The evolutionary origins of neurons remain unknown. Although recent genome data of extant early-branching animals have shown that neural genes existed in the common ancestor of animals, the physiological and genetic properties of neurons in the early evolutionary phase are still unclear. Here, we performed a mass spectrometry-based comprehensive survey of short peptides from early-branching lineages Cnidaria, Porifera and Ctenophora. We identified a number of mature ctenophore neuropeptides that are expressed in neurons associated with sensory, muscular and digestive systems. The ctenophore peptides are stored in vesicles in cell bodies and neurites, suggesting volume transmission similar to that of cnidarian and bilaterian peptidergic systems. A comparison of genetic characteristics revealed that the peptide-expressing cells of Cnidaria and Ctenophora express the vast majority of genes that have pivotal roles in maturation, secretion and degradation of neuropeptides in Bilateria. Functional analysis of neuropeptides and prediction of receptors with machine learning demonstrated peptide regulation of a wide range of target effector cells, including cells of muscular systems. The striking parallels between the peptidergic neuronal properties of Cnidaria and Bilateria and those of Ctenophora, the most basal neuron-bearing animals, suggest a common evolutionary origin of metazoan peptidergic nervous systems.
Although understanding their chemical composition is vital for accurately predicting the bioactivity of multicomponent drugs, nutraceuticals, and foods, no analytical approach exists to easily predict the bioactivity of multicomponent systems from complex behaviors of multiple coexisting factors. We herein represent a metabolic profiling (MP) strategy for evaluating bioactivity in systems containing various small molecules. Composition profiles of diverse bioactive herbal samples from 21 green tea extract (GTE) panels were obtained by a high-throughput, non-targeted analytical procedure. This employed the matrix-assisted laser desorption ionization–mass spectrometry (MALDI–MS) technique, using 1,5-diaminonaphthalene (1,5-DAN) as the optical matrix for detecting GTE-derived components. Multivariate statistical analyses revealed differences among the GTEs in their antioxidant activity, oxygen radical absorbance capacity (ORAC). A reliable bioactivity-prediction model was constructed to predict the ORAC of diverse GTEs from their compositional balance. This chemometric procedure allowed the evaluation of GTE bioactivity by multicomponent rather than single-component information. The bioactivity could be easily evaluated by calculating the summed abundance of a few selected components that contributed most to constructing the prediction model. 1,5-DAN-MALDI–MS-MP, using diverse bioactive sample panels, represents a promising strategy for screening bioactivity-predictive multicomponent factors and selecting effective bioactivity-predictive chemical combinations for crude multicomponent systems.
Opioid rotation has been proposed for management of cancer pain. No studies directly investigating dose equivalence between morphine injection (continuous IV administration) and the transdermal fentanyl patch have been reported. Therefore, we examined dose conversion ratios in patients undergoing opioid rotation from morphine injection to fentanyl patches. The subjects consisted of 45 patients admitted to Kitasato University East Hospital. Medical records were consulted to determine the``basic dose of morphine injection immediately prior to rotation'' and the``basic dose of fentanyl patch after rotation''. Equivalent doses and conversion ratios obtained with the expression of (daily dose of morphine injection (mg)/daily delivered dose of fentanyl patch (mg)) were determined from the relationship between the data by regression analysis. The regression equation obtained was Y=50.882X-13.96, r 2 =0.8922, where X and Y are daily doses of morphine injection and fentanyl patch, respectively. Equivalent doses and conversion ratios for daily dose of morphine injection (mg): daily delivered dose of fentanyl patch (mg) (patch dose mg/3 days) were 16.6 mg: 0.6 mg (2.5 mg)=28:1, 47.1 mg: 1.2 mg (5 mg) = 39:1 and 169.2 mg: 3.6 mg (15 mg)=47:1. In other reports, the ratio of morphine vs. fentanyl at 50:1 had no relation to the dose. While the present study suggested that in opioid rotation from low dose, 50:1 is not enough for the fentanyl patch. The dose conversion ratio of morphine injection to fentanyl patch was diŠerent at the low doses and high doses of morphine.
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