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https://www.readbyqxmd.com/read/27904525/exosomes-as-nanocarriers-for-sirna-delivery-paradigms-and-challenges
#1
Fahimeh Shahabipour, Maciej Banach, Amirhossein Sahebkar
Exosomes are nano-sized vesicles that facilitate intercellular communications through carrying genetic materials and functional biomolecules. Owing to their unique size and structure, exosomes have emerged as a useful tool to overcome the limitations of siRNA delivery. The use of exosomes as siRNA delivery vehicles lacks certain disadvantages of the existing foreign delivery systems such as viruses, polycationic polymers and liposomes, and introduces several advantages including inherent capacity to pass through biological barriers and escape from phagocytosis by the reticuloendothelial system, as well as being biocompatible, non-toxic, and immunologically inert...
December 1, 2016: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/27904150/regulating-the-balance-between-necroptosis-apoptosis-and-inflammation-by-inhibitors-of-apoptosis-proteins
#2
REVIEW
Lazaros Vasilikos, Lisanne M Spilgies, Janin Knop, WWei-Lynn Wong
Understanding how Inhibitors of APoptosis proteins (IAPs) regulate apoptosis and necroptosis has been fast-forwarded by the use of Smac mimetics to deplete or inhibit the IAPs, specifically cIAP1& 2 and XIAP. The loss or inhibition of cIAP1, cIAP2 and XIAP causes the majority of cells to be sensitized to death receptor induced cell death, particularly tumour necrosis factor (TNF). Mouse genetics shows that there is some functional redundancy and the use of Smac mimetics has allowed us to understand how changing the composition of proteins recruited to TNF receptor 1 upon TNF ligation can alter protein complex formation and activation of apoptosis or necroptosis, particularly when caspases are inhibited...
December 1, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27904046/cocl2-decreases-ec-sod-expression-through-histone-deacetylation-in-cos7-cells
#3
Shuhei Hattori, Tetsuro Kamiya, Hirokazu Hara, Masayuki Ninomiya, Mamoru Koketsu, Tetsuo Adachi
Extracellular-superoxide dismutase (EC-SOD), one of the SOD isozymes, is negatively regulated under hypoxic conditions, and decreases in its expression may exacerbate vascular diseases. Moreover, epigenetics, such as DNA methylation and histone modifications, are known to play a critical role in the progression of cancer, type 2 diabetes, and atherosclerosis. We previously investigated the involvement of reactive oxygen species (ROS) and p38 mitogen-activated protein kinase (MAPK) in decreases in EC-SOD expression in hypoxic COS7 cells; however, the role of epigenetics in this process currently remains unknown...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27903748/hepatic-expression-of-adenovirus-36-e4orf1-improves-glycemic-control-and-promotes-glucose-metabolism-via-akt-activation
#4
Travis B McMurphy, Wei Huang, Run Xiao, Xianglan Liu, Nikhil V Dhurandhar, Lei Cao
Considering that impaired proximal insulin signaling is linked with diabetes, approaches that enhance glucose disposal independent of insulin signaling are attractive. In vitro data indicate that the E4ORF1 peptide derived from human adenovirus 36 (Ad36) interacts with cells from adipose tissue, skeletal muscle and liver to enhance glucose disposal, independent of proximal insulin signaling. Adipocyte-specific expression of Ad36E4ORF1 improved hyperglycemia in mice. To determine the hepatic interaction of Ad36E4ORF1 in enhancing glycemic control, we expressed E4ORF1 of Ad36 or adenovirus 5, or fluorescent tag alone using recombinant adeno-associated viral vector in the livers of three mouse models...
November 30, 2016: Diabetes
https://www.readbyqxmd.com/read/27903111/electric-stimulation-enhances-cardiac-differentiation-of-human-induced-pluripotent-stem-cells-for-myocardial-infarction-therapy
#5
Ruilian Ma, Jialiang Liang, Wei Huang, Linlin Guo, WenFeng Cai, Lei Wang, Christian Paul, Huang-Tian Yang, Ha Won Kim, Yigang Wang
AIM: Electrical stimulation (EleS) can promote cardiac differentiation, but the underlying mechanism is not well known. This study investigated the effect of EleS on cardiomyocyte (CM) differentiation of human induced pluripotent stem cells (hiPSCs) and evaluated the therapeutic effects for the treatment of myocardial infarction (MI). RESULTS: Cardiac differentiation of hiPSCs was induced with EleS after embryoid body formation. Spontaneously beating hiPSCs were observed as early at 2 days when treated with EleS as compared to control treatment...
