1.Research progress of mitochondrial quality control in methamphetamine-induced neurotoxicity
Qian-Yun NIE ; Wen-Juan DONG ; Gen-Meng YANG ; Li-Xiang QIN ; Chun-Hui SONG ; Li-Hua LI ; Shi-Jun HONG
Chinese Pharmacological Bulletin 2024;40(7):1201-1205
Methamphetamine abuse is a major public health problem in the world,and in recent years,methamphetamine is also the most abused synthetic drug in China.The neurotoxic or addiction mechanism of methamphetamine has not been fully clarified,and there is still a lack of specific withdrawal methods and drugs for methamphetamine abuse.Mitochondria are not on-ly the organelles to which methamphetamine directly produces toxic effects,but also participate in regulating the neurotoxic damage process of methamphetamine.Mitochondrial quality is the regulatory basis for maintaining mitochondrial homeostasis and is regulated by three main mechanisms,which are mitochon-drial biogenesis,mitochondrial dynamic,and mitophagy.This review summarizes the research progress of mitochondrial quality control in methamphetamine-induced neurotoxicity,which may provide theoretical support for further research on the mechanism of methamphetamine neurotoxicity and development the mito-chondria-targeting drugs.
2. Research progress on mechanisms of neuroinflammation induced by methamphetamine and HIV-1 Tat protein
Yi TAN ; Gen-Meng YANG ; Shu-Wei ZHANG ; Hui-Jie ZHANG ; Hao-Wei WANG ; Lin MIAO ; Yi LI ; Zhen LI ; Xiao-Feng ZENG ; Juan LI
Chinese Pharmacological Bulletin 2023;39(8):1417-1421
Methamphetamine abuse and HIV infection are extremely serious public health and social problems facing the world today. Methamphetamine and HIV-1 Tat protein can induce neurotoxicity in an individual and synergistic way, and neuroinflammation is one of the most important mechanisms for ca-using neurotoxicity. Neuroinflammation can be mediated by glial cells, cytokines, NLRP3 inflammasomes, etc. This paper reviews the research progress of neuroinflammation induced by methamphetamine and HIV-1 Tat protein in recent years, with the aim of providing reference and basis for further exploration of the mechanisms of neuroinflammation caused by them and effective drug intervention targets in the future.
3.Effects of early enteral nutrition on postoperative rehabilitation and inflammation after laparoscopic radical gastrectomy for gastric cancer
Lu-Gen ZUO ; Zhen ZHANG ; Lian WANG ; Meng ZHAO ; Qiu-Sheng WANG ; Yi-Qun YANG ; Ping-Sheng ZHU ; De-Li CHEN ; Mu-Lin LIU ; Si-Tang GE
Parenteral & Enteral Nutrition 2023;30(5):287-291
Objective:To investigate the effect of early postoperative enteral nutrition(EN)on postoperative rehabilitation and inflammation after laparoscopic radical gastrectomy for gastric cancer,in order to provide reference for postoperative rehabilitation of such patients.Methods:Patients who received laparoscopic assisted radical gastrectomy in Department of Gastrointestinal Surgery of The First Affiliated Hospital of Bengbu Medical College from January 2020 to December 2022 were included in the analysis.According to the different ways of postoperative nutritional treatment,patients were divided into the observation group(early postoperative EN group)and the control group(parenteral nutrition group),and indexes such as postoperative rehabilitation,abdominal drainage flow and the level of inflammatory mediators in drainage fluid were compared between the two groups.Results:A total of 81 patients were included,including 41 in the observation group and 40 in the control group.Interval of the first postoperative exhaust(t=3.806;P<0.001)and resuming diet day(t=5.510;P<0.001),and length of postoperative hospital stay(t=2.401;P=0.019)in the observation group were shorter than those in the control group.Levels of peripheral blood albumin(t=14.040;P<0.001)and prealbumin(t=9.832;P<0.001)of the observation group at postoperative day(POD)5 were significantly higher than those of the control group,but there was no significant difference in hemoglobin level(t=1.477;P=0.144).The level of CRP in peripheral blood of the observation group at POD 5(t=7.758;P<0.001)and the incidence of postoperative SIRS[(12.2%,5/41)vs(32.5%,13/40),x2=4.830;P=0.028)]were significantly lower than those in the control group.The average drainage volume(t=6.858;P<0.001),drainage removal time(t=5.016;P<0.001),and TNF-α level(t=4.993;P<0.001)and IL-6 level(t=20.640;P<0.001)in postoperative drainage at POD 5 were significantly lower in the observation group than those in the control group.Conclusion:Early postoperative EN could accelerate the rehabilitation process after laparoscopic radical gastrectomy,improve postoperative nutritional status,and reduce abdominal inflammation.
