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Rongchang and Xifeng capsules suppress pentylenetetrazole-induced seizures and change rest/wake behavior in zebrafish larvae

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Journal of Traditional Chinese Medicine 2019年第6期39卷 875-884页

作者： Zhang Shuhui Xu Jia Wang Chao Feng Daofu Dai Liangti Kuang Xiangyu Zhu Shuyi Fang Yongchun Chen Dongyan He Xianghui Feng Xizeng State Key laboratory of Medicinal Chemical Biology The Key Laboratory of Bioactive MaterialsMinistry of Education/College of Life ScienceNankai UniversityTianjin 300071China Tianjin Key laboratory of tumor Microenvironment and Neurovascular Regulation Department of Histology and EmbryologySchool of MedicineNankai UniversityTianjin 300071China The Institute of Robotics and Automatic Information systems Tianjin Key Laboratory of Intelligent RoboticsNankai UniversityTianjin 300071China Department of General Surgery Tianjin Medical University General HospitalTianjin300052China

OBJECTIVE:To evaluate the effects of Rongchang capsule and Xifeng capsule on pentylenetetrazoleinduced epilepsy in zebrafish larvae and to explore the possible mechanisms behind their ***:We utilized a trajectory tracking system to monitor seizures in zebrafish larva to confirm that certain concentrations of Rongchang capsule and Xifeng capsule produce antiepileptic effects.c-fos expression was assessed by quantitative reverse transcription-polymerase chain reaction to validate the efficacy of the ***/wake behavior and correlation analysis predicted the targets of Rongchang capsule and Xifeng ***:Larval movement times and total distances traveled by zebrafish larvae experiencing pentylenetetrazole(PTZ)-induced seizures were ***(500μg/m L)and Xifeng(200μg/m L)rescued the epileptic behaviors and down-regulated c-fos expression in the brains of larvae,which indicated antiepileptic *** rest/wake behavioral profiles showed that Rongchang and Xifeng differentially decreased rest time at night and increased larval locomotor activities during the *** on correlation between the actions of the two capsules and known compounds,we predicted that they might change rest/wake behaviors by affecting serotonin,GABAergic and histamine signaling ***:The efficacy of Rongchang capsule and Xifeng capsule in alleviating epilepsy-like behaviors and molecular responses was *** study provides insight into the capsules'effect on epilepsy.

关键词： Zebrafish Larva Anticonvulsants Rongchang capsule Xifeng capsule Rest/wake behavior

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Artificial intelligence in cancer target identification and drug discovery

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Signal Transduction and Targeted Therapy 2022年第6期7卷 1951-1974页

作者： Yujie You Xin Lai Yi Pan Huiru Zheng Julio Vera Suran Liu Senyi Deng Le Zhang College of Computer Science Sichuan UniversityChengdu 610065China laboratory of systems tumor immunology Friedrich-Alexander-Universität Erlangen-Nürnberg(FAU)and Universitätsklinikum ErlangenErlangen 91052Germany Faculty of Computer Science and Control Engineering Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesRoom D5131068 Xueyuan AvenueShenzhen University TownShenzhen 518055China School of Computing Ulster UniversityBelfast BT151EDUK Institute of Thoracic Oncology Department of Thoracic SurgeryWest China HospitalSichuan UniversityChengdu 610065China Key laboratory of systems Biology Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesChinese Academy of SciencesHangzhou 310024China Key laboratory of systems Health Science of Zhejiang Province Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China

Artificial intelligence is an advanced method to identify novel anticancer targets and discover novel drugs from biology networks because the networks can effectively preserve and quantify the interaction between components of cell systems underlying human diseases such as ***,we review and discuss how to employ artificial intelligence approaches to identify novel anticancer targets and discover ***,we describe the scope of artificial intelligence biology analysis for novel anticancer target ***,we review and discuss the basic principles and theory of commonly used network-based and machine learning-based artificial intelligence ***,we showcase the applications of artificial intelligence approaches in cancer target identification and drug *** together,the artificial intelligence models have provided us with a quantitative framework to study the relationship between network characteristics and cancer,thereby leading to the identification of potential anticancer targets and the discovery of novel drug candidates.

