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ABSTRACT: A simple method is developed to construct anticoagulant surfaces via passive adsorption of heparin onto the protonated plasma-polymerized allylamine (PPAam) films from phosphate-buffered saline (PBS). These protonated PPAam surfaces are found to have high affinity to heparin. Importantly, the heparin-functionalized PPAam (Hep-PPAam) surfaces show good retention of heparin after long-term immersion in PBS. The Hep-PPAam surface prolongs the activated partial thromboplastin time for about 20 s as compared to 316L stainless steel even though the adsorption amount of heparin is only about 300 ng/cm(2) . This indicates that the heparin bound to the protonated PPAam surfaces in this way maintains a high bioactivity. Blood platelet adhesion and activation on this surface is remarkably reduced and adsorption and activation of fibrinogen is inhibited. Thus, Hep-PPAam surface modification leads to a significant improve of the hemocompatibility. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:3124-3133, 2012.
Journal of Biomedical Materials Research Part A 07/2012; 100(11):3124-33. · 2.63 Impact Factor
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ABSTRACT: To investigate the role of IL-18 and IL-18BP balance in aplastic anemia (AA).
A total of 29 AA patients and 22 controls were recruited in present research. The expressions of IL-18 and IL-18BP were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of IL-18 and IL-18BP were measured in all subjects using real-time quantitative polymerase chain reaction (RT-PCR).
The levels of the IL-18 in plasma of AA and normals were (365.5 ± 160.6) pg/ml and (175.9 ± 92.8) pg/ml (P < 0.01); and the expression of IL-18 in severe AA patients (441.3 ± 116.9) pg/ml were higher than that in non-severe AA patients (326.4 ± 167.0) pg/ml (P < 0.05). The level of IL-18BP was increased in plasma of AA (1788.6 ± 523.8) pg/ml than in normals (1083.6 ± 489.6) pg/ml (P < 0.05). But the ratio of IL-18/IL-18BP in AA patients was much higher than that in controls (P < 0.05). RT-PCR revealed the levels of IL-18 and IL-18BP mRNA were up-regulated in AA patients when compared to controls, but the ratio of IL-18/IL-18BP was significantly elevated in AA patients.
IL-18/IL-18BP imbalance may play an important role in pathogenesis of AA and regulating the balance of IL-18 and IL-18BP may be a therapeutic approach to AA.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 11/2011; 32(11):783-5.
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ABSTRACT: To determine the effects of IL-18BPa/Fc on the cytokine production and survival of peripheral blood mononuclear cells (PBMCs) of immune thrombocytopenia (ITP), PBMCs isolated from patients with ITP and healthy donors were treated with or without of IL-18BPa/Fc. The production of IFN-γ, IL-2, tumor necrosis factor (TNF)-α, IL-4, IL-5 and IL-10 was measured by ELISA, and mRNA expression of IFN-γ and IL-18R was evaluated by RT-PCR. Besides, flow cytometric analysis of cell apoptosis was performed by staining with annexin V-FITC/ Propidium Iodide (PI). The proliferation rate of PBMCs was examined by CCK-8 assay. IL-18BPa/Fc at 10 ng/ml significantly stimulated IL-10 secretion from PBMCs in patients with ITP and healthy donors, while it decreased IFN-γ release. Further, IL-18BPa/Fc enhanced dexamethason(DEX) reduction of PHA-induced IFN-γ production by an additional 38.9%(DEX 20 nmol/l) and 49.9%(DEX 50 nmol/l) in ITP patients. Interestingly, the treatment of PBMCs with IL-18BPa/Fc increased the percentage of early apoptotic cells in patients with ITP. In conclusion, IL-18BPa/Fc, via neutralizing the biologic activity of mature IL-18, accelerates lymphocyte apoptosis and downregulates IFN-γ, while permitting the production of Th2 cytokine IL-10. These observations suggest a role of IL-18BPa/Fc in the recovery of Th1/Th2 balance, as well as its therapeutic potential in the treatment of ITP.
Thrombosis Research 09/2011; 128(6):e119-24. · 2.44 Impact Factor
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ABSTRACT: This study was aimed to investigate the expression and clinical significance of IL-18, IL-18 binding protein (IL-18BP), IFN-γ and IL-4 secreted from splenocytes of patients with idiopathic thrombocytopenic purpura (ITP) in vitro. Spleen mononuclear cells (MNC) were prepared by using routine sterile method, and were cultured in RPMI 1640 complete medium containing 10 µg/ml PHA, 10% fetal calf serum at 37°C and 5% CO2. The levels of IFN-γ, IL-4, IL-18 and IL-18BP secreted from MNC of ITP patients and normal controls were determined after culture for 48 hours. The results showed that after culture of spleen MNC for 48 hours, the levels of IL-18 and IFN-γ were significantly higher in patients with ITP than that in controls, but the levels of IL-18BP was not significantly elevated in ITP patients. The level of IL-4 was below the detectable limit of the assay used. It is concluded that imbalance between IL-18 and IL-18BP may play an important role in pathogenesis of ITP, and regulation of balance between IL-18 and IL-18BP may be a therapeutic approach against ITP.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 07/2011; 19(4):975-8.
