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https://www.readbyqxmd.com/read/28440948/novel-reduction-sensitive-micellar-nanoparticles-assembled-from-rituximab-doxorubicin-conjugates-as-smart-and-intuitive-drug-delivery-systems-for-the-treatment-of-non-hodgkin-s-lymphoma
#1
Huabin Yin, Tong Meng, Ling Shu, Min Mao, Lei Zhou, Haiyan Chen, Dianwen Song
In this study, a novel reduction-sensitive drug delivery system, the Rituximab-Doxorubicin (RTX-DOX) micellar nanoparticle (RDMN), was specially designed for targeted delivery and release of DOX in Non-Hodgkin's Lymphoma (NHL) cells. The RDMN was fabricated by self-assembling of amphiphilic RTX-DOX conjugates (RDCs), which were synthesized by conjugating the hydrophilic Fab fragments of RTX (an anti-CD20 monoclonal antibody) and hydrophobic DOXs by a reduction-responsive linker, 3-(2-Pyridyldithio) propionyl hydrazide (PDPH)...
April 25, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28437437/use-of-short-interfering-rna-delivered-by-cationic-liposomes-to-enable-efficient-down-regulation-of-ptpn22-gene-in-human-t-lymphocytes
#2
Valentina Perri, Marsha Pellegrino, Francesca Ceccacci, Anita Scipioni, Stefania Petrini, Elena Gianchecchi, Anna Lo Russo, Serena De Santis, Giovanna Mancini, Alessandra Fierabracci
Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target...
2017: PloS One
https://www.readbyqxmd.com/read/28436294/overexpression-of-vla-4-in-glial-restricted-precursors-enhances-their-endothelial-docking-and-induces-diapedesis-in-a-mouse-stroke-model
#3
Anna Jablonska, Daniel J Shea, Suyi Cao, Jeff Wm Bulte, Miroslaw Janowski, Konstantinos Konstantopoulos, Piotr Walczak
The loss of oligodendrocytes after stroke is one of the major causes of secondary injury. Glial-restricted progenitors (GRPs) have remylenating potential after intraparenchymal cerebral transplantation. The intraarterial (IA) injection route is an attractive gateway for global brain delivery, but, after IA infusion, naive GRPs fail to bind to the cerebral vasculature. The aim of this study was to test whether overexpression of Very Late Antigen-4 (VLA-4) increases endothelial docking and cerebral homing of GRPs in a stroke model...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28436114/all-trans-retinoic-acid-stimulates-overexpression-of-tumor-protein-d52-tpd52-isoform-3-and-neuronal-differentiation-of-imr-32-cells
#4
Sudha Sravanti Kotapalli, Chandrashekhar Dasari, Divya Duscharla, Karthik Reddy Kami Reddy, Manjula Kasula, Ramesh Ummanni
Tumor protein D52 (TPD52), a proto-oncogene is overexpressed in a variety of epithelial carcinomas and plays an important role in cell proliferation, migration and cell death. In the present study we found that the treatment of IMR-32 neuroblastoma (NB) cells with retinoic acid (RA) stimulates an increase in expression of TPD52. TPD52 expression is detectable after 72 h, can be maintained till differentiation of NB cells suggesting that TPD52 is involved in differentiation. Here, we demonstrate that TPD52 is essential for RA to promote differentiation of NB cells...
April 24, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28435150/ym155-down-regulates-survivin-and-induces-p53-up-regulated-modulator-of-apoptosis-puma-dependent-in-oral-squamous-cell-carcinoma-cells
#5
Xiang Yan, Han Su
BACKGROUND YM155, which inhibits the anti-apoptotic protein survivin, is known to exert anti-tumor effects in various cancers. However, there were few reports describing the inhibitory effect of YM155 on human oral squamous cell carcinoma (OSCC) cells that highly express survivin. In this study, we investigated the anti-tumor effects of YM155 on OSCC cells and then examined its molecular mechanisms. MATERIAL AND METHODS SCC9 cells of OSCC were treated with series of concentrations of YM155 (0.01, 0.1, 1, and 10 ng/ml) for 6, 12, and 24 h...
