Forensic Toxicology
·
2017
·Vol. 35
·期 2
·275-283
·
IF 3.744
Minakata Kayoko,Yamagishi Itaru,Nozawa Hideki,Hasegawa Koutaro,Suzuki Masako,Gonmori Kunio,Suzuki Osamu,Watanabe Kanako
Human urine samples are easier to obtain than human blood samples due to noninvasiveness. The urine levels of synthetic cannabinoids (SCs) in unchanged forms, however, are usually much lower than their blood and tissue levels and cannot be detected in most cases. Therefore, in the present work a sensitive analytical method was devised for the determination of urine levels of six SCs in unchanged forms such as N -(1-amino-3-methy-1-oxobutan-2-yl)-1-pentyl-1 H -indazole-3-carboxamide (AB-PINACA), N -(1-amino-3-methy-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1 H -indazole-3-carboxamide (AB-FUBINACA), N -[(1 S )-1-(1-aminocarbonyl)-2-methyl-propyl]-1-(cyclohexylmethyl)-1 H -indazole-3-carboxamide (AB-CHMINACA), N -(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1 H -indazole-3-carboxamide (MAB-CHMINACA), methyl-2-[1-(5-fluoropentyl)-1 H -indazole-3-carboxamido]-3-methylbutanoate (5F-AMB) and methyl-2-[1-(5-fluoropentyl)-1 H -indazole-3-carboxamido]-3,3-dimethylbutanoate (5F-ADB). These SCs were extracted from urine via liquid–liquid extraction. The identification and quantitation were performed by a relatively new type of an instrument for liquid chromatography–tandem mass spectrometry. The limits of detection were as low as 3–8 pg/mL, and the quantitation range was 10–1000 pg/mL using 400 μL of urine. The urine levels of AB-PINACA and AB-FUBINACA of victim 1 were 23 and 10 pg/mL, those of AB-CHMINACA and 5F-AMB of victim 2 were 239 and 19 pg/mL, and those of MAB-CHMINACA and 5F-ADB of victim 3 were 229 and 19 pg/mL, respectively. To our knowledge, this is the first report dealing with successful analysis of low levels of parent synthetic cannabinoids in authentic human urine specimens.
研究领域:
毒理学
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药物代谢
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法医学
·
分析化学
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DOI
高影响因子
NEUROPSYCHOPHARMACOLOGY
·
2021
·Vol. 47
·期 3
·652-663
·
IF 7.855
Manz Kevin M.,Coleman Benjamin C.,Jameson Alexis N.,Ghose Dipanwita G.,Patel Sachin,Grueter Brad A.
Parvalbumin-expressing fast-spiking interneurons (PV-INs) within feedforward microcircuits in the nucleus accumbens (NAc) coordinate goal-directed motivational behavior. Feedforward inhibition of medium spiny projection neurons (MSNs) is initiated by glutamatergic input from corticolimbic brain structures. While corticolimbic synapses onto MSNs are targeted by the psychostimulant, cocaine, it remains unknown whether cocaine also exerts acute neuromodulatory actions at collateralizing synapses onto PV-INs. Using whole-cell patch-clamp electrophysiology, optogenetics, and pharmacological tools in transgenic reporter mice, we found that cocaine decreases thalamocortical glutamatergic drive onto PV-INs by engaging a monoamine-independent mechanism. This mechanism relies on postsynaptic sigma-1 (σ 1 ) activity, leading to the mobilization of intracellular Ca 2+ stores that trigger retrograde endocannabinoid signaling at presynaptic type-1 cannabinoid receptors (CB 1 R). Cocaine-evoked CB 1 R activity occludes the expression of CB 1 R-dependent long-term depression (LTD) at this synaptic locus. These findings provide evidence that acute cocaine exposure targets feedforward microcircuits in the NAc and extend existing models of cocaine action on mesolimbic reward circuits.