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ABSTRACT: To evaluate the efficacy and safety of rituximab on B-lymphocytes and anti-platelet glycoprotein-specific antibodies in patients with refractory primary immune thrombocytopenic (ITP).
Thirty-one ITP patients with a median age of 36 years (range 16 - 56 years) received solely intravenous rituximab at the dose of 375 mg/m(2) once weekly for consecutive 4 weeks. Lab studies included complete blood count, serum concentrations of IgG, IgM and IgA. CD3(+), CD4(+), CD8(+), CD19(+) and CD20(+) cell numbers were assayed by flow cytometry and anti-platelet glycoprotein-specific antibodies (GPIIb/IIIa, GPIb/IX) were assayed by monoclonal antibody-specific immobilisation of platelet antigens (MAIPA) prior to and following rituximab therapy. The response was evaluated according to the response criteria of international working group of ITP.
Complete responses were achieved in 12 cases, response in 7 cases, and no response in 12 cases. Responses were sustained 2 to 28 months (median 6 months) with 4 cases relapsed. After 4 weeks of rituximab therapy, GPIIb/IIIa and GPIb/IX disappeared in responded patients, and CD 19(+)/CD20(+) cells were almost depleted in all patients. As expected, the serum concentrations of IgG, IgM, IgA, and the T cell counts were not changed after therapy. Four patients developed infusion-related reaction, 1 impaired renal function, and 3 secondary infections.
Rituximab is effective and safe, and the adverse reaction is tolerable.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 03/2011; 32(3):163-7.
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ABSTRACT: To investigate the role of IL-18 and IL-18BP balance in the spleens of patients with primary immune thrombocytopenia (ITP).
A total of 12 active ITP patients and 10 normal controls were recruited. Their expressions of IL-18 and IL-18BP were measured by immunohistochemistry (IHC) and immunofluorescence. The mRNA expressions of IL-18, IL-18BP, IFN-γ and IL-4 were studied by reverse transcription-polymerase chain reaction (RT-PCR) in all subjects.
The positive rate of IL-18 was higher in the ITP patients than that of the normal control group (100% vs 90.0%). And the positive rate of IL-18BP was higher in the ITP patients than that of the normal control spleen (83.3% vs 60.0%). The relative amount of mRNA gene expression of IL-18 was increased 6.0-fold in active patients compared to controls (P<0.05). But the elevated mRNA content of IL-18BP failed to compensate for the sharply elevated content of IL-18. As compared with the normal control group, the expression level of IFN-γ mRNA expression was significantly increased 10.2-fold in ITP patients (P<0.05). The decrease observed in IL-4 was 41.7% in active patients compared to controls (P<0.05).
The IL-18/IL-18BP imbalance plays an important role in pathogenesis of ITP and its correction may become a potential therapeutic target for ITP.
Zhonghua yi xue za zhi 01/2011; 91(4):239-42.
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ABSTRACT: The antitumor mechanisms of adriamycin (ADR) have been thought to contribute to induction of apoptosis and inefficiency of DNA repair, processes that are to a large extent mediated by mitochondria. This study aimed to investigate characteristics of ADR, including its antineoplastic activity, drug resistance, and unexpected toxicity in non-Hodgkin lymphoma (NHL) Raji cells at the mitochondrial proteomic level. The alterations of the mitochondrial proteome of Raji cells treated with ADR were analyzed by two-dimensional differential in-gel electrophoresis (2D-DIGE) coupled with linear ion trap quadrupole-electrospray ionization tandem mass spectrometry (LTQ-ESI-MS/MS).The altered patterns of three identified proteins were validated by Western blot and analyzed by pathway studio software. The results showed that 34 proteins were downregulated and 3 proteins upregulated in the study group compared with the control group. The differentially expressed proteins distributed their functions in reduction-oxidation reactions, DNA repair, cell cycle regulation, transporters and channels, and oxidative phosphorylation. Furthermore, heat shock protein 70 (HSP70), ATP-binding cassette transporter isoform B6 (ABCB6), and prohibitin (PHB) identified in this study may be closely related to chemoresistance and could serve as potential chemotherapeutic targets for NHL. Collectively, these results suggest that specific mitochondrial proteins are uniquely susceptible to alterations in abundance following exposure to ADR and carry implications for the investigation of therapeutic and prognostic markers. Further studies focusing on these identified proteins will be used to predict treatment response and reverse apoptosis resistance,and to explore drug-combination strategies associated with ADR for NHL therapy.
Molecular Medicine 03/2009; 15(5-6):173-82. · 3.76 Impact Factor
