Integrative biology : quantitative biosciences from nano to macro最新文献_第9页

Target: ligand interactions of the vascular endothelium. Implications for molecular imaging in inflammation. 目标:血管内皮的配体相互作用。炎症分子成像的意义。

IF 2.5

Integrative biology : quantitative biosciences from nano to macro Pub Date : 2010-10-01 Epub Date: 2010-09-08 DOI: 10.1039/c0ib00022a

Rohan S Wijesurendra, Andrew Jefferson, Robin P Choudhury

{"title":"Target: ligand interactions of the vascular endothelium. Implications for molecular imaging in inflammation.","authors":"Rohan S Wijesurendra, Andrew Jefferson, Robin P Choudhury","doi":"10.1039/c0ib00022a","DOIUrl":"https://doi.org/10.1039/c0ib00022a","url":null,"abstract":"Molecular imaging refers to the non-invasive visualisation of biological processes at the molecular and cellular levels within a living organism, and offers a wide range of potential benefits to both clinical medicine and research into novel therapeutic agents. Inflammation plays an important role in a wide variety of pathological processes and imaging the molecular and cellular machinery that underlies chronic inflammation is attractive and feasible. In this review, we present an overview of molecular imaging of inflammation. We start by characterising molecular and cellular events in early inflammation, identifying current and potential future imaging targets. We focus on the imaging of endothelial cells, which mediate the important first steps in inflammation in any tissue, are readily accessible to imaging probes and which present an approach that can be applied across multiple modalities. We then review the generic requirements for imaging contrast agents and focus on the important considerations in respect of ligands, ligand-target interactions and contrast vehicles. We aim to provide an integrated view of current progress with a focus on promising recent developments in experimental and translational molecular imaging.","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"467-82"},"PeriodicalIF":2.5,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c0ib00022a","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40059594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Targeting novel integrative nuclear FGFR1 signaling by nanoparticle-mediated gene transfer stimulates neurogenesis in the adult brain. 通过纳米颗粒介导的基因转移靶向新的综合核FGFR1信号传导刺激成人大脑中的神经发生。

IF 2.5

Integrative biology : quantitative biosciences from nano to macro Pub Date : 2009-06-01 Epub Date: 2009-05-08 DOI: 10.1039/b902617g

Ewa K Stachowiak, Indrajit Roy, Yu-Wei Lee, Mariolina Capacchietti, John M Aletta, Paras N Prasad, Michal K Stachowiak

{"title":"Targeting novel integrative nuclear FGFR1 signaling by nanoparticle-mediated gene transfer stimulates neurogenesis in the adult brain.","authors":"Ewa K Stachowiak, Indrajit Roy, Yu-Wei Lee, Mariolina Capacchietti, John M Aletta, Paras N Prasad, Michal K Stachowiak","doi":"10.1039/b902617g","DOIUrl":"https://doi.org/10.1039/b902617g","url":null,"abstract":"Neurogenesis, the process of differentiation of neuronal stem/progenitor cells (NS/PC) into mature neurons, holds the key to the treatment of various neurodegenerative disorders, which are a major health issue for the world's aging population. We report that targeting the novel integrative nuclear FGF Receptor 1 signaling (INFS) pathway enhances the latent potential of NS/PCs to undergo neuronal differentiation, thus promoting neurogenesis in the adult brain. Employing organically modified silica (ORMOSIL)-DNA nanoplexes to efficiently transfect recombinant nuclear forms of FGFR1 and its FGF-2 ligand into the brain subventricular zone, we find that INFS stimulates the NS/PC to withdraw from the cell cycle, differentiate into doublecortin expressing migratory neuroblasts and neurons that migrate to the olfactory bulb, subcortical brain regions and in the brain cortex. Thus, nanoparticle-mediated non-viral gene transfer may be used to induce selective differentiation of NS/PCs, providing a potentially significant impact on the treatment of a broad range of neurological disorders.","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"394-403"},"PeriodicalIF":2.5,"publicationDate":"2009-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/b902617g","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28605633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 39

Multidimensional degradomics identifies systemic autoantigens and intracellular matrix proteins as novel gelatinase B/MMP-9 substrates. 多维降解组学鉴定系统自身抗原和细胞内基质蛋白作为新的明胶酶B/MMP-9底物。

IF 2.5

Integrative biology : quantitative biosciences from nano to macro Pub Date : 2009-06-01 Epub Date: 2009-05-12 DOI: 10.1039/b904701h

Bénédicte Cauwe, Erik Martens, Paul Proost, Ghislain Opdenakker

{"title":"Multidimensional degradomics identifies systemic autoantigens and intracellular matrix proteins as novel gelatinase B/MMP-9 substrates.","authors":"Bénédicte Cauwe, Erik Martens, Paul Proost, Ghislain Opdenakker","doi":"10.1039/b904701h","DOIUrl":"https://doi.org/10.1039/b904701h","url":null,"abstract":"The action radius of matrix metalloproteinases or MMPs is not restricted to massive extracellular matrix (ECM) degradation, it extends to the proteolysis of numerous secreted and membrane-bound proteins. Although many instances exist in which cells disintegrate, often in conjunction with induction of MMPs, the intracellular MMP substrate repertoire or degradome remains relatively unexplored. We started an unbiased exploration of the proteolytic modification of intracellular proteins by MMPs, using gelatinase B/MMP-9 as a model enzyme. To this end, multidimensional degradomics technology was developed by the integration of broadly available biotechniques. In this way, 100-200 MMP-9 candidate substrates were isolated, of which 69 were identified. Integration of these results with the known biological functions of the substrates revealed many novel MMP-9 substrates from the intracellular matrix (ICM), such as actin, tubulin, gelsolin, moesin, ezrin, Arp2/3 complex subunits, filamin B and stathmin. About 2/3 of the identified candidates were autoantigens described in multiple autoimmune conditions and in cancer (e.g. annexin I, nucleolin, citrate synthase, HMGB1, alpha-enolase, histidyl-tRNA synthetase, HSP27, HSC70, HSP90, snRNP D3). These findings led to the insight that MMPs and other proteases may have novel (immuno)regulatory properties by the clearance of toxic and immunogenic burdens of abundant ICM proteins released after extensive necrosis. In line with the extracellular processing of organ-specific autoantigens, proteolysis might also assist in the generation of immunodominant 'neo-epitopes' from systemic autoantigens. The study of proteolysis of ICM molecules, autoantigens, alarmins and other crucial intracellular molecules may result in the discovery of novel roles for proteolytic modification.","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"404-26"},"PeriodicalIF":2.5,"publicationDate":"2009-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/b904701h","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28605634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 78

