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      1. Author :
        Park, Ji Sun; Yi, Se Won; Kim, Hye Jin; Kim, Seong Min; Shim, Sung Han; Park, Keun-Hong
      2. Title :
        Sunflower-type nanogels carrying a quantum dot nanoprobe for both superior gene delivery efficacy and tracing of human mesenchymal stem cells
      3. Type :
        Journal Article
      4. Year :
        2015
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Sunflower-type;; Nanogel;; Gene Delivery;; Bioimaging; IVIS; IVIS FLI
      12. Abstract :
        Sunflower-type nanogels carrying the QD 655 nanoprobe can be used for both gene transfection and bioimaging of hMSCs. The entry of sunflower-type nanogels into hMSCs can be possibly controlled by changing the formation of QDs. The physico-chemical properties of sunflower-type nanogels internalized by hMSCs were confirmed by AFM, SEM, TEM, gel retardation, and ζ-potential analyses. The bioimaging capacity was confirmed by confocal laser microscopy, Kodak imaging, and Xenogen imaging. Specifically, we investigated the cytotoxicity of sunflower-type nanogels via SNP analysis. Internalization of sunflower-type nanogels does not cause malfunction of hMSCs.
      13. URL :
        N/A
      14. Call Number :
        PKI @ user @ 10354
      15. Serial :
        20512
      1. Author :
        Yu, Na; Swevers, Luc; Nachman, Ronald J; Smagghe, Guy
      2. Title :
        Development of cell-based bioassay with Sf9 cells expressing TcSKR1 and TcSKR2 and differential activation by sulfated and non-sulfated SK peptides
      3. Type :
        Journal Article
      4. Year :
        2014
      5. Publication :
        Peptides
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Sulfakinin;; Sulfakinin receptor;; G-protein-coupled receptor;; Cell-based assay;; Gαs-protein
      12. Abstract :
        Insect sulfakinin receptors (SKRs) are G-protein-coupled receptors (GPCRs) that interact with sulfakinins (SKs) to modulate diverse biological processes. One of the indispensable roles of SKs is in the regulation of food intake in insects. In this project we report on the development of a cell-based receptor assay system with insect Sf9 cells, expressing TcSKR1 and TcSKR2 from the red flour beetle Tribolium castaneum, a model and important pest insect in agriculture. In this system, a stable presence of the two TcSKRs was supported by Western blotting. The expressed TcSKRs were coupled to Gαs-protein upon activation and stimulated cAMP accumulation in Sf9 cells. Exposure of the transfected cell lines to sulfated SK (sSK) activated TcSKR1 at 1 nM; the EC50 of sSK to obtain 50% of receptor activation was similar for both receptors. In contrast, μM concentrations of non-sulfated SK were necessary to activate both TcSKRs. In conclusion, this cell-based TcSKR assay system is useful to screen SK-related peptides and mimetics and to better document ligand-receptor structure-activity relationships. Given the importance of SK signaling system in insects, the present study may provide new insights on the development of new methods to control pest insects.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 7109
      15. Serial :
        13129
      1. Author :
        Slocinska, Malgorzata; Marciniak, Pawel; Jarmuszkiewicz, Wieslawa; Rosinski, Grzegorz
      2. Title :
        New metabolic activity of the nonsulfated sulfakinin Zopat-SK-1 in the insect fat body
      3. Type :
        Journal Article
      4. Year :
        2014
      5. Publication :
        Peptides
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Sulfakinin;; Nonsulfated sulfakinin Zopat-SK-1;; Lipid;; Carbohydrate and protein fat body metabolism;; Zophobas atratus;; Beetles
      12. Abstract :
