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Specialty: Hematology

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Total 236 results found since Jan 2013.

TLR9-mediated siRNA delivery for targeting of normal and malignant human hematopoietic cells in vivo
Key Points CpG(A)-siRNA oligonucleotides allow for targeting genes specifically in human TLR9+ immune cells and blood cancer cells. Tumoricidal and immunostimulatory properties of CpG(A)-STAT3 siRNA provide a novel therapeutic opportunity for hematologic malignancies.
Source: Blood - February 21, 2013 Category: Hematology Authors: Zhang, Q., Hossain, D. M. S., Nechaev, S., Kozlowska, A., Zhang, W., Liu, Y., Kowolik, C. M., Swiderski, P., Rossi, J. J., Forman, S., Pal, S., Bhatia, R., Raubitschek, A., Yu, H., Kortylewski, M. Tags: Gene Therapy Source Type: research

The carotenoid lutein enhances matrix metalloproteinase-9 production and phagocytosis through intracellular ROS generation and ERK1/2, p38 MAPK, and RARβ activation in murine macrophages.
Abstract Early studies have demonstrated the ability of dietary carotenoids to enhance immune response, but the mechanism underlying their influence on macrophage activity remains unclear. Here, we investigated the effects of carotenoids on macrophage activity. Carotenoids, including lutein and lycopene, enhanced MMP-9 activity in RAW264.7 macrophages. Lutein was chosen as a representative and analyzed further in this study. It increased the synthesis, activity, and release of MMP-9 in murine RAW264.7 and primary-cultured peritoneal macrophages. MMP-9 induction by lutein was through the transcriptional regulation ...
Source: Journal of Leukocyte Biology - February 19, 2013 Category: Hematology Authors: Lo HM, Chen CL, Yang CM, Wu PH, Tsou CJ, Chiang KW, Wu WB Tags: J Leukoc Biol Source Type: research

siRNA down-regulation of FGA mRNA in HepG2 cells demonstrated that heterozygous abnormality of the Aα-chain gene does not affect the plasma fibrinogen level
Conclusions: Our results suggest that FGG mRNA levels limit fibrinogen expression in normal liver and HepG2 cells and that 50% reduction of FGA mRNA levels would not limit fibrinogen expression in normal liver and HepG2 cells.
Source: Thrombosis Research - February 15, 2013 Category: Hematology Authors: Yuka Takezawa, Kazuyuki Matsuda, Fumiko Terasawa, Mitsutoshi Sugano, Takayuki Honda, Nobuo Okumura Tags: Coagulation and Fibrinolysis Source Type: research

An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe-/- mice and ameliorates anemia and iron overload in murine {beta}-thalassemia intermedia
Key Points Tmprss6 siRNA induces hepcidin and diminishes iron in hemochromatosis or thalassemia mice, improving the anemia seen in the latter model. Manipulation of TMPRSS6 with RNAi therapeutics may be an approach to treating iron overload diseases associated with low hepcidin levels.
Source: Blood - February 14, 2013 Category: Hematology Authors: Schmidt, P. J., Toudjarska, I., Sendamarai, A. K., Racie, T., Milstein, S., Bettencourt, B. R., Hettinger, J., Bumcrot, D., Fleming, M. D. Tags: Red Cells, Iron, and Erythropoiesis Source Type: research

RAD001-mediated STAT3 upregulation and megakaryocytic differentiation.
Conclusion, the present study demonstrated that RAD001 might have the capacity to induce MK differentiation through the up-regulation of STAT3 signalling. PMID: 23329056 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - January 17, 2013 Category: Hematology Authors: Su YC, Li SC, Peng HY, Ho YH, Chen LJ, Liao HF Tags: Thromb Haemost Source Type: research

Sodium selenite alters microtubule assembly and induces apoptosis in vitro and in vivo
Conclusions: Taken together, the results from our study indicate that microtubules are novel targets of selenite in leukemic HL60 cells.
Source: Journal of Hematology and Oncology - January 17, 2013 Category: Hematology Authors: Kejian ShiQian JiangZhushi LiLei ShanFeng LiJiaJia AnYang YangCaimin Xu Source Type: research

Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2.
Abstract Certain biogenic amines, such as 2-PEA, TYR, or T1AM, modulate blood pressure, cardiac function, brain monoaminergic systems, and olfaction-guided behavior by specifically interacting with members of a group of rhodopsin-like receptors, TAAR. A receptor that is absent from olfactory epithelia but had long been identified in the brain and a variety of peripheral tissues, TAAR1 has been found recently in blood B cells, suggesting a functional role of TAAR1 in these cells. With the present study, we have set out to clarify the expression and functional roles of TAAR in different isolated human blood leukocyt...
Source: Journal of Leukocyte Biology - January 11, 2013 Category: Hematology Authors: Babusyte A, Kotthoff M, Fiedler J, Krautwurst D Tags: J Leukoc Biol Source Type: research

Distinct roles for the α , β and γ1 isoforms of protein phosphatase 1 in the outside-in αIIbβ3 integrin signalling-dependent functions.
Abstract Although protein kinases and phosphatases participate in integrin αIIbβ3 signalling, whether integrin functions are regulated by the catalytic subunit of protein phosphatase 1(PP1c)isoforms are unclear. We show that siRNA mediated knockdown of all PP1c isoforms(α, β and γ1)in 293 αIIbβ3 cells decreased adhesion to immobilised fibrinogen and fibrin clot retraction. Selective knockdown of only PP1cγ1 did not alter adhesion or clot retraction, while depletion of PP1cβ decreased both functions. Unexpectedly, knockdown of PP1cα enhanced αIIbβ3 adhesion to fibrinogen and clot retraction. Protein int...
Source: Thrombosis and Haemostasis - January 8, 2013 Category: Hematology Authors: Alrehani N, Pradhan S, Khatlani T, Kailasam L, Vijayan KV Tags: Thromb Haemost Source Type: research

Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cells
Conclusions: Notch1 signalling is required for hypoxia/HIF-1alpha-induced proliferation, invasion and chemoresistance in T-ALL. Pharmacological inhibitors of HIF-1alpha or Notch1 signalling may be attractive interventions for T-ALL treatment.
Source: Journal of Hematology and Oncology - January 5, 2013 Category: Hematology Authors: Jie ZouPeng LiFei LuNa LiuJianjian DaiJingjing YeXun QuXiulian SunDaoxin MaJino ParkChunyan Ji Source Type: research

Integrin-substrate interactions underlying shear-induced inhibition of the inflammatory response of endothelial cells.
Abstract Conditioning of endothelial cells by shear stress suppresses their response to inflammatory cytokines. We questioned whether signalling through different integrin-matrix interactions, previously associated with the pathogenic effects of disturbed flow, supported the anti-inflammatory action of steady shear. Primary human endothelial cells were cultured on different substrates and exposed to shear stress (2.0Pa) for varying periods before stimulation with tumour necrosis factor-α (TNF). Shear-conditioning inhibited cytokine-induced recruitment of flowing neutrophils. However, the effect was similar for cu...
Source: Thrombosis and Haemostasis - December 13, 2012 Category: Hematology Authors: Luu NT, Glen KE, Egginton S, Rainger GE, Nash GB Tags: Thromb Haemost Source Type: research

Imatinib and Nilotinib inhibit Bcr–Abl-induced ROS through targeted degradation of the NADPH oxidase subunit p22phox
In this study, using the K562 CML cell line we showed that inhibition of Bcr–Abl signalling, by either Imatinib or Nilotinib, led to a significant reduction in ROS levels which was concurrent with the GSK-3β dependent, post-translational down-regulation of the small membrane-bound protein p22phox, an essential component of the Nox complex. Furthermore, siRNA knockdown of p22phox in these cells established its importance in ROS production and proliferation. Taken together we believe our results provide a possible link between Bcr–Abl signalling and ROS production through Nox activity and demonstrate a novel mechanism o...
Source: Leukemia Research - December 5, 2012 Category: Hematology Authors: William D. Landry, John F. Woolley, Thomas G. Cotter Tags: Laboratory Studies Source Type: research