研究领域:
神经科学
·
药理学
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DOI
PubMed
高影响因子
BioDesign Research
·
2025
·
IF 4.7
Yuxiang Hong,Yang Gu,Dewei Lin,Zizhao Wu,Wenhao Chen,Tianjian Lu,Pornpatsorn Lertphadungkit,Jingbo Ma,Haili Wang,Bo Zhou,Gil Bar-Sela,Idan Cohen,Peng Xu
Cannabis sativa has long been a cornerstone of both medicinal and cultural practices, with its therapeutic use spanning over 2,700 years. Central to its therapeutic effects are cannabinoids, which interact with the endocannabinoid system to influence various physiological processes such as anxiety, pain, and inflammation. Despite its benefits, cannabinoid production faces challenges and scarcity from plant extraction. This work leverages Yarrowia lipolytica as a platform for cannabinoid biosynthesis. By optimizing precursor supply, engineering biomolecular condensate-like dual prenyltransferase expression and expanding endogenous metabolism with a noncanonical polyketide synthase, we achieved the de novo biosynthesis of various cannabinoid and its analogs. Our engineered Y. lipolytica produced ∼3.5 mg/L of cannabigerolic acid, 18.8 mg/L of orsellinic acid, and 0.5 mg/L of cannabigerorcinic acid. Additionally, CBGA titer reached 15.7 mg/L with olivetolic acid supplement. This work demonstrates Y. lipolytica 's versatility as a promising host for cannabinoid and its analogs production, which opens avenues for further research and medicinal applications.
研究领域:
合成生物学
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代谢工程
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植物化学
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生物技术
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Litao Shao,Yuling Zhong,Yujie Chen,Zirun Ren,Moying Yang,Zhendong Hua,Bin Di,Mengxiang Su
Breath analysis has emerged as a promising noninvasive method for detecting drug abuse, offering potential advantages over traditional blood or urine samples. However, the capture and analysis of trace analytes in exhaled breath (EB) remains a challenge for practical applications. In this study, we explore the utilization of poly (methacrylic anhydride-co-ethylene glycol dimethacrylate)-functionalized cotton fiber (poly (MAA-co-EGDMA)-functionalized cotton fiber) for the capture of MDMB-4en-PINACA and ADB-4en-PINACA, two popular synthetic cannabinoids, from exhaled breath. Capture efficiencies of 92 % and 88 % for MDMB-4en-PINACA and ADB-4en-PINACA were achieved demonstrating robust performance across batches and excellent stability. Animal experiments were conducted and exhaled breath samples were collected and analyzed. Shorter half-lives were shown for MDMB-4en-PINACA and ADB-4en-PINACA in EB than in plasma. The detection window for MDMB-4en-PINACA was 210 min, while 150 min for ADB-4en-PINACA. This pilot study presents a novel approach for the capture of MDMB-4en-PINACA and ADB-4en-PINACA in exhaled breath using functionalized cotton fiber. The demonstrated efficacy in capturing MDMB-4en-PINACA and ADB-4en-PINACA highlights the potential of this low-cost and stable platform for noninvasive drug abuse detection. By offering a viable alternative to invasive methods, our findings demonstrate a new noninvasive method of drug abuse detection using exhaled breath holds great promise for enhancing public health efforts to combat drug abuse.
