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The speed-limiting role in the onset of antidepressants: the re-establishment of the excitation/inhibition(E/I) function balance in the mPFC of rats

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中国药理学与毒理学杂志 2023年第7期37卷 527-528页

作者： YAN Jiaozhao YIN Yongyu LI Yunfeng Beijing Institute of Basic Medical Sciences Beijing Institute of Pharmacology and toxicology State Key Laboratory of Toxicology and Medical Countermeasures Beijing Key Laboratory of Neuropsychopharmacology

OBJECTIVE There are serious hazards in depression, and the precise mechanism underlying the delayed onset of clinical antidepressants remains *** purpose of this study was to investigate the regular pattern of the speed-limiting role of excitation/inhibition(E/I) function balance in the mechanism of antidepressant action. METHODS Based on the previous study, we focused on glutamatergic pyramidal neurons in the medial prefrontal cortex(mPFC) here and used its excitability to represent the establishment of a new E/I functional balance. We studied the changes in the firing activity of glutamatergic pyramidal neuron in the mPFC at different administration times for five types of antidepressants that act on different pharmacological targets and different onset times, including fluoxetine(SSRI), duloxetine(SNRI), vilazodone [serotonin 1A receptor(5-HT1A) agonist and SSRI], ketamine [N-methyl-D-aspartate(NMDA)receptor antagonist], and hypidone hydrochloride(YL-0919, new antidepressant with sigma-1 receptor agonist and SSRI). We first examined the initial onset time of activation of pyramidal neurons using multichannel electrophysiological recordings and tested the antidepressant behavioral effects using the FST. We then selected three antidepressants(fluoxetine, ketamine, and vilazodone) to explore its effects on the BDNF-mTOR pathway by Western blotting. In addition, we disrupted the E/I function balance using chemogenetics to investigate the antidepressant-like effects of YL-0919 and ketamine in the FST and TST. RESULTS We found that treatment with fluoxetine for 17 days significantly increased the firing activity of pyramidal neurons and decreased the immobility duration in the FST. Similarly, it took duloxetine for 10 d, vilazodone for 4 d, YL-0919 for 3 d and ketamine for 24 h, to exert such effects. Meanwhile, Western blotting results suggested that the expression of BDNF and phosphorylation of mTOR in the mPFC significantly increased. However, haloperidol, a

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Research progress in the estimation of the postmortem interval by Chinese forensic scholars

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forensic Sciences Research 2016年第1期1卷 3-13页

作者： Chengzhi Li Qi Wang Yinming Zhang Hancheng Lin Ji Zhang Ping Huang Zhenyuan Wang School of forensic Science and Medicine Xi’an Jiaotong UniversityXi’anChina Shanghai key laboratory of forensic Science Shanghai Forensic Service PlatformInstitute of Forensic ScienceMinistry of JusticePRCShanghaiChina

The determination of time since death or the postmortem interval(PMI)is one of the most important and frequently asked questions in forensic *** scholars and forensic pathologists around the world have studied the estimation of PMI extensively in the past,and many novel methods and advanced technologies have now been applied in the *** several centuries,Chinese forensic examiners have also worked on the estimation of the PMI,and there are a large number of excellent studies published in Chinese rather than in English,and these are not easily accessible or known *** we have conducted a review of relevant studies published by Chinese forensic scholars in the last few *** scope of this review is to provide a concise summary of the current progress in the estimation of PMI by Chinese forensic researchers using molecular biology,spectroscopic technology,entomological methods,energy changes,thanatochemistry and other methods.

关键词： forensic science forensic pathology postmortem interval methods Chinese

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Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats

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Neuroscience Bulletin 2016年第6期32卷 523-530页

作者： Xiao-Fei Wang Tai-Yun Zhao Rui-Bin Su Ning Wu Jin Li State key laboratory of toxicology and Medical Countermeasures Beijing Key Laboratory of NeuropsychopharmacologyBeijing Institute of Pharmacology and Toxicology

Abstract Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hip- pocampal extracellular glutamate level induced by nalox- one （2 mg/kg, i.p.） precipitation. Agmatine （20 mg/kg, s.c.） administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synapto- somes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agrnatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors （NMDARs） was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine pre- vented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including mod- ulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.

