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Nowadays, the abuse of illegal drugs has been an increasingly grim problem in the world. Excitation–emission matrix fluorescence combined with parallel factor analysis was used to make a quantitative analysis of the simulated amphetamine-type illegal drugs. Satisfactory results were achieved for simultaneous determination of methamphetamine (MAM) and 3, 4-methylenedioxymethamphetamine (MDMA) in the presence of adulterants. The average recoveries were (99.8 ± 0.6)% and (101.6 ± 5.7)% for MAM and MDMA, respectively. Figures of merit including root-mean-square error of calibration and prediction, sensitivity and selectivity were investigated to evaluate the performance of the proposed method. The limits of detection were 0.054 and 0.002 1 μg/mL for MAM and MDMA, respectively. [ABSTRACT FROM AUTHOR]

Paraquat poisoning usually results from suicide, occupational, or accidental exposure. Herein, we report a rare fatal case of homicidal paraquat poisoning. A 58‐year‐old man was poisoned by taking paraquat‐mixed medicine and wearing paraquat‐soaked underwear. In the absence of a history of paraquat exposure, the patient was misdiagnosed with pulmonary infection and scrotal dermatitis and died of respiratory failure 24 days after the initial exposure to paraquat. Ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) was applied to detect and quantify paraquat in postmortem specimens. The concentration of paraquat in postmortem specimens from high to low is lung (0.49 μg/g), brain (0.32 μg/g), kidney (0.24 μg/g), liver (0.20 μg/g), cardiac blood (0.11 μg/mL), and stomach wall (

Gastric cancer (GC) is the fourth most common type of malignant tumor worldwide, and causes the second highest number of cancer-associated mortalities in 2012. Gastric tumorigenesis is a multistep and multifactorial process. In the present study, tissue microarray and immunohistochemistry analysis were used to detect cytotoxin-associated gene A (CagA), c-Met, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and Beclin-1 expression in 121 GC tumors and 120 normal gastric tissues. The clinical relevance and prognostic implications of CagA, c-Met, PI3K and Beclin-1 expression in GC patients were analyzed. Furthermore, the Cox proportional hazards model was performed to indicate the independent prognostic factors for GC patients, including various clinicopathological parameters and CagA, c-Met, PI3K and Beclin-1 expression. The results indicated that CagA-positive H. pylori infection, c-Met, PI3K and Beclin-1 may have major roles in the oncogenesis, invasion and lymph node metastasis of GC. The disease-free survival rate was negatively associated with the expression of c-Met and CagA in tissues, and was positively associated with Beclin-1 expression. Overall survival was also negatively associated with the expression of c-Met and PI3K, and was positively associated with Beclin-1 expression. This indicated that c-Met and Beclin-1 may be independent and efficient biomarkers for predicting the DFS of patients with GC. Furthermore, in CagA-positive H. pylori infection-associated GC, c-Met expression was significantly upregulated and Beclin-1 expression was significantly downregulated. CagA-positive H. pylori infection therefore associated with the c-Met signaling pathway and the suppression of autophagy in the neoplasia, invasion and metastasis of GC. [ABSTRACT FROM AUTHOR]