关键词： drugs cancer drug

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Enforced PGC-1α expression promotes CD8 T cell fitness, memory formation and antitumor immunity

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Cellular & Molecular immunology 2021年第7期18卷 1761-1771页

作者： Nina Dumauthioz Benjamin Tschumi Mathias Wenes Bastien Marti Haiping Wang Fabien Franco Wenhui Li Isabel CLopez-Mejia Lluis Fajas Ping-Chih Ho Alena Donda Pedro Romero Lianjun Zhang Translational tumor immunology Group Ludwig Cancer ResearchUniversity of LausanneEpalingesSwitzerland Department of Fundamental Oncology University of LausanneEpalingesSwitzerland Department of Fundamental Oncology University of LausanneEpalingesSwitzerland Ludwig Cancer Research Institute Lausanne BranchEpalingesSwitzerland Center for systems Medicine Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical College100005BeijingChina Suzhou Institute of systems Medicine SuzhouJiangsu215123China Center for Integrative Genomics University of LausanneLausanneSwitzerland

Memory CD8 T cells can provide long-term protection against tumors,which depends on their enhanced proliferative capacity,self-renewal and unique metabolic rewiring to sustain cellular ***,memory CD8 T cells engage oxidative phosphorylation and fatty acid oxidation to fulfill their metabolic *** contrast,tumor-infiltrating lymphocytes(TILs)display severe metabolic defects,which may underlie their functional ***,we show that overexpression of proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),the master regulator of mitochondrial biogenesis(MB),favors CD8 T cell central memory formation rather than resident memory ***-1α-overexpressing CD8 T cells persist and mediate more robust recall responses to bacterial infection or peptide ***,CD8 T cells with enhanced PGC-1αexpression provide stronger antitumor immunity in a mouse melanoma ***,TILs overexpressing PGC-1αmaintain higher mitochondrial activity and improved expansion when rechallenged in a tumor-free ***,our findings indicate that enforcing mitochondrial biogenesis promotes CD8 T cell memory formation,metabolic fitness,and antitumor immunity in vivo.

关键词： PGC-1α Mitochondria CD8 Memory Anti-tumor immunity

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Progress and perspectives on targeting nanoparticles for brain drug delivery

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Acta Pharmaceutica Sinica B 2016年第4期6卷 268-286页

作者： Huile Gao Key laboratory of Drug Targeting and Drug Delivery systems West China School of Pharmacy Sichuan University

Due to the ability of the blood–brain barrier(BBB) to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood–brain tumor barrier(BBTB), and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting diseased cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed.

关键词： Brain targeting Nanoparticles Dual targeting Intranasal delivery Blood–brain barrier

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Loss of 4.1N in epithelial ovarian cancer results in EMT and matrix-detached cell death resistance

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Protein & Cell 2021年第2期12卷 107-127页

作者： Dandan Wang Letian Zhang Ajin Hu Yuxiang Wang Yan Liu Jing Yang Ningning Du Xiuli An Congying Wu Congrong Liu Department of Pathology School of Basic Medical SciencesThird HospitalPeking University Health Science CenterBeijing 100191China Institute of systems Biomedicine Beijing Key Laboratory of Tumor Systems BiologySchool of Basic Medical SciencesPeking University Health Science CenterPeking UniversityBeijing 100191China College of Life Science Zhengzhou UniversityZhengzhou 450051China Red Cell Physiology laboratory New York Blood CenterNew YorkNY 10065USA

Epithelial ovarian cancer(EOC)is one of the leading causes of death from gynecologic cancers and peritoneal dissemination is the major cause of death in patients with *** the loss of 4.1N is associated with increased risk of malignancy,its association with EOC remains *** explore the underlying mechanism of the loss of 4.1N in constitutive activation of epithelial-mesenchymal transition(EMT)and matrixdetached cell death resistance,we investigated samples from 268 formalin-fixed EOC tissues and performed various in vitro and in vivo *** report that the loss of 4.1N correlated with progress in clinical stage,as well as poor survival in EOC *** loss of 4.1N induces EMT in adherent EOC cells and its expression inhibits anoikis resistance and EMT by directly binding and accelerating the degradation of 14-3-3 in suspension EOC ***,the loss of 4.1N could increase the rate of entosis,which aggravates cell death resistance in suspension EOC ***,xenograft tumors in nude mice also show that the loss of 4.1N can aggravate peritoneal dissemination of EOC ***-agent and combination therapy with a ROCK inhibitor and a 14-3-3 antagonist can reduce tumor spread to varying *** results not only define the vital role of 4.1N loss in inducing EMT,anoikis resistance,and entosis-induced cell death resistance in EOC,but also suggest that individual or combined application of 4.1N,14-3-3 antagonists,and entosis inhibitors may be a promising therapeutic approach for the treatment of EOC.

