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Enhanced lysosome escape mediated by 1,2-dicarboxylic-cyclohexene anhydride-modified poly-L-lysine dendrimer as a gene delivery system

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Asian Journal of Pharmaceutical sciences 2020年第6期15卷 759-776页

作者： Jianmin Shen Jing Chen Jingbo Ma Linlan Fan Xiaoli zhang Ting Yue yaping Yan Yuhang zhang School of Life sciences Lanzhou UniversityLanzhou 730000China Shenzhen Following Precision Medical Research institute Shenzhen 518001China School of Basic Medical sciences Lanzhou UniversityLanzhou 730000China

Antisense oligodeoxynucleotide(ASODN)can directly interfere a series of biological events of the target RNA derived from tumor cells through Watson-Crick base pairing,in turn,plays antitumor therapeutic *** the study,a novel HIF-1αASODN-loaded nanocomposite was formulated to efficiently deliver gene to the target *** physicochemical properties of nanocomposite were characterized using TEM,FTIR,DLS and zeta *** mean diameter of resulting GEL-DGL-FA-ASODN-DCA nanocomposite was about 170–192 nm,and according to the agarose gel retardation assay,the loading amount of ASODN accounted for 166.7 mg/*** results of cellular uptake showed that the nanocomposite could specifically target to HepG2 and Hela *** cytotoxicity assay demonstrated that the toxicity of vectors was greatly reduced by using DCA to reversibly block the cationic *** subcellular distribution images clearly displayed the lysosomal escape ability of the DCA-modified *** vitro exploration of molecular mechanism indicated that the nanocomposite could inhibit m RNA expression and HIF-1αprotein translation at different *** vivo optical images and quantitative assay testified that the formulation accumulated preferentially in the tumor *** vivo antitumor efficacy research confirmed that this nanocomposite had significant antitumor activity and the tumor inhibitory rate was 77.99%.These results manifested that the GEL-DGL-FA-ASODNDCA nanocomposite was promising in gene therapeutics for antitumor by interacting directly with target RNA.

关键词： Antisense oligodeoxynucleotide(ASODN) Gene delivery Dendrigraft poly-L-lysines(DGL) Lysosomal escape Tumor targeting

Upregulation of stromal cell-derived factor-1 alpha/CXCR4 axis-induced migration of human neural progenitors by tumor necrosis factor-alpha and interleukin-8

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Neural Regeneration Research 2009年第11期4卷 832-837页

作者： Jing Qu Hongtao zhang Guozhen hui Xueguang zhang Huanxiang zhang Department of Cell Biology Medical College of Soochow University Suzhou 215123 Jiangsu Province China Jiangsu Province Key laboratory of Stem Cell Research Suzhou 215016 Jiangsu Province China Department of Orthopaedics First Affiliated Hospital of Soochow University Suzhou 215007 Jiangsu Province China Department of Neurosurgery First Affiliated Hospital of Soochow University Suzhou 215007 Jiangsu Province China

BACKGROUND： Studies of several animal models of central nervous system diseases have shown that neural progenitor cells （NPCs） can migrate to injured tissues. Stromal cell-derived factor 1 alpha （SDF-la）, and its primary physiological receptor CXCR4, have been shown to contribute to this process. OBJECTIVE： To investigate migration efficacy of human NPCs toward a SDF-1α gradient, and the regulatory roles of tumor necrosis factor-α （TNF-α） and interleukin-8 （IL-8） in SDF-1α/CXCR4 axis-induced migration of NPCs. DESIGN, TIME AND SETTING： An in vitro, randomized, controlled, cellular and molecular biology study was performed at the laboratory of Department of Cell Biology, Medical College of Soochow University between October 2005 and November 2007. MATERIALS： SDF-1α and mouse anti-human CXCR4 fusion antibody were purchased from R＆D Systems, USA. TNF-αwas purchased from Biomyx Technology, USA and IL-8 was kindly provided by the Biotechnology Research {3. of Soochow University. METHODS： NPCs isolated from forebrain tissue of 9 to 10-week-old human fetuses were cultured in vitro. The cells were incubated with 0, 20, and 40 ng/mL TNF-α, or 0, 20, and 40 ng/mL IL-8, for 48 hours prior to migration assay. For antibody-blocking experiments, cells were further pretreated with 0, 20, and 40 μg/mL mouse anti-human CXCR4 fusion antibody for 2 hours. Subsequently, the transwell assay and CXCR4 blockade experiments were performed to evaluate migration of human NPCs toward a SDF-1α gradient. Serum-free culture medium without SDF-1α served as the negative control. MAIN OUTCOME MEASURES： The transwell assay was performed to evaluate migration of human NPCs toward a SDF-1α gradient, which was blocked by fusion antibody against CXCR4. In addition, CXCR4 expression in human NPCs stimulated by TNF-α and IL-8 was measured by flow cytometry. RESULTS： Results from the transwell assay demonstrated that SDF-1α was a strong chemoattractant for human NPCs （P 〈 0.01）, and 20 ng/mL produced