关键词： Agmatine Opioid addiction HippocampusExtracellular glutamate NMDA receptors

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Research progress of disinfection and disinfection by-products in China

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Journal of Environmental Sciences 2019年第7期31卷 52-67页

作者： Xuefeng Sun Miao Chen Dongbin Wei Yuguo Du State key laboratory of Environmental Chemistry and Eco-toxicology Research Center for Eco-Environmental Sciences Chinese Academy of Sciences University of Chinese Academy of Sciences

Disinfection is an indispensable water treatment process for killing harmful pathogens and protecting human health. However, the disinfection has caused significant public concern due to the formation of toxic disinfection by-products(DBPs). Lots of studies on disinfection and DBPs have been performed in the world since 1974. Although related studies in China started in1980 s, a great progress has been achieved during the last three decades. Therefore, this review summarized the main achievements on disinfection and DPBs studies in China, which included:(1) the occurrence of DBPs in water of China,(2) the identification and detection methods of DBPs,(3) the formation mechanisms of DBPs during disinfection process,(4) the toxicological effects and epidemiological surveys of DBPs,(5) the control and management countermeasures of DBPs in water disinfection, and(6) the challenges and chances of DBPs studies in future. It is expected that this review would provide useful information and reference for optimizing disinfection process, reducing DBPs formation and protecting human health.

关键词： Disinfection Disinfection by-products Identification Formation mechanisms toxicology Control

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Review of the accreditation of digital forensics in China

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forensic Sciences Research 2018年第3期3卷 194-201页

作者： Hong Guo Junlei Hou Shanghai key laboratory Scienceof forensic Medicine Shanghai Forensic Service PlatformAcademy of Forensic ScienceShanghaiChina Cyber Security Department Ministry of PRCBeijingChina

As a result of the many developments in information technology,digital evidence plays an increasingly important role in criminal and civil *** digital evidence is necessary for litigation,the judicial system must be assured of its accuracy,reliability,and verifiability,which can be assured by *** paper focuses on a comparison of the evolution of the accreditation of digital forensics internationally and domestically,discusses the existing problems that such accreditation encounters,and proposes the corresponding ***,this paper discusses the future of digital forensic laboratory accreditation and its implementation.

关键词： Accreditation digital forensics forensic science methodology personnel training

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A highly potent and stable pan-coronavirus fusion inhibitor as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1652-1661页

作者： Jie Zhou Wei Xu Zezhong Liu Chao Wang Shuai Xia Qiaoshuai Lan Yanxing Cai Shan Su Jing Pu Lixiao Xing Youhua Xie Lu Lu Shibo Jiang Qian Wang key laboratory of Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical Sciences and BSL-3 FacilityShanghai Institute of Infectious Diseases and BiosecurityFudan UniversityShanghai 200032China State key laboratory of toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing 100850China

The development of broad-spectrum antivirals against human coronaviruses(HCoVs)is critical to combat the current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its variants,as well as future outbreaks of emerging *** have previously identified a polyethylene glycol-conjugated(PEGylated)lipopeptide,EK1C4,with potent pan-CoV fusion inhibitory ***,PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in ***,we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment(HR2-CF)of *** these lipopeptides,EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike(S)mutants,as well as other HCoVs and some bat SARS-related coronaviruses(SARSr-CoVs)*** dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes,better metabolic stability in mouse serum,higher thermostability than the PEGylated lipopeptide EK1C4,suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.