研究领域:
毒理学
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分析化学
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公共卫生
✓ 已验证
产品关联
DOI
高影响因子
Analytical Methods
·
2024
·Vol. 16
·期 24
·3968-3982
·
IF 2.7
Xiuchen Li,Le Jiang,Bin Di,Chi Hu
Concerns have been raised about synthetic cannabinoids (SCs), which are among the most often trafficked and used illegal substances. An analytical method that holds promise for determining illicit drug use in the general population is wastewater-based epidemiology (WBE). Unfortunately, the concentration of SCs in wastewater is often extremely low on account of their hydrophobic nature, thus presenting a significant obstacle to the accurate detection and quantification of SCs using WBE. In this study, we present novel magnetic nanomaterials as amphiphilic adsorbents for pretreatment of wastewater using magnetic solid phase extraction (MSPE). Polydopamine-modified Fe3O4 nanoparticles were used as the magnetic core and further functionalized with poly(divinylbenzene-N-vinylpyrrolidone). Coupled with UHPLC-MS/MS analysis, an analytical method to simultaneously detect nine SCs at trace-levels in wastewater was developed and validated, enriching 50 mL wastewater to 100 μL with limits of detection (LOD) being 0.005–0.5 ng L−1, limits of quantification (LOQ) being 0.01–1.0 ng L−1, recoveries ranging from 73.99 to 110.72%, and the intra- and inter-day precision's relative standard deviations less than 15%. In comparison to the time-consuming conventional column-based solid phase extraction, the entire MSPE procedure from sample pre-treatment to data acquisition could be finished in one hour, thus largely facilitating the WBE method for drug surveillance and control.
研究领域:
环境科学
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分析化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2021
·
IF 10.588
Sinuo Tian,Sen Yan,Zhiyuan Meng,Shiran Huang,Wei Sun,Ming Jia,Miaomiao Teng,Zhiqiang Zhou,Wentao Zhu
Bisphenols (BPs), as widely used plastic additives, penetrate into our daily lives. BPs are considered endocrine disruptors and could potentially induce obesity. In this study, the effects of bisphenol A (BPA) and tetrabromobisphenol A (TBBPA) on food intake and lipid metabolism in zebrafish were determined. Moreover, the impact of BPA and TBBPA on the endocannabinoid system (ECS) of zebrafish was further explored by metabolomics, transcriptomics, and molecular docking analysis. Here we show that exposure to BPA and TBBPA at concentrations commonly found in the environment (20, 100, and 500 μg/L) led to hyperphagia and obesity in adult male zebrafish. Metabolomics and histopathological analysis revealed significant lipid accumulation in the liver of zebrafish exposed to BPA and TBBPA. The expression of ECS-related genes, in conjunction with RNA-Seq results, further indicated that BPA and TBBPA increased appetite and induced obesity by activating cannabinoid receptor type 1(CB1). Furthermore, molecular docking revealed that six representative BPs including BPA and TBBPA could bind to the CB1 receptor. Collectively, these findings indicate that CB1 may be a potential target for BPs to induce obesity.
研究领域:
环境科学
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毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 24
·16055
·
IF 6.208
Yan-Ting Wu,Li-Shan Zhong,Chen Huang,Yu-Ying Guo,Fu-Jun Jin,Yu-Ze Hu,Zi-Bo Zhao,Zhe Ren,Yi-Fei Wang
Macrophage infiltration is one of the main pathological features of ulcerative colitis (UC) and ferroptosis is a type of nonapoptotic cell death, connecting oxidative stress and inflammation. However, whether ferroptosis occurs in the colon macrophages of UC mice and whether targeting macrophage ferroptosis is an effective approach for UC treatment remain unclear. The present study revealed that macrophage lipid peroxidation was observed in the colon of UC mice. Subsequently, we screened several main components of essential oil from Artemisia argyi and found that β-caryophyllene (BCP) had a good inhibitory effect on macrophage lipid peroxidation. Additionally, ferroptotic macrophages were found to increase the mRNA expression of tumor necrosis factor alpha (Tnf-α) and prostaglandin-endoperoxide synthase 2 (Ptgs2), while BCP can reverse the effects of inflammation activated by ferroptosis. Further molecular mechanism studies revealed that BCP activated the type 2 cannabinoid receptor (CB2R) to inhibit macrophage ferroptosis and its induced inflammatory response both in vivo and in vitro. Taken together, BCP potentially ameliorated experimental colitis inflammation by inhibiting macrophage ferroptosis. These results revealed that macrophage ferroptosis is a potential therapeutic target for UC and identified a novel mechanism of BCP in ameliorating experimental colitis.Keywords:ulcerative colitis;ferroptosis;β-caryophyllene;type 2 cannabinoid receptor;inflammation;macrophage
研究领域:
免疫学