关键词： human neural progenitor cells migration stromal cell-derived factor 1 alpha CXCR4 tumor necrosis factor-α interleukin-8

Expert Consensus on Pathological Diagnosis of Intrahepatic Cholangiocarcinoma(2022 version)

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Journal of Clinical and Translational Hepatology 2023年第7期11卷 1553-1564页

作者： Han Wang Jun Chen Xin zhang Xia Sheng Xiao-Yan Chang Jie Chen Min-Shan Chen hui Dong Guang-Jie Duan He-Ping Hu Zhi-Yong Huang Wei-Dong Jia Xiao-Qing Jiang Dong Kuang Shan-Shan Li Zeng-Shan Li Chang-Li Lu Shu-Kui Qin Xue-Shan Qiu Li-Juan Qu Chun-Kui Shao Feng Shen Guo-Ming Shi Su-Sheng Shi Yu-Jun Shi hui-Chuan Sun Xiao-Dong Teng Bin Wang Zhan-Bo Wang Tian-Fu Wen Jia-Mei {3. Qiao-Qiao {3. Sheng-Long Ye Hong-Fang Yin Zhen-Gang Yuan Jing-Ping Yun Feng-Lin Zang Hong-Qi zhang Li-Hong zhang Jing-Min Zhao Jian Zhou Wei-Xun Zhou Jia Fan Xiao-Ping Chen Wan Yee Lau Yuan Ji Wen-Ming Cong chinese Society of Liver Cancer of chinese Anti-Cancer Association Digestive Disease Group of chinese Society of Pathology,chinese Medical Association chinese Society of Pathology of chinese Anti-Cancer Association Hepatic Surgery Group of chinese Society of Surgery,chinese Medical Association Biliary Tract Tumor Committee of china Anti-Cancer Association chinese Society of Clinical Oncology IDepartment of Pathology Eastern Hepatobilary Surgery HospitalNaval Medical UniversityShanghaiChina Department of Pathology the Affiliated Drum Tower HospitalNanjing University Medical SchoolNanjingJiangsuChina Department of Pathology Zhongshan HospitalFudan UniversityShanghaiChina Department of Pathology Minhang HospitalFudan Uni-versityShanghaiChina Department of Pathology Peking Union Medical College HospitalChinese Academy of Medical Sci-ences and Peking Union Medical CollegeBeijingChina Department of Liver Surgery Sun Yat-Sen University Cancer CenterGuangzhouGuangdongChina Department of Pathology The First Affiliated HospitalArmy Medical UniversityChongqingChina Department of Hepatobiliary Medicine Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghaiChina Hepatic Surgery Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWu-hanHubeiChina Department of General Surgery The First Affliated Hospital of USTCDivision of Life Science and Medi-cineUniversity of Science and Technology of ChinaHefeiAnhuiChina Department of Biliary Surgery I Eastern Hepatobil-iary Surgery HospitalNaval Medical UniversityShanghaiChina Department of Pathology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina Department of Pathology The First Afiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenanChina Department of Pathology Xijing Hospi-talAir Force Medical UniversityXi'anShaanxiChina Department of Pathology West China HospitalSichuan UniversityChengduSichuanChina Cancer Center of Jinling Hospital Nanjing University of Chinese MedicineNanjingJiangsuChina Department of Pathology The First Affiliated HospitalChina Medical UniversityShenyangLiaoningChina Department of Pathology The 900 Hospital of the Chinese People's Liberation Army Joint Logistics TeamFuzhouFujianChina Department of Pathology The Third Affiliated HospitalSun Yat-Sen UniversityGuangz

