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      1. Author :
        Oertel, Stephanie; Scholich, Klaus; Weigert, Andreas; Thomas, Dominique; Schmetzer, Julia; Trautmann, Sandra; Wegner, Marthe-Susanna; Radeke, Heinfried H.; Filmann, Natalie; Brüne, Bernhard; Geisslinger, Gerd; Tegeder, Irmgard; Grösch, Sabine
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Cellular and Molecular Life Sciences
      6. Products :
      7. Volume :
        74
      8. Issue :
        16
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Sphingosine; Occludin; Cytokines; FITC dextran; Colon; IVIS; IVIS BLI in vivo
      12. Abstract :
        Loss of intestinal barrier functions is a hallmark of inflammatory bowel disease like ulcerative colitis. The molecular mechanisms are not well understood, but likely involve dysregulation of membrane composition, fluidity, and permeability, which are all essentially regulated by sphingolipids, including ceramides of different chain length and saturation. Here, we used a loss-of-function model (CerS2+/+ and CerS2−/− mice) to investigate the impact of ceramide synthase 2, a key enzyme in the generation of very long-chain ceramides, in the dextran sodium salt (DSS) evoked model of UC. CerS2−/− mice developed more severe disease than CerS2+/+ mice in acute DSS and chronic AOM/DSS colitis. Deletion of CerS2 strongly reduced very long-chain ceramides (Cer24:0, 24:1) but concomitantly increased long-chain ceramides and sphinganine in plasma and colon tissue. In naive CerS2−/− mice, the expression of tight junction proteins including ZO-1 was almost completely lost in the colon epithelium, leading to increased membrane permeability. This could also be observed in vitro in CerS2 depleted Caco-2 cells. The increase in membrane permeability in CerS2−/− mice did not manifest with apparent clinical symptoms in naive mice, but with slight inflammatory signs such as an increase in monocytes and IL-10. AOM/DSS and DSS treatment alone led to a further deterioration of membrane integrity and to severe clinical symptoms of the disease. This was associated with stronger upregulation of cytokines in CerS2−/− mice and increased infiltration of the colon wall by immune cells, particularly monocytes, CD4+ and Th17+ T-cells, and an increase in tumor burden. In conclusion, CerS2 is crucial for the maintenance of colon barrier function and epithelial integrity. CerS2 knockdown, and associated changes in several sphingolipids such as a drop in very long-chain ceramides/(dh)-ceramides, an increase in long-chain ceramides/(dh)-ceramides, and sphinganine in the colon, may weaken endogenous defense against the endogenous microbiome.
      13. URL :
        https://link.springer.com/article/10.1007%2Fs00018-017-2518-9
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13686
      15. Serial :
        13842
      1. Author :
        Vasquez, Erick S; Feugang, Jean M; Willard, Scott T; Ryan, Peter L; Walters, Keisha B
      2. Title :
        Bioluminescent magnetic nanoparticles as potential imaging agents for mammalian spermatozoa
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Journal of Nanobiotechnology
      6. Products :
      7. Volume :
        14
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Spermatozoa,; Bioluminescence Imaging,; Magnetic nanoparticles,; Nanocomposites,; Reproduction,; Core–shell nanoparticles,; Luciferase; IVIS; IVIS BLI
      12. Abstract :
        Background: Nanoparticles have emerged as key materials for developing applications in nanomedicine, nanobiotechnology, bioimaging and theranostics. Existing bioimaging technologies include bioluminescent resonance energy transfer-conjugated quantum dots (BRET-QDs). Despite the current use of BRET-QDs for bioimaging, there are strong concerns about QD nanocomposites containing cadmium which exhibits potential cellular toxicity. Results: In this study, bioluminescent composites comprised of magnetic nanoparticles and firefly luciferase (Photinus pyralis) are examined as potential light-emitting agents for imaging, detection, and tracking mammalian spermatozoa. Characterization was carried out using infrared spectroscopy, TEM and cryo-TEM imaging, and ζ-potential measurements to demonstrate the successful preparation of these nanocomposites. Binding interactions between the synthesized nanoparticles and spermatozoon were characterized using confocal and atomic/magnetic force microscopy. Bioluminescence imaging and UV–visible-NIR microscopy results showed light emission from sperm samples incubated with the firefly luciferase-modified nanoparticles. Therefore, these newly synthesized luciferasemodified magnetic nanoparticles show promise as substitutes for QD labeling, and can potentially also be used for in vivo manipulation and tracking, as well as MRI techniques. Conclusions: These preliminary data indicate that luciferase-magnetic nanoparticle composites can potentially be used for spermatozoa detection and imaging. Their magnetic properties add additional functionality to allow for manipulation, sorting, or tracking of cells using magnetic techniques.
