The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB) drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral administration of an anti-TB drug once a day for 30 days. Liver injury was evaluated by biochemical and histopathological examinations. Lipid peroxidation, mitochondrial function, and the activity of antioxidants were measured by spectrophotometric methods. Cytokines expression and CYP2E1 activity were determined by ELISA assay and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. The expressions of hepatic CYP2E1 and hepatocyte growth factor (HGF) were assessed by Western blotting. As a result, bicyclol significantly protected against anti-TB drug-induced liver injury by reducing the elevated serum aminotransferases levels and accumulation of hepatic lipids. Meanwhile, the histopathological changes were also attenuated in rats. The protective effect of bicyclol on anti-TB drug-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress, suppress the inflammatory cytokines and CYP2E1 expression, up-regulate the expression of HGF, and improve mitochondrial function. Furthermore, administration of bicyclol had no significant effect on the plasma pharmacokinetics of the anti-TB drug in rats.

Background: Drug rash with eosinophilia and systemic symptoms (DRESS) is a life-threatening severe cutaneous adverse reaction.Objective: This study aims to study fatal DRESS cases using FAERS database and systematic review.Methods: Data of the FDA Adverse Event Reporting System (FAERS) database were extracted and manipulated. Articles from Pubmed, Embase and CINAHL databases were screened.Results: 0.13% of the adverse events submitted to FAERS was identified as DRESS and the percentage of fatal cases was up to 6.62%. The top five drugs calculated to induce DRESS with the highest number of reported cases were allopurinol, lamotrigine, vancomycin, amoxicillin and carbamazepine. The top five drugs statistically related to fatal outcome with the highest number of reported cases were allopurinol, vancomycin, trimethoprim, sulfamethoxazole and lamotrigine. Skin manifestations remained the main reason for admission and the average time from dose to rash onset was 27.19 days. The most commonly cited culprit medication type were antibiotics (50.00%), anti-gout agents (15.38%) and anti-epileptic drug (11.54%).Conclusions: We discussed fatal cases of DRESS through FAERS system and case reports, hoping to raise awareness when using relevant drugs.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and severe cutaneous adverse drug reactions (SCARs) with high mortality. Antibiotics are the most frequent causative agents related to DRESS. However, it is rarely reported in cephalosporins, especially for ceftazidime. Here, we reported a case of ceftazidime-induced DRESS with HLA genotypic polymorphism as a risk factor. A 58-year-old woman with connective tissue disease was intravenously infused with ceftazidime for the treatment of pneumonia and intestinal infection, followed by the presence of fever, rash, and hematologic and hepatic laboratory abnormalities. DRESS was diagnosed and the positive polymorphism in HLA-B*15:02 was found. Our case illustrated the necessity to clarify the patho-mechanism and the use of pretreatment HLA analysis to prevent ceftazidime-related DRESS may be a valuable option soon.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with poor prognosis. Surgery is the only curative option for ACC, but recurrence remains high. Effective systemic therapies are still lacking in ACC. Diagnosis currently relies on integrated hormonal, imaging, and histopathological assessments. However, distinguishing ACC from benign adrenocortical adenoma (ACA) remains challenging. To address this, we performed untargeted plasma metabolomics on patients with ACC and ACA, as well as on healthy controls, to identify differential metabolites and elucidate the enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Notably, glycocholic acid emerged as a significantly upregulated metabolite in ACC with superior diagnostic accuracy. Furthermore, a metabolic model incorporating six plasma metabolites, including glycocholic acid, distinguished ACC from ACA and healthy controls with an area under the curve (AUC) of 0.9266. These findings demonstrate that plasma metabolomics might serve as a promising tool for the detection of ACC.

Exosomes have become one of the hotspots in life science research in recent years. As an important carrier of bio-information substances, they can mediate intercellular communication by carrying various bioactive substances, thereby activating specific signal transduction pathways within cells and ultimately regulating cell phenotypes and functions. Among the abundant cargoes carried by exosomes, drug-metabolizing enzymes have gradually attracted increasing attention from researchers. More and more evidence suggests that the abundance and activity levels of these specific drug-metabolizing enzymes encapsulated in exosomes can often reflect the dynamic gene expression in their parent cells, which is of great significance for studying inter-individual variability in drug exposure. Based on this, this article reviews the biological origin of exosomes, related regulatory programs, their potential as biomarkers indicating in vivo drug exposure, and related research results in the above fields in recent years, aiming to deepen the understanding of the role of exosomes in drug metabolism and provide more reference for future research on individualized drug administration of exosomes.