Identification of the molecular mechanism and diagnostic biomarkers in the thoracic ossification of the ligamentum flavum using metabolomics and transcriptomics
BMC MOLECULAR AND CELL BIOLOGY
Authors: Li, Jiahao; Yu, Lingjia; Guo, Shigong; Zhao, Yu
Abstract
Background To establish a metabolite fingerprint of ossification of the thoracic ligamentum flavum (OTLF) patients using liquid chromatography-mass spectrometry (LC-MS) in combination with transcriptomic data and explore the potential molecular mechanism of pathogenesis. Results The study cohort was composed of 25 patients with OTLF and 23 healthy volunteers as a control group. Thirty-seven metabolites were identified out by UPLC-MS including uric acid and hypoxanthine. Nine metabolites, including uric acid and hypoxanthine, were found with a Variable Importance in Projection (VIP) score over 1 (p < 0.05). Pathway enrichment indicated that purine metabolism pathways and the other four metabolism pathways were enriched. Transcriptomic data revealed that purine metabolism have a substantial change in gene expression of OTLF and that xanthine dehydrogenase (XDH) is the key regulatory factor. Receiver operating characteristic (ROC) analysis indicated that 17 metabolites, including uric acid, were found with an AUC value of over 0.7. Conclusion Uric acid might be the potential biomarker for OTLF and play an important role within the detailed pathway. XDH could affect purine metabolism by suppressing the expression of hypoxanthine and xanthine leading to low serum levels of uric acid in OTLF, which could be a focal point in developing new therapeutic methods for OTLF.
Effect of an external electric field on the dissociation energy and the electron density properties: The case of the hydrogen bonded dimer HF center dot HF
JOURNAL OF CHEMICAL PHYSICS
Authors: Mata, Ignasi; Molins, Elies; Alkorta, Ibon; Espinosa, Enrique
Abstract
The effect of a homogeneous external electric field parallel to the hydrogen bond in the FH center dot FH dimer has been studied by theoretical methods. The quantum theory of atoms in molecules methodology has been used for analyzing the electron distribution of the dimer, calculated with different hydrogen bond distances and external field magnitudes. It is shown that an electric field in the opposite direction to the dipole moment of the system strengthens the interaction due to a larger mutual polarization between both molecules and increases the covalent character of the hydrogen bond, while an external field in the opposite direction has the inverse effect. The properties of the complex at its equilibrium geometry with applied field have been calculated, showing that dependencies between hydrogen bond distance, dissociation energy, and properties derived from the topological analysis of the electron distribution are analogous to those observed in families of XDH center dot AY complexes. The application of an external field appears as a useful tool for studying the effect of the atomic environment on the hydrogen bond interaction. In the case of FH center dot FH, both the kinetic energy density and the curvature of the electron density along the hydrogen bond at the bond critical point present a surprisingly good linear dependence on the dissociation energy. The interaction energy can be modeled by the sum of two exponential terms that depend on both the hydrogen bond distance and the applied electric field. Moreover, as indicated by the resulting interaction energy observed upon application of different external fields, the equilibrium distance varies linearly with the external field, and the dependence of the dissociation energy on either the hydrogen bond distance or the external electric field is demonstrated to be exponential.