1.Methamphetamine: Mechanism of Action and Chinese Herbal Medicine Treatment for Its Addiction.
Rui ZENG ; Hong-Yu PU ; Xin-Yue ZHANG ; Meng-Lin YAO ; Qin SUN
Chinese journal of integrative medicine 2023;29(7):665-672
With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.
Humans
;
Methamphetamine/adverse effects*
;
Drugs, Chinese Herbal/therapeutic use*
;
Amphetamine/therapeutic use*
;
Behavior, Addictive/drug therapy*
;
Amphetamine-Related Disorders/drug therapy*
2.Mechanism of miR-186-5p Regulating PRKAA2 to Promote Ferroptosis in Lung Adenocarcinoma Cells.
Lu LIU ; Xin GUAN ; Yanqiao ZHAO ; Xiaona WANG ; Chonggao YIN ; Qinghua LIU ; Hongli LI
Chinese Journal of Lung Cancer 2023;26(11):813-821
BACKGROUND:
Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer, and any change of miRNAs expression will affect the degree of target regulation, thus affecting intracellular homeostasis. This study verified that miR-186-5p could inhibit the proliferation, migration and invasion of LUAD cells by regulating PRKAA2.
METHODS:
Previous investigations found that the expression of miR-186-5p was markedly suppressed in LUAD. Bioinformatics method is used to predict the target protein related to ferroptosis downstream and inquire about its expression level in LUAD and its influence on the survival of patients. Double luciferase verified the binding site of PRKAA2 and miR-186-5p. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of PRKAA2. The effects of miR-186-5p of LUAD cells as well as the mechanism by which miR-186-5p inhibits Fer-1's sensitivity to ferroptosis were confirmed by EdU, Transwell, and scratch assays. The effect of miR-186-5p on the amount of reactive oxygen species (ROS) in LUAD cells was discovered using ROS experiment. Malondialdehyde (MDA) and glutathione (GSH) experiments were used to detect the effects of miR-186-5p and PRKAA2 on ferroptosis index of LUAD cells. The concentration of lipid ROS (L-ROS) in LUAD cells were measured using the L-ROS tests to determine the effects of miR-186-5p and PRKAA2.
RESULTS:
The expression of PRKAA2 is up-regulated, and a high level of PRKAA2 expression was associated with a poor prognosis for patients with LUAD. Overexpression of miR-186-5p decreased the gene and protein expression of PRKAA2. By promoting ferroptosis, miR-186-5p overexpression prevented lung cancer cells from proliferating, invading, and migrating. ROS could be produced in higher amounts in LUAD cells due to miR-186-5p. Overexpression of miR-186-5p and knockdown PRKAA2 up-regulated MDA content and reduced GSH content in LUAD cells, respectively. miR-186-5p could increase the content of L-ROS and promote the ferroptosis sensitivity of LUAD cells by targeting PRKAA2.
CONCLUSIONS
miR-186-5p promotes ferroptosis of LUAD cells through targeted regulation of PRKAA2, thus inhibiting the proliferation, invasion and migration of LUAD.
.
Humans
;
Lung Neoplasms/genetics*
;
Carcinoma, Non-Small-Cell Lung
;
Ferroptosis/genetics*
;
Reactive Oxygen Species
;
Adenocarcinoma of Lung/genetics*
;
MicroRNAs/genetics*
;
3,4-Methylenedioxyamphetamine
;
Cell Proliferation/genetics*
;
Cell Movement/genetics*
;
Gene Expression Regulation, Neoplastic
;
Cell Line, Tumor
;
AMP-Activated Protein Kinases
3.Research Progress on the Effect of Synthetic Cathinones on Animal Behavior.
Zhi Bin HUANG ; Juan CAI ; Ze Bin LIN ; Zi Qin ZHAO ; Bei Xu LI
Journal of Forensic Medicine 2021;37(4):561-568
Synthetic cathinones are a class of new psychoactive substances with a structure similar to amphetamine drugs, which can produce excitatory effects similar to drugs such as amphetamine and cocaine after being taken. In recent years, the abuse of synthetic cathinones worldwide has become increasingly serious, posing a serious threat to social security and public health. This article focuses on several common synthetic cathinones, collects their research results in animal autonomous activity experiments and drug dependence model experiments and summarizes their relevant experimental conclusions in animal body temperature regulation, learning and memory, and anxiety, in order to provide data reference and method guidance for the domestic development of related drug research.
Alkaloids/pharmacology*
;
Amphetamine
;
Animals
;
Behavior, Animal
;
Illicit Drugs
4.Current Situation of Methamphetamine Abuse and Related Research Progress.
Shi-Jun HONG ; Bao-Yu SHEN ; Rong-Ji SUN ; Gen-Meng YANG ; Chun-Mei DUAN ; Qian-Yun NIE ; Cong-Bin ZHANG ; Wen-Juan DONG ; Hao YU ; Shang WANG ; Peng-Liang LIU ; Pin-Yuan WEN ; Li-Hua LI
Journal of Forensic Medicine 2021;37(6):763-775
Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. In order to solve the problem of drug abuse, it is of great theoretical value and practical significance to carry out all-round and multi-level scientific research on drug-related issues. Based on the current situation of drug abuse, this article reviews research progresses on the epidemiology of methamphetamine abuse, the monitoring technology, the basic researches on toxicity damage, the withdrawal drug screening, the related clinical comorbidity and the testing technologies, comprehensively presenting the development trend of methamphetamine abuse related issues.