November 30, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27899821/activation-of-tnfr2-sensitizes-macrophages-for-tnfr1-mediated-necroptosis
#6
Daniela Siegmund, Juliane Kums, Martin Ehrenschwender, Harald Wajant
Macrophages express TNFR1 as well as TNFR2 and are also major producers of tumor necrosis factor (TNF), especially upon contact with pathogen-associated molecular patterns. Consequently, TNF not only acts as a macrophage-derived effector molecule but also regulates the activity and viability of macrophages. Here, we investigated the individual contribution of TNFR1 and TNFR2 to TNF-induced cell death in macrophages. Exclusive stimulation of TNFR1 showed no cytotoxic effect whereas selective stimulation of TNFR2 displayed mild cytotoxicity...
September 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27895791/nedaplatin-enhanced-apoptotic-effects-of-abt-737-in-human-cancer-cells-via-mcl-1-inhibition
#7
Chong Zhang, Yang-Ling Li, Xu Weng, Li-Yan Li, Ming-Xian Zhou, Da-Yong Zhang, Neng-Ming Lin
Platinum compounds, such as cisplatin, carboplatin, oxaliplatin and nedaplatin, are widely used to treat a number of solid malignancies. Nedaplatin is a second-generation platinum complex, based on its pronounced anti-cancer activities against several solid tumors being equivalent to that of cisplatin, but with lower nephrotoxicity. In this context, the present study aimed to investigate the potential anti-cancer effect by combining nedaplatin with ABT-737. It was found that nedaplatin greatly increased ABT-737-mediated apoptosis in A549 and 95-D cells, accompanied by enhanced cleavage of poly(ADP-ribose) polymerase and caspase-3...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895126/versican-deficiency-significantly-reduces-lung-inflammatory-response-induced-by-polyinosine-polycytidylic-acid-stimulation
#8
Inkyung Kang, Ingrid A Harten, Mary Y Chang, Kathleen R Braun, Alyssa Sheih, Mary P Nivison, Pamela Y Johnson, Gail Workman, Gernot Kaber, Stephen P Evanko, Christina K Chan, Mervyn J Merrilees, Steven F Ziegler, Michael G Kinsella, Charles W Frevert, Thomas N Wight
Viral infection is an exacerbating factor contributing to chronic airway diseases such as asthma via mechanisms which are still unclear. Polyinosine-polycytidylic acid (poly I:C), a toll-like receptor (TLR) 3 agonist used as a mimetic to study viral infection, has been shown to elicit inflammatory responses in lungs and to exacerbate pulmonary allergic reactions in animal models. Previously, we have shown that poly I:C stimulates lung fibroblasts to accumulate an extracellular matrix (ECM), enriched in hyaluronan (HA) and its binding partner versican, which promotes monocyte adhesion...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27894387/-effect-of-hydrocinnamoyl-l-valyl-pyrrolidine-on-healing-quality-of-deep-partial-thickness-scald-wound-in-mice
#9
M L Yang, Y H Li, Q Tan, J T Li, L L Que
Objective: To observe the effect of Toll interleukin-1 recptor homology/BB-loop mimetic hydrocinnamoyl-L-valyl pyrrolidine (AS-1) on the healing quality of deep partial-thickness scald wound in mice. Methods: Forty-two adult C57BL/6 mice were divided into sham injury group (SI), scald group (S), early AS-1 treatment group (EAT), early dimethyl sulfoxide (DMSO) control group (EDC), late AS-1 treatment group (LAT), late DMSO control group (LDC) according to the random number table, with 7 mice in each group. Mice in group SI were sham injured without other treatment...
November 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/27893196/guiding-hmsc-adhesion-and-differentiation-on-supported-lipid-bilayers
#10
Gülistan Koçer, Pascal Jonkheijm
Mesenchymal stem cells (MSCs) are intensively investigated for regenerative medicine applications due to their ease of isolation and multilineage differentiation capacity. Hence, designing instructive microenvironments to guide MSC behavior is important for the generation of smart interfaces to enhance biomaterial performance in guiding desired tissue formation. Supported lipid bilayers (SLBs) as cell membrane mimetics can be employed as biological interfaces with easily tunable characteristics such as biospecificity, mobility, and density of predesigned ligand molecules...
