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Targeting cAMP in D1.MSNs in the nucleus accumbens, a new rapid antidepressant strategy

Acta Pharmaceutica Sinica B 2024年第2期14卷 667-681页

作者： Yue Zhang Jingwen Gao Na Li Peng Xu Shimeng Qu Jinqian Cheng Mingrui wang Xueru Li Yaheng Song Fan Xiao Xinyu Yang Jihong Liu Hao Hong Ronghao Mu Xiaotian Li Youmei wang Hui Xu Yuan {2. Tianming Gao Guangji wang Jiye Aa Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics State Key Laboratory of Natural MedicinesResearch Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical SciencesChina Pharmaceutical UniversityNanjing 210009China Key Laboratory of Drug Monitoring and Control Drug Intelligence and Forensic CenterMinistry of Public SecurityBeijing 100193China School of Pharmacy China Pharmaceutical UniversityNanjing 211198China School of Foreign Languages China Pharmaceutical UniversityNanjing 211198China department of Neurobiology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China department of Pharmacology China Pharmaceutical UniversityNanjing 211198China School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China

Studies have suggested that the nucleus accumbens(NAc)is implicated in the pathophysiology of major depression;however,the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been ***,we identified a specific reduction of cyclic adenosine monophosphate(cAMP)in the subset of dopamine D1.receptor medium spiny neurons(D1.MSNs)in the NAc that promoted stress susceptibility,while the stimulation of cAMP production in NAc D1.MSNs efficiently rescued depression-like *** treatment enhanced cAMP both in D1.MSNs and dopamine D2.receptor medium spiny neurons(D2.MSNs)of depressed mice,however,the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc *** discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 2. h after oral administration,but not a lower *** fast onset property of crocin was verified through multicenter ***,crocin specifically targeted at D1.MSN cAMP signaling in the NAc to relieve depression and had no effect on *** findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1.MSNs in the NAc,and provide a potential rapid antidepressant drug candidate,crocin.

关键词： CAMP Nucleus accumbens Depression D1.MSN D2.MSN

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Camrelizumab,apatinib and hepatic artery infusion chemotherapy combined with microwave ablation for advanced hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3481-3495页

作者： Meng-Xuan Zuo Chao An Yu-Zhe Cao Jia-Yu Pan Lu-Ping xie Xin-Jing Yang {1. Li Pei-Hong Wu department of Minimally Invasive Interventional Therapy Sun Yat-sen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina department of Interventional Ultrasound Chinese General PLA HospitalBeijing 100853China department of Medical Imaging and Interventional Radiology Sun Yatsen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina

BACKGROUND Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib(TRIPLET protocol)is promising for advanced hepatocellular carcinoma(Ad-HCC).However,the usefulness of microwave ablation(MWA)after TRIPLET is still *** To compare the efficacy and safety of TRIPLET alone(T-A)vs TRIPLET-MWA(TM)for *** From January 2.1. to March 2.2.,2.7 Ad-HCC patients were retrospectively *** them,1.0} were included in the T-A group,and 95 were included in the T-M group.A propensity score matching(PSM)was applied to balance *** survival(OS)was compared using the Kaplan-Meier curve with the log-rank *** overall objective response rate(ORR)and major complications were also *** After PSM,82.patients were included both the T-A group and the T-M *** ORR(85.4%)in the T-M group was significantly higher than that(65.9%)in the T-A group(P1..The cumulative 1.,2.,and 3.year OS rates were 98.7%,93.4%,and 82.0%in the T-M group and 85.1.,63.1.,and 55.0%in the T-A group(hazard ratio=0.2.;95%confidence interval:0.1.-0.49;P1..The incidence of major complications was 4.9%(6/1.0})in the T-A group and 5.3.(5/95)in the T-M group,which were not significantly different(P=1.000).CONCLUSION T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.

关键词： Hepatic arterial infusion chemotherapy Hepatocellular carcinoma Molecular targeting agent Programmed cell death protein 1.inhibitors Microwave ablation

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MDGA2.Constrains Glutamatergic Inputs Selectively onto CA1.Pyramidal Neurons to Optimize Neural Circuits for Plasticity,Memory,and Social Behavior

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Neuroscience Bulletin 2024年第7期40卷 887-904页

作者： Xuehui wang Donghui Lin Jie Jiang Yuhua Liu Xinyan Dong Jianchen Fan Lifen Gong Weida Shen Linghui Zeng Tonghui Xu Kewen Jiang Steven A.Connor Yicheng {1. School of Life Sciences Nanchang UniversityNanchang330031China department of Neurology Children's HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China department of Biology York University4700 Keele StreetTorontoON M3J 1P3Canada Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of MedicineHangzhou City UniversityHangzhou 310015China

