Combining Pharmacokinetics and Vibrational Spectroscopy: MCR-ALS Hard-and-Soft Modelling of Drug Uptake In Vitro Using Tailored Kinetic Constraints

Raman microspectroscopy is a label-free technique which is very suited for the investigation of pharmacokinetics of cellular uptake, mechanisms of interaction, and efficacies of drugs in vitro. However, the complexity of the spectra makes the identification of spectral patterns associated with the drug and subsequent cellular responses difficult. Indeed, multivariate methods that relate spectral features to the inoculation time do not normally take into account the kinetics involved, and important theoretical information which could assist in the elucidation of the relevant spectral signatures is excluded. Here, we propose the integration of kinetic equations in the modelling of drug uptake…

Analysis of longitudinal metabolomic data using multivariate curve resolution-alternating least squares and pathway analysis

Extraction of meaningful biological information from longitudinal metabolomic studies is a major challenge and typically involves multivariate analysis and dimensional reduction methods for data visualization such as Principal Component Analysis or Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS). Besides, a variety of computational tools have been developed to identify changes in metabolic pathways including functional analysis and pathway analysis. In this work, the joint analysis of results from MCR-ALS and metabolic pathway analysis is proposed to facilitate the interpretation of dynamic changes in longitudinal metabolomic data. The strategy is based on the use of MCR-A…

Metabolomic Diversity of Human Milk Cells over the Course of Lactation—A Preliminary Study

Human milk (HM) is a complex biofluid containing a wide cell variety including epithelial cells and leukocytes. However, the cellular compositions and their phenotypic properties over the course of lactation are poorly understood. The aim of this preliminary study was to characterize the cellular metabolome of HM over the course of lactation. Cells were isolated via centrifugation and the cellular fraction was characterized via cytomorphology and immunocytochemical staining. Cell metabolites were extracted and analyzed using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC–QqTOF-MS) in the positive and negative electrospray ionization mode…

Evaluación de la actividad antiherpética in vitro de moléculas híbridas de la combretastatina A4 y diterpenos