        Insect sulfakinins are multifunctional neuropeptides homologous to vertebrate gastrin/cholecystokin (CCK) neuropeptide hormones. We investigated the action of the nonsulfated sulfakinin Zopat-SK-1 (pETSDDYGHLRFa) on the levels of chosen metabolites in the Zophobas atratus beetle fat body. Samples of fat body were collected 2 h and 24 h after hormone injection. The administration of 20 pmol of Zopat-SK-1 to feeding larvae significantly increased concentrations of lipids and proteins and decreased the content of glycogen in fat body tissue in the 24 h experimental group. In contrast, the only increase in total lipid concentration in prepupal fat bodies was observed 24 h after Zopat-SK-1 treatment. Simultaneously, changes in the quality and quantity of free sugars in the hemolymph were measured. In larval hemolymph, a marked increase in free sugar concentration and a decrease in glucose content were observed 24 h and 2 h after Zopat-SK-1 application, respectively. No changes in the prepupal stage were observed. For the first time we show potent metabolic activity of sulfakinin in the fat body tissue of an insect. Our findings imply a physiological function of the nonsulfated form of sulfakinin in energy storage and release processes in fat body tissue of larvae and prepupae was indicated. We suggest a role for sulfakinin signaling in the regulation of energy metabolism in insect tissues.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 7463
      15. Serial :
        13151
      1. Author :
        Wu, Junchen; Zhou, Yuren; Li, Shang; Qu, Dahui; Zhu, Wei-Hong; Tian, He
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        120
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Substance P; 5-fluorouracil; Neurokinin-1 receptor; Near-infrared imaging; Anticancer; IVIS; IVIS FLI
      12. Abstract :
        Efficient and site-specific delivery of anticancer drugs to tumors is important in the development of effective cancer chemotherapy. As an undecapeptide of the tachykinin neuropeptide family, the substance P (SP)/neurokinin-1 receptor (NK1R) system has been identified as a promising ligand-receptor pair in tumor-specific drug delivery. However, the rational design of suitable theranostic agents with high drug loading capacity and tumor targeting for cancer patients remains a great challenge. Herein, we report a dendritic strategy that utilizes the two amine functionalities of lysine to create branch points that allow conjugation of the anticancer drug 5-fluorouracil (5-FU) to the tumor-targeting ligand substance P, along with an additional near-infrared (NIR) squaraine dye, to construct a theranostic dendritic agent, P-FU 4. This cytotoxic theranostic agent, containing four carboxyl-modified 5-FU molecules, has several desirable advantages: i) the ability to self-assemble into nanoparticles; ii) enhanced cytotoxicity with high drug loading capacity (16%) and a specific receptor-targeted interaction with NK1R through the SP moiety; and iii) a high NIR squaraine fluorescence efficiency due to the specific dendron isolation, avoiding aggregation-mediated quenching. As demonstrated in this report, the cytotoxic activity of P-FU 4 is dose-dependent against the tested cancer cells. The improved drug loading capacity with dendritic branching distinctly enhanced cytotoxicity to tumor cells but had little effect on the viability of normal cells. P-FU 4 was preferentially taken up by tumor cells through a receptor-mediated interaction, which was monitored by effective NIR fluorescence with high tissue penetration. Studies using a mouse model revealed that P-FU 4 can significantly inhibit tumor progression, with a tumor-inhibition rate of 60.2%. The receptor-targeted cytotoxic dendritic theranostic agent is highly preferable to standard chemotherapeutic treatments and decreases the negative side effects of medications on healthy cells, which establishes its utility in drug delivery and cancer chemotherapy.