Synapse organizers are essential for the development,transmission,and plasticity of *** as rare synapse suppressors,the MAM domain containing glycosylphosphatidylinositol anchor(MDGA)proteins contributes to synapse organization by inhibiting the formation of the synaptogenic neuroligin-neurexin complex.A previous analysis of MDGA2.mice lacking a single copy of Mdga2.revealed upregulated glutamatergic synapses and behaviors consistent with ***,MDGA2.is expressed in diverse cell types and is localized to both excitatory and inhibitory *** the network versus cell-specific effects of MDGA2.loss-of-function requires a cell-type and brain region-selective *** address this,we generated mice harboring a conditional knockout of Mdga2.restricted to CA1.pyramidal *** we report that MDGA2.suppresses the density and function of excitatory synapses selectively on pyramidal neurons in the mature *** deletion of Mdga2.in CA1.pyramidal neurons of adult mice upregulated miniature and spontaneous excitatory postsynaptic potentials,vesicular glutamate transporter 1.intensity,and neuronal *** effects were limited to glutamatergic synapses as no changes were detected in miniature and spontaneous inhibitory postsynaptic potential properties or vesicular GABA transporter ***,evoked basal synaptic transmission and AMPAR receptor currents were enhanced at glutamatergic *** a behavioral level,memory appeared to be compromised in Mdga2.cKO mice as both novel object recognition and contextual fear conditioning performance were impaired,consistent with deficits in long-term potentiation in the CA3.CA1.*** affiliation,a behavioral analog of social deficits in autism,was similarly *** results demonstrate that MDGA2.confines the properties of excitatory synapses to CA1.neurons in mature hippocampal circuits,thereby optimizing this network for plasticity,c

关键词： MDGA2 CA1.pyramidal neurons Glutamatergic inputs Synaptic plasticity Memory Social behaviors Autism Synapse organizers

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Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury

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Biomedical and Environmental Sciences 2024年第5期37卷 494-502页

作者： CAO Wei Hua JIANG Ting Ting SHEN Ge DENG Wen wang Shi Yu ZHANG Zi Yu LI Xin Xin LU Yao ZHANG Lu LIU Ru Yu CHANG Min WU {1. Ling GAO Yuan Jiao HAO Hong Xiao CHEN Xiao Xue HU Lei Ping XU Meng Jiao YI Wei {2. Yao LI Ming Hui department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China department of Hepatology Division 2 Peking University Ditan Teaching HospitalBeijing 100015China department of Gynecology and Obstetrics Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical *** The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with *** on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five *** were measured by Luminex *** characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were *** 73.patients were *** among five groups was statistically different(P=0.03.0}.Alanine aminotransferase(ALT)(P=0.03.)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine ***-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P1.TNF-α:P1.and cardiovascular medicine(IL-6:P=0.02.;TNF-α:P=0.001.were lower than those in NSAIDs *** was a positive correlation between ALT(r=0.697,P=0.02.),AST(r=0.72.,P=0.01.),and IL-6 in NSAIDs *** Older age may be more prone to *** with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.

关键词： Drug-induced liver injury Cytokines Non-steroidal anti-inflammatory drugs Inflammation

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A Comprehensive Study of the Association between LEPR Gene rs1.3.1.1.Variant and Risk of Digestive System Cancers

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Biomedical and Environmental Sciences 2024年第5期37卷 445-456页

作者： HU Wei Qiong ZHOU Wei Guang ZHOU Guang Wei LIAO Jia Xi SHI Jia Xing xie FengYang LI Shou Heng {1. Yong FENG Xian Hong GU Xiu Li CHEN Bi Feng department of Biological Science and Technology School of ChemistryChemical Engineering and Life SciencesWuhan University of TechnologyWuhan 430070HubeiChina Institute of WUT-AMU Wuhan University of TechnologyWuhan 430070HubeiChina department of Clinical Laboratory Wuhan Xinzhou District People’s HospitalWuhan 430499HubeiChina department of Reproductive Genetics Wuhan Huake Reproductive HospitalWuhan 430013HubeiChina

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1.3.1.1.Gln{1.3.rg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than ***,we performed a case–control study and subsequent meta-analysis to examine the association between rs1.3.1.1.and DS cancer *** A total of 1.7{1. patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were *** of rs1.3.1.1.was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger ***-four eligible studies were included in the *** After Bonferroni correction,the case–control study revealed that rs1.3.1.1.was significantly associated with the risk of liver cancer in the Hubei Chinese *** meta-analysis suggested that rs1.3.1.1.is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese *** The LEPR rs1.3.1.1.variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

