Latest Articles and News - Jul 14, 2025
post on 14 Jul 2025
post on 14 Jul 2025
Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is the most common complication after acute carbon monoxide (CO) poisoning. However, the pathogenesis of DEACMP remains ambiguous. The neuroprotective role of GPNMB has been observed in amyotrophic lateral sclerosis and Parkinson's disease. GPNMB was elevated in the brain tissues of DEACMP rats, while its function in DEACMP remains unclear. In this study, a CO poisoning rat model and oxygen-glucose deprivation (OGD)-treated PC-12 cells were established as an in vivo and in vitro DEACMP model, respectively. The ferroptosis inhibitor Ferrostatin-1 (Fer-1) ameliorated cognitive impairment, inflammation and oxidative stress of rats with DEACMP as assessed by Morris Water Maze test, ELISA assay and commercial kits of oxidative markers. Immunofluorescence, qRT-PCR or western blot showed that GPNMB was elevated in CA1 hippocampal tissues of CO-poisoned rats. Additionally, TUNEL staining, ELISA assay and western blot revealed that GPNMB rescued OGD-induced cell apoptosis, inflammation and ferroptosis in PC-12 cells. Mechanistical study showed that STAT3 was a transcriptional activator of GPNMB as detected by luciferase and ChIP assays, and co-immunoprecipitation and immunofluorescence staining revealed that GPNMB stabilized HIF-1α by direct binding. Functionally, GPNMB protected against OGD-induced impairments via inducing HIF-1α. Furthermore, GPNMB attenuated cognitive impairment, oxidative stress and neuronal ferroptosis of rats with DEACMP. In conclusion, GPNMB/HIF-1α exhibited neuroprotective effects via suppressing ferroptosis in DEACMP.
https://pubmed.ncbi.nlm.nih.gov/40653468/Bromazolam, an illegal benzodiazepine, has recently increased in toxicological samples in the United States. Little is known about other substances detected with bromazolam and use intentions. This study investigated bromazolam's prevalence, co-occurring substances, and self-reported substance use among patients with bromazolam exposure presenting to emergency departments (ED) for opioid/stimulant-related non-fatal overdose. The Toxicology Investigators Consortium (ToxIC) Drug Overdose Toxico-Surveillance (DOTS) Reporting Program prospectively collected interviews, chart reviews, and toxicological blood analyses among patients presenting to one of 17 EDs following a suspected acute opioid/stimulant overdose. Toxicological analyses were performed qualitatively via liquid chromatography (LC) quadrupole time-of-flight mass spectrometry (MS) and quantitatively with LC tandem quadrupole MS. Sociodemographic characteristics, intended substance use, and detected substances were examined in patients with and without bromazolam exposure (n = 341). Twenty-eight of 341 patients (8.2 %) were bromazolam positive, with an average concentration of 86.4 ng/mL (range: 3.5-310.0 ng/mL). Fentanyl concentrations were higher among bromazolam-positive patients (positive: mean=11.1 ng/mL; negative: mean=8.9 ng/mL; p = 0.03), although no qualitative significant differences were noted in fentanyl prevalence when stratified by bromazolam exposure (p = 0.22). Among the 20 bromazolam-positive patients reported using only one substance, none intended to use bromazolam, with fentanyl (n = 7, 35.0%) and heroin (n = 6, 30.0%) being the most reported intended substances. Snorting was the most common administration route (55.0%). Bromazolam exposure was associated with increased fentanyl concentrations compared to those without. Most patients with bromazolam exposure reported intended opioid use prior to their overdose. Future research should investigate bromazolam's clinical effects and patient outcomes following an overdose.
https://pubmed.ncbi.nlm.nih.gov/40652609/