关键词： Coronavirus Lipopeptide SARS-CoV-2 Polyethylene glycol Fusion inhibitor

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Self-anti-angiogenesis nanoparticles enhance anti-metastatic-tumor efficacy of chemotherapeutics

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Bioactive Materials 2022年第7期7卷 179-190页

作者： Jiamao Luo Xinxian Zhong Yingming Peng Chenyuan Hao Xiaomei Liang Yulu Yang Xiubo Shi Xuncai Chen Xiao Yi iaoxuan Li Jianhua Wu Jinheng Li Qian Xiao Chentian Wu b Ruojing Lu b Yao Pan Xuejiao Wang Jun-Bing Fan Yifeng Wang Ying Wang Department of Obstetrics&Gynecology Zhujiang HospitalSouthern Medical UniversityGuangzhou510280China Guangzhou key laboratory of Tumor Immunology Research Cancer Research InstituteSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou510515China Department of forensic toxicology School of Forensic MedicineSouthern Medical UniversityGuangzhou510515China

Beyond traditional endothelium-dependent vessel(EDV),vascular mimicry(VM)is another critical tumor angiogenesis that further forms in many malignant metastatic ***,the existing anti-angiogenesis combined chemotherapeutics strategies are only efficient for the treatment of EDV-based subcutaneous tumors,but remain a great challenge for the treatment of in situ malignant metastatic tumor associated with EDV and ***,we demonstrate a self-assembled nanoparticle(VE-DDP-Pro)featuring self-anti-EDV and-VM capacity enables to significantly enhance the treatment efficacy of cisplatin(DDP)against the growth and metastasis of ovarian *** VE-DDP-Pro is constructed by patching DDP loaded cRGD-folate-heparin nanoparticles(VE)onto the surface of protamine(Pro)*** demonstrated the self-anti-angiogenesis capacity of VE-DDP-Pro was attributed to VE,which could significantly inhibit the formation of EDV and VM by regulating signaling pathway of MMP-2/VEGF,AKT/mTOR/MMP-2/Laminin and AKT/mTOR/EMT,facilitating chemotherapeutics to effectively suppress the development and metastasis of ovarian ***,combing with the chemotherapeutics effectiveness of DDP,the VE-DDP-Pro can significantly enhance treatment efficacy and prolong median survival of mice with metastatic ovarian *** believe our self-assembled nanoparticles integrating the anti-EDV and anti-VM capacity provide a new preclinical sight to enhance the efficacy of chemotherapeutics for the treatment malignant metastasis tumor.

关键词： self-anti-angiogenesis Nanoparticles Metastatic ovarian cancer VM EDV

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Translocator protein ligand, YL-IPA08, attenuates lipopolysaccharide-induced depression-like behavior by promoting neural regeneration

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Neural Regeneration Research 2018年第11期13卷 1937-1944页

作者： Xiao-Ying Zhang Li-Ming Zhang Wei-Dong Mi Yun-Feng Li Anesthesia and Operation Center Chinese PLA General Hospital Beijing China State key laboratory of toxicology and Medical Countermeasures Beijing China

Translocator protein has received attention for its involvement in the pathogenesis of depression. This study assessed the effects of the new translocator protein ligand, YL-IPA08, on alleviating inflammation-induced depression-like behavior in mice and investigated its mechanism of action. Mice were intracerebroventricularly injected with 1, 10, 100 or 1000 ng lipopolysaccharide. The tail-suspension test and the forced swimming test confirmed that 100 ng lipopolysaccharide induced depression-like behavior. A mouse model was then established by intraventricular injection of 100 ng lipopolysaccharide. On days 16-24 after model establishment, mice were intragastrically administered 3 mg/kg YL-IPA08 daily. Immunohistochemistry was used to determine BrdU and NeuN expression in the hippocampus. YL-IPA08 effectively reversed the depression-like behavior of lipopolysaccharide-treated mice, restored body mass, increased the number of BrdU-positive cells, and the number and proportion of BrdU and NeuN double-positive cells. These findings indicate that YL-IPA08 can attenuate lipopolysaccharide-induced depression-like behavior in mice by promoting the formation of hippocampal neurons.