关键词： epithelial ovarian cancer 4.1N EMT anoikis entosis

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Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer

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Acta Pharmaceutica Sinica B 2019年第4期9卷 819-831页

作者： Jiaojie Wei Yang Long Rong Guo Xinlei Liu Xian Tang Jingdong Rao Sheng Yin Zhirong Zhang Man Li Qin He Key laboratory of Drug Targeting and Drug Delivery systems West China School of Pharmacy Sichuan University

Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin(DOX) and Toll-like receptor 7 agonist imiquimod(IMQ) in low molecular weight heparin(LMWH)-D-α-tocopheryl succinate(TOS) micelles(LT). In this process, LMWH and TOS were conjugated by ester bond and they were not only served as the hydrophilic and hydrophobic segments of the carrier, but also exhibited strong anti-metastasis effect. The direct killing of tumor cells mediated by DOX-loaded micelles(LT-DOX)generated tumor-associated antigens, initiating tumor-specific immune responses in combination with IMQ-loaded micelles(LT-IMQ). Furthermore, the blockade of immune checkpoint with programmed cell death ligand 1(PD-L1) antibody further elevated the immune responses by up-regulating the maturation of DCs as well as the ratios of CD8+ CTLs/Treg and CD4+ Teff/Treg. Therefore, such a multifunctional strategy exhibited great potential for inhibiting the growth of orthotopic and metastatic breast cancer.

关键词： Checkpoint blockade Immunotherapy Immunogenic cell death Anti-metastasis Nanoparticle

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Engineering intermolecular charge transfer in chiral organometallic crystals by rational doping for high-contrast CPL switches

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Science China Chemistry 2023年第7期66卷 2011-2018页

作者： Ying-Jie Liu Liang Chen Zhao-Yang Wang Xi-Yan Dong Ya-Ke Li Shuang-Quan Zang Henan Key laboratory of Crystalline Molecular Functional Materials Henan International Joint Laboratory of Tumor Theranostical Cluster MaterialsGreen Catalysis Center and College of ChemistryZhengzhou UniversityZhengzhou 450001China College of Chemistry and Chemical Engineering Henan Polytechnic UniversityJiaozuo 454003China

The development of circularly polarized luminescence(CPL)switches is of great importance but ***,a charge donor/acceptor pair comprising two chiral gold(I)-isocyanide complexes was designed to construct light-harvesting system via intermolecular charge-transfer(CT)*** doping nonemissive S-Au I into blue-emitting S-AuCN,(S-Au CN)_(1-x)(S-AuI)_(x)(0≤x≤3.4%)with tunable emission from blue to red was *** large red-shifted emission was realized based on the remarkable change of the electronic properties between the S-Au CN dimer and red-emitting(S-A CN)-(S-AuI)CT pair,and the resulting energy-transfer(En T)process between ***,the En T process can be switched off/on by external stimuli of grinding and CH_(2)Cl_(2)fuming,giving rise to high-contrast(blue versus red)CPL switching *** study opens a novel avenue for developing CPL switches by constructing light-harvesting CT-doped systems based on chiral organometallic complexes.

关键词： charge transfer energy transfer crystal engineering circularly polarized luminescence gold complex

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Neutrophil-mimicking therapeutic nanoparticles for targeted chemotherapy of pancreatic carcinoma

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Acta Pharmaceutica Sinica B 2019年第3期9卷 575-589页

作者： Xi Cao Ying Hu Shi Luo Yuejing Wang Tao Gong Xun Sun Yao Fun Zhirong Zhang Key laboratory of Drug Targeting and Drug Delivery systems Ministry of EducationWest China School of PharmacySichuan University

Due to the critical correlation between inflammation and carcinogenesis, a therapeutic candidate with anti-inflammatory activity may find application in cancer therapy. Here, we report the therapeutic efficacy of celastrol as a promising candidate compound for treatment of pancreatic carcinoma via na?ve neutrophil membrane-coated poly(ethylene glycol) methyl ether-block-poly(lactic-co-glycolic acid)(PEG-PLGA) nanoparticles. Neutrophil membranecoated nanoparticles(NNPs) are well demonstrated to overcome the blood pancreas barrier to achieve pancreas-specific drug delivery in vivo. Using tumor-bearing mice xenograft model, NNPs showed selective accumulations at the tumor site following systemic administration as compared to nanoparticles without neutrophil membrane coating. In both orthotopic and ectopic tumor models,celastrol-loaded NNPs demonstrated greatly enhanced tumor inhibition which significantly prolonged the survival of tumor bearing mice and minimizing liver metastases. Overall, these results suggest that celastrol-loaded NNPs represent a viable and effective treatment option for pancreatic carcinoma.