April 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28429362/wnt11-overexpression-promote-adipose-derived-stem-cells-differentiating-to-the-nucleus-pulposus-like-phenotype
#6
H-T Chen, A-B Huang, Y-L He, J Bian, H-J Li
OBJECTIVE: Our present study aimed to evaluate the effects of Wnt11 overexpression on the adipose-derived stem (ADSCs) cells differentiation to the nucleus pulposus (NP) cells and its function in the ADSCs cells growth, proliferation and induction of the NP cells markers. MATERIALS AND METHODS: The cell growth was detected using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) (MTT) assay and the cell cycle was assessed by the flow cytometry...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28425284/ph-triggered-size-increasing-gene-carrier-for-efficient-tumor-accumulation-and-excellent-antitumor-effect
#7
Zhaopei Guo, Jie Chen, Lin Lin, Xiuwen Guan, Pingjie Sun, Meiwan Chen, Huayu Tian, Xuesi Chen
High efficiency and serum resistant capacity are important for gene carrier in vivo usage. In this study, transfection efficiency and cell toxicity of polyethylenimine (PEI) (branched, Mw = 25K) was remarkably improved, when mixed with polyanion (polyethylene glycol-polyglutamic acid (PEG-PLG) or polyglutamic acid (PLG)). Different composite orders of PEI, polyanion, and gene, for example, PEI is first complexed with DNA, and then with polyanion, or PEI is first complexed with polyanion, and then with DNA, were studied...
April 25, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28418072/myb-gata1-fusion-promotes-basophilic-leukaemia-involvement-of-il33-and-nerve-growth-factor-receptors
#8
Stéphane Ducassou, Valérie Prouzet-Mauléon, Marie-Céline Deau, Philippe Brunet de la Grange, Bruno Cardinaud, Hayssam Soueidan, Cathy Quelen, Pierre Brousset, Jean-Max Pasquet, François Moreau-Gaudry, Michel Arock, François-Xavier Mahon, Eric Lippert
Acute basophilic leukaemia (ABL) is a rare subtype of acute myeloblastic leukaemia. We previously described a recurrent t(X;6)(p11;q23) translocation generating a MYB-GATA1 fusion gene in male infants with ABL. To better understand its role, the chimeric MYB-GATA1 transcription factor was expressed in CD34-positive hematopoietic progenitors which were transplanted into immunodeficient mice. Cells expressing MYB-GATA1 showed increased expression of markers of immaturity (CD34), of granulocytic lineage (CD33, CD117) and of basophilic differentiation (CD203c, FcƐRI)...
April 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28407530/redox-responsive-nanocarriers-for-drug-and-gene-co-delivery-based-on-chitosan-derivatives-modified-mesoporous-silica-nanoparticles
#9
Jian-Tao Lin, Zong-Kun Liu, Qing-Ling Zhu, Xiao-Hui Rong, Cui-Ling Liang, Jie Wang, Dong Ma, Jing Sun, Guan-Hai Wang
Stimuli-responsive nanocarriers for anticancer drug and gene co-delivery are promising strategy in cancer therapy. The ultimate goal is to deliver high local concentration of therapeutic agents with no premature release and result in synergistic effects for combination therapies. In this work, we developed a redox stimuli-responsive and synergistic co-delivery system for anticancer drug DOX and p53 gene for potential cancer therapy. A dendronized chitosan derivative (CP) as a "gatekeeper" to control release the drug was used to modify MSNs via a disulfide linker and improve the gene transfection efficiency...
April 5, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28405630/efficient-and-robust-paramyxoviridae-reverse-genetics-systems
#10
Shannon M Beaty, Arnold Park, Sohui T Won, Patrick Hong, Michael Lyons, Frederic Vigant, Alexander N Freiberg, Benjamin R tenOever, W Paul Duprex, Benhur Lee
The notoriously low efficiency of Paramyxoviridae reverse genetics systems has posed a limiting barrier to the study of viruses in this family. Previous approaches to reverse genetics have utilized a wide variety of techniques to overcome the technical hurdles. Although robustness (i.e., the number of attempts that result in successful rescue) has been improved in some systems with the use of stable cell lines, the efficiency of rescue (i.e., the proportion of transfected cells that yield at least one successful rescue event) has remained low...
March 2017: MSphere
https://www.readbyqxmd.com/read/28399862/chitosan-nanoparticle-mediated-co-delivery-of-shatg-5-and-gefitinib-synergistically-promoted-the-efficacy-of-chemotherapeutics-through-the-modulation-of-autophagy
#11
Yan Zheng, Chang Su, Liang Zhao, Yijie Shi
BACKGROUND: Autophagy reportedly plays vital and complex roles in many diseases. During times of starvation or energy deficiency, autophagy will occur at higher levels to provide cells with the nutrients or energy necessary to survive in stressful conditions. Some anti-cancer drugs induce protective autophagy and reduce cell apoptosis. Autophagy can adversely affect apoptosis, and blocking autophagy will increase the sensitivity of cells to apoptosis signals. METHODS: We designed chitosan nanoparticles (NPs) to promote the co-delivery of gefitinib (an anti-cancer drug) and shRNA-expressing plasmid DNA that targets the Atg-5 gene (shAtg-5) as an autophagy inhibitor to improve anti-cancer effects and autophagy mediation...
