Characterization of Oxidized Glycerophosphoethanolamines via Radical-Directed Dissociation Tandem Mass Spectrometry and the Paternò-Büchi Derivatization.

Oxidized glycerophosphoethanolamines (oxPEs) represent a subclass of bioactive lipids that have intricate roles in various physiological and pathological events. Conventional mass spectrometric methods cannot provide unambiguous information to locate the OH group and the sites of unsaturation. Herein, we report a combined strategy for in-depth structural characterization of oxPEs, including radical-directed dissociation tandem mass spectrometry (RDD-MS/MS) for localizing the OH group and the Paternò-Büchi derivatization coupled with tandem mass spectrometry for pinpointing carbon-carbon double-bond locations. The RDD-MS/MS method has been integrated on a reversed-phase liquid chromatography-mass spectrometry workflow. It enables the profiling of 24 distinct oxPE molecules with unequivocal assignment of the OH sites at nM sensitivity in bovine liver lipid extract treated by soybean 15-lipoxygenase. These findings showcase that the developed method has a good potential in analyzing biological systems where oxPEs may play important roles.

Visible-Light Paternò-Büchi Reaction for Lipidomic Profiling at Detailed Structure Levels.

The Paternò-Büchi (PB) derivatization of carbon-carbon double bond (C═C) has been increasingly employed with tandem mass spectrometry to analyze unsaturated lipids. It enables the discovery of altered or uncanonical lipid desaturation metabolism, which would be otherwise undetected by conventional methods. Although highly useful, the reported PB reactions only provide moderate yield (∼30%). Herein, we aim to determine the key factors that affect the PB reactions and develop a system with improved capabilities for lipidomic analysis. An Ir(III) photocatalyst is chosen as the triplet energy donor for the PB reagent under 405 nm light irradiation, while phenylglyoxalate and its charge-tagging version, pyridylglyoxalate, are developed as the most efficient PB reagents. The above visible-light PB reaction system provides higher PB conversions than all previously reported PB reactions. Around 90% conversion can be achieved at high concentrations (>0.5 mM) for different classes of lipids but drops as the lipid concentration decreases. The visible-light PB reaction has then been integrated with shotgun and liquid chromatography-based workflows. The limits of detection for locating C═C in standard lipids of glycerophospholipids (GPLs) and triacylglycerides (TGs) are in the sub-nM to nM range. More than 600 distinct GPLs and TGs have been profiled at the C═C location level or the sn-position level from the total lipid extract of bovine liver, demonstrating that the developed method is capable of large-scale lipidomic analysis.

Prognostic value of prealbumin, N-terminal pro-B-type natriuretic peptide, heart type fatty acid binding protein, and cardiac troponin I in elderly patients for heart failure and poor outcomes.

OBJECTIVES: This study aimed to investigate the prognostic value of serum prealbumin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), heart type fatty acid binding protein (hFABP), and cardiac troponin I (cTnI) for heart failure and cardiac death in elderly patients. METHODS: We studied 426 consecutive patients with New York Heart Association classes I to IV who were recruited between February 2014 and 2018. Cardiac mortality was the primary end point. Receiver operator characteristic curves were created to analyze predictive values. RESULTS: When prealbumin, NT-proBNP, hFABP, and cTnI were combined, the areas under the receiver operator characteristic curve reached 0.930 and 0.903 for heart failure and cardiac death, respectively. Prealbumin, NT-proBNP, hFABP, and cTnI levels changed differently during therapy in patients in different prognosis groups. These parameters improved in patients who did not develop major adverse cardiovascular events (MACEs), but were unchanged or deteriorated in patients with MACEs. Multivariate Cox regression analysis showed that these parameters were significant independent risk factors for MACEs and cardiac death. CONCLUSIONS: Our study shows that serum prealbumin, NT-proBNP, hFABP, and cTnI levels are significant prognostic factors for elderly patients with poor cardiac function. These parameters are more accurate for prognosis when used together.