关键词： Na■ve neutrophils membrane Celastrol PEG-PLGA nanoparticle Pancreatic carcinoma Inflammation

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Integration of enzyme immobilization and biomimetic catalysis in hierarchically porous metal-organic frameworks for multi-enzymatic cascade reactions

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Science China Chemistry 2022年第6期65卷 1122-1128页

作者： Shu-Fan Li Yan Chen Yi-Shu Wang Hui-Lin Mo Shuang-Quan Zang Henan Key laboratory of Crystalline Molecular Functional Materials Henan International Joint Laboratory of Tumor Theranostical Cluster MaterialsGreen Catalysis CenterCollege of ChemistryZhengzhou UniversityZhengzhou450001China School of Chemistry and Chemical Engineering Nanjing University of Science and TechnologyNanjing210094China

Multiple enzymes-induced biological cascade catalysis is indispensable in biotechnology and industrial processes. Nevertheless,the drawbacks of most natural enzymes, including poor stability and recyclability and sensitivity to the environment, have hindered their broader application. Here, we report a facile strategy to prepare a biomimetic cascade reaction system by combining the advantages of enzyme immobilization and biomimetic catalysis in a one-pot reaction system based on the hierarchically porous metal-organic frameworks(HP-MOFs). The hierarchically porous zirconium-porphyrin-based MOF(HPPCN-222(Fe)) synthesized by modulator-induced strategy possessed tunable hierarchical porous and peroxidase-like activity,permitting them to act as not only an efficient immobilization matrix for glucose oxidase(GOx) but also peroxidase mimics to catalyze the cascade for glucose detection. A stable, anti-interference and reusable colorimetric biosensor for glucose detection was successfully established through GOx@HP-PCN-222(Fe) on the basis of the artificial tandem catalysis. Moreover, the GOx@HP-PCN-222(Fe)-fabricated electrode was available for glucose detection by electrochemical method. This work provides a potentially universal method to design functional multi-enzymatic cascade reaction systems by integrating the merits of enzyme encapsulation and biomimetic catalysis in HP-MOFs.

关键词： hierarchically porous metal-organic frameworks enzyme immobilization biomimetic catalysis multi-enzymatic cascade reactions

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Differences in IFNβ secretion upon Rab1 inactivation in cells exposed to distinct innate immune stimuli

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Cellular & Molecular immunology 2021年第6期18卷 1590-1592页

作者： Jing Yang Xiang Zhou Rui Zhang Hui Sun Fuping You Zhengfan Jiang Key laboratory of Cell Proliferation and Differentiation of the Ministry of Education School of Life SciencesPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China Cuiying Biomedical Research Center Lanzhou University Second HospitalLanzhou 730030 GansuChina Institute of systems Biomedicine Department of ImmunologySchool of Basic Medical SciencesBeijing Key Laboratory of Tumor Systems BiologyPeking University Health Science CenterBeijing 100191China College of Life Sciences&Health Wuhan University of Science&TechnologyHubei 430065China College of Life Sciences&Health Wuhan University of Science&TechnologyHubei 430065China

Type I interferons(IFNs)are secretory cytokines with protective roles against viral *** studies have focused on the signaling pathways that regulate the transcriptional activation of type I IFNs;however,little is known about the secretory mechanism of these cytokines,except for information obtained from a few studies reporting the secretion polarity of IFNβin epithelial cells.1,2,3,4 Here,we investigate the role of Rab1,a small GTPase of the Rab family,in IFNβ*** show that Rab1 inactivation blocked the secretion of IFNβfrom human embryonic kidney 293T(HEK293T)cells transfected with IFNβ-inducing molecules(TRIF,MAVS,and TBK1)but not from cells stimulated with RNA ligands(Sendai virus)(SeV)or polyinosinic:polycytidylic acid(poly(I:C)).Despite the differential effects of Rab1 inactivation and regardless of the triggering stimuli,IFNβsecretion was inhibited by brefeldin A(BFA),a fungal metabolite that inhibits ER-to-Golgi *** addition,a proportion of endogenous 3×Flag-tagged IFNβcolocalized with the cis-Golgi marker GM130 within SeV-infected *** results indicate that IFNβsecretion generally requires the conventional ER-Golgi pathway while showing differential responses to Rab1 inactivation in cells exposed to distinct innate immune stimuli.

关键词： protective inhibited IFNβ

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