Gem against lethal PC. We demonstrate that circulating His levels are low in both human subjects and genetically engineered mice exhibiting pancreatic tumors. Interestingly, the expression of histidine ammonia lyase, an enzyme involved in His catabolism, is higher in PC compared to normal subjects. His + Gem exerts a more potent cytotoxic effect in PC cells compared to individual treatments. His treatment results in a profound increase in His accumulation, accompanied by a depletion of a number of AAs, promoting cancer cell survival and/or glutathione (GSH) synthesis. His but not Gem increases hydrogen peroxide and depletes cellular GSH. Supplementation with GSH protects cells against His + Gem-induced cytotoxicity. Further, our in vivo studies demonstrate that His + Gem potently reduced tumor mass and improved mouse survival. Taken together, our data suggest that PC cells exhibit an aberrant His uptake/accumulation which, in turn, leads to oxidative stress and depletion of AA pool, thereby enhancing the anticancer effect of Gem.