November 28, 2016: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/27892652/aliphatic-polyethers-with-sulfate-carboxylate-and-hydroxyl-side-groups-do-they-show-anticoagulant-properties
#11
Jagadeesh Malineni, Smriti Singh, Sabine Tillmann, Helmut Keul, Martin Möller
There is increasing interest in the synthesis of low molecular weight heparin and heparan sulfate mimetic polymers because of their various potential biomedical applications. The functional activity of heparin and heparan sulfate is believed to arise from the presence of a number of functional groups, such as hydroxyl, carboxylate and sulfate groups. The design and synthesis of novel heparin-mimetic polymers with a particular functionality poses a formidable challenge and requires carefully control of the selective conversion of functional groups on the polymer chain...
November 28, 2016: Macromolecular Bioscience
https://www.readbyqxmd.com/read/27892554/an-%C3%AE-helical-peptidomimetic-scaffold-for-dynamic-combinatorial-library-formation
#12
Nathalie Busschaert, Sam Thompson, Andrew D Hamilton
A novel oligobenzamide-based α-helix mimetic was designed and synthesised with either imine or hydrazone functionalities that serve both to pre-organise the side-chain vectors to mimic the i, i + 4 and i + 7 residues of an α-helix, and to allow for the facile creation of dynamic libraries.
November 28, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27890930/histone-deacetylase-inhibitors-interrupt-hsp90-rasgrp1-and-hsp90-craf-interactions-to-upregulate-bim-and-circumvent-drug-resistance-in-lymphoma-cells
#13
H Ding, K L Peterson, C Correia, B Koh, P A Schneider, G S Nowakowski, S H Kaufmann
Histone deacetylase (HDAC) inhibitors, which are approved for the treatment of cutaneous T cell lymphoma and multiple myeloma, are undergoing evaluation in other lymphoid neoplasms. How they kill susceptible cells is incompletely understood. Here we show that trichostatin A, romidepsin, and panobinostat induce apoptosis across a panel of malignant B cell lines, including lines that are intrinsically resistant to bortezomib, etoposide, cytarabine, and BH3 mimetics. Further analysis traces the pro-apoptotic effects of HDAC inhibitors to increased acetylation of the chaperone heat shock protein 90 (HSP90), causing release and degradation of the HSP90 client proteins RASGRP1 and CRAF, which in turn leads to downregulation of mitogen activated protein kinase pathway signaling and upregulation of the pro-apoptotic BCL2 family member BIM in vitro and in vivo...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890795/inhibition-of-histone-lysine-acetyltransferase-activity-kills-cocl2-treated-and-hypoxia-exposed-gastric-cancer-cells-and-reduces-their-invasiveness
#14
Suvasmita Rath, Lopamudra Das, Shrikant Babanrao Kokate, Nilabh Ghosh, Pragyesh Dixit, Niranjan Rout, Shivaram P Singh, Subhasis Chattopadhyay, Hassan Ashktorab, Duane T Smoot, Mahadeva M Swamy, Tapas K Kundu, Sheila E Crowe, Asima Bhattacharyya
Hypoxia enhances immortality and metastatic properties of solid tumors. Deregulation of histone acetylation has been associated with several metastatic cancers but its effect on hypoxic responses of cancer cells is not known. This study aimed at understanding the effectiveness of the hydrazinocurcumin, CTK7A, an inhibitor of p300 lysine/histone acetyltransferase (KAT/HAT) activity, in inducing apoptosis of gastric cancer cells (GCCs) exposed to cobalt chloride (CoCl2), a hypoxia-mimetic chemical, or 1% O2. Here, we show that CTK7A-induced hydrogen peroxide (H2O2) generation in CoCl2-exposed and invasive gastric cancer cells (GCCs) leads to p38 MAPK-mediated Noxa expression and thereafter, mitochondrial apoptotic events...
