Steroid hormones such as glucocorticoids and their metabolites are closely related to mental diseases and neuroendocrine diseases. Quantitative analysis of these substances will help in understanding their roles in related research fields. In this study, an ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed to detect the concentration of corticosterone (CORT) and its metabolites, progesterone (PROG) and testosterone in rat plasma and prefrontal cortex (PFC), and was applied to investigate the changes in hormones in rats with depression induced by chronic unpredictable mild stress (CUMS). The method was shown to be linear in the quantitation range for all analytes. Intra‐ and inter‐day accuracy and precision were between 80% and 120%. Furthermore, we found that the level of CORT in plasma and PFC increased, whereas that of 11‐dehydrocorticosterone (11‐DHCORT) as well as the ratio of 11‐DHCORT and CORT declined in rats with CUMS‐induced depression. The trends of these changes in central PFC and peripheral plasma were consistent. In conclusion, this study successfully established an UPLC–MS/MS method for simultaneous measurement of CORT and its metabolites, PROG and testosterone in rat plasma and PFC, and applied it to rats with depression. The method could be further applied to the research of depression and diseases related to these steroid hormones.
Transarterial chemoembolization (TACE) has been widely used for hepatocellular carcinoma. Reducing hypoxia in the tumor microenvironment after TACE remains a challenge as tumor progression is common in post‐TACE patients due to the hypoxic tumor microenvironment. In this study, melatonin loaded on p(N‐isopropyl‐acrylamide‐co‐butyl methylacrylate) (PIB‐M) was used for tumor embolism. Two types of human hepatoma cell lines were used to explore the mechanism by which melatonin prevents the growth and metastasis of cancer cells in vitro. A VX2 rabbit tumor model was used to evaluate the efficacy, mechanism, and safety of PIB‐M in vivo. We found that under hypoxic condition, melatonin could inhibit tumor cell proliferation and migration by targeting hypoxia inducible factor‐1α (HIF‐1α) and vascular endothelial growth factor A (VEGF‐A) in vitro. In vivo, PIB‐M inhibited tumor growth and metastasis in rabbit VX2 tumors by promoting apoptosis of tumor cells and targeting related angiogenic proteins and vascular permeability proteins. A high concentration of melatonin in the PIB‐M group could be maintained in tumor tissue for 72 h after embolization. The liver and kidney functions were most damaged on the first day but recovered to normal on the seventh day after embolization in the PIB‐M group. This novel method may open avenues for reduction of tumor growth and metastasis after TACE and is efficacy and safety, which may be used for treatment for other solid tumors and clinical translation.
Background Major depression disorder (MDD) is a mental disease that seriously endangers human physical and mental health. The purpose of present study is to detect the differences of plasma metabolic profiles between MDD patients and healthy controls. Moreover, the hospitalization process of MDD patients was followed to explore the reversal of metabolic abnormalities in MDD patients by conventional treatment in the form of self-control.Methods Ultra-Performance Liquid Chromatography- Mass Spectrometry (UPLC-MS) was used to detect the metabolic profiles in 47 plasma samples from 12 controls and 12 MDD patients. Multivariate statistical analysis and K-means clustering were operated to search for significantly different metabolites (SDMs) between pair-comparison groups and specific metabolites (SMs) with ideal variation trend in relative content. Finally, the metabolites were integrated into Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways to preliminarily explore the potential mechanism of MDD disrupting the metabolic process.Results There were significant differences in plasma metabolic profiles between healthy controls and MDD patients. A total of 14 SDMs between untreated MDD patients and healthy controls were classified into the top ten KEGG pathways enrichment, among which the relative contents of 4 SMs, 9-HPODE, imidazoleacetic acid, thromboxane B2 (TXB2), and arachidonic acid (AA) showed a regular variation trend after MDD patients’ treatment. A new metabolite-pathway network containing 4 SMs and 8 pathways was accessed after further integration analysis. The sample size calculation showed that a verification set of 84-135 subjects (containing healthy controls and MDD paients) was desired to confirm the results of this study.Conclusion The results indicate that the transition in metabolic pathways during the occurrence and treatment process of MDD is mainly dominated by transformations in lipid metabolism and its relevant signaling pathway system. Additionally, histidine metabolism is also engaged. Subsequent large-scale validation study is acquired to evaluate whether the selected metabolites have the potential to diagnose and access the therapeutic effect of MDD, and to explore the probable mechanism of MDD in combination with other technologies.
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