Intrahepatic cholangiocarcinoma(iCCA)can originate from the large bile duct group(segment bile ducts and area bile ducts),small bile duct group(septal bile ducts and interlobular bile ducts),and terminal bile duct group(bile ductules and canals of Hering)of the intrahepatic biliary tree,which can be histopathological corresponding to large duct type iCCA,small duct type iCCA and iCCA with ductal plate malformation pattern,and cholangiolocarcinoma,*** challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies,tissue structures,growth patterns,invasive behaviors,immunophenotypes,molecular mutations,and surgical *** these reasons,this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA,mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

关键词： Intrahepatic cholangiocarcinoma Pathology Histological type Immunohistochemistry molecular variation

SEL1L preserves CD8^(+) T-cell survival and homeostasis by fine-tuning PERK signaling and the IL-15 receptor-mediated mTORC1 axis

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cellular & molecular Immunology 2023年第10期20卷 1232-1250页

作者： Yafeng Gao Wenhui Li Zhenghao Wang Cangang zhang yaping He Xiaowei Liu Kexin Tang Weiguo zhang Qiaoming Long Yong Liu Jinping zhang Baojun zhang Lianjun zhang National Key laboratory of Immunity and Inflammation Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhou215123JiangsuChina Key laboratory of Synthetic Biology Regulatory Elements Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhou215123JiangsuChina School of Life Science and Technology China Pharmaceutical UniversityNanjing211198JiangsuChina Department of Pathogenic Microbiology and Immunology School of Basic Medical SciencesXi’an Jiaotong UniversityXi’anShaanxiChina institute of Infection and Immunity Translational Medicine InstituteXi’an Jiaotong University Health Science CenterXi’anShaanxiChina Key laboratory of Environment and Genes Related to Diseases Xi’an Jiaotong UniversityXi’anShaanxiChina Xi’an Key laboratory of Immune Related Diseases Xi’anShaanxiChina Department of Radiotherapy and Oncology The Second Affiliated Hospital of Soochow UniversitySuzhouChina Department of Endocrinology The Second Affiliated Hospital of Soochow UniversitySuzhouChina Jiangsu Key laboratory of Neuropsychiatric Diseases and Cam-Su Mouse Genomic Resources Center Medical College of Soochow UniversitySuzhouJiangsuChina Hubei Key laboratory of Cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesThe Institute for Advanced StudiesFrontier Science Center for Immunology and MetabolismWuhan UniversityWuhanChina institute of Biology and Medical sciences(IBMS) Soochow UniversitySuzhou215123JiangsuChina

SEL1L-mediated endoplasmic reticulum-associated degradation(ERAD)plays critical roles in controlling protein homeostasis by degrading misfolded or terminal unfolded ***,it remains unclear how SEL1L regulates peripheral T-cell survival and ***,we found that SEL1L deficiency led to a greatly reduced frequency and number of mature T cells,which was further validated by adoptive transfer experiments or bone marrow chimera experiments,accompanied by the induction of multiple forms of cell ***,SEL1L deficiency selectively disrupted naïve CD8+T-cell homeostasis,as indicated by the severe loss of the naïve T-cell subset but an increase in the memory T-cell *** also found that SEL1L deficiency fueled mTORC1/c-MYC activation and induced a metabolic shift,which was largely attributable to enhanced expression of the IL-15 receptorαandβ***,single-cell transcriptomic profiling and biochemical analyses further revealed that Sel1l−/−CD8+T cells harbored excessive ER stress,particularly aberrant activation of the PERK-ATF4-CHOP-Bim pathway,which was alleviated by supplementing IL-7 or ***,PERK inhibition greatly resolved the survival defects of Sel1l−/−CD8+T *** addition,IRE1αdeficiency decreased mTORC1 signaling in Sel1l−/−naïve CD8+T cells by downregulating the IL-15 receptorα***,these observations suggest that the ERAD adaptor molecule SEL1L acts as an important checkpoint for preserving the survival and homeostasis of peripheral T cells by regulating the PERK signaling cascade and IL-15 receptor-mediated mTORC1 axis.