Amphetamine-Related Disorders/epidemiology*
;
Heroin
;
Humans
;
Illicit Drugs
;
Methamphetamine/adverse effects*
;
Substance Abuse Detection
5.Ezrin-radixin-moesin proteins are regulated by Akt-GSK3β signaling in the rat nucleus accumbens core
Wha Young KIM ; Wen Ting CAI ; Ju Kyong JANG ; Jeong Hoon KIM
The Korean Journal of Physiology and Pharmacology 2020;24(1):121-126
The ezrin-radixin-moesin (ERM) proteins are a family of membrane-associated proteins known to play roles in cell-shape determination as well as in signaling pathways. We have previously shown that amphetamine decreases phosphorylation levels of these proteins in the nucleus accumbens (NAcc), an important neuronal substrate mediating rewarding effects of drugs of abuse. In the present study, we further examined what molecular pathways may be involved in this process. By direct microinjection of LY294002, a PI3 kinase inhibitor, or of S9 peptide, a proposed GSK3β activator, into the NAcc core, we found that phosphorylation levels of ERM as well as of GSK3β in this site are simultaneously decreased. These results indicate that ERM proteins are under the regulation of Akt-GSK3β signaling pathway in the NAcc core. The present findings have a significant implication to a novel signal pathway possibly leading to structural plasticity in relation with drug addiction.
Amphetamine
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Animals
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Glycogen Synthase Kinases
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Humans
;
Membrane Proteins
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Microinjections
;
Negotiating
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Neurons
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Nucleus Accumbens
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Phosphorylation
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Phosphotransferases
;
Plastics
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Proto-Oncogene Proteins c-akt
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Rats
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Reward
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Signal Transduction
;
Street Drugs
;
Substance-Related Disorders
6.Recurrent Psychosis after Phentermine Administration in a Young Female: A Case Report
Hyun Sic JO ; Sheng Min WANG ; Jung Jin KIM
Clinical Psychopharmacology and Neuroscience 2019;17(1):130-133
Phentermine is a sympathomimetic amine, like amphetamine, which is one of the most often prescribed drugs for weight loss. Although exact mechanism of phentermine causing psychosis is still not clear, numerous reports already showed that phentermine can induce psychosis. Psychotic symptoms are generally resolved once the medications are stopped. In contrast, we present a case of a 25-years-old Asian female patient who developed psychotic symptoms repeatedly after phentermine administrations. This case suggests that phentermine can cause psychotic episodes repeatedly, resulting in chronic occupational and social impairment. Therefore, a precautious measure such as government regulations for physicians prescribing and an education for patients taking phentermine are urgently needed.
Amphetamine
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Asian Continental Ancestry Group
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Education
;
Female
;
Government Regulation
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Humans
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Phentermine
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Psychotic Disorders
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Recurrence
;
Weight Loss
7.Imaging changes in brain microstructural in long-term abstinent from methamphetamine-dependence.
Lidan FAN ; Qingqing ZHANG ; Shengxiang LIANG ; Huabing LI ; Zhong HE ; Jianning SUN ; Weijun SITU ; Zhixue ZHANG ; Dawei WU ; Zishu ZHANG ; Zhifeng KOU ; Jun ZHANG ; Jun LIU
Journal of Central South University(Medical Sciences) 2019;44(5):491-500
To explore the mechanism for changes in brain microstructure in long-term abstinent from methamphetamine-dependence by using the diffusion tensor imaging (DTI).
Methods: A total of 26 patients with long-term abstinent methamphetamine-dependence, whose abstinence time more than 14 months, and 26 normal controls all underwent cognitive executive function tests and DTI scans. We used voxel-based analysis to compare the fractional anisotropy (FA) and mean diffusivity (MD) to obtain the abnormal brain regions of DTI parameters between the two groups. Spearman correlation analysis was used to explore the correlation between FA, MD of the brain regions with abnormal parameters and cognitive executive function tests.
Results: There were no statistical differences in the cognitive executive function tests between the two groups (P>0.05). Compared with the normal control group, the long-term abstinent from methamphetamine-dependence group showed the decreased FA in the right precuneus, right superior frontal gyrus, right calcarine, left inferior temporal gyrus and the increased MD in the right triangular part of inferior frontal gyrus, right precuneus, right posterior cingulate, right middle temporal gyrus, bilateral middle occipital gyrus, left superior parietal lobule, and lobule VIII of cerebellar hemisphere. The MD values of the right middle temporal gyrus in the long-term abstinent group were negatively correlated with the number of completions within 60 seconds (r=-0.504) and within 120 seconds (r=-0.464) .