April 11, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28399858/ku80-correlates-with-neoadjuvant-chemotherapy-resistance-in-human-lung-adenocarcinoma-but-reduces-cisplatin-pemetrexed-induced-apoptosis-in-a549-cells
#12
Bin Shang, Yang Jia, Gang Chen, Zhou Wang
BACKGROUND: Ku80 is a DNA repair protein which involves in cell apoptosis and chemoresistance. However, it is unclear whether Ku80 correlates with the efficiency of neoadjuvant chemotherapy in human lung adenocarcinoma, and modulates cisplatin/pemetrexed-induced lung cancer cell apoptosis in vitro. METHODS: We recruited 110 patients with stage IIIA lung adenocarcinoma, who received 2 cycles of neoadjuvant chemotherapy, and their lungs were reevaluated by CT scan...
April 11, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28393560/evaluating-polyethyleneimine-dna-nanoparticles-mediated-damage-to-cellular-organelles-using-endoplasmic-reticulum-stress-profile
#13
Maryam Dabbaghi, Reza Kazemi Oskuee, Khadijeh Hashemi, Amir Afkhami Goli
Gene therapy has emerged as an influential tool for treating the genetic and specific acquired disorders. Among all kinds of gene delivery systems, the cationic polymer polyethyleneimine (PEI) is considered as a promising non-viral gene delivery vector, although there are still concerns about its magnitude of cytotoxicity. While any cell insult leads to unfolded/misfolded protein accumulation and its consequent unfold protein response, evaluating the expression profile of ER-stress genes would be a sensitive indicator of cell stress...
April 10, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28389406/simultaneous-overexpression-of-human-e5nt-and-entpd1-protects-porcine-endothelial-cells-against-h2o2-induced-oxidative-stress-and-cytotoxicity-in-vitro
#14
Elisa Chisci, Marco De Giorgi, Elisa Zanfrini, Angela Testasecca, Elena Brambilla, Alessandro Cinti, Laura Farina, Barbara Kutryb-Zajac, Cristina Bugarin, Chiara Villa, Emanuela Grassilli, Romina Combi, Giuseppe Gaipa, Maria Grazia Cerrito, Ilaria Rivolta, Ryszard Tomasz Smolenski, Marialuisa Lavitrano, Roberto Giovannoni
Ischemia-reperfusion injury (IRI) and oxidative stress still limit the survival of cells and organs in xenotransplantation models. Ectonucleotidases play an important role in inflammation and IRI in transplantation settings. We tested the potential protective effects derived by the co-expression of the two main vascular ectonucleotidases, ecto-5'-nucleotidase (E5NT) and ecto nucleoside triphosphate diphosphohydrolase 1 (ENTPD1), in an in vitro model of H2O2-induced oxidative stress and cytotoxicity. We produced a dicistronic plasmid (named pCX-DI-2A) for the co-expression of human E5NT and ENTPD1 by using the F2A technology...
April 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28387759/characterization-of-retroviral-infectivity-and-superinfection-resistance-during-retrovirus-mediated-transduction-of-mammalian-cells
#15
J Liao, Q Wei, J Fan, Y Zou, D Song, J Liu, F Liu, C Ma, X Hu, L Li, Y Yu, X Qu, L Chen, X Yu, Z Zhang, C Zhao, Z Zeng, R Zhang, S Yan, T Wu, X Wu, Y Shu, J Lei, Y Li, W Zhang, J Wang, R R Reid, M J Lee, W Huang, J M Wolf, T-C He, J Wang
Retroviral vectors including lentiviral vectors are commonly-used tools to stably express transgenes or RNA molecules in mammalian cells. Their utilities are roughly divided into two categories, stable overexpression of transgenes and RNA molecules, which requires maximal transduction efficiency, or functional selection with retrovirus-based libraries, which takes advantage of retroviral superinfection resistance. However, the dynamic features of retrovirus-mediated transduction are not well-characterized. Here, we engineered two MSCV-based retroviral vectors expressing dual fluorescence proteins and antibiotic markers and analyzed virion production efficiency and virion stability, dynamic infectivity and superinfection resistance in different cell types, and strategies to improve transduction efficiency...