关键词： T-cell homeostasis Endoplasmic reticulum-associated degradation ER stress response PERK IRE1a

Identification of DH166 as a novel Plk1 inhibitor

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Identification of DH166 as a novel Plk1 inhibitor

Stable all-solid-state Li-Te battery with Li_(3.TbBr_(6) superionic conductor

2009医学前沿论坛暨第十一届全国肿瘤药理与化疗学术会议

作者： Jing zhang~#,Yan Li~#,Pei Zhao,Xue Li,Yanni Xu,Jikai Liu, Wei Jiang,Yanchang Wang~*,Shuyi Si~* institute of Medicinal Biotechnology,chinese {3. of Medical sciences & Peking Union Medical College,Beijing,100050,china.

Objective:The Polo-like kinase 1(Plk1),a highly conserved mitotic serine/threonine kinase,plays a pivotal role in the regulation of cellular proliferation and is found to be overexpressed in a variety of human *** observations have validated Plk1 as an attractive candidate for mitotic targeting of cancer *** the present study,we have made an attempt at seeking possible Plk1 inhibitors and discovered a candidate molecular- *** investigation on DH166 inhibition profile of Plk1 kinase activity in vivo and in vitro demonstrated it as a potent Plk1 ***:We employed budding yeast as a model system to look for novel Plk1 inhibitors via high throughput ***-linked ImmunoSorbent Assay,MTT proliferation assay,immunohistochemistry and flow cytometric analysis were used to measure the effect of the compound on purified Plk1 protein activity,cellular toxicity,cell cycle progression, protein alterations and apoptosis-related *** docking was also operated to assess the binding mode of DH166 with PLK1 by virtue docking program FlexX encoded in SYBYL7.3.(Tripos Inc).Results:Screening of chemically diverse,druglike,synthetic and natural compound library of led to the identification of aβ-carboline derivative-DH166 as a hit of PLK1 kinase *** 24 h of incubation,the presence of 10μg/mL DH166 inhibited 50%of the growth of cdc5-1(the only budding yeast counterpart of vertebrate Plks) temperature-sensitive mutant cells,whereas the MIC(minimum inhibition concentration) for wild -type cells were determined to be 40μg/*** vitro,DH166 inhibited purified Plk1 enzyme activity at low micromolar concentrations in a ATP-competitive manner,competing for the kinase domain of the *** vivo,DH 166 dependent Plk1 downregulation of cellular PLK1 kinase activity:1) inhibited the proliferation of A549 and 7402 human cell lines with IC50 values of 1.85μM and 3.89992μM, respectively;2) modulated cell cycle distribution mod

关键词： Polo-like kinase 1 inhibitor β-carboline derivatives high throughput screening

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Nano Research 2023年第7期16卷 9344-9351页

作者： Zhichao Zeng Xiaomeng Shi Mingzi Sun Hongtu zhang Wei Luo Yunhui Huang Bolong Huang yaping Du Chun-Hua Yan Tianjin Key Lab for Rare Earth Materials and Applications Center for Rare Earth and Inorganic Functional MaterialsHaihe Laboratory of Sustainable Chemical TransformationsSmart Sensing Interdisciplinary Science CenterSchool of Materials Science and EngineeringNational Institute for Advanced MaterialsNankai UniversityTianjin 300350China Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic UniversityHung HomKowloonHong Kong 999077China institute of New Energy for Vehicles School of Materials Science and EngineeringTongji UniversityShanghai 201804China Beijing National laboratory for molecular sciences State Key Laboratory of Rare Earth MaterialsChemistry and ApplicationsPKU-HKU Joint Laboratory in Rare Earth Materials and Bioinorganic ChemistryCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China College of Chemistry and Chemical Engineering Lanzhou UniversityLanzhou 730000China

Rare-earth(RE)halide solid electrolytes(HSEs)have been an emerging research area due to their good electrochemical and mechanical properties for all-solid-state lithium batteries(ASSBs).However,only very limited types of HSEs have been reported with high *** this work,tens of grams of RE-HSE Li_(3.TbBr_(6)(LTbB)was synthesized by a vacuum evaporationassisted *** as-prepared LTbB displays a high ionic conductivity of 1.7 mS·cm^(-1),a wide electrochemical window,and good ***,the assembled solid lithium-tellurium(Li-Te)battery based on the LTbB HSE exhibits excellent cycling stability up to 600 cycles,which is superior to most previous *** processes and the chemicals during the discharge/charge of Li-Te batteries have been studied by various in situ and ex situ *** calculations have demonstrated the dominant conductivity contributions of the direct[octahedral]-[octahedral]([Oct]-[Oct])pathway for Li ion migrations in the *** Tb sites guarantee efficient electron transfer while the Li 2s orbitals are not affected during migration,leading to a low activation ***,this successful fabrication and application of LTbB have offered a highly competitive solution for solid electrolytes in ASSBs,indicating the great potential of RE-based HSEs in energy devices.