4.Protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae against myocardial injury in septic mice.
Yuan YUAN ; Feng NIAN ; Hui Hui LI ; Hui Juan YANG ; Yu Zhi WU ; Meng Xi MA ; Kai Gui WANG ; Xue Ling CHEN ; Zi Qiang ZHANG ; Gen LI ; Xiao Di YANG ; Qiang WU
Journal of Southern Medical University 2022;42(6):824-831
OBJECTIVE:
To evaluate the protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae (Ts-MES) on sepsis-induced myocardial injury in mice.
METHODS:
Eighty male BALB/C mice were randomized equally into sham-operated group, myocardial injury group, Ts-MES treatment group and dexamethasone treatment group. In the latter 3 groups, sepsis-induced myocardial injury models were established by cecal ligation and perforation; the sham operation was performed by exposure of the cecum without ligation or perforation. Forty minutes after the operation, the mice were given intraperitoneal injections 150 μL PBS, 20 μg TS-MES or 0.3 mg/kg dexamethasone as indicated. At 12 h after the operation, 6 mice were randomly selected from each group for echocardiography, and 8 mice were used for observing the survival rate within 72 h. The remaining 6 mice were examined for myocardial pathologies with HE staining and serum levels of NTPro-BNP and cTnI with ELISA; the expressions of TNF-α, IL-6, IL-10 and TGF-β in the serum and myocardial tissue were detected using ELISA and qRT-PCR.
RESULTS:
Compared with the sham-operated mice, the septic mice showed significantly decreased cardiac function indexes (LVEF, LVFS, and E/A) with lowered survival rate within 72 h (P < 0.001) and significantly higher myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.01). Treatment with TS-MES significantly improved the cardiac function and 72-h survival rate (P < 0.05) and lowered the myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.05) in the septic mice. Compared with the sham-operated mice, the septic mice had obviously increased TNF-α and IL-6 levels in the serum and myocardial tissue (P < 0.001), which were significantly lowered by treatment with TS-MES (P < 0.05). TS-MES and dexamethasone both increased the levels of IL-10 and TGF-β in the septic mice, but the changes were significant only in TS-MES-treated mice (P < 0.05).
CONCLUSION
Ts-MES are capable of protecting against myocardial injury in septic mice by reducing the production of pro-inflammatory cytokines and enhancing the levels of regulatory cytokines.
Animals
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Cytokines
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Dexamethasone
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Heart Injuries
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Interleukin-10
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Interleukin-6
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Larva
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Male
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Mice
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Mice, Inbred BALB C
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Myocardium
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Sepsis
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Transforming Growth Factor beta
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Trichinella spiralis
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Tumor Necrosis Factor-alpha
5.Optimization and evaluation of Xiaoer Pudilan Xiaoyan Syrup based on characterization of material properties.