      13. URL :
        N/A
      14. Call Number :
        PKI @ user @ 11296
      15. Serial :
        19422
      1. Author :
        Oliemuller, Erik; Kogata, Naoko; Bland, Philip; Kriplani, Divya; Daley, Frances; Haider, Syed; Shah, Vandna; Sawyer, Elinor J; Howard, Beatrice A
      2. Title :
        SOX11 promotes invasive growth and DCIS progression
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        The Journal of Pathology
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        SOX11; DCIS; embryonic mammary marker; mammary progenitor/stem cells; invasion; ALDH1A1; IVIS; IVIS BLI in vivo
      12. Abstract :
        Here, we show that SOX11, an embryonic mammary marker, normally silent in postnatal breast cells, is expressed in many ER- preinvasive DCIS lesions. Mature mammary epithelial cells engineered to express SOX11 display alterations in progenitor cell populations, including an expanded basal-like population with increased ALDH activity, and increased mammosphere forming capacity. DCIS.com cells engineered to express SOX11 display increased ALDH activity, a feature of cancer stem cells. CD44+/CD24 /ALDH+ cell population is increased in DCIS.com cells that express SOX11. Upregulating SOX11 expression in DCIS.com cells leads to increased invasive growth both in vitro and when injected intraductally in a mouse model of DCIS that recapitulates human disease. Invasive lesions form sooner and tumour growth is augmented in vivo, suggesting SOX11 contributes to the progression of DCIS to invasive breast cancer. We identify potential downstream effectors of SOX11 during both microinvasive and invasive tumour growth stages, including several with established links to regulation of progenitor cell function and prenatal developmental growth. Our findings suggest SOX11 is a potential biomarker for DCIS lesions containing cells harbouring distinct biological features, which are likely to progress to invasive breast cancer.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 14100
      15. Serial :
        13834
      1. Author :
        Xu, Junjie; Lin, Hui; Li, Gonghui; Sun, Yin; Shi, Liang; Ma, Wen-Lung; Chen, Jiang; Cai, Xiujun; Chang, Chawnshang
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        International Journal of Cancer
      6. Products :
      7. Volume :
        140
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Sorafenib; ASC-J9®; hepatocellular carcinoma; synergism; IVIS; IVIS BLI in vivo
      12. Abstract :
        Sorafenib is currently used as a standard treatment to suppress the progression of hepatocellular carcinoma (HCC), especially in advanced stages. However, patients who receive Sorafenib treatment eventually develop resistance without clear mechanisms. There is a great need for better efficacy of Sorafenib treatment in combination with other therapies. Here, we demonstrated that the treatment combining Sorafenib with ASC-J9® could synergistically suppress HCC progression via altering cell-cycle regulation, apoptosis and invasion. Mechanism dissection suggests that while Sorafenib impacts little or even slightly increases the activated/phosphorylated STAT3 (p-STAT3), a key stimulator to promote the HCC progression, adding ASC-J9® significantly suppresses the p-STAT3 expression and its downstream genes including CCL2 and Bcl2. Interrupting these signals via constitutively active STAT3 partially reverses the synergistic suppression of Sorafenib-ASC-J9® combination on HCC progression. In vivo studies further confirmed the synergistic effect of Sorafenib-ASC-J9® combination. Together, these results suggest the newly developed Sorafenib-ASC-J9® combination is a novel therapy to better suppress HCC progression.