      13. URL :
        http://www.sciencedirect.com/science/article/pii/S0142961216306184
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13023
      15. Serial :
        13630
      1. Author :
        Jennewine, Brenton; Fox, Jonathan; Ramamurthi, Anand
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Acta Biomaterialia
      6. Products :
      7. Volume :
        52
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Submicron particles; Elastic matrix; Regenerative matrix repair; Matrix metalloproteinases (MMPs); Cathepsin K; Drug delivery; IVIS; IVIS FLI
      12. Abstract :
        Abdominal Aortic Aneurysms (AAA) involve slow dilation and weakening of the aortic wall due to breakdown of structural matrix components, such as elastic fibers by chronically overexpressed matrix metalloproteinases (MMPs), primarily, MMPs-2 and -9. Auto-regenerative repair of disrupted elastic fibers by smooth muscle cells (SMCs) at the AAA site is intrinsically poor and together with chronic proteolysis prevents restoration of elastin homeostasis, necessary to enable AAA growth arrest or regression to a healthy state. Oral doxycycline (DOX) therapy can inhibit MMPs to slow AAA growth, but has systemwide side-effects and inhibits new elastin deposition within AAA tissue, diminishing prospects for restoring elastin homeostasis preventing the arrest/regression of AAA growth. We have thus developed cationic amphiphile (DMAB)-modified submicron particles (SMPs) that uniquely exhibit pro-elastogenic and anti-proteolytic properties, separate from similar effects of the encapsulated drug. These SMPs can enable sustained, low dose DOX delivery within AAA tissue to augment elastin regenerative repair. To provide greater specificity of SMP targeting, we have conjugated the DOX-SMP surface with an antibody against cathepsin K, a lysosomal protease that is highly overexpressed within AAA tissue. We have determined conditions for efficient cathepsin K Ab conjugation onto the SMPs, improved SMP binding to aneurysmal SMCs in culture and to injured vessel walls ex vivo, conjugation did not affect DOX release from the SMPs, and improved pro-elastogenic and anti-proteolytic effects due to the SMPs likely due to their increased proximity to cells via binding. Our study results suggest that cathepsin K Ab conjugation is a useful targeting modality for our pro-regenerative SMPs. Future studies will investigate SMP retention and biodistribution following targeting to induced AAAs in rat models through intravenous or catheter-based aortal infusion and thereafter their efficacy for regenerative elastic matrix repair in the AAA wall. Statement of Significance Proactive screening of high risk elderly patients now enables early detection of Abdominal Aortic Aneurysms (AAAs). Current management of small, growing AAAs is limited to passive, imaging based growth monitoring. There are also no established drug-based therapeutic alternatives to surgery for AAAs, which is unsuitable for many elderly patients, and none which can achieve restore disrupted and lost elastic matrix in the AAA wall, which is essential to achieve growth arrest or regression. We seek to test the feasibility of a regenerative therapy based on localized, one time delivery of drug-releasing Sub-Micron-sized drug delivery polymer Particles (SMPs) that are also uniquely chemically functionalized on their surface to also provide them pro-elastin-regenerative & anti-matrix degradative properties, and also conjugated with antibodies targeting cathepsin K, an elastolytic enzyme that is highly overexpressed in AAA tissues; the latter serves as a modality to enable targeted binding of the SMPs to the AAA wall following intravenous infusion, or intraoartal, catheter-based delivery. Such SMPs can potentially stimulate structural repair in the AAA wall following one time infusion to delay or prevent AAA growth to rupture. The therapy can provide a non-surgical treatment option for high risk AAA patients.
      13. URL :
        http://www.sciencedirect.com/science/article/pii/S1742706117300326 http://ac.els-cdn.com/S1742706117300326/1-s2.0-S1742706117300326-main.pdf?_tid=a335a218-36ca-11e7-9f80-00000aacb35d&acdnat=1494563140_1aa8c7d2309bdc794f432a1b27bd6af1
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13181
      15. Serial :
        14019
      1. Author :
        Korupalli, Chiranjeevi; Huang, Chieh-Cheng; Lin, Wei-Chih; Pan, Wen-Yu; Lin, Po-Yen; Wan, Wei-Lin; Li, Meng-Ju; Chang, Yen; Sung, Hsing-Wen
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        116
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Subcutaneous abscesses; Photothermal therapy; pH-responsive nanoparticles; Charge conversion; Imaging guiding; IVIS; IVIS FLI in vivo
      12. Abstract :
        Focal infections that are caused by antibiotic-resistant bacteria are becoming an ever-growing challenge to human health. To address this challenge, a pH-responsive amphiphilic polymer of polyaniline-conjugated glycol chitosan (PANI-GCS) that can self-assemble into nanoparticles (NPs) in situ is developed. The PANI-GCS NPs undergo a unique surface charge conversion that is induced by their local pH, favoring bacterium-specific aggregation without direct contact with host cells. Following conjugation onto GCS, the optical-absorbance peak of PANI is red-shifted toward the near-infrared (NIR) region, enabling PANI-GCS NPs to generate a substantial amount of heat, which is emitted to their neighborhood. The local temperature of the NIR-irradiated PANI-GCS NPs is estimated to be approximately 5 °C higher than their ambient tissue temperature, ensuring specific and direct heating of their aggregated bacteria; hence, damage to tissue is reduced and wound healing is accelerated. The above results demonstrate that PANI-GCS NPs are practical for use in the photothermal ablation of focal infections.
