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Environmentally responsive dual-targeting nanotheranostics for overcoming cancer multidrug resistance

Science Bulletin 2019年第10期64卷 705-714页

作者： Caixia Yang Xin Pang Weihai Chen Xiaoyong Wang Gan Lin Chengchao Chu Xianzheng Zhang Xianming Deng Xiaoyuan Chen Gang Liu State Key Laboratory of molecular Vaccinology and molecular Diagnostics and Center for molecular Imaging and Translational Medicine School of Public Health Xiamen University Xiamen 361102 China Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry Wuhan University Wuhan 430072 China State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signaling Network School of Life Sciences Xiamen University Xiamen 361102 China Laboratory of molecular Imaging and Nanomedicine National Institute of Biomedical Imaging and Bioengineering (NIBIB) National Institutes of Health (NIH) Bethesda MD 20892 USA

The development of multiple drug resistance(MDR) to chemotherapy and subsequent treatment failures are major obstacles in cancer therapy. An attractive option for combating MDR is inhibiting the expression of P-glycoprotein(P-gp) in tumor cells. Here, we report a novel chemosensitizing agent, XMD8-92,which can down-regulate P-gp. To enhance the specificity of MDR chemotherapy, a promising nanotheranostic micelle system based on poly(ethylene glycol)-blocked-poly(L-leucine)(PEG-b-Leu) was developed to simultaneously carry the anticancer drug doxorubicin, chemosensitizing agent XMD8-92, and superparamagnetic iron oxide nanoparticles(SPIOs). Featured with MDR environmentally responsive dual-targeting capability, controllable drug delivery, and efficient magnetic resonance(MR) imaging characteristics, the prepared nanotheranostics(DXS@NPs) showed outstanding in vitro cytotoxicity on MDR cells(SCG 7901/VCR) with only 53% of cells surviving compared to 90% of DOX-treated ***, efficient tumor inhibition and highly reduced systemic toxicity were exhibited by MDR tumor-bearing mice treated with DXS@NPs. Overall, the environmentally responsive dual-targeting nanotheranostics represent a promising approach for overcoming cancer MDR.

关键词： Cancer chemosensitization Multidrug resistance P-glycoprotein pH-responsive Magnetic resonance imaging

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Application of magnetic solid phase extraction in separation and enrichment of glycoproteins and glycopeptides

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Chinese Chemical Letters 2021年第9期32卷 2629-2636页

作者： He Qi Liyan Jiang Qiong Jia College of Chemistry Jilin UniversityChangchun 130012China Key Laboratory for molecular Enzymology and Engineering of Ministry of Education School of Life SciencesJilin UniversityChangchun 130012China

The analysis of endogenous glycoproteins and glycopeptides in human body fluids is of great importance for screening and discovering disease biomarkers with clinical ***,the presence of interfering substances makes the direct quantitative detection of low-abundance glycoproteins and glycopeptides in human body fluids one of the great challenges in analytical *** solid phase extraction(MSPE)has the advantages of easy preparation,low cost and good magnetic *** adsorbents are the core of MSPE technology,and magnetic adsorbents based on different functional materials are widely used in the quantitative analysis of glycoproteins and glycopeptides in human body fluids,making it possible to analyze glycoproteins and glycopeptides with low abundance as well as multiple types,which provides a technical platform for screening and evaluating glycoproteins and glycopeptides in body fluids as disease *** this paper,we focus on the recent advances in the application of MSPE technology and magnetic adsorbents for the separation and enrichment of glycoproteins and glycopeptides in human body fluids,and the future trends and application prospects in this field are also presented.

关键词： Glycoproteins Glycopeptides Magnetic solid phase extraction(MSPE) Separation Enrichment Human body fluids

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A cellular mechanism underlying the restoration of thermo/photoperiod-sensitive genic male sterility

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molecular Plant 2021年第12期14卷 2104-2114页

作者： Qiang-Sheng Shi Yue Lou Shi-Yi Shen Sheng-Hong Wang Lei Zhou Jun-Jie Wang Xing-Lu Liu Shuang-Xi Xiong Yu Han Hai-Sheng Zhou Xue-Hui Huang Shui Wang Jun Zhu Zhong-Nan Yang Shanghai Key Laboratory of Plant molecular sciences College of Life SciencesShanghai Normal UniversityShanghai 200234China College of Resources&Environment Jiujiang UniversityJiujiangJiangxi 332005China Development Center of Plant Germplasm Resources College of Life SciencesShanghai Normal UniversityShanghai 200234China