      13. URL :
        http://dx.doi.org/10.1002/ijc.30446 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215679/pdf/IJC-140-705.pdf
      14. Call Number :
        PKI @ catherine.lautenschlager @ 12549
      15. Serial :
        13618
      1. Author :
        Yang, Shaomei; Zhang, Bo; Gong, Xiaowei; Wang, Tianqi; Liu, Yongjun; Zhang, Na
      2. Title :
        In vivo biodistribution, biocompatibility, and efficacy of sorafenib-loaded lipid-based nanosuspensions evaluated experimentally in cancer
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        International Journal of Nanomedicine
      6. Products :
      7. Volume :
        11
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        sorafenib,; lipid-based nanosuspensions,; HCC,; distribution,; antitumor effect; IVIS; IVIS FLI in vivo
      12. Abstract :
        Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. In this study, sorafenib-loaded lipid-based nanosuspensions (sorafenib-LNS) were first developed as an intravenous injectable formulation to increase the efficacy of sorafenib against HCC. LNS were used as nanocarriers for sorafenib owing to their desired features in increasing the solubility and dissolution velocity, improving the bioavailability of sorafenib. Sorafenib-LNS were prepared by nanoprecipitation and consisted of spherical particles with a uniform size distribution (164.5 nm, polydispersity index =0.202) and negative zeta potential (−11.0 mV). The drug loading (DL) was 10.55%±0.16%. Sorafenib-LNS showed higher in vitro cytotoxicity than sorafenib against HepG2 cells (P0.05) and Bel-7402 cells (P0.05). The in vivo biodistribution, biocompatibility, and antitumor efficacy of sorafenib-LNS were evaluated in H22-bearing liver cancer xenograft murine model. The results showed that sorafenib-LNS (9 mg/kg) exhibited significantly higher antitumor efficacy by reducing the tumor volume compared with the sorafenib oral group (18 mg/kg, P0.05) and sorafenib injection group (9 mg/kg, P0.05). Furthermore, the results of the in vivo biodistribution experiments demonstrated that sorafenib-LNS injected into H22 tumor-bearing mice exhibited increased accumulation in the tumor tissue, which was confirmed by in vivo imaging. In the current experimental conditions, sorafenib-LNS did not show significant toxicity both in vitro and in vivo. These results suggest that sorafenib-LNS are a promising nanomedicine for treating HCC.
      13. URL :
        N/A
      14. Call Number :
        PKI @ user @ 11793
      15. Serial :
        19343
      1. Author :
        Shen, Song; Wu, Lin; Liu, Jiejie; Xie, Meng; Shen, Haijun; Qi, Xueyong; Yan, Yongmin; Ge, Yanru; Jin, Yi
      2. Title :
        Core–shell structured Fe 3 O 4@ TiO 2-doxorubicin nanoparticles for targeted chemo-sonodynamic therapy of cancer
      3. Type :
        Journal Article
      4. Year :
        2015
      5. Publication :
        International journal of pharmaceutics
      6. Products :
      7. Volume :
        486
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Sonodynamic therapy;; Magnetic iron oxide;; Tumor targeting;; Doxorubicin;; Combined therapy; Maestro
      12. Abstract :
        To facilitate targeting drug delivery and combined therapy, we develop titanium dioxide-encapsulated Fe3O4 nanoparticles (Fe3O4@TiO2 NPs). Titanium dioxide (TiO2), which is employed as a sonosensitizer for sonodynamic therapy (SDT), can also be used for the loading of doxorubicin (DOX). The fabricated Fe3O4@TiO2 NPs exhibit pH-dependent loading and release of doxorubicin (DOX) in vitro. After incubation with cancer cells, reactive oxygen species (ROS) are generated efficiently upon the irradiation of ultrasound. In the biodistribution experiments, extremely high in vivo tumor accumulation of Fe3O4@TiO2 NPs and long-time retention effect are observed. Compared with chemotherapy or sonodynamic treatment alone, the combined therapy demonstrated a synergistic effect, resulting in stronger cytotoxicity and higher therapeutic efficacy. Thus, the constructed NPs are endowed with multifunctions which allow them to selectively deliver combinatorial therapeutic payload to tumor with enhanced therapeutic effectiveness and minimal side effects.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 9250
      15. Serial :
        13044
      1. Author :
        Neto, Manoel Figueiredo; Letteri, Rachel; Chan-Seng, Delphine; Emrick, Todd; Figueiredo, Marxa L
      2. Title :
        Sonodelivery Facilitates Sustained Luciferase Expression from an Episomal Vector in Skeletal Muscle
      3. Type :
        Journal Article
      4. Year :
        2015
      5. Publication :
        Materials
      6. Products :
      7. Volume :
        8
      8. Issue :
        7
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        sonodelivery;; episome;; polymer;; nanoplex;; microbubbles;; non-viral vector;; skeletal muscle;; sustained expression;; luciferase; IVIS; IVIS BLI in vivo
      12. Abstract :
        Successful gene delivery to skeletal muscle is a desirable goal, not only for treating muscle diseases, but also for immunization, treatment of metabolic disorders, and/or delivering gene expression that can treat systemic conditions, such as bone metastatic cancer, for example. Although naked DNA uptake into skeletal muscle is possible, it is largely inefficient in the absence of additional chemical or physical delivery methods. We describe a system for delivery of non-viral or plasmid DNA to skeletal muscle using ultrasound-assisted sonoporation of a nanoplex combining plasmid DNA and a branched polymer based on poly(cyclooctene-graft-oligopeptide). The materials and methods described herein promise to advance the field of sonodelivery and of gene delivery to muscle for therapeutic applications since a simple system is presented that enables long-term gene expression in vivo with the promise of a minimal inflammatory gene expression profile.