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药理学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Jing Zhou,Hongyu Ning,Haixing Wang,Sen Zhao,Yu Xu,Yilei Fan,Zhongping Huang,Jianhong Gao
Cannabis is the most frequently abused drug worldwide, and the number of cannabis users is still growing. The high lipophilicity of cannabinoids results in extremely low concentrations in wastewater, which poses difficulties and challenges for monitoring cannabinoids. In this study, a hyperbranched mixed-mode anion exchange magnetic adsorbent Fe 3 O 4 @poly(GMA/DVB-WAX) was designed based on the structural characteristics of cannabinoids, which was prepared through copolymerization of glycidyl methacrylate (GMA) and divinylbenzene (DVB) on the surface of oleic acid coated Fe 3 O 4 microspheres followed by hyperbranched modification with ethylenediamine (EDA) and 1,4-butanediol glycidyl ether (BDDGE). This magnetic solid-phase extraction (MSPE) adsorbent can selectively extract four cannabinoids, Δ 9 -tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), 11-nor-9-carboxy-Δ 9 -tetrahydrocannabinol (THC-COOH), from wastewater through the synergistic effects of hydrophobic interactions, electrostatic interactions, π-π stacking interactions, and hydrogen bonding interactions. The entire extraction time of the adsorbent only takes five minutes and the extraction recovery rates were in the range of 69.4 %-94.0 % for four cannabinoids after the MSPE procedure optimization. An MSPE-UHPLC-MS/MS quantitative method for determination of four cannabinoids in wastewater was established and validated. The results showed that this method had a good linearity within the range of 0.5–100 ng/L (r 2 > 0.9962). The limits of detection and the limits of quantification were 0.17–0.33 ng/L and 0.50–1.00 ng/L, respectively. The proposed MSPE-UHPLC-MS/MS method based on Fe 3 O 4 @poly(GMA/DVB-WAX) is a convenient, sensitive and reliable strategy and has great application prospects in the analysis of trace cannabinoids in wastewater.
研究领域:
分析化学
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环境科学
·
毒理学
✓ 已验证
产品关联
DOI
高影响因子
MICROCHIMICA ACTA
·
2025
·Vol. 192
·期 5
·1-15
·
IF 5.3
Cao Rui,Chen Jiawei,Pang Ningjia,Li Siyu,Chen Mengyi,Di Bin,Xiao Deli
Nowadays, the abuse of synthetic cannabinoids has aroused the world’s great attention. However, the determination of synthetic cannabinoids in wastewater faces the bottleneck of complex species and very low content. Therefore, this work integrated GO-Fe 3 O 4 with an ionic liquid (ILs-GO-Fe 3 O 4 ) to create a mixed hemimicelles magnetic solid-phase extraction (MHMSPE) system for the detection of synthetic cannabinoids (SCs) in wastewater samples using ultrahigh-performance liquid chromatography—tandem mass spectrometry (UHPLC-MS/MS). Because of the multiple interaction sites of mixed hemimicelles’ magnetic solid-phase extraction materials, multi-structural synthetic cannabinoids can be enriched simultaneously. Under the optimized conditions, the limits of quantitation (LOQ) of the method were as low as 10–50 pg/L, lower than other methods. The average recoveries of 18 analytes were in the range 71.23–96.08% with relative standard deviations (RSD) lower than 15% ( n = 6). To our knowledge, this is the first development of magnetic solid-phase extraction for large-volume samples pretreatment (1 L) and ultra-high sensitive detection of synthetic cannabinoids (10 pg/L), due to the high enrichment factor (10,000-fold). The extraction process was convenient, accurate, and rapid, and offers significant potential for ultra-high sensitivity detection in large-volume samples, providing a valuable tool for simultaneous broad-spectrum extraction and drug abuse monitoring. Graphical abstract
研究领域:
环境科学
·
分析化学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 19
·10699
·
IF 4.9
Jia-Rui Bi,Hai-Wei Zha,Qing-Lin Gao,Hui Wu,Zhen-Jiang Liu,Dong Sun
Anxiety disorder is one of the most common neuropsychiatric disorders, and affects many people’s daily activities. Although the pathogenesis and treatments of anxiety disorder have been studied for several decades, the underlying mechanisms remain elusive. Here, we provide evidence that olfactory stimuli with inhaled linalool or 2-phenylethanol decreased mouse anxiety-like behaviors and increased the activities of hippocampal dentate granule cells (DGCs). RNA-sequencing analysis identified retrograde endocannabinoid signaling, which is a critical pathway for mood regulation and neuron activation, is altered in the hippocampus of both linalool- and 2-phenylethanol-exposed mice. Further studies found that selective inhibition of endocannabinoid signaling by injecting rimonabant abolished the activation of DGCs and the anxiolytic effect induced by linalool or 2-phenylethanol. Together, these results uncovered a novel mechanism by which linalool or 2-phenylethanol decreases mouse anxiety-like behaviors and increases DG activity likely through activating hippocampal retrograde endocannabinoid signaling.