关键词： nerve regeneration YL-IPA08 hippocampus dentate gyrus lipopolysaccharide neuroinflammation depression translocator protein neural regeneration

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Simultaneous determination of 15 pesticide residues in Chinese cabbage and cucumber by liquid chromatography-tandem mass spectrometry utilizing online turbulent flow chromatography

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Food Science and Human Wellness 2021年第1期10卷 78-86页

作者： Sufang Fan Junmei Ma Meirong Cao Juan Wang Leilei Zhang Yan Zhang Qiang Li Jia Chen Hebei key laboratory of forensic Medicine College of Forensic MedicineHebei Medical UniversityShijiazhuang 050017China Hebei Food Safety key laboratory Hebei Food Inspection and Research Institute050227ShijiazhuangChina College of Food Science and Technology Hebei Agricultural University071001BaodingChina

In this experiment,a liquid chromatography tandem mass spectrometry method was built to determine 15 pesticide residues in Chinese cabbage and cucumber samples based on online turbulent flow chromatography *** modified quick,easy,cheap,effective,rugged,and safe(QuEChERS)extraction,extracts were directly injected to the TLX(TurboFlow Liquid Xcalibur)system and brought to TurboFlow™columns for on-line purification and then transferred to analytical column for further separation and ***™columns types,transfer flow rate,and transfer time were *** of detection and limits of quantification of the method obtained for 15 pesticide residues were ranged between 0.2–1.0μg/kg and 0.5–2.0μg/kg in Chinese cabbage and cucumber *** of pesticide residues were in range of 75.3%–103.7%.Matrix effects for 15 pesticides were in range of 5.6%–106.6%.The developed method has been successfully used for the determination of 15 pesticide residues in real samples.

关键词： Pesticide residues Online turbulent flow chromatography Liquid chromatography-tandem mass spectrometry

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Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma

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Bioactive Materials 2021年第12期6卷 4402-4414页

作者： Yueyue Fan Yuexin Cui Wenyan Hao Mengyu Chen Qianqian Liu Yuli Wang Meiyan Yang Zhiping Li Wei Gong Shiyong Song Yang Yang Chunsheng Gao College of Pharmacy Henan UniversityKaifeng475000PR China State key laboratory of toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing100850PR China

Nanosuspensions,as a new drug delivery system for insoluble drugs,are only composed of a drug and a small amount of stabilizer,which is dispersed in an aqueous solution with high drug-loading,small particle size,high dispersion,and large specific surface *** can significantly improve the dissolution,bioavailability,and efficacy of insoluble *** this study,paclitaxel nanosuspensions((PTX)NS)were prepared by an ultrasonic precipitation method,with the characteristics of simple preparation and easy *** the help of a homologous targeting mechanism,a kind of glioma C6 cancer cell membrane(CCM)-coated(PTX)NS was developed and modified with DWSW peptide to obtain DWSW-CCM-(PTX)NS with the functions of BBB penetration and tumor *** results showed that the cancer cell membrane could effectively camouflage the nanosuspensions so that it was not cleared by the immune system and could cross the blood-brain-barrier(BBB)and selectively target tumor *** uptake experiments and in vivo imaging confirmed that the uptake of DWSW-CCM-(PTX)NS by tumor cells and the distribution in intracranial gliomas *** test and in vivo anti-glioma studies showed that DWSW-CCM-(PTX)NS could significantly inhibit the growth of glioma cells and significantly prolong the survival time of glioma-bearing ***,the cancer cell membrane coating endowed the nanosuspensions with the biological properties of homologous adhesion and immune *** study provides an integrated solution for improving the targeting of nanosuspensions and demonstrates the encouraging potential of biomimetic nanosuspensions applicable to tumor therapy.

关键词： Nanosuspensions Cancer cell membrane Biomimetic drug-delivery systems Gliomas Blood-brain barrier Paclitaxel

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