Perilla frutescens (L.) Britt., a medicinal herb and edible plant, is very popular among East Asian countries. The perilla leaves, stems and seeds can be used as traditional medicines and foods. Polycyclic aromatic hydrocarbons (PAHs) and halogenated PAHs (HPAHs) are organic pollutants that are widely present in the environment, such as in water, air and soil, and are harmful to humans. In this study, the contents of 16 PAHs and 4 HPAHs in perilla leaves, stems and seeds were determined by gas chromatography tandem mass spectrometry (GC-MS). A total of 12 PAHs were detected in all samples, and no HPAHs were detected. The total contents of PAHs in perilla leaves, stems and seeds varied from 41.93 to 415.60 ng/g, 7.02 to 51.52 ng/g and 15.24 to 180.00 ng/g, respectively. The statistical analyses showed that there were significant differences in the distribution of PAHs in perilla leaves, stems and seeds. On the basis of the toxic equivalent quantity (TEQ) and incremental lifetime cancer risk (ILCR) model, the cancer risks of the intake of perilla leaves, stems and seeds were assessed to be from 3.30 × 10−8 to 2.11 × 10−5, 5.52 × 10−9 to 5.50 × 10−8 and 1.20 × 10−8 to 1.41 × 10−7, respectively. These were lower than 10−4 (the priority risk level of the EPA) and suggested that there may be almost no cancer risk from the intake of these traditional Chinese medicines (TCMs).
Tofacitinib citrate (RR-isomer) is a janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis (RA) in adults who have had an inadequate response or intolerance to methotrexate. The presence of the enantiomer of tofacitinib citrate (SS-isomer) is monitored for quality control as a possible impurity in the final product. In this study, a reversed-phase high-performance liquid chromatography (RP-HPLC) method based on a chiral recognition mechanism for the separation of tofacitinib citrate and its enantiomer was established based on the principles of green analytical chemistry. A CHIRALPAK IH column was used with a mobile phase of ammonium acetate buffer (pH 8.0) and acetonitrile in a gradient elution at a detection wavelength of 285 nm. The calibration curve exhibited excellent linearity over the range of 0.1002–20.04 μg/mL (r = 0.9999). The average recovery of the enantiomer was 98.6% with a relative standard deviation (RSD) of 0.7%. The limit of detection (LOD) and the limit of quantitation (LOQ) were 0.04 and 0.1 μg/mL, respectively. This RP-HPLC method was suitable for detecting the enantiomers of tofacitinib citrate in tablets. Furthermore, the method proved to be environmentally friendly based on the evaluation by Analytical Eco-Scale, Analytical GREEnness (AGREE) and Green Analytical Procedure Index (GAPI).
Ilaprazole is a proton pump inhibitor used to treat digestive diseases. In this study, blood samples were collected after oral administration of ilaprazole and prepared by liquid–liquid extraction. The metabolites of ilaprazole were detected by liquid chromatography–high-resolution mass spectrometry (LC-HRMS) and LC-MSn. A total of twelve in vivo metabolites were detected in rat plasma and six new metabolites of ilaprazole, including one reductive metabolite with sulfide (M3), two hydroxylated metabolites with sulfoxide (M7 and M8), and three oxidative metabolites with sulfone (M9, M11, and M12), were identified. The possible metabolic pathways of ilaprazole and the fragmentation behaviors of its metabolites were elucidated. The result of the in silico prediction indicates that all the new metabolites showed the potential ability to inhibit H+/K+-ATPase activity.
Background: Glioblastoma is highly heterogeneous, highly invasive, and resistant to temozolomide, with an extremely low 5-year survival rate. The spatial association between polyamine metabolism and ferroptosis remains unclear. Spatial metabolic heterogeneity is a core challenge in glioblastoma treatment. Methods: In this study, 17 patients with primary or recurrent high-grade glioma were included. Spatial metabolomics (n = 9), multiplex immunofluorescence (exploratory experiment n = 10, observational experiment n = 1), flow cytometry (n = 13), and mouse orthotopic models (n = 3) were combined to analyze the characteristics of the polyamine–ferroptosis axis in the para-carcinoma, tumor, and necrotic regions. Results: Differences in the polyamine-metabolism–ferroptosis axis were observed across distinct pathological regions of glioblastoma. Regional differences in polyamine distribution were associated with regional differences that lower lipid-peroxidation signals in the tumor region and higher lipid-peroxidation signals in the necrotic region. Moreover, in glioblastoma patient specimens, lipid-peroxidation-associated signals were detected in immune-cell compartments, alongside immune-cell phenotypic features suggestive of dysfunction, which show correlation with an immunosuppressive microenvironment. At the regional level, enzymes related to polyamine metabolism, namely GLS and SMS, exhibited spatial co-localization trends with lipid-peroxidation markers. Alterations in markers of the GSH-GPX4 and FSP1 antioxidant systems were spatially associated with the tumor-region-specific lipid-peroxidation profile. Partial spatial patterns of polyamine metabolism observed in human samples were partially recapitulated in mouse orthotopic tumor models. Conclusions: Glioblastoma exhibits spatially distinct distribution of the polyamine–ferroptosis-associated molecular signature. Notable correlative spatial features include spermidine and spermine enrichment, altered regional abundance within the glutamine–glutamate metabolic axis, immune-cell lipid-peroxidation-associated signals and immune-cell-dysfunction-related phenotypes, and regional shifts in GSH-GPX4/FSP1-related markers. This study identifies potential targets and provides a correlative spatial framework for region-specific therapeutic investigation, but the establishment of the causal relationship still requires further functional verification.