Xuan LI ; Ke DING ; Dang YANG ; Meng-Hua JIANG ; Chao LI ; Fa-Gen ZHU ; Jian-Guo SHAO ; E SUN ; Liang FENG ; Xiao-Bin JIA
China Journal of Chinese Materia Medica 2022;47(21):5746-5756
According to the taste analysis of Pudilan Xiaoyan Oral Liquid, the unpleasant taste of the oral liquid is mainly caused by the inherent taste of Chinese medicine and the taste introduced in the preparation process, which leads to its unpopularity among children. Therefore, aiming at the special children patient group, Xiaoer Pudilan Xiaoyan Syrup was developed via technology optimization and dosage form improvement to improve the unpleasant taste and enhance the medication compliance among children. Based on the material properties of Pudilan Xiaoyan Oral Liquid and Xiaoer Pudilan Xiaoyan Syrup extracts, the authors compared the properties(pH, density, turbidity, viscosity, chromaticity, particle size), taste, content of five quality markers and in vivo pharmacokinetic characteristics of these two preparations, to evaluate the suitability of Xiaoer Pudilan Xiaoyan Syrup. The results showed that compared with those of Pudilan Xiaoyan Oral Liquid, the pH, density, turbidity, viscosity and chromaticity of Xiaoer Pudilan Xiaoyan Syrup were significantly changed, and the unpleasant taste was reduced by 26%; the transfer rate of the main active ingredients chicoric acid was increased, while the transfer rate of baicalin had small difference from that of the oral liquid. In addition, pharmacokinetics revealed that the total absorption amount of baicalin in vivo was higher, and the time to peak T_(max) of baicalin and oroxindin in the syrup and the mean residence time MRT_(last )of corynoline in vivo were significantly prolonged. The absorption degree of Xiaoer Pudilan Xiaoyan Syrup and Pudilan Xiaoyan Oral Liquid in the body was the same: baicalin>oroxindin>corynoline. The new dosage form process was simpler than that of the original dosage form, safe, environmentally friendly, reasonable and feasible, meeting the mass production demand. This provided a basis for the reasonable and scientific optimization of Xiaoer Pudilan Xiaoyan Syrup, and also laid a foundation for its further safe and rational use, so as to expand the clinical application in children.
Child
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Humans
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Drugs, Chinese Herbal
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Glucuronates
6. Role of microRNA-132 and Mecp2 in methamphetamine dependence
Zhen-Jin SHI ; Rui-Lin ZHANG ; Yi-Hang WANG ; Gen-Meng YANG ; Bao-Yu SHEN ; Shang WANG ; Peng-Liang LIU ; Li-Hua LI ; Dong-Xian ZHANG ; Shi-Jun HONG ; Zhen-Jin SHI ; Ya-Mei WU ; Ya-Mei WU ; Ting-Na ZHU ; Yong-Na ZHAO
Chinese Pharmacological Bulletin 2022;38(1):73-78
Aim To explore the roles of miRNA-132 and its related proteins(Mecp2, CREB)in the mechanism of methamphetamine(MA)-induced neurotoxicity and dependence.Methods The rats were intraperitioneally injected(ip)with MA(10 mg·kg-1·d-1)to establish methamphetamine dependence model with different dependent time courses of 1 week, 2 weeks, and 4 weeks respectively.The miRNA-132 and Mecp2 mRNA were detected by RT-qPCR, and the Mecp2, p-Mecp2, CREB and p-CREB proteins were detected by Western blot in the tissues of frontal cortex and hippocampus.Results In the frontal cortex, the miRNA-132 and Mecp2 mRNA were up-regulated in MA-dependent groups(P<0.05 and P<0.01), while the Mecp2 protein were down-regulated(P<0.01).MA could promote the phosphorylation of Mecp2 protein in the frontal cortex(P<0.01).In hippocampus, the miRNA-132 was down-regulated in the MA-dependent groups, but Mecp2 mRNA was up-regulated(P<0.05).Mecp2 protein increased in MA-dependent 1 week group(P<0.05), and then recovered with the prolonged time of MA dependence, then decreased in MA-dependent 4 weeks groups(P<0.05)in hippocampus.The phosphorylation level of Mecp2 was significantly decreased in the 1 week group(P<0.01), and then increased in the 2 weeks group(P<0.01)in hippocampus.Conclusions MA could induce an abnormal expression of miRNA-132 in the frontal cortex and hippocampus, and miRNA-132 might inhibit the translation of Mecp2 mRNA and induce the decrease expression of Mecp2 protein in the frontal cortex.But in hippocampus, miRNA-132 does not show the correlation with the Mecp2 expression trend of the frontal cortex.And miRNA-132 regulation does not depend on the expression of Mecp2 in hippocampus.