In vivo characterization of activatable cell penetrating peptides for targeting protease activity in cancer. 靶向癌症蛋白酶活性的可活化细胞穿透肽的体内表征。

Integrative biology : quantitative biosciences from nano to macro Pub Date : 2009-06-01 Epub Date: 2009-05-11 DOI: 10.1039/b904890a

Emilia S Olson, Todd A Aguilera, Tao Jiang, Lesley G Ellies, Quyen T Nguyen, Edmund H Wong, Larry A Gross, Roger Y Tsien

{"title":"In vivo characterization of activatable cell penetrating peptides for targeting protease activity in cancer.","authors":"Emilia S Olson, Todd A Aguilera, Tao Jiang, Lesley G Ellies, Quyen T Nguyen, Edmund H Wong, Larry A Gross, Roger Y Tsien","doi":"10.1039/b904890a","DOIUrl":"10.1039/b904890a","url":null,"abstract":"Activatable cell penetrating peptides (ACPPs) are novel in vivo targeting agents comprised of a polycationic cell penetrating peptide (CPP) connected via a cleavable linker to a neutralizing polyanion (). Adsorption and uptake into cells are inhibited until the linker is proteolyzed. An ACPP cleavable by matrix metalloproteinase-2 (MMP-2) in vitro was the first one demonstrated to work in a tumor model in vivo, but only HT-1080 xenografts and resected human squamous cell carcinomas were tested. Generality to other cancer types, in vivo selectivity of ACPPs for MMPs, and spatial resolution require further characterization. We now show that ACPPs can target many xenograft tumor models from different cancer sites, as well as a thoroughly studied transgenic model of spontaneous breast cancer (mouse mammary tumor virus promoter driving polyoma middle T antigen, MMTV-PyMT). Pharmacological inhibitors and genetic knockouts indicate that current ACPPs are selective for MMP-2 and MMP-9 in the above in vivo models. In accord with the known local distribution of MMP activity, accumulation is strongest at the tumor-stromal interface in primary tumors and associated metastases, indicating better spatial resolution (<50 mum) than other currently available MMP-cleavable probes. We also find that background uptake of ACPPs into normal tissues such as cartilage can be decreased by appending inert macromolecules of 30-50 KDa to the polyanionic inhibitory domain. Our results validate an approach that should generally deliver imaging agents and chemotherapeutics to sites of invasion, tumor-promoting inflammation, and metastasis.","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"382-93"},"PeriodicalIF":0.0,"publicationDate":"2009-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796841/pdf/nihms136754.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28605632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hematopoietic stem and progenitor cells in adhesive microcavities. 粘附微腔中的造血干细胞和祖细胞。

IF 2.5

Integrative biology : quantitative biosciences from nano to macro Pub Date : 2009-06-01 Epub Date: 2009-04-29 DOI: 10.1039/b903711j

Ina Kurth, Katja Franke, Tilo Pompe, Martin Bornhäuser, Carsten Werner

{"title":"Hematopoietic stem and progenitor cells in adhesive microcavities.","authors":"Ina Kurth, Katja Franke, Tilo Pompe, Martin Bornhäuser, Carsten Werner","doi":"10.1039/b903711j","DOIUrl":"https://doi.org/10.1039/b903711j","url":null,"abstract":"The homeostasis of hematopoietic stem and progenitor cells (HSC) in the bone marrow is regulated by a complex interplay of exogenous signals, including extracellular matrix (ECM) molecules, cell-cell contacts, and cytokines. To investigate the influence of spatial restriction and adhesive interactions on HSC fate decisions, we prepared a set of fibronectin-coated micrometer-sized cavities. Analysis of human CD133+ HSCs isolated after culture on these surfaces revealed that proliferation and differentiation is decreased when HSCs are supported by substrates with small microcavities. Single cell analysis of adherent cells also revealed decreased DNA synthesis and higher levels of HSC marker expression inside the smaller cavities. Increasing the cytokine concentration highlighted the tight balance of adhesion related signals and soluble cues acting on HSC fate decisions. Our results suggest that confining human HSCs in ECM-coated microcavities is a possible method to maintain these cells in a quiescent and immature state, an important advantage for several HSC applications.","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"427-34"},"PeriodicalIF":2.5,"publicationDate":"2009-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/b903711j","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28605636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 59

Miniaturized thermocontrol devices enable analysis of biomolecular behavior on their timescales, second to millisecond. 小型化的温控装置能够在秒到毫秒的时间尺度上分析生物分子的行为。

IF 2.5

Integrative biology : quantitative biosciences from nano to macro Pub Date : 2009-06-01 Epub Date: 2009-05-06 DOI: 10.1039/b901902b

Hideyuki F Arata, Hiroyuki Fujita

引用次数: 15