November 23, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27889915/constitutive-regulation-of-the-glutamate-aspartate-transporter-eaat1-by-calcium-calmodulin-dependent-protein-kinase-ii
#15
Aarti R Chawla, Derrick E Johnson, Agnes S Zybura, Benjamin P Leeds, Ross M Nelson, Andy Hudmon
Glutamate clearance by astrocytes is an essential part of normal excitatory neurotransmission. Failure to adapt or maintain low levels of glutamate in the central nervous system is associated with multiple acute and chronic neurodegenerative diseases. The primary excitatory amino acid transporters in human astrocytes are EAAT1 and EAAT2 (GLAST and GLT-1 respectively in rodents). While the inhibition of calcium/calmodulin-dependent kinase (CaMKII), a ubiquitously-expressed serine/threonine protein kinase, results in diminished glutamate uptake in cultured primary rodent astrocytes (Ashpole et al...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27889784/targeted-therapy-of-cll
#16
Othman Al-Sawaf, Kirsten Fischer, Barbara Eichhorst, Michael Hallek
The landscape of chronic lymphocytic leukemia (CLL) has undergone profound changes in the past years. First, the addition of CD20-targeting antibodies to conventional chemotherapy has improved the therapeutic outcome in the majority of CLL patients. Since the establishment of the critical role of the B cell receptor signaling pathway in the pathogenesis of CLL, several agents have been developed to target this pathway. Ibrutinib and idelalisib, 2 potent kinase inhibitors, have both become available for CLL therapy in the first and second line...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27889666/yap-dependent-mechanotransduction-is-required-for-proliferation-and-migration-on-native-like-substrate-topography
#17
Shamik Mascharak, Patrick L Benitez, Amy C Proctor, Christopher M Madl, Kenneth H Hu, Ruby E Dewi, Manish J Butte, Sarah C Heilshorn
Native vascular extracellular matrices (vECM) consist of elastic fibers that impart varied topographical properties, yet most in vitro models designed to study the effects of topography on cell behavior are not representative of native architecture. Here, we engineer an electrospun elastin-like protein (ELP) system with independently tunable, vECM-mimetic topography and demonstrate that increasing topographical variation causes loss of endothelial cell-cell junction organization. This loss of VE-cadherin signaling and increased cytoskeletal contractility on more topographically varied ELP substrates in turn promote YAP activation and nuclear translocation, resulting in significantly increased endothelial cell migration and proliferation...
November 16, 2016: Biomaterials
https://www.readbyqxmd.com/read/27889570/inhibitor-of-apoptosis-protein-1-regulates-tumor-necrosis-factor-mediated-destruction-of-intestinal-epithelial-cells
#18
Thomas Grabinger, Konstantin J Bode, Janine Demgenski, Carina Seitz, M Eugenia Delgado, Feodora Kostadinova, Cindy Reinhold, Nima Etemadi, Sabine Wilhelm, Matthias Schweinlin, Kay Hänggi, Janin Knop, Christof Hauck, Heike Walles, John Silke, Harald Wajant, Ueli Nachbur, W Wei-Lynn Wong, Thomas Brunner
BACKGROUND AND AIMS: Tumor necrosis factor (TNF) is a cytokine that promotes inflammation and contributes to pathogenesis of inflammatory bowel diseases. Unlike other cells and tissues, intestinal epithelial cells undergo rapid cell death upon exposure to TNF, by unclear mechanisms. We investigated the roles of inhibitor of apoptosis proteins (IAPs) in the regulation of TNF-induced cell death in the intestinal epithelium of mice and intestinal organoids. METHODS: RNA from cell lines and tissues and analyzed by quantitative PCR, protein levels were analyzed by immunoblot assays...
November 23, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27889389/exercise-mimetics-impact-on-health-and-performance
#19
REVIEW
Weiwei Fan, Ronald M Evans
The global epidemic of obesity and its associated chronic diseases is largely attributed to an imbalance between caloric intake and energy expenditure. While physical exercise remains the best solution, the development of muscle-targeted "exercise mimetics" may soon provide a pharmaceutical alternative to battle an increasingly sedentary lifestyle. At the same time, these advances are fueling a raging debate on their escalating use as performance-enhancing drugs in high-profile competitions such as the Olympics...
November 18, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27887844/anthraquinones-from-morinda-longissima-and-their-insulin-mimetic-activities-via-amp-activated-protein-kinase-ampk-activation
#20
Phi-Hung Nguyen, Hong Seok Choi, Thi Kim Quy Ha, Ji Yeon Seo, Jun-Li Yang, Da-Woon Jung, Darren R Williams, Won-Keun Oh
AMP-activated protein kinase (AMPK) activators are known to increase energy metabolism and to reduce body weight, as well as to improve glucose uptake. During for searching AMPK activators, a new anthraquinone, modasima A (10), along with eighteen known analogues (1-9 and 11-19) were isolated from an ethanol extract of the roots of Morinda longissima Y. Z. Ruan (Rubiaceae). Using the fluorescent tagged glucose analogues, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy-D-glucose (2-NBDG), insulin mimetics were screened with compounds 1-19 in 3T3-L1 adipocytes...
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
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