During anther development,the transformation of the microspore into mature pollen occurs under the pro-tection of first the tetrad wall and later the pollen *** in genes involved in this wall transition often lead to microspore rupture and male sterility;some such mutants,such as the reversible male sterile(rvms)mutant,are thermo/photoperiod-sensitive genic male sterile(P/TGMS)*** studies have shown that slow development is a general mechanism of P/TGMS fertility *** this study,we iden-tified restorer of rvms-2(res2),which is an allele of QUARTET3(QRT3)encoding a polygalacturonase that shows delayed degradation of the tetrad pectin *** found that MS188,a tapetum-specific transcrip-tion factor essential for pollen wall formation,can activate QRT3 expression for pectin wall degradation,indicating a non-cell-autonomous pathway involved in the regulation of the cell wall *** as-says showed that a delay in degradation of the tetrad pectin wall is responsible for the fertility restoration of rvms and other P/TGMS lines,whereas early expression of QRT3 eliminates low temperature restoration of rvms-2 *** together,these results suggest a likely cellular mechanism of fertility restoration in P/TGMS lines,that is,slow development during the cell wall transition of P/TGMS microspores may reduce the requirement for their wall protection and thus support their development into functional pollens,leading to restored fertility.

关键词： thermo-sensitive male sterility pectin wall rvms-2 qrt

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Prolonged existence of SARS-CoV-2 RNAs in the extracellular vesicles of respiratory specimens from patients with negative reverse transcription-polymerase chain reaction

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Liver Research 2023年第3期7卷 228-236页

作者： P.Debishree Subudhi Sheetalnath Rooge Chhagan Bihari Swati Thangariyal Sivang Goswami Reshu Agarwal Savneet Kaur Ekta Gupta Sukriti Baweja Department of molecular and Cellular Medicine Institute of Liver and Biliary SciencesNew DelhiIndia Department of Virology Institute of Liver and Biliary SciencesNew DelhiIndia Department of Pathology Institute of Liver and Biliary SciencesNew DelhiIndia

Background and aim:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is primarily in the respiratory tract,particularly in patients with underlying *** study aimed to investigate the presence of the virus inside the extracellular vesicles(EVs)in patients with and without chronic liver disease(CLD).Methods:Eighty patients with positive SARS-CoV-2,including twenty-four patients with CLD and fiftysix patients without CLD,and five healthy controls with negative SARS-CoV-2 were *** swab specimens were tested for the detection of SARS-CoV-2 using reverse transcription-polymerase chain reaction(RT-PCR).Patients with coronavirus disease 2019(COVID-19)were followed up on days 7 and *** swab,collected in viral transport media(VTM),and plasma samples were investigated at each time *** were isolated from the nasal swabs(collected in VTM)and plasma using differential ultracentrifugation and estimated at each time *** transmission or replication by the EVs was assessed in Vero E6 ***:In patients with baseline RT-PCR positive,SARS-CoV-2 RNAs inside the EVs were found in 68/80(85%)patients with higher viral load in the nasal swabs than in the EVs(cycle threshold(Ct)value,23.4±5.7 vs.30.3±5.0,P<0.001).On follow-up at day 7,of the 32 patients negative for COVID-19,15(46.9%)had virus persistence in the EVs(Ct value,30.7±2.7),and on day 14,of the 56 patients with negative SARS-CoV-2,16 patients(28.6%)had positive SARS-CoV-2 RNAs in the EVs(Ct value,31.4±3.0).The mean viral load decreased on days 7 and 14 compared to baseline in the nasal swabs(P<0.001)but not in the ***,SARS-CoV-2 RNAs were undetectable in the plasma,but 12.5% of patients were positive in the plasma *** prolonged and high viral load was found in the EVs on day 14 in COVID-19 patients combined with CLD compared with COVID-19 patients(P?0.0004).We found significant higher levels of EV-associated with endothelial cells and hepatocytes

关键词： Coronavirus disease 2019(COVID-19) Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)RNAs Recurrence Extracellular vesicles(EVs) Chronic liver disease(CLD)

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FBXO38 regulates macrophage polarization to control the development of cancer and colitis

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Cellular & molecular Immunology 2023年第11期20卷 1367-1378页

作者： Xin Zheng Qi Jiang Mingshun Han Fenfen Ye Mingchang Wang Ying Qiu Jialu Wang Minxia Gao Fajian Hou Hongyan Wang School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou310024China State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai200031China

Macrophages are highly plastic cells that differentially regulate multiple pathological conditions,including cancer and autoimmune *** response to various stimuli,macrophages activate different intrinsic signaling pathways and polarize into distinct macrophage *** aimed to identify key new effectors that could control macrophage polarization and impact the development of cancer or *** treatment with the supernatants of tumor cells,macrophages showed an upregulation in Fbxo38 ***,we further identified that FBXO38 promotes macrophage immunosuppressive function by upregulating the expression of M2-like genes via MAPK and IRF4 signaling without affecting M1-like macrophage *** of Fbxo38 in macrophages was found to block tumor development and protect against DSS-induced *** the distinct regulation of tumor development by FBXO38 in T cells and macrophages,we suggest that a comprehensive understanding of FBXO38 function in different cell types is critical for its further translational usage.

