ER stress-related protein, CHOP, may serve as a biomarker of mechanical asphyxia: a primary study.

The precise authentication of death from mechanical asphyxia (DMA) has been a complex problem in forensic medicine. Besides the traditional methods that concern the superficial characterization of the body, researchers are now paying more attention to the biomarkers that may help the identification of DMA. It has been reported that the extremely hypoxic environment created by DMA can cause the specific expression of mitochondria-related protein, which may sever as the biomarkers of DMA authentication. Since endoplasmic reticulum stress (ER stress) has been found to be related to the dysfunction of mitochondria, it is promising to look for the biomarkers of DMA among ER stress-related proteins. In this article, animal and cell experiments were conducted to examine how ER-mitochondria interaction may be influenced in the hypoxic condition caused by DMA primarily. Human samples were then used to verify the possible biomarkers of DMA. We found that ER stress-related protein CHOP was significantly up-regulated within a short-term postmortem interval (PMI) in brain tissue of DMA samples, which may interact with a series of ER stress- and mitochondria-related protein, leading to the apoptosis of the cells. It was also verified in human samples that the expression level of CHOP can sever as a potential biomarker of DMA within a specific PMI.

Simultaneous determination of N-ethylpentylone, dopamine, 5-hydroxytryptamine and their metabolites in rat brain microdialysis by liquid chromatography tandem mass spectrometry.

N-Ethylpentylone (NEP) is a popular synthetic cathinone abused worldwide. To obtain more information about its pharmacokinetics and pharmacodynamics, a rapid, simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the determination of NEP, two important neurotransmitters, dopamine and serotonin, and their metabolites, including 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and 5-hydroxyindole-3-acetic acid, in rat brain microdialysate. The analytes were separated on a Phnomenex Polar C18 column, with a mobile phase of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B) under gradient elution to shorten the total chromatographic run time. A triple quadruple mass spectrometer coupled with an electrospray ionization source in both positive and negative ion mode was used to detect the analytes. This method showed excellent accuracy (87.4-113.5%) and precision (relative standard deviation <15%) at three quality control levels. The limits of detection were 0.2 ng/mL for NEP and 0.2-50 nm for the others and good linearity was obtained. This study pioneered a method to integrate exogenous drugs and endogenous neurotransmitters as the drugs act on the same determination system, which means that this innovation can provide support for further study of the addictive effects of NEP or other synthetic cathinones on extracellular levels of dopamine and 5-hydroxytryptamine.