关键词： LEPR gene rs1.3.1.1 Digestive system cancers Genetic susceptibility Meta-analysis

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Advanced nano drug delivery systems for neuroprotection against ischemic stroke

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Chinese Chemical Letters 2024年第2期35卷 151-162页

作者： Chenchen xie Jun Liao Ning Zhang Yuhan Sun Yi Li Liyan Xiong Yingnan Zhang Xiaoyan Liu Wei Su Heming Chen Ping Zeng Xiaoqing Zhang Ying Lu Tingfang {1. Chuan Zhang Shanghai Engineering Research Center of Organ Repair School of MedicineShanghai UniversityShanghai 200444China department of Pharmaceutical Science School of PharmacyNaval Medical UniversityShanghai 200433China department of pharmacy the International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200030China School of Pharmacy Shanghai Jiao Tong UniversityShanghai 200040China

Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability *** efficacy of small-molecule neuroprotective agents has been impeded by challenges associated with traversing the blood-brain barrier(BBB)and limited ***,advanced nano drug delivery systems hold promise for overcoming these obstacles by facilitating efficient transportation across the BBB and maintaining optimal drug *** review aims to explore advanced neuroprotective nano drug delivery systems as a means of effectively administering neuroprotective agents to the brain using pharmaceutical approaches in the treatment of *** examining these systems,researchers and clinicians can gain valuable insights and innovative concepts,illuminating the potential of advanced neuroprotective nano drug delivery *** these advancements can drive the progress of pioneering and efficacious therapeutic interventions for IS.

关键词： Target Blood-brain barrier Ischemic stroke Nano drug delivery Neuroprotection

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Inducing dopaminergic differentiation of expanded rat mesencephalic neural stem cells by ascorbic acid in vitro

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Progress in Natural Science:Materials International 2004年第1期 27-31+98页

作者： ZHENG Min 1.2. , {1. Dongmei 1. HOU Lingling 1. LI Haimin 1. xie Chao 1. JIAO Wencang 1. BAI Cixian 1. {1. Yaping 2.and PEI Xuetao 1.*(1. department of Stem Cell Biology, Beijing Institute of Transfusion Medicine, Beijing 1.0850, china 2. Institute of Basic Medical Sciences, Chongqing University of Medical Sciences, Chongqing 40001., china) InstituteofBasicMedicalSciences ChongqingUniversityofMedicalSciencesChongqing400016China departmentofStemCellBiology BeijingInstituteofTransfusionMedicineBeijing100850China

Ascorbic acid (AA) induced differentiation of neural stem cells (NSCs) into dopaminergic (DAergic) neurons is reported. NSCs derived from rat mesencephalon were maintained and expanded in a defined medium containing mitogens of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Compared with the control, ascorbic acid treatment led to more DAergic neuronal differentiation as indicated by the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT), which are specific markers of dopamine neurons. AA induction also enhanced expression of Nurr1.and Shh. PD98059, an inhibitor of mitogen activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) pathway, could block AA induced Nurr1. TH and DAT mRNA expression. The results might suggest a new strategy to provide enough dopaminergic cells for the therapy of Parkinson’s disease (PD), and Nurr1.and ERK signaling pathway might participate in the AA induced DAergic differentiation.

关键词： neural stem cells differentiation Parkinson’s disease mitogen activated protein kinase(MAPK)/extracellular signal-regulated kinase (ERK) pathway signal transduction

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Estimation of Soot and Airborne Radionuclide Emission Factors from Coal-Fired Power Plants in china

Estimation of Soot and Airborne Radionuclide Emission Factor...

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The Second Asian and Oceanic Congress for Radiation Protection

作者： JIANG Ziying1 3. PAN Ziqiang2. LIU Senlin1, CHENG Jianping3. wang Jue3. wang {2.1 1. Division of Health Physics, china Institute of Atomic Energy, Beijing, china 2. Science & Technology Committee, CNNC, Beijing, china 3. department of Engineering Physics, Tsinghua University, Beijing, china