关键词： FBXO38 Macrophage polarization Tumor progression Colitis

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ADAMTS-7 promotes vascular smooth muscle cells proliferation in vitro and in vivo

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Science China(Life sciences) 2015年第7期58卷 674-681页

作者： ZHANG Lu YU Fang WANG Li ZHENG JinGang DU YaoYao HUANG YaQian LIU Bo WANG Xian KONG Wei Department of Physiology and Pathophysiology School of Basic Medical Sciences Peking University Key Laboratory of molecular Cardiovascular Science Ministry of Education Department of Cardiology China-Japan Friendship Hospital

Vascular smooth muscle cell(VSMC) proliferation and migration are pivotal for the pathogenesis of atherosclerosis and post-angioplasty restenosis. We have recently reported that a disintegrin and metalloproteinase with thrombospondin motifs-7(ADAMTS-7), a novel metalloproteinase, contributes directly to neointima formation by mediating VSMC migration. However, whether ADAMTS-7 affects VSMC proliferation remains unclear. In this study, we found that luminal adenoviral delivery of ADAMTS-7 aggravated intimal hyperplasia 7 d after injury, paralleled by an increased percentage of PCNA-positive cells in both intima and media. In contrast, perivascular administration of ADAMTS-7 si RNA, but not scrambled si RNA to injured arteries attenuated intimal thickening at day 7, paralleled with reduced intimal VSMC replication, without alteration of VSMC proliferation in the media. In accordance, [3H]-thymidine incorporation assay in primary cultured rat VSMCs revealed an enhanced replication rate(by 61%) upon ADAMTS-7 overexpression and retarded proliferation(by 23%) upon ADAMTS-7 si RNA administration. Our data demonstrates that ADAMTS-7 promotes VSMC proliferation both in vitro and in vivo. ADAMTS-7 may therefore serve as a novel therapeutic target for atherosclerosis and post-angioplasty restenosis.

关键词： vascular smooth muscle cell ADAMTS-7 proliferation

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Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite

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Acta Pharmaceutica Sinica B 2021年第11期11卷 3655-3664页

作者： Zhiguo Liu Wei Li Peng Zhang Jie Fan Fangbo Zhang Caixia Wang Shuming Li Yi Sun Shilin Chen Wenbing Yin Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China State Key Laboratory of Mycology CAS Key Laboratory of Microbial Physiological and Metabolic EngineeringInstitute of MicrobiologyChinese Academy of SciencesBeijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China Institut für Pharmazeutische Biologie und Biotechnologie Fachbereich PharmaziePhilipps-Universitat MarburgMarburg 35037Germany

Tyrosine-decahydrofluorene derivatives feature a fused[6.5.6]tricarbocyclic core and a 13-membered para-cyclophane ***,we identified new xenoacremones A,B,and C(1-3)from the fungal strain Xenoacremonium sinensis ML-31 and elucidated their biosynthetic pathway using gene deletion in the native strain and heterologous expression in Aspergillus *** hybrid polyketide synthaseenonribosomal peptide synthetase(PKS-NRPS)XenE together with enoyl reductase XenG were confirmed to be responsible for the formation of the tyrosine-nonaketide *** skeleton was subsequently dehydrated by XenA to afford a pyrrolidinone *** catalyzed a novel sigmatropic rearrangement to yield a key cyclohexane intermediate as a prerequisite for the formation of the multi-ring *** oxidation catalyzed by XenD supplied the substrate for XenC to link the para-cyclophane ether,which underwent subsequent spontaneous Diels-Alder reaction to give the end ***,the results indicated that three novel enzymes XenF,XenD,and XenC coordinate to assemble the[6.5.6]tricarbocyclic ring and para-cyclophane ether during biosynthesis of complex tyrosine-decahydrofluorene derivatives.

