Background: Intensive use of pesticides in agriculture has led to widespread contamination of the environment. A number of studies suggest ubiquitous exposure of the population, with potential health effects. However, characterizing pesticide exposure in natural conditions is not straightforward because of the many sources of exposure, the high diversity of pesticide molecules, their low doses and the spatio-temporal dynamic of the pesticide uses.

Aims: In this study, we focus on household dust to assess home contamination by pesticides in a rural area and indirectly estimate residents pesticide exposure.

Methods: Indoor dust samples were collected on wipes in houses of residents of four villages in a cereal plain of western France, the Zone Atelier Plaine & Val de Sèvre. Three samples were collected at three different locations per house at two seasons. A total of 459 dust were collected. Pesticides in the wipe-dust were extracted by liquid/liquid extraction and analyzed by UHPLC-MS/MS (Qtrap6500;Sciex) with a qualitative and quantitative method validated in accordance with the European Medicines Agency guidelines.

Results: Preliminary results from two villages revealed the presence of 4 to 22 pesticides per wipe. The most frequently detected pesticides were dichlorodiphenyltrichloroethane (DDT), carbendazim, imidacloprid and pendimethalin. The same pesticides were found in both seasons, but with different contamination levels.

Conclusions: This study demonstrates the feasibility of an indirect and inexpensive measurement of pesticide indoor contamination. Further studies should be conducted to understand the links between pesticide exposure from indoor dusts and human pesticides exposure.

Key words: pesticides, dust, mass spectrometry, cohort

Background: Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury. Lipocalin-2 (LCN2), an acute-phase protein, has emerged as a potential modulator of inflammatory responses, but its role in APAP hepatotoxicity and Kupffer cells (KCs) dynamics remains unclear.

Aims: This study aimed to elucidate the mechanism by which LCN2 protects against APAP-induced liver injury (AILI), focusing on liver regeneration through KCs polarization reprogramming.

Methods: We performed time-course transcriptome sequencing on the livers of AILI mice. The polarization level of KCs was analyzed by flow cytometry. The regenerative phenotypes and the paracrine HGF/c-MET pathway were detected using molecular biology techniques.

Results: We found that the LCN2 were significantly elevated in the livers under AILI, and the injection of LCN2 recombinant protein before injury could significantly reduce the levels of ALT/AST. Flow cytometry showed that the ratio of CD206+ KCs were significantly increased after LCN2 administration. Meanwhile, the expression of regeneration indicators was significantly upregulated. Mechanistically, LCN2 could activate the polarization reprogramming of KCs, which releasing HGF to paracrine to hepatocytes, targeting c-MET to activate the downstream nuclear translocation of β-catenin. In addition, the protective effect of LCN2 was reversed by depletion of macrophages with clodronate liposomes, injection of LCN2 neutralizing antibodies, or antagonism with a c-MET inhibitor.

Conclusions: LCN2 protects against AILI by reprogramming KCs toward an M2 phenotype to release HGF, which stimulates hepatocyte proliferation via c-Met/β-catenin signaling. Targeting the LCN2-HGF-β-catenin axis may offer therapeutic strategies for liver regeneration post-injury.