As main energy resource in china, coal-fired power is one of the major causes of atmosphere pollution. Comparison of environment impacts for coal, nuclear and other energy provides important information for energy sustainable development decision-making. Study on soot and airborne radionuclide emission factors for coal-fired power plants is important part as atmosphere environment impacts of coal energy. Based on the data that effect soot emission, such as installed capacity, dust removal technique, boiler and combustion conditions of coal-fired power plant at present in china, three type emission levels （high, middle and low） of coal-fired plants are analyzed and the general soot emission factor is estimated with the result: 4.4g/kWh. It is much higher in china than foreign advanced countries’ level and the main reasons are: high energy consumption of electricity production, various levels of dust precipitation and low efficiency in whole, and some high pollution, low parameters and small capacity coal-fired plants still taking certain proportion. With soot some natural radionuclide and their descendant （U series, Th series and 40K） in coal emit to atmosphere. Based on collection and analysis of survey data and experiment results on radionuclide content in coal and coal-fired ashes, the airborne radionuclide emission factors are estimated with the results: {3.6Ra is 0.68Bq/kWh, {3.{3.h is 0.56Bq/kWh, {3.8U is 0.74Bq/kWh, {3.0Pb is 3.54Bq/kWh, {3.0Po is {3.79Bq/kWh and 40K is 1.3.Bq/kWh, which perform the practical emission level for coal-fired power plant in china.

关键词： soot radionuclide emission factor coal-fired power plant

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Boosting photocatalytic hydrogen evolution enabled by SiO_(2.-supporting chiral covalent organic frameworks with parallel stacking sequence

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Chinese Journal of Catalysis 2024年第9期64卷 87-97页

作者： Zheng Lin Wanting xie Mengjing Zhu Changchun {1. Jia Guo State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular ScienceFudan UniversityShanghai 200438China

Two-dimensional covalent organic frameworks(2. COFs)feature extendedπ-conjugation and ordered stacking sequence,showing great promise for high-performance *** atomic frameworks of 2. COFs facilitate the in-plane photogenerated charge transfer,but the precise ordered alignment is limited due to the non-covalentπ-stacking of COF layers,accordingly hindering out-of-plane transfer ***,we address a chiral induction method to construct a parallelly superimposed stacking chiral COF ultrathin shell on the support of SiO_(2. *** to the achiral COF analogues,the chiral COF shell with the parallel AA-stacking structure is more conducive to enhance the built-in electric field and accumulates photogenerated electrons for the rapid migration,thereby affording superior photocatalytic performance in hydrogen evolution from water *** the simplest ketoenamine-linked chiral COF as a shell of SiO_(2. particle,the resulting composite exhibits an impressive hydrogen evolution rate of 1.7.1.mmol g^(-1.h^(-1.along with the apparent quantum efficiency of 1..3.%at 475 ***,the composite photocatalysts could be fabricated into a film device,displaying a remarkable photocatalytic performance of 1.8.0 mmol m^(-2.h^(-1.for hydrogen *** work underpins the surface engineering of organic photocatalysts and illustrates the significance of COF stacking structures in regulating electronic properties.

关键词： Covalent organic framework Photocatalysis Hydrogen generation Chiral induction Core-shell structure

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Identification and Characterization of a Rat Novel Gene RSEP4 Expressed Specifically in Central Nervous System

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Acta Biochimica et Biophysica Sinica 2004年第7期36卷 501-507页

作者： Xi-Dao wang1,2. Ling-Wei KONG1, Zhi-Qin xie1, Yu-Qiu ZHANG3. Zhi-Xin LIN2. Zhi-Qi ZHAO3.Lei YU4, and Nai-He JING1* 1 Laboratory of Molecular Cell Biology, Laboratory of Stem Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 2.003., {2. School of Life Science and Biotechnology, 2. Shanghai Jiaotong University, Shanghai 2.003., {2. Institute of Neurobiology, Fudan University, Shanghai 2.043., {2. 3. 4 department of Cell Biology, Neurobiology and Anatomy, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA Laboratory of Molecular Cell Biology and Stem Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences Shanghai China

The low-abundantly expressed genes composed the majorities of the mRNAs expressed in the central nervous system (CNS), and were thought to be important for the normal brain functions. Through differential screening a low-abundance cDNA sublibrary with mRNA from neuropathic pain of chronic constriction injury (CCI) model, we have identified a novel rat gene, rat spinal-cord expression protein 4 gene (RSEP4). The total length of RSEP4 cDNA is 2.06 bp, with a 501.nucleotide open reading frame (ORF) that encodes a 1.7 amino acid polypeptide. Northern blot revealed that RSEP4 was expressed specifically in the CNS. In situ hybridization showed that the mRNA of RSEP4 was strongly expressed in the CA1. CA2. CA3. and DG regions of hippocampus, the Purkinje cells of cerebellum, and the small sensory neurons of dorsal horn and large motor neurons of ventral horn of spinal cord. Over-expression of RSEP4-EGFP fusion protein in the human embryonic kidney 2.3. cells showed that RSEP4 protein was mainly localized in the cell cytoplasm. These results suggest that RSEP4 may play some roles in the CNS.

关键词： central nervous system (CNS) rat Northern blot in situ hybridization

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