Search

Tyrosine kinase inhibitors (TKIs) and triazole antifungals are the first-line drugs for treating chronic myeloid leukemia (CML) and fungal infections, respectively, but both suffer from large exposure differences and narrow therapeutic windows. Moreover, these two types of drugs are commonly used together in CML patients with fungal infections. Multiple studies and guidelines have suggested the importance of therapeutic drug monitoring (TDM) of TKIs and triazoles. Currently, methods for the simultaneous determination of both types of drugs are limited. We developed a simple, rapid, and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of three commonly used TKIs (imatinib, dasatinib, and nilotinib) and three commonly used triazoles (voriconazole, itraconazole, and posaconazole) in human plasma. The analytes were eluted on a Welch XB-C 18 analytical column (50 × 2.1 mm, 5 µm) at 0.7 mL/min, using a gradient elution of 10 mM ammonium formate (A) and methanol-acetonitrile-isopropanol (80:10:10, v/v/v) containing 0.2 % formic acid (B) with a total analysis time of 3.5 min. The calibration curves were linear over the range from 20 to 4000 ng/mL for imatinib and nilotinib, from 2 to 400 ng/mL for dasatinib, and from 50 to 10,000 ng/mL for voriconazole, itraconazole, and posaconazole. Selectivity, accuracy, precision, recovery, matrix effect, and stability all met the validation requirements. The method was successfully used for TDM in CML patients who co-treated with both TKIs and triazoles. Drug-drug interaction analysis between TKIs and triazoles showed that a significant positive correlation was observed between imatinib and voriconazole, as well as dasatinib and voriconazole. Therefore, this method can be well applied in clinical TDM for patients receiving TKIs, triazoles, or both simultaneously., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Triclocarban (TCC) is a widely used environmental endocrine-disrupting chemical (EDC). Articular injury of EDCs has been reported; however, whether and how TCCs damage the joint have not yet been determined. Herein, we revealed that exposure to TCC caused osteoarthritis (OA) within the zebrafish anal fin. Mechanistically, TCC stimulates the expression of DNMT1 and initiates DNA hypermethylation of the type II collagen coding gene, which further suppresses the expression of type II collagen and other extracellular matrices. This further results in decreased cartilage tissue and narrowing of the intraarticular space, which is typical of the pathogenesis of OA. The regulation of OA occurrence by TCC is conserved between zebrafish cartilage tissue and human chondrocytes. Our findings clarified the hazard and potential mechanisms of TCC towards articular health and highlighted DNMT1 as a potential therapeutic target for OA caused by TCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The associations between particulate matter (PM) exposure, psychosocial stress and blood cell parameters are bringing novel insights to characterize the early damage of multiple diseases. Based on two studies conducted in three Chinses cities using cross-sectional (Beijing, 425 participants) and panel study (Tianjin and Shanghai, 92 participants with 361 repeated measurements) designs, this study explored the associations between short-term exposure to ambient PM and blood cell parameters, and the effect modification by psychosocial stress. Increasing PM 2.5 exposure was significantly associated with decreases in red blood cell (RBC) count and mean corpuscular hemoglobin concentration (MCHC), and increases in mean corpuscular volume (MCV), platelets count (PLT) and platelet hematocrit (PCT) in both studies. For instance, a 10 μg/m 3 increment in PM 2.5 concentration was associated with a 1.04% (95%CI: 0.16%, 1.92%) increase in PLT (4-d) and a 1.09% (95%CI: 0.31%, 1.87%) increase in PCT (4-d) in the cross-sectional study, and a 0.64% (95%CI: 0.06%, 1.22%) increase in PLT (1-d) and a 0.72% (95%CI: 0.33%, 1.11%) increase in PCT (1-d) in the panel study, respectively. In addition, stronger increases in MCV, PLT, and PCT associated with PM 2.5 exposure were found in higher psychosocial stress group compared to lower psychosocial stress group (p for interaction <0.10), indicating that blood cell parameters of individuals with higher psychosocial stress might be more susceptible to the early damages of PM 2.5 exposure., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Microplastic particles (MP) has been detected in the environment widespread. Human beings are inevitably exposed to MP via multiple routines. However, the hazard identifications, as direct evidence of exposure and health risk, have not been fully characterized in human beings. Many studies suggest the liver is a potential target organ, but currently no study regarding the MP on human liver has been reported. In this study, we used a novel in vitro 3D model, the liver organoids (LOs) generated from human pluripotent stem cells, as an alternative model to the human liver, to explore the adverse biological effect of 1 μm polystyrene-MP (PS-MP) microbeads applying a non-static exposure approach. When the LOs were exposed to 0.25, 2.5 and 25 μg/mL PS-MP (the lowest one was relevant to the environmental concentrations, calculated to be 102 ± 7 items/mL). The potential mechanisms of PS-MP induced hepatotoxicity and lipotoxicity, in aspects of cytotoxicity, levels of key molecular markers, ATP production, alteration in lipid metabolism, ROS generation, oxidative stress and inflammation response, were determined. Specifically, it has been firstly observed that PS-MP could increase the expression of hepatic HNF4A and CYP2E1. Based on these findings, the potential adverse outcome pathways (AOPs) relevant to PS-MP were proposed, and the potential risks of PS-MP on liver steatosis, fibrosis and cancer were implicated. The combined application of novel LOs model and AOPs framework provides a new insight into the risk assessment of MP. Further studies are anticipated to validate the hepatotoxic molecular mechanism of PS-MP based on HNF4A or CYP2E1, and to investigate the MP-induced physical damage and its relationship to hepatic adverse effect for human beings. CAPSULE: Microplastics cause hepatotoxicity and disrupt lipid metabolism in the human pluripotent stem cells-derived liver organoids, providing evidence for human implication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)