      13. URL :
        N/A
      14. Call Number :
        PKI @ user @ 9906
      15. Serial :
        20541
      1. Author :
        Esposito, E; Vries, HED; Pol, SMA; Boschi, F; Calderan, L
      2. Title :
        Production, Physico-Chemical Characterization and Biodistribution Studies of Lipid Nanoparticles
      3. Type :
        Journal Article
      4. Year :
        2015
      5. Publication :
        J Nanomed Nanotechnol
      6. Products :
      7. Volume :
        6
      8. Issue :
        256
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Solid lipid nanoparticles;; Nanostructured lipid carriers;; Cryogenic transmission electron microscopy;; Sedimentation field flow fractionation;; Photon correlation spectroscopy;; In vitro uptake;; In vivo biodistribution; IVIS; IVIS FLI in vivo; IVIS FLI in vitro
      12. Abstract :
        This study describes the preparation, characterization, in vitro uptake and in vivo biodistribution in mice of solid lipid nanoparticles and nanostructured lipid carriers. The effect of nanoparticle lipid matrix, presence of fluorescent and functionalization by polysorbate 80 on dimensional distribution and morphology have been studied by sedimentation field flow fractionation, photon correlation spectroscopy and cryogenic transmission electron microscopy. The complementary use of different techniques demonstrated that lipid matrix composition, presence of fluorescent dye and polysorbate 80 functionalization have little effect on nanoparticle morphology and size distribution. Uptake of fluorescent nanoparticles was determined in vitro by human brain endothelial cells, showing that nanoparticles treated by polysorbate 80 displayed lower uptake values with respect to the corresponding control nanoparticles. Biodistribution of solid lipid nanoparticles treated by polysorbate 80 was evaluated by fluorescent luminescent imaging after intraperitoneal administration in mice. The in vivo images indicate that nanoparticles were able to reach the brain, even if they prevalently accumulated in liver and spleen.
      13. URL :
        N/A
      14. Call Number :
        PKI @ user @ 8972
      15. Serial :
        20876
      1. Author :
        Esposito, Elisabetta; Cortesi, Rita; Drechsler, Markus; Fan, Jie; Fu, Bingmei M.; Calderan, Laura; Mannucci, Silvia; Boschi, Federico; Nastruzzi, Claudio
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        European Journal of Pharmaceutics and Biopharmaceutics
      6. Products :
      7. Volume :
        115
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Solid lipid nanoparticles; Dimethyl fumarate; Brain delivery; Multiple sclerosis; biodistribution; Fluorescent luminescence imaging; IVIS; IVIS FLI in vivo
      12. Abstract :
        Dimethyl fumarate has been demonstrated useful in relapsing remitting multiple sclerosis treatment (Tecfidera®). Nevertheless, since Tecfidera® capsules induce flushing, gastro-intestinal events and other more serious drawbacks, in this investigation a nanoparticle based system to be administered by an alternative way is proposed. In particular this study describes the preparation and characterization of dimethyl fumarate-containing solid lipid nanoparticles (SLN). Namely SLN based on tristearin, tristearin SLN treated with polysorbate 80 and cationic SLN constituted of tristearin in mixture with dimethyldioctadecylammonium chloride were investigated. The effect of the presence of dimethyl fumarate, functionalization by polysorbate 80 and dimethyldioctadecylammonium chloride was studied on morphology and dimensional distribution of SLN, by photon correlation spectroscopy and cryogenic transmission electron microscopy. Dimethyl fumarate release from SLN, studied by Franz cell, evidenced a Fickian dissolutive type kinetic in the case of SLN treated by polysorbate 80. Moreover fluorescent SLN were produced and characterized in order to investigate their in vitro permeability and in vivo biodistribution in mice. An in vitro study of fluorescent SLN permeability performed through a model of mouse brain microvascular endothelial cells, indicated that cationic SLN displayed higher permeability values with respect to neutral SLN and SLN treated by polysorbate 80. Biodistribution of polysorbate 80 treated SLN was studied by fluorescent imaging after intraperitoneal or intranasal administration in mice. The in vivo images indicate that polysorbate 80 treated SLN were able to reach the brain, even if they prevalently accumulated in liver and spleen, especially by intraperitoneal route.
      13. URL :
        http://www.sciencedirect.com/science/article/pii/S0939641117304587
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13677
      15. Serial :
        14104
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