关键词： rare-earth halide solid electrolytes all-solid-state lithium batteries superionic conductor Li-Te solid battery

Plant cuticles repress organ initiation and development during skotomorphogenesis in Arabidopsis

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Plant Communications 2024年第6期5卷 100-116页

作者： Yuru Ma Wenwen Chang Yongpeng Li Jiahui Xu Yongli Song Xinmiao Yao Lei Wang Yu Sun Lin Guo Hao zhang Xigang Liu Ministry of Education Key laboratory of molecular and cellular Biology College of Life SciencesHebei Normal UniversityShijiazhuangHebei 050024China Hebei Research Center of the Basic Discipline of Cell Biology College of Life SciencesHebei Normal UniversityShijiazhuangHebei 050024China Hebei Collaboration Innovation Center for Cell Signaling and Environmental Adaptation College of Life SciencesHebei Normal UniversityShijiazhuangHebei 050024China Hebei Key laboratory of molecular and cellular Biology College of Life SciencesHebei Normal UniversityShijiazhuangHebei 050024China State Key laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuangHebei 050021China

After germination in the dark,plants produce a shoot apical hook and closed cotyledons to protect the quiescent shoot apical meristem(SAM),which is critical for seedling survival during *** factors that coordinate these processes,particularly SAM repression,remain *** cuticles,multilayered structures of lipid components on the outermost surface of the aerial epidermis of all land plants,provide protection against desiccation and external environmental *** and how cuticles regulate plant development are still ***,we demonstrate that mutants of BODYGUARD1(BDG1)and long-chain acyl-CoA synthetase2(LACS2),key genes involved in cutin biosynthesis,produce a short hypocotyl with an opened apical hook and cotyledons in which the SAM is activated during *** signaling represses expression of BDG1 and LACS2,as well as cutin *** analysis revealed that cuticles are critical for skotomorphogenesis,particularly for the development and function of *** and molecular analyses showed that decreased HOOKLESS1 expression results in apical hook opening in the *** hypoxia-induced expression of LITTLE ZIPPER2 at the SAM promotes organ initiation in the mutants,the de-repressed expression of cell-cycle genes and the cytokinin response induce the growth of true *** results reveal previously unrecognized developmental functions of the plant cuticle during skotomorphogenesis and demonstrate a mechanism by which light initiates photomorphogenesis through dynamic regulation of cuticle synthesis to induce coordinated and systemic changes in organ development and growth during the skotomorphogenesis-to-photomorphogenesis transition.

关键词： plant cuticles SAM quiescence organ initiation skotomorphogenesis photomorphogenesis

ATP depletion triggers mitochondria permibility transition and superoxide flashes in astrocytes

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ATP depletion triggers mitochondria permibility transition a...

A correlative analysis on the social disability and the criminal responsibility of the alcohol-related offender

第十七届国际钙结合蛋白与钙在健康和疾病中作用会议

作者： Ning Guo,Wan-Rui zhang,Zhuan Zhou and Heping Cheng institute of molecular Medicine,Peking University,Beijing 100871,{3.

Mitochondria have important functions in developmental and synaptic plasticity,regulation of Ca,and redox signaling(1).Reactive oxygen species(ROS),including superoxide,are indispensable in many cellular signaling processes(2) and cell death(3..In a previous study,we reported that individual mitochondria undergo spontaneous transient bursts of quantal superoxide generation, termed "superoxide flashes",in many cell types(4).However,the upstream signal that regulates superoxide flashes remains unknown. Here,we revealed a new type of superoxide flash in astrocytes and its regulating *** flash can occur either

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A correlative analysis on the social disability and the crim...