7.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*
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Heroin
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Humans
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Illicit Drugs
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Methamphetamine/adverse effects*
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Substance Abuse Detection
8. Role of NR2B and CREB in ginsenoside Rbl regulation of methamphetamine-induced conditioned place preference in rats
Chinese Pharmacological Bulletin 2020;36(5):604-608
Aim To study the effect of ginsenoside Rbl on methamphetamine-induced CPP in rats and to explore the role of NR2B/CREB in it. Methods METH(2mg·kg-1, i.p) was administered to establish METH-induced CPP model in rats. 0 ∼3 d was the adaptation stage and 4 ∼ 13 d was the experimental stage. METH (2 mg · kg-1, i. p) or saline (10 mg · kg-1, i. p) was injected every other day. Rb1 (10 mg · kg-1, i.p) or saline was pre-injected lh before injection of METH or saline. After perfusion, the hippocampus was isolated from brain on ice, and the expression levels of NR2B, CREB and p-CREB were detected by Western blot. Results The animal model of METH-induced CPP was successfully established. The rats were pretreated with Rbl (10 mg · kg-1) for 1 h, and the time that the rats stayed in drug-paired was significantly reduced compared with METH group. Western blot results showed that NR2B, p-CREB and p-CREB/CREB significantly increased in METH group and without altering CREB expression levels compared with control group. However, after pre-treated with Rbl, the expression levels of NR2B, p-CREB and p-CREB/CREB decreased compared with METH group. Conclusions METH can significantly induce CPP in rats. Rbl may inhibit METH-induced CPP in rats by regulating NR2B and p-CREB.
9.Progress of Functional Imaging in Brain Structure and Functional Changes in People with Amphetamine Addiction
Feng-Lin XUE ; Shi-Jun HONG ; Xiao-Feng ZENG ; Jing YANG ; Gen-Meng YANG ; Yi-Qing ZHOU ; Li-Hua LI
Journal of Kunming Medical University 2018;39(8):129-133
Amphetamines abuse is defined as a chronic recurrent encephalopathy, and it is a global public health problem which seriously threatens the health of human and the social stability. Long-term abuse and addiction of amphetamines leads to structural and functional changes of specific encephalic regions. Further researches on these encephalic regions, the network of brain and biological information may be helpful to understanding drug abuse mechanism and possible therapeutic measures. Recently, a series of functional imaging techniques, including magnetic resonance imaging (MRI), functional magnetic resonance imaging (f MRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and positron emission tomography (PET), were used to detect different brain structural changes of the volume and density of encephalic regions, functional changes of cerebral blood flow and brain cognition. The results showed functional imaging techniques play significant roles to detect different structural and functional changes of the brain. Based on these results, the researchers aim to clarify the mechanisms of drug abuse. That is the main focus of this review.
10.Effects of gastrodin against SH-SY5Y cell autophagy induced by methamphetamine and underlying mechanisms
Gen-Meng YANG ; Juan LI ; Shi-Jun HONG ; Feng-Lin XUE ; Yong-Wang HE ; Yi-Qing ZHOU ; Xiao-Feng ZENG ; Li-Hua LI
Chinese Pharmacological Bulletin 2018;34(4):577-583
Aim To investigate the effects of gastrodin on SH-SY5Y cell autophagy induced by methamphet-amine (METH) and the underlying mechanisms. Methods SY5Y cells were treated by METH with the concentration of 0.5,1.0,1.5,2.0,2.5,3.0 mmol·L-1for 24 h. The morphological changes were ob-served by microscopy,the expression of LC3-Ⅱ,Bec-lin-1,Akt,p-Akt,mTOR and p-mTOR were detected by Western blot. Gastrodin was added to the medium 1 h before METH treatment. Results The SY 5 Y cells were morphologically featured by shrinkage and den-drite disruption after exposed to METH(0~3 mmol· L-1),and autophagic vacuoles occurred in cytoplasm. The expression of LC3-Ⅱ increased over METH dose. Confocal results showed that LC3-Ⅱsignificantly in-creased in METH group as compared with control, while decreased in METH+ Gastrodin group. The ex-pression levels of LC3-Ⅱand Beclin-1 significantly in-creased (P<0.01) in METH group, p-mTOR and p-Akt decreased, and mTOR and Akt showed no signifi-cant difference as compared with control. However, the gastrodin could decrease the expression of LC3-Ⅱand Beclin-1 and increase the expression of mTOR,p-mTOR,Akt and p-Akt as compared with METH-trea-ted groups. Conclusions METH can induce SY5Y cells autophagy. The protective effect of gastrodin a-gainst METH-induced autophag may be related to gast-rodin regulation mTOR and Akt signaling pathway.

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