关键词： Tyrosine-decahydrofluorene Biosynthesis PKS-NRPS Xenoacremone Heterologous expression

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Multifunctional Nanoplatform Based on pH-responsive Micelle Coated with Discontinuous Gold Shell for Cancer Photothermo-chemotherapy and Photoacoustic Tomography

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Chinese Journal of Polymer Science 2018年第10期36卷 1139-1149页

作者： Yi Huang Xiao-Xia Li Lu Zhang Xiao-Yan Chen Cheng-Bo Liu Jing-Qin Chen Yong Wang Xin-Tao Shuai PCFM Lab of Ministry of Education School of Materials Science and Engineering Sun Yat-Sen University Research Laboratory for Biomedical Optics and molecular Imaging Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences

Photothermo-chemotherapy, as a new strategy for cancer treatment, incorporates the complementary advantages of photothermal therapy and chemotherapy. In this study, a pH-sensitive diblock copolymer poly（aspartic acid-butanediamine）-poly（2- （diisopropylamino）ethyl methacrylate）（PAsp（DAB）-PDPA） was synthesized and self-assembled into doxorubicin-loaded micelle, which was further used as a template to form a gold nanoshell. After fitrther modification with poly（ethylene glycol）, the resulting nanoplatform provided good biocompatibility and desirable photo-thermal conversion efficiency to facilitate photothermal therapy. Meanwhile the nanoparticle also exhibited pH sensitivity, which prevented drug loss while circulating in the blood but enabled rapid drug release after endocytosis. An improved effect was achieved with the combination of photothermal therapy and chemotherapy. In addition, systemic delivery of the nanoplatform could be monitored by photoacoustic tomography. Thereby, this multifunctional nanoplatform would be highly potential for the diagnosis and therapy of cancer.

关键词： Gold nanoshell Photoacoustic tomography Photothermo-chemotherapy pH-sensitive micelle

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Facile construction of carbon dots via acid catalytic hydrothermal method and their application for target imaging of cancer cells

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Nano Research 2016年第1期9卷 214-223页

作者： Zhenggang Wang Boshi Fu Siwei Zou Bo Duan Chunyu Chang Bai Yang Xiang Zhou Lina Zhang College of Chemistry and molecular sciences Wuhan University Wuhan 430072 China State Key Laboratory of Supramolecular Structure and Materials College of Chemistry Jilin University Changchun 130012 China

To solve the problem of high temperature or long reaction time in hydrothermal synthesis of carbon dots （CDs）, a novel method based on the promoting carbonization by hydrochloric acid as catalysis was developed in present work. The acid catalyzed carbon dots （ACDs） were prepared facilely from tryptophan and phenylalanine at 200 ~C for 2 h. In our findings, the acids could promote significantly the formation of the ACDs＂ carbon core, as a result of the accelerating of the carbonization due to the easy deoxidation. The ACDs showed an average size of 4.8 nm, and consisted of high carbon crystalline core and various surface groups. The ACDs exhibited good optical properties and pH-dependent photoluminescence （PL） intensities. Furthermore, the ACDs were safe and biocompatible. The experimental results demonstrated that such new ACDs were connected with DNA-aptamer by EDC/NHS reaction maintaining both the bright fluorescence and recognizing ability on the cancer cells, which so could be served as an effective PL sensing platform. The resultant DNA-aptamer with ACDs （DNA-ACDs） could stick to human breast cancer cells （MCF-7） specifically, and exhibited high sensitivity and selectivity, indicating the potential applications in the cancer cells targeted imaging fields.

关键词： hydrothermal method carbon dots carbon nanomaterials DNA-aptamer bioimaging

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From filaments to function: The role of the plant actin cytoskeleton in pathogen perception,signaling and immunity

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Journal of integrative Plant Biology 2016年第4期58卷 299-311页

作者： Katie Porter Brad Day Graduate Program in Cell and molecular Biology Michigan State University Department of Plant Soil and Microbial Sciences Michigan State University Graduate Program in Genetics Michigan State University

The eukaryotic actin cytoskeleton is required for numerous cellular processes, including cell shape, development and movement, gene expression and signal transduction, and response to biotic and abiotic stress. In recent years,research in both plants and animal systems have described a function for actin as the ideal surveillance platform, linking the function and activity of primary physiological processes to the immune system. In this review, we will highlight recent advances that have defined the regulation and breadth of function of the actin cytoskeleton as a network required for defense signaling following pathogen infection. Coupled with an overview of recent work demonstrating specific targeting of the plant actin cytoskeleton by a diversity of pathogens,including bacteria, fungi and viruses, we will highlight the importance of actin as a key signaling hub in plants, one that mediates surveillance of cellular homeostasis and the activation of specific signaling responses following pathogen perception. B4 ased on the studies highlighted herein, we propose a working model that posits changes in actin filament organization is in and of itself a highly specific signal, which induces, regulates and physically directs stimulus-specific signaling processes, most importantly, those associated with response to pathogens.

关键词： Actin cytoskeleton immunity pathogen plant Pseudomonas syringae surveillance

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