Key Words: APAP,LCN2,Kupffer cells,DILI,liver regeneration

Abstract
Background
Polymyxin B (PMB), a last-line antibiotic for multidrug-resistant infections, is limited by dose-dependent nephrotoxicity. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, shows potential in chronic kidney diseases, but its role in PMB-induced acute kidney injury (AKI) remains unexplored.
Objective
This study investigates the molecular mechanisms underlying Finerenone’s renoprotective effects against PMB-induced AKI, focusing on multi-target interventions.
Methods
Network pharmacology identified PMB and AKI-related targets. Transcriptomics analyzed PMB-treated HK-2 cells. GO and KEGG enrichment elucidated biological pathways. Molecular docking validated Finerenone’s binding affinity to core targets.
Results
Intersection analysis revealed 111 shared targets, with STAT3, CASP3, and HIF1A as hubs regulating oxidative stress, apoptosis, and fibrosis. Transcriptomics identified 144 upregulated and 361 downregulated genes, enriched in TNF, NF-κB, and HIF-1 pathways. Finerenone exhibited strong binding to STAT3 (−6.3 kcal/mol), CASP3 (−6.3 kcal/mol), and HIF1A (−6.2 kcal/mol), suggesting direct inhibition.
Conclusion
Finerenone mitigates PMB nephrotoxicity by targeting the STAT3-CASP3-HIF1A axis, offering a novel multi-target strategy for drug-induced AKI.

Background: Cisplatin has been widely used in clinical, however, its toxic side effects are poorly understood. Understanding how cisplatin interacts with proteins in cells is crucial for unravelling the complex mechanisms underlying its toxic side effects.

Aims: To explore the reaction between cisplatin and calmodulin (CaM), a pivotal protein in signal transduction pathways and gain insights into how cisplatin disrupt normal cellular functions, which could be related to its neurotoxicity.

Methods: 19F and 2D HSQC NMR were employed to analyze the interaction of cisplatin with CaM in vitro. 13CH3 - methionine selective labeling and ICP-MS were used to detect protein - drug interactions within cells.

Results: The results revealed that cisplatin readily reacts with CaM, leading to the mobilization of bound calcium ions and inhibition of CaM/MLCK complex formation. The preformed CaM/MLCK complex exhibited greater resilience to cisplatin compared to free CaM, due to the more embedded methionine residues within the complex. Although the complex survived platination, some destabilization occurred, as evidenced by the mobilization of some calcium ions and collapse of the complex under chromatographic conditions. In-cell NMR indicates that cisplatin can enter cells and react with CaM and CaM/MLCK complex. Notably, the 1H-13C HSQC NMR spectra obtained in cell were directly comparable to those obtained in vitro.

Conclusions: Cisplatin can disrupt the interaction between CaM and the kinase, implying that the platination of CaM could underlie the mechanism of cisplatin induced neurotoxicity.

Keywords: CaM, CaM/MLCK complex, Cisplatin, In-cell NMR, Selective labeling, Neurotoxicity

Background: Spiking involves intentionally administering a substance to someone without their knowledge or consent, aiming to make the person unconscious or incapacitated. Despite widespread public and media attention, scientific research involving studies with comprehensive toxicology testing remains limited.

Aims: This prospective multicenter-study aims to investigate the characteristics and outcomes of suspected spiking incidents in Ghent, Belgium.

Methods: Over a two-year period, patients presenting after a suspected spiking incident at the emergency department were included in the study. Urine samples were collected within 5 and blood samples within 2 days of the alleged spiking. Toxicological testing included screening for alcohol (blood only), benzodiazepines, opiates, amphetamines, cocaine, cannabinoids, and GHB. Additionally, a comprehensive HRMS-screening method was applied to detect other drugs, medications, and NPS.

Results: To date, 76 patients (median age 26 years; female-to-male ratio 0.67) have been included. The median time between the incident and sample collection was 5 hours. Most incidents (92%) were reported at pubs/nightclubs or events. Common symptoms included nausea, sleepiness, dizziness, and amnesia. Alcohol was detected in 54/71 blood samples, with an average concentration of 1.16 g/L. Illicit and medicinal drugs were detected in samples of 27 participants, most of which were reported as voluntary use. Six plausible spiking cases were retained, involving cannabis, MDMA, ketamine, diazepam, and zolpidem.

Conclusions: Spiking suspicion is common in Ghent, and it’s essential to take victims seriously with prompt sample collection and thorough toxicological analysis. However, even when substances are detected, determining if they were administered involuntarily remains challenging.

Keywords: spiking,drink-spiking,toxicology-testing,ER-presentations,multi-center-study