Conclusion: The DTI parameters in multiple brain regions from the methamphetamine-dependence patients are still abnormal after a long-term abstinence. DTI can provide imaging evidence for brain microstructural abnormalities in long-term abstinent from methamphetamine-dependence.
Amphetamine-Related Disorders
;
Anisotropy
;
Brain
;
Diffusion Tensor Imaging
;
Humans
;
Methamphetamine
8.Evaluation of Matrix Effects in Quantifying Microbial Secondary Metabolites in Indoor Dust Using Ultraperformance Liquid ChromatographeTandem Mass Spectrometer
Mukhtar JADERSON ; Ju Hyeong PARK
Safety and Health at Work 2019;10(2):196-204
BACKGROUND: Liquid chromatographyetandem mass spectrometry (LC-MSMS) for simultaneous analysis of multiple microbial secondary metabolites (MSMs) is potentially subject to interference by matrix components. METHODS: We examined potential matrix effects (MEs) in analyses of 31 MSMs using ultraperformance LC-MSMS. Twenty-one dust aliquots from three buildings (seven aliquots/building) were spiked with seven concentrations of each of the MSMs (6.2 pg/µl–900 pg/µl) and then extracted. Another set of 21 aliquots were first extracted and then, the extract was spiked with the same concentrations. We added deepoxy-deoxynivalenol (DOM) to all aliquots as a universal internal standard. Ten microliters of the extract was injected into the ultraperformance LC-MSMS. ME was calculated by subtracting the percentage of the response of analyte in spiked extract to that in neat standard from 100. Spiked extract results were used to create a matrix-matched calibration (MMC) curve for estimating MSM concentration in dust spiked before extraction. RESULTS: Analysis of variance was used to examine effects of compound (MSM), building and concentration on response. MEs (range: 63.4%–99.97%) significantly differed by MSM (p < 0.01) and building (p < 0.05). Mean percent recoveries adjusted with DOM and the MMC method were 246.3% (SD = 226.0) and 86.3% (SD = 70.7), respectively. CONCLUSION: We found that dust MEs resulted in substantial underestimation in quantifying MSMs and that DOM was not an optimal universal internal standard for the adjustment but that the MMC method resulted in more accurate and precise recovery compared with DOM. More research on adjustment methods for dust MEs in the simultaneous analyses of multiple MSMs using LC-MSMS is warranted.
2,5-Dimethoxy-4-Methylamphetamine
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Calibration
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Dust
;
Mass Spectrometry
;
Methods
9.Identification of the New Psychoactive Substance Dibutylone.
Kua Dou WANG ; Fang Qi CAO ; Xue JIANG ; Hong CHEN ; Xie Liang YUAN ; Yong Sheng CHEN ; Jun Jian HU
Journal of Forensic Medicine 2019;35(6):682-686
Objective To establish a method to identify unknown samples based on combined use of gas chromatography-mass spectrometry (GC-MS), high resolution mass spectrometry (HRMS) and nuclear magnetic resonance spectrum (NMR) technique. Methods The unknown samples were dissolved in methanol solution containing internal standard SKF525A and detected by GC-MS and HRMS. The mixed samples were separated and purified by silica gel column chromatography, and then dissolved in methanol-d4 solution for structural analysis of 1H nuclear magnetic resonance spectroscopy (1H NMR). Results The characteristic fragment ions (m/z) were 86.1 (base peak), 71.2, 121.1, and 149.0, and the accurate mass number of molecular ion peak was measured by HRMS to be 236.128 89. By combined use of data analysis and database comparison, a new psychoactive substance of the cathinone class, Dibutylone, was detected in the sample, and the sample also contained a small amount of caffeine. The sample was purified, then identified using 1H NMR, and was further confirmed to be Dibutylone. In addition, the GC-MS retention time and characteristic fragment ions of the main components of the sample were consistent with those of Dibutylone reference material. Conclusion The method established in this study can be used for the identification of Dibutylone in mixed samples.
Chromatography, Liquid
;
Gas Chromatography-Mass Spectrometry
;
Magnetic Resonance Spectroscopy
;
Mass Spectrometry
;
N-Methyl-3,4-methylenedioxyamphetamine/isolation & purification*
;
Psychotropic Drugs/chemistry*
10.Research Progress on Detection Methods of Amphetamines in Human Hair.
Guan-heng REN ; Qi-jiang YAN ; Ying TANG ; Jun-jin WU ; Jing-hong ZHANG ; Jian-wen SONG ; Ning-guo LIU
Journal of Forensic Medicine 2019;35(1):89-94
Amphetamines are chemical synthetic drugs that are becoming increasingly popular in China. As a common sample in the inspection of poisons, hair has the advantages of easy storage, good stability, and long detection time compared with traditional human body fluid samples (blood, urine), thus possesses an unique application value in the field of forensic toxicology analysis. By now, methods for detecting amphetamines in human hair have been widely used, and validity of the results has been recognized and adopted by the court. This paper reviews domestic and foreign research progress of the detection of amphetamines in hair samples, including the pretreatment and analytic methods.
Amphetamines/analysis*
;
China
;
Forensic Toxicology
;
Hair/chemistry*
;
Humans
;
Substance Abuse Detection

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