April 7, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28384720/mirna-copy-number-variants-confer-susceptibility-to-acute-anterior-uveitis-with-or-without-ankylosing-spondylitis
#16
Lu Yang, Liping Du, Yingying Yue, Yike Huang, Qingyun Zhou, Shuang Cao, Jian Qi, Liang Liang, Lili Wu, Chaokui Wang, Zi Ye, Yuan Tian, Aize Kijlstra, Shengping Hou, Peizeng Yang
Purpose: To investigate the association of microRNA (miRNA) copy number variants (CNVs) with acute anterior uveitis (AAU) with or without ankylosing spondylitis (AS) and to assess underlying disease mechanisms. Methods: This study included 768 patients with AAU+AS+ or AAU+AS- and 660 controls from a Chinese Han population. Genotyping of CNVs was performed by TaqMan PCR. The expression of miRNAs, transfection efficiency of miR-9-3, and cytokine production were measured by real-time PCR, flow cytometry, or ELISA...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28370835/design-of-ph-sensitive-peptides-from-natural-antimicrobial-peptides-for-enhancing-polyethylenimine-pei-mediated-gene-transfection
#17
Shi-Kun Zhang, Jin-Wen Song, Su-Bo Li, Hong-Wei Gao, Hong-Yu Chang, Li-Li Jia, Feng Gong, Ying-Xia Tan, Shou-Ping Ji
BACKGROUND: Poor endosomal release is a major barrier of polyplex-mediated gene transfection. Antimicrobial peptides (AMPs) are commonly used to improve PEI-mediated gene transfection by increasing endosomal release. In the present study, we designed novel pH-sensitive peptides that highly enhance transfection efficiency compared to their parent peptides. METHODS: Two analogues of melittin (Mel) and RV-23 (RV) were synthesized by replacing the positively charged residues in their sequences with glutamic acid residues...
April 1, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28366765/non-invasive-oil-based-method-to-increase-topical-delivery-of-nucleic-acids-to-skin
#18
Manika Vij, Shamshad Alam, Nidhi Gupta, Vishvabandhu Gotherwal, Hemlata Gautam, Kausar M Ansari, Deenan Santhiya, Vivek T Natarajan, Munia Ganguli
Topical delivery of nucleic acids to skin has huge prospects in developing therapeutic interventions for cutaneous disorders. In spite of initial success, clinical translation is vastly impeded by the constraints of bioavailability as well as stability in metabolically active environment of skin. Various physical and chemical methods used to overcome these limitations involve invasive procedures or compounds that compromise skin integrity. Hence, there is an increasing demand for developing safe skin penetration enhancers for efficient nucleic acid delivery to skin...
March 30, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28363979/densin-180-controls-the-trafficking-and-signaling-of-l-type-voltage-gated-cav1-2-ca-2-channels-at-excitatory-synapses
#19
Shiyi Wang, Ruslan I Stanika, Xiaohan Wang, Jussara Hagen, Mary B Kennedy, Gerald J Obermair, Roger J Colbran, Amy Lee
Voltage-gated Cav1.2 and Cav1.3 (L-type) Ca(2+) channels regulate neuronal excitability, synaptic plasticity, and learning and memory. Densin-180 (densin) is an excitatory synaptic protein that promotes Ca(2+)-dependent facilitation of voltage-gated Cav1.3 Ca(2+) channels in transfected cells. Mice lacking densin (densin KO) exhibit defects in synaptic plasticity, spatial memory, and increased anxiety-related behaviors --phenotypes that more closely match those in mice lacking Cav1.2 than Cav1.3. Thus, we investigated the functional impact of densin on Cav1...
March 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28358418/with-no-interaction-knockdown-of-apollon-and-mdr1-reverse-the-multidrug-resistance-of-human-chronic-myelogenous-leukemia-k562-adm-cells
#20
Jie-Ru Chen, Xiu-Hong Jia, Hong Wang, Ying-Jie Yi, You-Jie Li
Chemotherapy is the main treatment method for patients with chronic myeloid leukemia (CML) and has achieved marked results. However, the acquisition of multidrug resistance (MDR) has seriously affected the quality of life and survival rate of patients. The overexpression of the inhibitors of apoptosis proteins (IAPs) and the adenosine triphosphate (ATP)-dependent binding cassette (ABC) transporters are the two main causes of MDR. Apollon and MDR1 are the most important and representative members, respectively, among the IAPs and ABC transporters...
March 29, 2017: Oncology Reports
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