研究领域:
神经科学
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药理学
·
行为学
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2023
·Vol. 148
·期 19
·4850-4856
·
IF 4.2
Jiajia Li,Yong Wang,Anran Liu,Songqin Liu
Synthetic cannabinoids (SCs) are a series of artificial chemical substances with pharmacological properties similar to those of natural cannabinoids and their abuse poses a great risk to social security and human health. However, the highly sensitive detection of low concentrations of SCs in human serum remains a great challenge. In this work, we developed a highly sensitive, rapid and highly selective method for the detection of SCs in human serum. Magnetic molecularly imprinted polymer (MIP) nanocomposites were prepared through self-polymerization of dopamine and template molecules on the surfaces of magnetic beads. 9H-Carbazole-9-hexanol (9CH) was used as a template molecule because of its long chain structure shared with six synthetic cannabinoids and its ability to provide specific recognition sites. With these magnetic MIP nanoparticles, six SCs could be rapidly and effectively extracted from human blood. The concentrations of six SCs could be accurately determined by high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. The limits of detection were in the range of 0.1–0.3 ng mL−1. The proposed method is characterized by high sensitivity and selectivity, and has great potential for application in the analysis of practical samples.
研究领域:
分析化学
·
毒理学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COMPARATIVE NEUROLOGY
·
2022
·Vol. 531
·期 2
·294-313
·
IF 3.028
Xulin Li,Gaoyang Zhao,Hongren Huang,Jialin Ye,Junfeng Xu,Yuan Zhou,Xiaojuan Zhu,Liping Wang,Feng Wang
Many brain functions that underlie behavior, cognition, and emotions vary with age, as does susceptibility to neuropsychological disorders. The expression of specific genes that are involved in these functions, such as the genes encoding for oxytocin, its receptors, and apolipoprotein D, varies with age across different brain regions. The cannabinoid 1 receptor (CB 1 R) is one of the most widely spread G-protein coupled receptors in the central nervous system and is increasingly recognized for its important contribution to various brain functions. Although changes in CB 1 R expression with age have been reported in the male mouse brain, they have not been well investigated in the female brain. Here, we used fluorescence in situ hybridization to target CB 1 R mRNA in the whole brains of female C57BL/6J mice aged 4, 6, 12, 52 (12 months) and 86 weeks (20 months), and quantified CB 1 R-positive cells in 36 brain regions across the whole brain. The results showed that CB 1 R-positive cells number changed with age. Specifically, CB 1 R expression increased with age in some subregions of the cortex, decreased with age in the lateral septal area, and reached its lowest level at 52 weeks in the thalamus, hypothalamus, and hindbrain subregions. Cluster analysis revealed that some brain regions shared similar temporal characteristics in CB 1 R-positive cell number across the lifespan. Our results provide evidence that investigation of the neural basis of age-related characteristics of female brain functions is not only warranted but required.
研究领域:
神经科学
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分子生物学
·
衰老
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）