      13. URL :
        http://www.sciencedirect.com/science/article/pii/S014296121630669X
      14. Call Number :
        PKI @ catherine.lautenschlager @ 12976
      15. Serial :
        13983
      1. Author :
        Pan, Pengyu; Zhang, Xuan; Li, Qiang; Zhao, Hengli; Qu, Jie; Zhang, John H.; Liu, Xin; Feng, Hua; Chen, Yujie
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Neuroscience Letters
      6. Products :
      7. Volume :
        649
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Subarachnoid hemorrhage; Early brain injury; Cyclosporine A; Blood-brain barrier; Matrix metalloproteinase 9; IVIS; IVIS FLI in vivo
      12. Abstract :
        The aim of this study was to investigate whether Cyclosporine A (CsA) attenuates early brain injury by alleviating matrix metalloproteinase 9 (MMP-9) associated blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH). A standard intravascular perforation model was used to produce the experimental SAH in C57B6J mice. Dosages of 5mg/kg, 10mg/kg and 15mg/kg CsA were evaluated for effects on neurological score, brain water content, Evans blue extravasation and fluorescence, P-p65, MMP-9 and BBB components’ alterations after SAH. We found that CsA 15mg/kg is effective in attenuating BBB disruption, lowering edema, and improving neurological outcomes. In addition, Collagen IV, ZO-1, Occludin and Claudin 5 expressions in ipsilateral/left hemisphere were downregulated after SAH, but increased after CsA treatment. Our results suggest that CsA exert a neuroprotective role in SAH pathophysiology, possibly by alleviating MMP-9 associated BBB disruption.
      13. URL :
        http://www.sciencedirect.com/science/article/pii/S030439401730280X
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13591
      15. Serial :
        13825
      1. Author :
        Geng, Lingling; Wang, Zihua; Yang, Xiaoliang; Li, Dan; Lian, Wenxi; Xiang, Zhichu; Wang, Weizhi; Bu, Xiangli; Lai, Wenjia; Hu, Zhiyuan
      2. Title :
        Structure-based Design of Peptides with High Affinity and Specificity to HER2 Positive Tumors
      3. Type :
        Journal Article
      4. Year :
        2015
      5. Publication :
        Theranostics
      6. Products :
      7. Volume :
        5
      8. Issue :
        10
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        structure-based design,; HER2 targeted peptide,; breast cancer,; MD simulation; Maestro
      12. Abstract :
        To identify peptides with high affinity and specificity against human epidermal growth factor receptor 2 (HER2), a series of peptides were designed based on the structure of HER2 and its Z(HER2:342) affibody. By using a combination protocol of molecular dynamics modeling, MM/GBSA binding free energy calculations, and binding free energy decomposition analysis, two novel peptides with 27 residues, pep27 and pep27-24M, were successfully obtained. Immunocytochemistry and flow cytometry analysis verified that both peptides can specifically bind to the extracellular domain of HER2 protein at cellular level. The Surface Plasmon Resonance imaging (SPRi) analysis showed that dissociation constants (KD) of these two peptides were around 300 nmol/L. Furthermore, fluorescence imaging of peptides against nude mice xenografted with SKBR3 cells indicated that both peptides have strong affinity and high specificity to HER2 positive tumors.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 9950
      15. Serial :
        13089
      1. Author :
        Sharkey, Jack; Scarfe, Lauren; Santeramo, Ilaria; Garcia-Finana, Marta; Park, Brian K; Poptani, Harish; Wilm, Bettina; Taylor, Arthur; Murray, Patricia
      2. Title :
        Imaging technologies for monitoring the safety, efficacy and mechanisms of action of cell-based regenerative medicine therapies in models of kidney disease
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        European Journal of Pharmacology
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Stemcells; Preclinical imaging; Multispectral optoacoustictomography; Cell tracking; Biodistribution; Kidney Function Tests; IVIS; IVIS BLI in vivo