Ketamine is a noncompetitive antagonist of N -methyl-D-aspartate receptors (NMDARs). We have shown that ketamine can induce cognitive impairments and schizophrenia-like symptoms in mice. However, the detailed metabolic profile changes in the progression of ketamine-induced schizophrenia-like symptoms are still not fully elucidated. In this study, an ultra-performance liquid chromatography-Q-Exactive hybrid quadrupole-Orbitrap mass spectrometry-based untargeted hippocampus high-throughput metabolomics method was first performed to screen for potential biomarkers in a schizophrenia-like state in a chronically administered ketamine-induced mouse model. Our results identified that the amino acid and energy metabolism pathways were significantly affected in mouse models of ketamine-induced schizophrenia. The detailed amino acid profiles were subsequently quantified in the hippocampus. The results showed that ketamine dramatically decreased the Lys, Gly, and Ser levels while significantly increasing the Gln level and relative Glu-to-GABA ratio. Our study suggested that Gln, Gly and Ser metabolism disturbances might be involved in ketamine-induced schizophrenia-like phenotypes. This research offers a fresh viewpoint for creating new neuroleptic medications and contributes to understanding the mechanisms underlying ketamine-induced schizophrenia. • Ketamine-induced experimental schizophrenia can alter the amounts of a variety of metabolites in the hippocampus. • Changed metabolites mainly involved amino acids and enriched in synaptic signaling and amino acid metabolism pathway. • Gln, Gly and Ser may be potential biomarkers for ketamine-induced schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Tea, the world's second most popular drink, is an essential part of some people's lives. Thus, this study aimed to explore potential tea-drug interactions with a view to promoting the rational administration of drugs., Methods: A specific and sensitive approach involving high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and a probe cocktail was established and validated to evaluate the inhibitory effects of four teas on five cytochrome P450 (CYP450) enzymes in rats. Metoprolol tartrate (MT), omeprazole (OMP), phenacetin (PNT), tolbutamide (TOL), and testosterone (T) were selected as the probe drugs for CYP2D6, CYP2C19, CYP1A2, CYP2C6, and CYP3A1/2, respectively, and were simultaneously quantified in the multiple reaction monitoring (MRM) mode with positive electrospray ionization (ESI+) in a single 12-min run., Results: The extraction recoveries, matrix effect values, as well as intra/interday accuracy and precision met the determination standards. CYP1A2 and CYP2C6 were strongly inhibited by green tea, and CYP2C6 was also strongly inhibited by Pu'er tea. Ti Kuan Yin tea had a weak inhibitory effect, and black tea had only a slight inhibitory effect, on CYP1A2. Furthermore, the four types of tea did not have significantly altered the activity of CYP2D6, CYP2C19, and CYP3A1/2 in vitro ., Conclusions: The method used in the present study was successfully applied to assess the inhibitory effects of aqueous extracts of four types of tea on CYP450 isoforms in vitro . The results suggest that different types of tea have different effects on drug metabolism., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-5490/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Objective: In order to evaluate whether the role of chicken ovalbumin upstream promoter transcription factor II (COUP-TF II) could sever as a predictor to stratify risk of human colorectal cancer (CRC) patients, and to elucidate the preliminary molecular mechanisms of COUP-TF II involved in the development and advancement of CRC reflected by investigating the relationship of COUP-TF II with PTEN, Smad4., Methods: 112 cases tissue microarray and immunohistochemical SP method were used to detect the expression of COUP-TF II, PTEN and Smad4 in CRC tissues and adjacent non-tumorous tissues. The clinical relevance and prognosis of COUP-TF II, PTEN, Smad4 in CRC patients were analyzed. Furthermore, Cox proportional hazards model was performed to indicate the independent prognostic factors for CRC patients using various clinicopathological parameters and COUP-TF II, PTEN and Smad4., Results: COUP-TF II proteins were positively expressed in 65.2% of CRC tissues and 15.5% paired non-CRC tissues, respectively. The expression of COUP-TF II was significantly correlated with TNM stage and lymph node metastasis and a negative correlation with Smad4 expression. Patients bearing higher levels of COUP-TF II expression showed lower DFS and OS. Most importantly, Cox proportional hazards regression analyses showed COUP-TF II positive/Smad4 negative status (DFS, P=0.001; OS, P=0.005) were independent prognostic factors for CRC patients., Conclusion: Positive COUP-TF II expression levels has significant value in determining CRC stage and metastasis and cooperates with negative Smad4 expression contributing to assess prognosis in patients with colorectal cancer, suggesting Smad4 may be involved in the above regulation progress probably.

Chronic liver diseases are commonly associated with tissue hypoxia that may cause inflammation, oxidative stress, liver cell injury and increased nuclear transcriptional regulation. The hepatic response to chronic hypoxia at the molecular level has not yet been clearly understood until now. The aim of this study is to investigate whether nuclear transcription factors [hypoxia-inducible factor-1 (HIF-1α), activator protein-1 (AP-1), nuclear factor-kappa B (NF-κB)] exhibit activity changes during hepatic response to chronic hypoxia. Blood and liver samples were collected from adult Sprague-Dawley rats living in atmospheric air or 10% oxygen for four weeks. Levels of serum alanine aminotransferase (ALT), 8-isoprostane and nitrotyrosine were measured. The activities of nuclear transcription factors and the expression of downstream genes (iNOS, eNOS, ET-1 and VEGF) were measured using RT-PCR, Western blotting and Gel shift analysis. Results showed that serum ALT level, 8-isoprostane level and formation of nitrotyrosine were within normal range at all time-points. In the hypoxic liver, DNA-binding activities of HIF-1α, NF-κB and AP-1 increased significantly. Expression levels of iNOS, VEGF and ET-1 progressively increased from day 7 to day 28. eNOS was also elevated in the hypoxic liver. In conclusion, our study suggests that increased activity of HIF-1α, AP-1 and NF-κB may partly play a significant role in the hepatic response to oxidative stress and liver injury under chronic hypoxia. The increased expression of VEGF, ET-1, iNOS and eNOS may be partly due to the compensatory mechanism in the vascular beds of the liver in response to chronic hypoxia.

Objective: To investigate polymorphisms in the gene for lipoprotein lipase (LPL) in Chinese populations with coronary heart disease (CHD) and to inquire into the relationship between these polymorphisms in LPL gene and CHD., Methods: Genomic DNA was extracted from patients with CHD and normal control subjects using a salting out method. The entire coding region and flanking sequences of all coding exons of the LPL gene were amplified by PCR technique and PCR products were detected by denaturing high-performance liquid chromatography (DHPLC) and sequenced with a dideoxy terminal termination method., Results: A novel polymorphic site, G830A, that is within the fifth exon of the LPL gene was found. The 192 codon CGA was changed into CAA and resulted in the substitution of glutamine for arginine. Between the control and CHD groups, chi-square test showed no significant difference in the frequencies of the A/A genotype and A allele (P > 0.05). However, the frequencies of A/A genotype and A allele (0.653 and 0.786) in CHD patients with high plasma triglyceride/lowed plasma high density lipoprotein cholesterol were higher than those (0.415 and 0.642) in CHD patients without hyperlipidemia (P < 0.05)., Conclusion: No direct association was found between the LPL Arg192-->Gln substitution polymorphism and CHD, but there is a significant positive correlation between the A/A genotype of the LPL gene and CHD associated with high triglyceride/lowed high density lipoprotein cholesterol. This study may provide new data for exploring the molecular mechanism of CHD.