      12. Abstract :
        The incidenceofendstagekidneydiseaseisrisingannuallyanditisnowaglobalpublichealthproblem. Current treatmentoptionsaredialysisorrenaltransplantation,whichapartfromtheirsignificant drawbacksintermsofincreasedmorbidityandmortality,areplacinganincreasingeconomicburdenon society.Cell-basedRegenerativeMedicineTherapies(RMTs)haveshowngreatpromiseinrodentmodels of kidneydisease,butclinicaltranslationishamperedduetothelackofadequatesafetyandefficacy data. Furthermore,themechanismswherebythecell-basedRMTsameliorateinjuryareill-defined. For instance, itisnotalwaysclearifthecellsdirectlyreplacedamagedrenaltissue,orwhetherparacrine effects aremoreimportant.Knowledgeofthemechanismsresponsibleforthebeneficial effectsofcell therapies iscrucialbecauseitcouldleadtothedevelopmentofsaferandmoreeffectiveRMTsinthe future. Toaddressthesequestions,novelinvivoimagingstrategiesareneededtomonitorthebiodis- tribution ofcell-basedRMTsandevaluatetheirbeneficial effectsonhosttissuesandorgans,aswellas anypotentialadverseeffects.Inthisreviewwewilldiscusshowstate-of-the-artimagingmodalities, including bioluminescence,magneticresonance,nuclearimaging,ultrasoundandanemergingimaging technology calledmultispectraloptoacoustictomography,canbeusedincombinationwithvarious imaging probestotrackthefateandbiodistributionofcell-basedRMTsinrodentmodelsofkidney disease, andevaluatetheireffectonrenalfunction.
      13. URL :
        N/A
      14. Call Number :
        PKI @ user @ 11867
      15. Serial :
        19504
      1. Author :
        Han, Dong; Huang, Wei; Li, Xiang; Gao, Lei; Su, Tao; Li, Xiujuan; Ma, Sai; Liu, Tong; Li, Congye; Chen, Jiangwei
      2. Title :
        Melatonin facilitates Adipose‐Derived Mesenchymal Stem Cells to repair the murine infarcted heart via the SIRT1 signaling pathway
      3. Type :
        Journal Article
      4. Year :
        2015
      5. Publication :
        Journal of pineal research
      6. Products :
      7. Volume :
        60
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        stem cells;; melatonin;; myocardial infarction;; oxidative stress;; SIRT1 signaling; IVIS; IVIS BLI
      12. Abstract :
        Mesenchymal stem cells (MSCs)-based therapy provides a promising therapy for the ischemic heart disease (IHD). However, engrafted MSCs are subjected to acute cell death in the ischemic microenvironment, characterized by excessive inflammation and oxidative stress in the host's infarcted myocardium. Melatonin, an indole, which is produced by many organs including pineal gland, has been shown to protect bone marrow MSCs against apoptosis although the mechanism of action remains elusive. Using a murine model of myocardial infarction (MI), this study was designed to evaluate the impact of melatonin on adipose derived mesenchymal stem cells (AD-MSCs) based therapy for MI and the underlying mechanism involved with a focus on silent information regulator 1(SIRT1) signaling. Our results demonstrated that melatonin promoted functional survival of AD-MSCs in infarcted heart and provoked a synergetic effect with AD-MSCs to restore heart function. This in vivo effect of melatonin was associated with alleviated inflammation, apoptosis, and oxidative stress in infarcted heart. In vitro studies revealed that melatonin exert cytoprotective effects on AD-MSCs against hypoxia/serum deprivation (H/SD) injury via attenuating inflammation, apoptosis, and oxidative stress. Mechanistically, melatonin enhanced SIRT1 signaling, which was accompanied with the increased expression of anti-apoptotic protein Bcl2, and decreased expression of Ac-FoxO1, Ac-p53, Ac-NF-ΚB, and Bax. Taken together, our findings indicated that melatonin facilitated AD-MSCs-based therapy in MI, possibly through promoting survival of AD-MSCs via SIRT1 signaling. Our data support the promise of melatonin as a novel strategy to improve MSC-based therapy for IHD, possibly through SIRT1 signaling evocation.
      13. URL :
        N/A
      14. Call Number :
        PKI @ user @ 10443
      15. Serial :
        20818
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